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Efficient physical extraction of active constituents from edible fungi and their potential bioactivities: A review
Accepted Manuscript Efficient physical extraction of active constituents from edible fungi and their potential bioactivities: A review Yanan Sun, Min Zhang, Zhongxiang Fang PII:
S0924-2244(18)30101-8
DOI:
https://doi.org/10.1016/j.tifs.2019.02.026
Reference:
TIFS 2432
To appear in:
Trends in Food Science & Technology
Received Date: 13 February 2018 Revised Date:
7 November 2018
Accepted Date: 6 February 2019
Please cite this article as: Sun, Y., Zhang, M., Fang, Z., Efficient physical extraction of active constituents from edible fungi and their potential bioactivities: A review, Trends in Food Science & Technology, https://doi.org/10.1016/j.tifs.2019.02.026. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Efficient physical extraction of active constituents from edible
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fungi and their potential bioactivities: A review Abstract
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Background: Edible fungi are a great source of active constituents, including
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polysaccharides, proteins, terpenoids, minerals and vitamins. In particular, they have
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potential antitumor, antioxidant, immunological activity and could be applied for
7
clinical disease treatment. Conventional extraction methods for active constituents
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usually involve organic solvents and may result in environmental problem and
9
noticeable degradation of the constituents. The efficient physical extraction
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technologies have gained much more attention worldwide which can improve
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efficiency and reduce degradation of active ingredients.
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Scope and approach: This review discusses the recent developments of efficient
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physical extraction technologies including ultrasound-assisted extraction (UAE),
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microwave-assisted extraction (MAE), supercritical fluid extraction (SFE), ultrahigh
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pressure-assisted extraction (UPE) and pulsed electric field extraction (PEF) for active
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constituents from edible fungi and presents a brief summary of their potential
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bioactivities.
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Key findings and conclusions: These technologies have been demonstrated to
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increase the extraction yield, improve product quality, and are energy efficient and
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environmentally friendly. It is expected that these efficient physical technologies will
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be gradually used in extraction of a variety of active constituents in the near future.
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Future research needs to consider varieties of further combined applications of
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physical technologies, which may allow a better maintenance of the functionality of
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active ingredients. The great potential of these extracted edible fungi active
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compounds could be used as the ingredients for health care medicine and foods.
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Meanwhile, consumer's acceptance, safety and legal aspects, and commercial
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availability of health products should also be taken into consideration in future
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studies.
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Keywords: Edible fungi, Active constituents, Physical extraction, Application
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ACCEPTED MANUSCRIPT 1
Efficient physical extraction of active constituents from edible
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fungi and their potential bioactivities: A review
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State Key Laboratory of Food Science and Technology, Jiangnan University, 214122 Wuxi, Jiangsu, China
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Jiangsu Province Key Laboratory of Advanced Food Manufacturing Equipment and Technology, Jiangnan University, China
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Yanan Sun1, Min Zhang1,2*, Zhongxiang Fang 3
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Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia
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*Corresponding author: Professor Min Zhang, School of Food Science and
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Technology, Jiangnan University, 214122 Wuxi, Jiangsu Province, China.
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E-mail: [email protected]
Tel.: 0086-510-85877225; Fax: 0086-510-85877225.
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ACCEPTED MANUSCRIPT Abstract
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Background: Edible fungi are a great source of active constituents, including
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polysaccharides, proteins, terpenoids, minerals and vitamins. In particular, they have
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potential antitumor, antioxidant, immunological activity and could be applied for
19
clinical disease treatment. Conventional extraction methods for active constituents
20
usually involve organic solvents and may result in environmental problem and
21
noticeable degradation of the constituents. The efficient physical extraction
22
technologies have gained much more attention worldwide which can improve
23
efficiency and reduce degradation of active ingredients.
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Scope and approach: This review discusses the recent developments of efficient
25
physical extraction technologies including ultrasound-assisted extraction (UAE),
26
microwave-assisted extraction (MAE), supercritical fluid extraction (SFE), ultrahigh
27
pressure-assisted extraction (UPE) and pulsed electric field extraction (PEF) for active
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constituents from edible fungi and presents a brief summary of their potential
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bioactivities.
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Key findings and conclusions: These technologies have been demonstrated to increase
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the extraction yield, improve product quality, and are energy efficient and
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environmentally friendly. It is expected that these efficient physical technologies will
33
be gradually used in extraction of a variety of active constituents in the near future.
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Future research needs to consider varieties of further combined applications of
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physical technologies, which may allow a better maintenance of the functionality of
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active ingredients. The great potential of these extracted edible fungi active
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compounds could be used as the ingredients for health care medicine and foods.
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Meanwhile, consumer's acceptance, safety and legal aspects, and commercial
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availability of health products should also be taken into consideration in future
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studies.
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Keywords: Edible fungi, Active constituents, Physical extraction, Application
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1. Introduction Edible fungi have the large fruiting body, taste delicious and have high edible,
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medicinal and economic values. China is the global biggest producer of edible fungi
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where Lentinus edodes, Pleurotus ostreatus, Volvariella vovlaca, Flammulina
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velutipes, Hericium erinaceus, Auricularia auricula, Tremella fuciformis, Grifola
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frondosa, Pleurotus eryngii, Agaricus bisporus, and Agrocybe cylindracea are the
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major species (Hua et al, 2018; Wang et al, 2017). In 2013, edible fungus production
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in China reached 31.4 million tons according to Chinese Edible Fungi Association,
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with a value of more than 26 billion US dollars (Zhuang et al, 2015). Edible fungi are
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also considered as a healthy food because they are rich in bioactive compounds
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including polysaccharides (e.g. α- and β-glucan), proteins, peptides, polyphenols,
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terpenoids, vitamins and dietary fiber (Yan et al, 2018; Asaduzzaman et al, 2012; Reis
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et al, 2012). It has been reported that the fungus β-glucan has a broad spectrum of
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biological activity (Xu et al, 2014; Moradali, et al, 2007), and terpenoids and sterol
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compounds have antibacterial, antiviral and antioxidant activities (Kim et al, 2010;
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Mori et al, 2008; Zhang et al, 2013). Currently, edible fungues components of
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polysaccharide, saponin, triterpene, adenosine and flavonoids are the top five efficacy
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components in the approved health foods (Gu et al, 2016). Ganoderma lucidum,
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caterpillar fungus and poria cocos account for 68%, 15% and 10% of the total
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approved health food of edible fungus in China. Their attractive flavor/taste, high
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nutritional value and potential biological functions have made edible fungi not only
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popular in China and Asia, but also around the world.
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The health food can be classified into three generations according to the product
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characteristics and marketing time in China (Zhuang et al, 2015). The first generation
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products refer to health food by enhanced nutrition elements and active ingredients.
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For example, a health food is added with external components of calcium, magnesium,
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iron, zinc, selenium, vitamin, beta-carotene, folic acid, amino acids, and dietary fiber.
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The second generation products must have some specific physiological functions
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through strict animal and human study. This generation products are the majority of
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generation of health products not only needs to pass the above animal and human
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clinical study, but also know the functional components, their chemical structure and
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human health mechanisms. Therefore, understand the functional factors/constitues
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and their efficacy mechanisms of edible fungi are very important in development of
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this group of functional foods.
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How effectively destroy the cell wall to release the intracellular material is a
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main problem of obtaining active constituents from edible fungi. Conventional
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extraction methods usually involve large amounts of organic solvent and long
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extraction time, which are high cost and time consuming, have negative environment
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impact, and may result in the degradation and coagulation of active constituents. To
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alleviate these disadvantages, some new extraction methods have been developed (Yin
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et al, 2018; Yan et al, 2018; Chen et al, 2018). Efficient physical extraction techniques
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usually refers to the processing of cell disruption by physical means to increase the
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extraction yield and improve product quality (López et al, 2018; Milad et al, 2019;
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Münevver et al, 2019; Pataro et al, 2018). These technologies are energy efficient and
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environmentally friendly, showing the great potential for health care medicine and
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foods of active constituents. This review focuses on the recent developments in
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application of the efficient physical extraction techniques (UAE, MAE, SFE, UPE and
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PEF) to obtain active constituents from edible fungus and their potential applications
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in functional foods.
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2. Efficient physical extraction of active constituents from edible
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fungi
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2.1 Ultrasound-assisted extraction (UAE)
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In the process of ultrasound extraction, the crushed sample was dissolved in
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appropriate solvent and put into the ultrasonic bath, where the extraction temperature
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and extraction time are set already (Klejdusa et al., 2009). The ultrasound frequencies
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(greater than 20 kHz) can promote the hydration of edible fungi which cause the
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increase of the cell walls pores, lead to cell wall rupture. Therefore, the extraction
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(Golmohamadi et al., 2013; Huie, 2002; Cintas et al., 1999). Compared with
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conventional extraction techniques, utilization of ultrasound to assist the extraction of
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active constituents from edible fungi have numerous advantages. Firstlt, the UAE
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techniques can overcome the major limitations of the conventional extraction process
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for long extraction time and numerous solvent dosage. Secondly, the bioactivity
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preservation of extract products are higher due to lower extraction temperatures.
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Finally, the UAE process have lesser energy consumption and higher yield of
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production (Vinatoru et al., 2001; Rombaut et al., 2014; Alzorqi and Manickam, 2015).
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The ultrasound to assist extraction have demonstrated the improvements in extraction
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yield ranging from 6 to 35% in both aqueous and solvent extraction systems (Vilkhu
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et al., 2008).
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The application of ultrasound as a technique for assisting extraction of active
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constituents from edible fungi has been widely reported (Qiao et al., 2012; Chen et al.,
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2014a). In some studies, quadratic regression models have been used to optimize
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UAE of polysaccharides from edible fungi (Clemente et al., 2014; Yan et al., 2016).
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The polysaccharide extraction yield from Agaricus bisporus was approximately 5.5 %
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with ultrasound assisted water extraction by applying the response surface
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experiments (Tian et al., 2012; Chen et al., 2014a,b). Cheung et al (2013) extracted
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the polysaccharide from Grifola. Frondosa and Lentinus edodes with UAE, the
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polysaccharides yield was 0.05 %, and 0.13 % respectively after 60 min extraction
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and the edible fungus have loose particle structure.
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The highest polysaccharides yield from Agaricus bisporus of 6.02% was
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obtained under the optimized condition of ultrasonic power 230 W, extraction
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temperature 70 °C, extraction time 62 min, and solid-liquid ratio (W/M ratio) 30 ml/g
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(Tian et al. 2012). Under the ultrasonic power 30W, W/M ratio 40 ml/g, extraction
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time 8 h, polysaccharide extraction yield from Yunzhi mushroom was 5.95% (Pan et
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al., 2010). By using UAE, the polysaccharide yield from Lentinus edodes was around
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14.39 % under ultrasound power 340 W, water-material ratio 30:1 (ml:g), and
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ultrasound treatment time 14 min, which was obviously higher than water heating
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Tricholoma matsutake using UAE and response surface of quadratic regression design,
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the polysaccharide extraction yield was 7.97% under ultrasonic power 365W, W/M
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ratio 53.5ml/g, and extraction time 160 s. In a recent study, three extraction methods
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have been used to the extraction of β-D-glucan polysaccharides from cultivated
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mushroom by Alzorqi et al. (2017). The UAE extraction resulted in a higher yield of
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polysaccharides with higher content of β-D-glucan at shorter extraction time, and
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more importantly the extraction process in a state of low temperature all the time as
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compared to the conventional extraction methods of hot water extraction (HWE) and
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Soxhlet extraction (SE). The amount of β-D-glucan by UAE extraction (44.42 mg/g)
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was remarkably higher than HWE (37.73 mg/g) and SE (25.03 mg/g) respectively.
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Ingrid et al. (2017) applied the ultrasound to assist the extraction of polysaccharides
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from edible fungi by-products, and the extraction yields of 4.70 and 4.35% were
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obtained under the condition of ultrasonic amplitudes 100 mum and treatment times
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15 min after precipitation times of 1 h and 18 h, respectively.
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2.2 Microwave-assisted extraction (MAE)
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Microwave-assisted extraction (MAE) is a quickly and efficiently extraction
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technique that uses microwaves to evenly heat both solvent and material to facilitate
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the extraction of target components. The microwave is a non-ionizing electromagnetic
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wave with the frequency between 300 MHz and 300 GHz and is positioned between
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X-ray and infrared rays in the electromagnetic spectrum (Ajila et al., 2011). Recently,
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MAE has been applied in extraction of active constituents from soil, plant, and food
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matrices as it is more effective compared with conventional solvent extraction method
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(Mandal et al., 2007). The principle of MAE is that when hydrated biomaterial tissues
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cells are heated, water absorbs energy, evaporates and generates high pressures in the
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cells. The high pressures pushes the cell walls from within the cell and leads to cell
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rupture, therefore, the active constituents released into the extracellular solvents.
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(Letellier and Budzinski, 1999; Wang and Weller, 2006; Garofulic et al., 2013). This
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technique have several advantages over conventional heating extraction, including
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required shorter extraction time, less solvent amount and reduced energy consumption
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ACCEPTED MANUSCRIPT (Armenta et al., 2008; Garofulic et al., 2013). In addition, the enhancement of active
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constituents diffusion form intracellular to solvent increases the extraction yield
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(Armenta et al., 2008; Garofulic et al., 2013; Liazid et al., 2011). The effect of the
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microwave extraction is affected by microwave power, solvent-to-solid ratio, and
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extraction time. The choice of solvent is the other important factors for MAE which
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depends on the solubility of the active compounds and the microwave absorbing
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properties of the solvent (Antonietta et al., 2016).
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A study showed that tiny amounts of Agaricomycetes material and shorter time
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were required in MAE extraction of DNA for subsequent DNA PCR amplifications
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(Dornte et al., 2013). This technique had high reliability (about 90 %) and was
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suitable for fresh and aged fungal cultures, avoiding specific expensive and dangerous
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chemicals for cell lysis and reagent residual used in conventional extraction
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technology. The MAE technique was also used in isolating fungal metabolite
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ergosterol from Agaricus bisporus and compared the difference of ergosterol from
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MAE and classical solvent extraction (Young et al., 1995). However, the MAE
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process is simple, fast, reliable, and economical with respect to amounts of solvent
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required, especially when compared with traditional solvent methods (Elena et al.,
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2016).
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Ahmad et al. (2014) applied MAE to extract natural dyes from Pycnoporus
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sanguineus mushroom, and the results indicated that it is an attractive alternative to
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conventional boiling water extraction method. Fhernanda et al. (2017) reported that
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both MAE and pressurized solvent extraction are easy, rapid and efficient approaches
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to extract edible fungi polysaccharides. Heleno et al. (2016) observed that the
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extraction temperature, extraction time, microwave power and solid to liquid ratio had
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significant effects on the ergosterol extraction yield from Agaricus bisporus L. By
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using distilled water as solvent at microwave power of 400 W, temperature (132.8 °C)
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and solid-liquid ratio (1.6 g/L) for 19.4 min, about 556 mg ergosterol/100g dw edible
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fungi was obtained. Maeng et al. (2017) extracted the total phenolic constituent from
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Coriolus versicolor mushroom, 40% ethanol concentration, 125 W microwave power
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and 3.8 min extraction time were found to be the optimal conditions. However for
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phenolic content was achieved at extraction temperature 80 °C, extraction time 5 min,
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and ethanol concentration 80% (Mustafa et al. 2014). These studies indicate that MAE
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conditions should be optimized for extraction of different active constituent from
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different edible fungi species.
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2.3 Supercritical fluid extraction (SFE)
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Supercritical fluid extraction (SFE) is a modern technique that supercritical
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fluids are used to extract the active constituents from a solid or even liquid material.
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(Junior et al., 2010). The traditional solvent extraction is based on the diffusion
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process, solvent must be spread to the edible fungi tissue and active constituents
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dissolving out to solvent. The diffusivities of supercritical fluid are much faster than
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in liquids and therefore extraction time is more shorter. In addition, there is no surface
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tension between fluid and material, and the viscosity of supercritical fluid is lower
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than liquids. For the same extraction process, organic solvent extraction requires
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several hours whereas SFE only take 10 to 60 minutes (Antonietta et al, 2016; Skoog,
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2006). Fig. 1 is a laboratory-scale SEF extraction plant, where the system contains a
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pump for the gas cylinder, a pressure cell to contain the sample, a means of
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maintaining pressure in the system, and a collecting vessel. In operation, the fluid
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(usually carbon dioxide) is heated to supercritical condition, and then it quickly
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diffuses into the material internal and dissolve target active constituents in the
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extraction container. The dissolved active constituents is separated at lower pressure
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separator. The supercritical fluid after extraction can be cooled, re-compressed and
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recycling, or emissions into the atmosphere (Antonietta et al, 2016). Compared with
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the traditional method, the SFE technology presents various advantages, such as
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reduce energy consumption, operating under low temperature and high product
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quality with no solute in the solvent phase. However, this technology application is
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limited because of its scope of the only extraction low or medium polar active
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constituents and its production costs are the major drawback of this approach
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(Garcia-Salas et al., 2010; Silva et al., 2017; Kitzberger et al., 2009).
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Generally, carbon dioxide (CO2) have the particular characteristics of moderate
ACCEPTED MANUSCRIPT critical conditions (31.1°C and 73.8MPa), SFE is performed using only CO2 as
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supercritical fluid to extracts nonpolar compounds. For polar molecules extraction
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(such as anthocyanins), a polar solvent such as ethanol or methanol must also be
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added to supercritical fluid. Therefore the choice of the polar solvent may play an
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important part for the success of the extraction process. Due to ethanol and water are
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nontoxic, availability, and chemically inert (Ghafoor et al., 2014). The water/ethanol
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fraction are soluble in supercritical CO2 (scCO2) at the pressure and temperature, so
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the mixture can be considered supercritical (Ghafoor et al., 2014; Herrero et al., 2006).
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Consequently the CO2, ethanol and water were mixed according to the different
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proportions as the supercritical fluid is the most common method (Ghafoor et al.,
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2014; Junior et al., 2010).
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Simone et al. (2012) studied the extraction of antioxidant and antimicrobial
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compounds from Agaricus brasiliensis using SFE technology. The results showed that
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the optimal conditions of SFE were at temperature of 50 °C and 30 MPa in the
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presence of 10% ethanol, at which the extraction yields were reached 4.2%. The
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results were similar to that reported by Li et al. (2016) for the extraction from
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Ganoderma lucidum spores, and those reported by Kitzberger et al. (2007) for the
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extraction from Lentinula edodes, where 20 MPa and 40 °C with 15% aqueous
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ethanol as a co-solvent were used. It is not common to extract heat sensitive active
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compounds such as anthocyanins use temperatures above 40 °C, but the extraction of
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other phenolic constituents need higher temperatures. Diego et al. (2017) extracted
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vitamin D-enriched compounds from Shiitake mushrooms (Lentinula edodes) by
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supercritical fluid extraction combined with UV-irradiation. Fractions containing up to
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18% (w/w) ergosterol and other ergosterol derivatives (provitamin D2) was obtained,
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and they can be partially transformed into vitamin D2 by UV-light irradiation.
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The subcritical carbon dioxide extraction is a process that consists in using
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carbon dioxide under high pressure to maintain it in the liquid state. In the process of
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the extraction, the subcritical state can be reached under the critical temperature and
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pressure. With the development of extraction technology, supercritical extraction and
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subcritical extraction technology gradually replaced the traditional extraction
ACCEPTED MANUSCRIPT technology, which widely used in active constituents extraction. Senka et al. (2011)
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compared the efficacy of subcritical against supercritical carbon dioxide extraction of
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fatty acids from Boletus edulis. They found that increasing operational pressure and
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extraction time leads to increases in extraction yield in both subcritical and
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supercritical carbon dioxide extraction. An extraction yield of around 2.4% was
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achieved using subcritical extraction at the conditions of 27 °C, 344 bar and 3.6 h,
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whereas an extraction yield of 2.1% was obtained for supercritical extraction at the
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conditions of 40 °C, 238 bar and 4.8 h. The results suggest that both methods are
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effective on the extraction of fatty acids from Boletus edulis and the selection of
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which method could be depended on the availability of facilities and operational cost.
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2.4 Ultrahigh pressure-assisted extraction (UPE)
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The ultrahigh pressure-assisted extraction (UPE) is a developing rapidly novel
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technology in recent years to enhance extraction of active component from edible
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fungi. The extract solvent rapidly permeated to the plant internal vascular bundles and
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glandular cell under ultra high pressure, causing the volume change of cell and
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promoting the moving of chemical equilibrium (Ji et al., 2011; Zhang et al., 2012a;
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Zhu et al., 2012; Liu et al., 2013a,b). Pressure relief are usually performed in a few
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seconds, the pressure of the tissue cells from a few hundred MPa quickly reduced to
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atmospheric pressure (Xi et al., 2013). In the opposite direction of pressure, the cell
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wall and cell membrane are strongly impacted leding to the distortion, the solvent
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dissolved active component in cells rapidiy transfer to the outside of the cell under
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high osmotic pressure to achieve the extraction (Xi, et al., 2010; Joo et al., 2012). A
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laboratory-scale batch type prototype of UPE system (pressure 100 to 500 MPa;
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temperature 20-50 °C) is shown in Fig. 2 (Xi et al., 2011b; Chen et al., 2009a,b). The
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general procedures of UPE are illustrated in Figure 3 and were discussed
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systematically by Xi (2017). Briefly, dried edible fungi pulverized materials are mixed
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with the suitable solvent according to the similar dissolve mutually theory in the
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germfree storage bags. Then put the bag into a pressure vessel after ruling out the air
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in the bag, the pressure and temperature are controled by pressure vessel (Prasad et al.,
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2009; Lee et al., 2011). The pressure vessel is pressurized with the fluid (usually water)
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ACCEPTED MANUSCRIPT by an ultrahigh pressure booster pump (Xi, 2017; Zhang et al., 2012b). After
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centrifuged (4,000 up to 8,000 rpm for 10-15 minutes), the filtered supernatant liquid
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is usually evaporated by a rotary evaporator under vacuum at 45-65 °C, and then
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stored at 4 °C in refrigerator (Xi, 2017). Thus, the edible fungus extracts that contain
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active compounds are obtained.
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The properties of water is hardly affected by the pressure, as long as it remained
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in the liquid state. However, higher pressure helps water into the sample tissue rapidly,
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resulting in improved mass transfer rate and extraction efficiency. The ultrahigh
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pressure-assisted extraction can be effectively used to extract the thermolabile active
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component (vitamins, anthocyanins) because of the mild processing temperature (Lee
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et al., 2011; Zhang et al., 2011a,b). The UPE improve the extraction rate by rupturing
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the cellular wall (Xi et al., 2011a; Chen et al., 2009a, b), membrane and organelles to
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reduced treatment time and solvent dosage. The UPE has been widely used to the
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extraction of plant active component in recent years (Xi et al., 2011b; Joo et al., 2011;
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Altuner et al., 2012; Guo et al., 2012; Joo et al., 2012; Xi and Wang, 2013), as can be
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deduced from a great mass of papers published dealing with this subject based on the
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publications available in web of knowledge since 2011. This technique has become
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relatively mature and can be effectively used for extraction of active constituents from
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edible fungi.
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Jiang (2011) studied the extraction of Lentinus edodes polysaccharide with UPE,
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the cell tissue were observed. Fig. 4 reveals that the Lentinus edodes tissues of the
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untreated samples (a,b) were basically intact, compared with the structures of the
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samples treated with UPE (c,d). Fig 4 shown that the cell structure of the untreated
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samples had a certain degree of damage through smash and homogeneous, but there
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are still large particles and cellular structure was not destroyed completely. After 140
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MPa of ultrahigh pressure treatment, the cellular structure has obvious changes which
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larger particles were broken, it has been difficult to observe the cellular structure
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significantly. Compared with control group, UPE treatment can further destroy the
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cellular structure and reduce the mass transfer resistance to improve the efficiency of
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extraction (Chen et al., 2009a,b). In addition, similar study results have also been
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reported by Chen et al. (2014a), who reported that UPE treatment could result in the
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disruption of the Cordyceps militaris tissue, which enhanced the mass transfer of the
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solvents into the edible fungi materials and the soluble active component into the
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solvents. Chen et al. (2015) extracted polysaccharides from Cordyceps militaris under the
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optimal UPE conditions. At the pressure of 300 MPa, solid–liquid ratio 1:40, and 2
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min of extraction time at 70 °C, a maximum polysaccharide yield 9.33% was obtained.
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A polysaccharide extraction yield of 2.762% was achieved when the mushroom of
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Ganoderma lucidum was extracted at the pressure 400 MPa, temperature 50 °C,
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material (g) to solvent (ml) ratio 1:40, and extraction time 6 min, which was 37.1%
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higher than that of water extraction (Du et al., 2009). It was also reported that the
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polysaccharide extraction yield from dried fruit bodies of Lentinus edodes was 8.96%
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at the optimal conditions of extraction time 4 min, extraction temperature 55 °C,
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pressure 350 MPa, and solid-liquid ratio 1:35. This was 2.23 times higher than that by
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water extraction, and 48.8% higher than that by ultrasonic combined with enzymatic
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hydrolysis extraction.
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2.5 Pulsed electric field extraction (PEF)
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Pulsed electric field (PEF) technology is used to extract intracellular active
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component as a non-thermal technique, the principle is requiring placement of target
330
material between the poles in a batch or continuous treatment chamber and using short
331
pulses of high voltage to promote polar material high speed move to the direction of
332
electrode under the effect of electric field. The tissue cells was irreversible damaged
333
because of cell membrane electroporation lead to the dissolution of bioactive
334
substances (Antonietta and Matteo, 2016; Vorobiev and Lebovka, 2010). Used as
335
intensification pretreatment, PEF has shown great potential to replace conventional
336
extraction technology as a moderate effective extraction technology (Donsi et al.,
337
2010) and improve the extraction yields of bioactive component.
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A laboratory-scale prototype of PEF extraction system is represented in Fig. 5. It
339
has three main components: a pulse generator, a treatment chamber and a pumping
340
system. Material in the treatment chamber under high voltage (up to 40 kV) pulse
ACCEPTED MANUSCRIPT should avoid air bubbles which causing electric spark. Once produced electric spark,
342
the electrode will be corrosion and material be electrolysis. Therefore, the electrode
343
surface should smooth as far as possibles to reduce the escape of the electron, the
344
circular electrode was used to avoid electric field transition concentration and provide
345
a uniform high voltage pulse electric field for materials when designing treatment
346
chamber (Barba et al., 2015). The system is generally monitored and controlled by a
347
computer and an oscilloscope. The effect of PEF-assisted extract mainly has been
348
influenced by two aspects: on the one hand is the physicochemical properties of the
349
material. The conductivity and resistance are determined by different material types
350
and cell size, the greater the volume of the cell is sensitive to the pulsed electric field;
351
On the other hand, extraction effect is influenced by temperature, pH, conductivity
352
and viscosity (Elena et al., 2016; Vorobiev et al., 2010). In PEF-assisted extraction
353
process, the electric field strength is the decisive factor, pulse width, treatment time,
354
number of pulses and energy density affect the extraction effect indirectly. The total
355
specific energy are principally impacted by the applied voltage, the treatment time,
356
and the resistance of the treatment chamber. (Elena et al., 2016; Puertolas et al.,
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2012).
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PEF technology is widely used in the extraction of active compounds from edible
359
fungi, many studies have been reported by different authors. For instance, Yin et al.
360
(2008) extracted polysaccharides from inonotus obliquus by PEF technology, the
361
extraction yield of polysaccharide reached 49.8% which is 1.67 times of hot alkali
362
extraction under the best optimize extraction conditions of 30 kV/cm field intensity,
363
pulse number 6, liquor ratio 25 mg/mL, pH 10. Compared with the traditional
364
extraction method, PEF have short extraction time (12 µs), high extraction efficiency
365
and less impurity in the extract. Zhang et al. (2011c) found that PEF technology
366
enhanced exopolysaccharides (EPS) extraction yield from Tibetan spiritual
367
mushrooms significantly. The EPS extraction yield was increased by 84.3% under the
368
conditions of number of pulses 8, electric field intensity 40 kV/cm and pH 7. Li et al.
369
(2013) compared the efficiency of PEF, ultrasonic and microwave assisted methods on
370
extraction of active components (fungal polysaccharide) from Auricularia auricula,
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and the highest yield of anti-coagulant activity fungal polysaccharide was obtained by
372
using PEF method under field strength of 24 kV/cm. In other study, PEF (100-1000 V/cm)-assisted pressure technique was used to
374
extract polysaccharide, proteins, and terpenoids from Agaricus bisporus. Parniakov et
375
al (2014) used PEF-assisted pressure technique and solvent technique to extract
376
proteins from Agaricus bisporus under electric field strength 800 V/cm. The
377
maximum protein extraction yield approximately was 0.26 under the condition of
378
pressure extraction (PE) alone. Combined with PEF-assisted extraction, the highest
379
extraction yield of 0.42 was achieved approximately. In addition, the protein extracts
380
from water extraction under 70 °C for 2 h and ethanol extraction under 25 °C for 24 h
381
were cloudy and their extract have impurities, whereas the extracts from PE+PEF was
382
clear. In addition, another study reported that combination of PEF with pressure
383
extraction allowed production of edible fungus extracts with higher extraction yield of
384
polysaccharides and proteins compared with pressure extraction alone (Elena et al.,
385
2016). The above studies show that PEF technology is an effective extraction method
386
which can improve the dissolution rate of active constituent in different materials by
387
controlling the PEF treatment conditions and the molecular structure of the natural
388
active constituent is not easy to be damaged.
389
2.6 Advantages and disadvantages of different technologies
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According to the existing researches, the UAE, MAE, SFE, UPE and PEF are all
391
fast and efficient for extracting active constituents from edible fungi. These physical
392
extraction techniques decrease the extraction time greatly because of working at
393
elevated pressure or/and temperature. Each technology has its own advantages and
394
disadvantages, which are listed in Table 1. According to the target extracting active
395
constituents, a suitable technology can be chosen.
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Compared with the traditional extraction technology, the UAE and MAE
397
operation are easier in many cases, almost no pollution to the environment, low cost
398
and relatively accurate results, which opens up a new research for the extraction of
399
active
400
ultrasonic-microwave synergistic extraction makes full use of the cavitation effect of
ingredients
from
edible
fungi.
The
innovation
technology
of
ACCEPTED MANUSCRIPT ultrasonic vibration and the high energy effect of microwave, complementing the
402
disadvantages of single UAE and MAE technology (Yin et al., 2018). The high
403
efficiency extraction for solid samples at low temperature and atmospheric pressure
404
are achieved. Cell wall is mainly composed of cellulose, hemicellulose and lignin.
405
The combination of ultrasound and microwave can change the size of cellulose
406
crystallization zone, reduce its crystallinity, and partially degrade lignin and
407
hemicellulose, so that solvent can quickly enter cells, which can effectively shorten
408
the extraction time and improve the extraction rate. In addition, the technology is
409
conducive to extracting components with poor polarity and thermal stability, and can
410
avoid decomposition caused by long time extraction under high temperature and
411
pressure, so that the molecular structure of the extract can not be destroyed.
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Supercritical CO2 is a common supercritical fluid, which is safe, non-toxic,
413
cheap and recyclable. However, supercritical CO2 extraction has a long time, high
414
extraction pressure and temperature, especially for solid materials, it is not only
415
inefficient but also has many cycles, so the large-scale application of supercritical
416
CO2 extraction technology is limited. In view of these shortcomings of supercritical
417
CO2 extraction, researchers at home and abroad have carried out extensive research on
418
ultrasound-enhanced supercritical CO2 extraction (Chemat et al., 2017; Wei et al.,
419
2016). Ultrasound-enhanced supercritical CO2 extraction technology refers to the
420
traditional supercritical CO2 extraction technology strengthened by external
421
ultrasound field to reduce the extraction temperature and pressure, as well as the
422
amount of entrainer, which can shorten the extraction time, improve the extraction
423
rate, while maintaining the unchanged structure of the extraction object.
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The cells are broken through membrane perforation produced by high-voltage
425
pulses during the process of PEF extraction, which can break cells in an instant and
426
take less time (Liu et al., 2018a,b). Compared with SFE and SCFE, PEF has lower
427
cost and higher universality of equipment, the heating process can be saved due to
428
rapid increase of temperature in the breaking process. However, there are still a series
429
of problems to be solved urgently in the application of PEF technology in industrial
430
production. PEF system should be standardized, including the structure of treatment
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room, operation mode and construction materials. Then perfect control system should
432
be designed to avoid changes caused by secondary effects. In addition electrochemical
433
reactions in the process of treatment should be considered to avoid the production of
434
toxic substances. The cell structure is changed by ultra-high pressure (reach up to 700 MPa), the
436
contact area with the solvent is increased and the mass transfer resistance is lowered,
437
causing the active ingredient dissolved quickly, and the extraction efficiency can be
438
significantly improved. UPE can be carried out at near room temperature, which not
439
result in structural changes and physiological activity reduction of small molecule
440
substances caused by thermal effects. Compared with traditional thermal extraction,
441
the volume of liquid decreases in the process of UPE, and there is no energy
442
consumption for solvent phase transformation. At the same time, the heat exchange
443
between the system and the external environment is also less because of the little
444
change of temperature in the extraction process. Therefore, only the volume
445
compression process of extracting solvent consumes part of the energy in the boosting
446
stage, and the energy loss of the whole process is very low. UPE technology has the
447
advantages of high efficiency and purity in the extraction of natural active ingredients
448
(Chen et al., 2014a). Especially, the extraction process can be carried out at room
449
temperature, avoiding the damage of thermal effect to natural active ingredients,
450
which has been affirmed by many researchers. Although UPE technology has many
451
unique advantages in extraction, in order to promote this new technology from
452
laboratory research to large-scale industrial production, the following aspects are
453
needed to continue to develop. The UPE equipment should be improved, such as
454
installation of real-time temperature monitoring equipment, in order to control
455
temperature more accurately. The synergistic extraction of natural active ingredients
456
by UPE technology and other technologies should be studied, such as the combination
457
of UPE technology and homogenization, enzyme-assisted UPE.
458
3. Bioactivities of edible fungi active constituents
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3.1 Research and application of active constituents
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3.1.1 Polysaccharide The active constituents such as polysaccharides, glycoprotein, peptides,
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terpenoids and ergosterol derived from cultured mycelia, fruiting bodies, and filtrates
463
of edible fungi have displayed strong antitumor activities. Chihara (1969) assessed the
464
antitumor activities of extracted polysaccharides from edible fungi for the first in the
465
1960s. Since then, the fungal polysaccharide antitumor activity and its mechanisms of
466
action have been extensively investigated. The structural diversified polysaccharides
467
from edible fungi have been isolated by numerous researchers who proved the strong
468
antitumor activity (Yan et al., 2018; Ren et al., 2012; Zong et al., 2012; Chen et al.,
469
2011). Compared with the traditional antitumor drugs, the antitumor activities of
470
polysaccharides obtained from edible fungi exhibit several mechanisms of action,
471
which
472
(immune-enhancing activity); and (2) direct antitumor activity by inhibiting growth of
473
various types of tumor cells and tumor metastasis in the body, inducing apoptosis of
474
tumor cells (direct tumor inhibition activity) (Yan et al., 2018; Zhang et al., 2011d;
475
Wasser, 2002; Zhang et al., 2007).
(1)
enhancement
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against
bearing
tumors
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Fig. 6 illustrates the mechanisms of antitumor activity of polysaccharides from
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Lentinus edodes. Lentinan is a β-(1→3)-D-glucan isolated from Lentinus edodes,
478
which can activate many immune cells to regulate the release cell signal
479
semiochemicals such as cytokines for the indirect immunostimulatory anti-cancer. The
480
increase of cytokine secretion in immune system have been observed in a mass of
481
research (Hou et al, 2008 a,b; Lull et al, 2005; Shin et al., 2003). Moreover, treatment
482
with lentinan can destroy cancer cells migration by increasing the phagocytosis of
483
immune cells in the human body and increase the production of chemical messengers
484
such as nitric oxide (NO) and hydrogen peroxideto (H2O2) to stimulate the immune
485
system. (Hou et al, 2008 a,b). In addition, hormonal factors play an important role in
486
cancer growth, which may be related to the immune-activating ability of lentinan.
487
These researches suggested that lentinan have the effect of inhibit the growth and
488
even kill cancer cells directly through a variety of pathways, human immune system
489
ars activated by different mechanisms such as the various immune cells stimulation
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ACCEPTED MANUSCRIPT and the cell signal messengers production. (Zhang et al., 2011d). Hamuro et al (1994)
491
demonstrated that the combination of cytokine interleukin IL-2 (a cell signaling
492
molecule) and lentinan for the reduction of lung metastasis colony numbers expressed
493
a synergistic effect which the reduction reach to 85%, the reduction reach to 28.4% or
494
7.1% reduction respectively when IL-2and lentinan alone. Drandarska et al (2005)
495
found that the combination of vaccine with lentinan can enhance against tuberculosis
496
by inducing the activation of immune cells in the lung tissue causing immune
497
response in lung and reduce its side effects. Moreover, better clinical results could be
498
obtained for cancer patients when lentinan is added to chemotherapy, the immune
499
responses was improved by regressing the lesions or tumors to prolongate the in
500
patients life (Zhang et al., 2011d).
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As the antineoplastic mechanism research, numerous encouraging clinical studies
502
results from all over the world have been reported. Kosaka et al (1995) displayed that
503
the mixture of lentinan with hormonal therapy was more effective for the
504
enhancement of hormonal parameters such as follicle-stimulating hormone, serum
505
levels of estradiol, luteinizing hormone, and prolactin compare to hormonal therapy
506
alone. Fujimoto et al (2006) utilized adaptive immunotherapy and lentinan to treated a
507
case of recurrent ovarian cancer successfully. Zhang et al (2011d) have displayed the
508
potential anti-HIV activity of lentinan by clinical experiments. A Chinese patent
509
which applied the lentinan as orally or intravenously medicinal and as health-care
510
products have been registered (Jin et al., 2007).
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Fig. 7 are the mechanisms of antitumor activity of polysaccharides from
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Phellinus s. l. species. An acidic glycoprotein was isolated by Kim et al. (2003a,b)
513
from the fruiting body of Phellinus, demonstrated that not only selectively stimulates
514
proliferation of murine peritoneal macrophages in vitro but also markedly improved
515
the production of semiochemicals (NO and H2O2) for antitumor activity. Kim et al.
516
(2006) also demonstrated that a polysaccharide-protein clathrate extracted from the
517
fruiting body of Phellinus significantly increased B-cell proliferation, stimulated
518
macrophages to release the cytokines and semiochemicals NO in vitro. Moreover, a
519
proteoglycan extracted from the submerged fermentation mycelium of Phellinus
ACCEPTED MANUSCRIPT exhibited antitumor activity in vivo by enhancing lymphocytes proliferation and
521
increasing production of cytokines TNF-α and semiochemicals NO (Li et al., 2011;
522
Song et al., 2011; Xue et al., 2011; Liu et al., 2009). The results consistent with Li et
523
al. (2008). Li et al. (2004) found that a glycoprotein from Phellinus inhibited the
524
proliferation of SW480 colon cancer cells by induction of apoptosis. Polysaccharide
525
were extracted with different concentrations of ethanol (30%, 50% and 70% ethanol)
526
from Phellinus baumii showed higher macrophages stimulation activities (Li et al.,
527
2015). The fruiting body (or fungal mycelium) of Phellinus linteus is shown in Figure
528
8 and it has been commercially developed as Phellinus health food and cosmetic
529
products, mainly by using its polysaccharides and protein-bound polysaccharides.
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In addition, a novel polysaccharide is the mainly active component extracted
531
from Ganoderma atrum namely PSG-1 which markedly inhibited growth of CT26
532
tumor from tumor-bearing mice by causing apoptosis of CT26 cells (Hsiao et al., 2008;
533
Ma et al., 2011; Zeng et al., 2012). Moreover, PSG-1 enhanced the levels of cytokine
534
in serum and promoted the proliferation of lymphocyte as well as immune organ
535
index. Shi et al (2013) fractionated an acidic polysaccharide fraction with a molecular
536
weight of 3.68×105 Da from the fruiting bodies of Pleurotus abalonus, was the most
537
active in inhibiting MCF-7 cancer cells with an IC50 of 193 mg/mL. Ma et al (2015)
538
showed that a novel polysaccharide (namely GFP-A) with molecular mass of 889 kDa
539
from Grifola frondosa can significantly abate the inhibition of immune responses
540
induced by cyclophosphamide in vivo.
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edible fungi are studied more mature, bioactivities of other edible fungi active
543
component is also studied. The hypoglycemic activity of polysaccharide from three
544
fruiting bodies of Coprinus comatus (CC30, CC60, and CC80) was investigated by
545
Zhou et al (2015), the results showed the polysaccharide from CC60 can significantly
546
inhibit the promotion of blood glucose concentration when administered orally at a
547
dosage of 1000 mg/kg for 120 min. It also presents a long-term hypoglycemic effect
548
during 21 days of injection at the same dosage. Based on these results, polysaccharide
549
from CC60 has potential applications in diabetes patients as a natural medicine with
ACCEPTED MANUSCRIPT hypoglycemic activity. The antioxidant activity of polysaccharide from fruiting bodies
551
of Tricholoma lobayense was investigated by Ding et al (2016), the results showed
552
that polysaccharide not only could improve the cell viability, reduce the production of
553
reactive oxygen species (ROS) and inhibit oxidative damage, but also markedly
554
inhibite the formation of malondialdehyde (MDA) and improve the activities of
555
superoxide dismutase (SOD) and catalase (CAT) in mice liver and serum.
556
Furthermore, the antioxidant activity of polysaccharide from fruiting bodies of wild
557
Russula griseocarnosa was also investigated by Yuan et al (2017), the antioxidant
558
activities proved by reducing power to scavenge the DPPH, ABTS, superoxide radical
559
and hydroxyl radical.
560
3.1.2 Protein
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There are many kinds of active proteins in edible fungi, the most common of
562
which are agglutinin and fungal immunomodulatory proteins (FIP). FIP is a small
563
molecular protein with molecular weight ranging from 12 kD to 15 kD, while lectin
564
has molecular weight ranging from 12 kD to 190 kD, most of which are
565
macromolecular proteins, composed of four subunits. In different edible fungi, FIP
566
contains at least one α-helix and seven β-folds, and the amino acid sequences of these
567
proteins are highly homologous. Due to the differences in structure, edible fungus
568
proteins are involved in regulating various physiological functions such as anti-cancer,
569
anti-virus, anti-bacterial and immune regulation. In addition, antiviral proteins,
570
ribosomal inactivating proteins, laccase and other active proteins are also found in
571
edible fungi, which are different in molecular weight and structure (Ditamo et al.,
572
2015; Gao et al., 2013; Singe et al., 2010).
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FIP is a protein extracted from edible fungi or fungal fruiting bodies, which is
574
similar to the structure and function of immunoglobulin (Ig). There are mainly
575
Flammulina velutipes fungal immunomodulatory proteins (FIP-fve) and Volvariella
576
volvacea immunomodulatory proteins (FIP-vvo). FIP stimulates antigen presenting
577
cell (APC) to release cytokines of NO and IL-12 by combined with TLRs, which can
578
activate and promote the proliferation and differentiation of T cells (Th0) to form Th1
579
and Th2 cells, further activate macrophages and B cells, and producing a variety of
ACCEPTED MANUSCRIPT cytokines (Fig. 9). This process involves the phosphorylation of p38/MAPK and the
581
activation of nuclear transcription factor NF-κB. Therefore, the immune mechanism
582
of edible fungi immunoregulatory protein can be summarized as the activation of
583
p38/MAPK and NF-κB signaling pathways after combined with TLRs. Studies have
584
shown that FIP-fve can up-regulate the expression of intercellular adhesion
585
molecule-1 (ICAM-1) by phosphorylating p38/MAPK, and activate Th1 cells to
586
promote the production of IL-2 and IFN-γ, thus which played an immunoregulatory
587
role. FIP-vvo can not only activate Th1 cells and enhance the transcriptional
588
expression of IL-2, TNF-α and IFN-γ, but also induce Th2 cells to produce IL-4 and
589
further differentiate B cells, which can promote immunoglobulin transformation and
590
produce Ig E antibody. Sheu et al. showed that Pleurotus citrinopileatus
591
immunomodulatory protein (PCi P) activated macrophages to produce NO and TNF-α,
592
stimulated spleen cells to release IFN-γ, and speculated that this regulation process
593
was related to TLRs signaling pathway. In addition, studies have shown that
594
p38/MAPK and NF-κB are activated by FIP through TLRs, PI3K/Akt signaling
595
pathway is activated by Ganoderma tsugae fungal immunomodulatory protein
596
(FIP-gts) which stimulating human peripheral blood monocytes to produced IFN-γ.
597
Sun et al. (2017) investigated that the polypeptide from Pleurotus eryngii mycelium
598
inhibited the proliferation of cancer cells (cervical, breast, and stomach cancer cells),
599
but promoted the proliferation of macrophages (Ana-1 cell), TNF-α and IL-6 secretion,
600
TLR2 and TLR4 expression and increased macrophage phagocytic ability through NO
601
and H2O2 release.
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Edible fungus agglutinin is a bioactive protein or glycoprotein, which can induce
603
cell agglutination and participate in various physiological processes, such as
604
anti-cancer, anti-virus, immune regulation. Lectins can cross-link carbohydrates on
605
the cell surface and agglutinate red blood cells, which can activate cell signal
606
transduction pathways by binding to glycosylation receptors on the cell surface.
607
Clitocybe nebularis lectin (CNL) regulates p65 through TLR-4 signaling pathway,
608
stimulates the transcriptional expression of NF-κB, promotes the maturation of
609
dendritic cells, mediates T cells to produce IL-4, IL-6, IFN-γ and other cytokines, and
ACCEPTED MANUSCRIPT participates in the immune response (Svajger et al., 2011). Pleurotus ostreatus
611
agglutinin as an immunoadjuvant can stimulate DC maturation, promote IFN-γ
612
production in Th2 and Tc1 cells, and enhance the immunogenicity of hepatitis B virus
613
DNA vaccine. Agaricus bisporus lectin (ABL) inhibits NO production by M1
614
macrophages through TLR/Akt signaling pathway. It can be seen that the immune
615
regulation mechanism of edible fungus agglutinin is mainly through TLRs signaling
616
pathway, stimulating the proliferation and differentiation of macrophages, DC and
617
other immune cells, activating the production of cytokines by NF-κB (Pohleven et al.,
618
2012; Pushparajah et al., 2016).
619
3.1.3 Polyphenols and terpenes
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Polyphenols in edible fungi are a class of important natural antioxidants, which
621
can scavenge free radicals and quench reactive oxygen species, mainly including
622
phenolic acids, flavonoids, tannins and anthocyanins and other plant secondary
623
metabolites. Palacios et al (2011) found that the content of phenolic substances in the
624
edible fungi of Agaricus bisporus, A. sinensis, Chanterelle, Pine mushroom,
625
Pleurotus ostreatus were 1~6mg/g, The content of flavonoids was 0.9~3.0mg/g,
626
which all showed inhibition of linoleic acid autooxidation. Terpenoids in edible fungi
627
are mostly sesquiterpenoids, diterpenoids and triterpenoids. Most of them have
628
anti-inflammatory, anti-bacterial and anti-oxidative biological activities. Ganoderma
629
lucidum acid, a common triterpenoid compound in Ganoderma lucidum, is an
630
important active substance, more than 100 species were isolated from Ganoderma
631
lucidum.
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The antioxidant mechanisms of edible fungi mainly include free radical
633
scavenging, lipid oxidation inhibition, chelating transition metal ions and activating
634
antioxidant-related enzymes in vivo. Free radicals are metabolites of normal
635
physiological activities of cells, which mainly include hydroxyl radicals (·OH),
636
superoxide anion radicals (O2-), lipid peroxide, hydrogen peroxide and singlet oxygen.
637
Hydroxyl radicals can produce very strong oxidation, which are the main free radicals
638
causing protein and polysaccharide decomposition, lipid peroxidation and nucleic acid
639
breakdown. Superoxide anion free radicals can induce lipid peroxidation in vivo,
ACCEPTED MANUSCRIPT accelerate the aging of the body, and cause a series of diseases such as cancer and
641
cardiovascular diseases. Flavonoids and polyphenols in edible fungi can directly
642
quench singlet oxygen, prevent free radical chain reaction and lipid peroxidation to
643
avoid oxidative damage. Jayakumar et al. (2009) found that the clearance rate of
644
ethanol extracts from 10 mg/mL of Pleurotus ostreatus to O2- reached 60.02%.
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Oxygen free radical reaction and lipid peroxidation are in a dynamic equilibrium
646
state in the process of metabolism, maintaining many normal biochemical reactions
647
and immune reactions. Once the balance is unbalanced, oxygen radical chain reaction
648
is induced to form lipid peroxide (LPO), malondialdehyde (MDA) and 4-hydroxy
649
nonanenoic acid (HNE), which changed the fluidity and permeability of cell
650
membranes. Terpenoids and flavonoids in edible fungi can react with intermediates of
651
lipid chain oxidation (lipid free radicals or lipid oxygen free radicals), terminating the
652
chain reaction and inhibiting lipid oxidation. Wang et al. (2012a,b) isolated several
653
sesquiterpenoids from Flammulina velutipes with antioxidant, antitumor and
654
antimicrobial activities. The lipid peroxidation can be avoided by complexing ·OH on
655
polyphenol rings with Fe2+ or Cu2+, thus inhibiting the production of oxygen free
656
radicals. Yaltirak et al. (2009) demonstrated that the chelating ability of ethanol
657
extract of Russula edodes reached 58% at the concentration of 5 mg/mL. Gursoy et al.
658
(2009) showed that the chelating ability of methanol extracts from seven different
659
Morchella species for transition metal ions increased with the increase of extract
660
concentration.
661
3.2 Potential applications of active ingredients
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Fluorescence imaging is an important disease diagnosis technology, which has
663
outstanding advantages of high sensitivity and adjustable fluorescence characteristics
664
compared with radiography, magnetic resonance imaging, Raman imaging and
665
ultrasound imaging. The inorganic nanoparticles include semiconductor quantum dots,
666
metal nanoclusters, rare metal doped nanoparticles, carbon quantum dots and silicon
667
quantum dots and organic nanoparticles, such as organic dyes, conjugated polymers
668
and aggregation-induced emission are fluorescent imaging materials (Liu et al., 2016;
669
Huang et al., 2018). Compared with inorganic nanoparticles, organic nanomaterials
ACCEPTED MANUSCRIPT have attracted much attention, especially in the field of bioimaging, due to the
671
characteristic of adjustable molecular structure, biodegradability and low toxicity.
672
Therefore, the development of new fluorescent organic nanoparticles has always been
673
a hot research topic. Zhang et al. (2012b) prepared polydopamine fluorescent organic
674
nanoparticles for the first time and successfully applied them to bioimaging. The
675
co-assembly of dopamine with other functional molecules can further enrich the
676
structure and function of dopamine-based nanomaterials. The active ingredients of
677
edible fungi have unique physicochemical properties and functionality, such as
678
universal adhesion, excellent biocompatibility and biodegradability, which can be
679
considered to be used in fluorescent nanomaterials. In addition, polysaccharides and
680
proteins from edible fungi can be considered for drug delivery and controlled release
681
because of their structural diversity and easy surface modification of functional
682
molecules. The preparation, stability and biodegradability of active ingredient
683
nanomaterials of edible fungi were studied in order to better control the morphology
684
and function of nanomaterials. Structuring functional nano-platform based on active
685
ingredient materials, integrating the functions of bioimaging, drug delivery and cancer
686
treatment, will greatly bring the advantages of nano-materials into play.
687
4. Conclusion and future outlook
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This paper has systematically reviewed efficient physical technologies in
689
extraction of bioactive compounds from edible fungi which have potential antitumor
690
and antioxidant activities. These physical technologies including UAE, MAE, SFE,
691
UPE and PEF can greatly increase the extraction yield, reduce energy and solvent
692
consumption, and also improve the quality of the extracted compounds. However,
693
some extraction processes are complex and may have negative effect on the
694
bioactivity of the constituent. Consequently, it is important to create a database
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including the optimal conditions to extract different active constituent with the
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corresponding technology for specific edible fungus. Last but not least, further
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progress in terms of the efficacy, legislation, cost-effectiveness ratio and convenient
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manipulation of these efficient physical technologies should also be highlighted in the
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future works. Most of bioactive compounds from edible fungi have been proven to have the
701
potential for the prevention and treatment of diseases, mainly due to their antioxidant
702
activity, immune activity and antitumor activity. Although the bioactivity and
703
mechanisms of bioactive compounds from edible fungi have been largely reported, it
704
is necessary to study the structure-activity relationship between structure parameters
705
and biological activity. On the other hand, application of some bioactive compounds
706
is still in an early stage of development and only exists at the laboratory research level.
707
This requires extensive trials at pilot scale and industrial scale in the future work.
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Acknowledgments
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This work was financially supported by China State Key Research Program (Contract
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No. 2017YFD0400901), Jiangsu Province Key Agricultural Project (Contract No.
711
BE2016362), Jiangsu Province Collaborative Innovation Center for Food Safety and
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Quality Control “Industry Development Program”, Jiangsu Province Infrastructure
713
Project (Contract No. BM2014051).
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Fig. 1. Laboratory-scale SEF extraction plant
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Fig. 2. Schematic representation of a laboratory-scale prototype of an UPE system.
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Fig. 3. Schematic procedures of UPE processing
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Fig. 4. SEM images of the control group (a,b), ×400&×l500; SE Mimages of the test
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Fig. 5. Schematic representation of a pulsed electric field (PEF) system
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Fig. 6. Mechanisms of antitumor activity of lentinan as a β-D-glucan.
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Fig. 7. Summary of mechanisms of antitumor activity of polysaccharides from
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Phellinus s. l. species.
Fig. 8. The fruiting body (or fungal mycelium) of Phellinus linteus and commercial
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Phellinus health food and cosmetic products.
Fig. 9. Immunomodulatory mechanism of edible mushroom proteins.
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Fig. 1. Laboratory-scale SEF extraction plant
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1. Gas cylinder 2. Cooling circulating water bath 3. CO2 pump 4. Air compressor 5. CO2 preheater
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6. Buffer tank 7. Extraction kettle 8. Micro valve 9. Collection bottle 10. Wet gas flowmeter
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(Senka et al., 2011).
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Fig. 4. SEM images of the control group (a,b), ×400&×l500; SE Mimages of the test group (c,d),
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Fig. 5. Schematic representation of a pulsed electric field (PEF) system (Elena et al., 2016)
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Fig. 7. Summary of mechanisms of antitumor activity of polysaccharides from Phellinus s. l.
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Fig. 8. The fruiting body (or fungal mycelium) of Phellinus linteus and commercial Phellinus
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Table 1 The advantages and disadvantages of each technology Characteristics
Advantages
Disadvantages
Conventional extraction methods
Solvent-assisted (water or organic solvents)extraction is a widely employed technique
An economic method, and does not requires any special equipment
Ultrasound-as sisted extraction
Edible fungus cells are disrupted by shock waves from cavitation bubbles, thus facilitating mass transfer hence an increase in the extraction yield
Microwave-as sisted extraction
A process that includes heating the material causing moisture to evaporate, which generates tremendous pressure, and the rupture of cells facilitates the release of the desired intracellular contents The density of a supercritical fluid is similar to a liquid and its viscosity is similar to a gas, its diffusivity is intermediate between the two states, thus favoring the extraction of intracellular compounds. Works under a super-high pressure ranging from 100 to 500 MPa and temperature of 20-50°C
An inexpensive and simple method which can be combined with solvent extraction methods and allows to decrease the extraction time and the temperature of the extraction Suitable for extraction of bioactive compounds; rapid sample preparation with reduced solvent usage Shorter extraction time and high separation efficiency; improved product purity
longer extraction times, lower yields, more organic solvent consumption, and poor extraction efficiency, which incorporate risk of thermal degradation of thermolabile active compounds Long ultrasonic time may cause fracture of functional structure and reduce extraction rate
Pulsed electric field extraction
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Technologies
The technique requires placement of food between two electrodes in a batch or continuous treatment chamber and its exposure to a pulsed voltage (typically, 0.1–5 kV/cm with pulses of 10–1000 μs for electroporation of plant cells). The duration and number of pulses should be limited to reduce the temperature increase, which is generally of no more than 3–5°C
Shorter extraction time, decreased solvent consumption, increased extraction yields, lower operating temperature, allowing the extraction of thermolabile compounds, fewer impurities Possible continuous operation; very short treatment times and suitable for thermolabile compounds extraction.
Uneven heating uniformity
High capital cost
the UPE requires the higher investment costs, such as, the elevated pressure needs expensive equipments；an additional filtration or centrifugation is necessary to remove the solid residue during UPE High capital cost
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Efficient physical extraction of active constituents from
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edible fungi and their potential bioactivities: A review
Highlights
Bullet point 1: Five efficient physical extraction technologies (UAE, MAE, SFE, UPE
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and PEF) are introduced.
technologies are discussed.
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Bullet point 2: The advantages and disadvantages over conventional extraction
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Bullet point 3: The potential bioactivities of active constituents are also mentioned.
S0924-2244(18)30101-8
DOI:
https://doi.org/10.1016/j.tifs.2019.02.026
Reference:
TIFS 2432
To appear in:
Trends in Food Science & Technology
Received Date: 13 February 2018 Revised Date:
7 November 2018
Accepted Date: 6 February 2019
Please cite this article as: Sun, Y., Zhang, M., Fang, Z., Efficient physical extraction of active constituents from edible fungi and their potential bioactivities: A review, Trends in Food Science & Technology, https://doi.org/10.1016/j.tifs.2019.02.026. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Efficient physical extraction of active constituents from edible
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fungi and their potential bioactivities: A review Abstract
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Background: Edible fungi are a great source of active constituents, including
5
polysaccharides, proteins, terpenoids, minerals and vitamins. In particular, they have
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potential antitumor, antioxidant, immunological activity and could be applied for
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clinical disease treatment. Conventional extraction methods for active constituents
8
usually involve organic solvents and may result in environmental problem and
9
noticeable degradation of the constituents. The efficient physical extraction
10
technologies have gained much more attention worldwide which can improve
11
efficiency and reduce degradation of active ingredients.
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Scope and approach: This review discusses the recent developments of efficient
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physical extraction technologies including ultrasound-assisted extraction (UAE),
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microwave-assisted extraction (MAE), supercritical fluid extraction (SFE), ultrahigh
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pressure-assisted extraction (UPE) and pulsed electric field extraction (PEF) for active
16
constituents from edible fungi and presents a brief summary of their potential
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bioactivities.
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Key findings and conclusions: These technologies have been demonstrated to
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increase the extraction yield, improve product quality, and are energy efficient and
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environmentally friendly. It is expected that these efficient physical technologies will
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be gradually used in extraction of a variety of active constituents in the near future.
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Future research needs to consider varieties of further combined applications of
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physical technologies, which may allow a better maintenance of the functionality of
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active ingredients. The great potential of these extracted edible fungi active
25
compounds could be used as the ingredients for health care medicine and foods.
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Meanwhile, consumer's acceptance, safety and legal aspects, and commercial
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availability of health products should also be taken into consideration in future
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studies.
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Keywords: Edible fungi, Active constituents, Physical extraction, Application
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ACCEPTED MANUSCRIPT 1
Efficient physical extraction of active constituents from edible
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fungi and their potential bioactivities: A review
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State Key Laboratory of Food Science and Technology, Jiangnan University, 214122 Wuxi, Jiangsu, China
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Jiangsu Province Key Laboratory of Advanced Food Manufacturing Equipment and Technology, Jiangnan University, China
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Yanan Sun1, Min Zhang1,2*, Zhongxiang Fang 3
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Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia
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*Corresponding author: Professor Min Zhang, School of Food Science and
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Technology, Jiangnan University, 214122 Wuxi, Jiangsu Province, China.
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E-mail: [email protected]
Tel.: 0086-510-85877225; Fax: 0086-510-85877225.
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ACCEPTED MANUSCRIPT Abstract
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Background: Edible fungi are a great source of active constituents, including
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polysaccharides, proteins, terpenoids, minerals and vitamins. In particular, they have
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potential antitumor, antioxidant, immunological activity and could be applied for
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clinical disease treatment. Conventional extraction methods for active constituents
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usually involve organic solvents and may result in environmental problem and
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noticeable degradation of the constituents. The efficient physical extraction
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technologies have gained much more attention worldwide which can improve
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efficiency and reduce degradation of active ingredients.
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Scope and approach: This review discusses the recent developments of efficient
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physical extraction technologies including ultrasound-assisted extraction (UAE),
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microwave-assisted extraction (MAE), supercritical fluid extraction (SFE), ultrahigh
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pressure-assisted extraction (UPE) and pulsed electric field extraction (PEF) for active
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constituents from edible fungi and presents a brief summary of their potential
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bioactivities.
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Key findings and conclusions: These technologies have been demonstrated to increase
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the extraction yield, improve product quality, and are energy efficient and
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environmentally friendly. It is expected that these efficient physical technologies will
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be gradually used in extraction of a variety of active constituents in the near future.
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Future research needs to consider varieties of further combined applications of
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physical technologies, which may allow a better maintenance of the functionality of
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active ingredients. The great potential of these extracted edible fungi active
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compounds could be used as the ingredients for health care medicine and foods.
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Meanwhile, consumer's acceptance, safety and legal aspects, and commercial
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availability of health products should also be taken into consideration in future
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studies.
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Keywords: Edible fungi, Active constituents, Physical extraction, Application
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1. Introduction Edible fungi have the large fruiting body, taste delicious and have high edible,
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medicinal and economic values. China is the global biggest producer of edible fungi
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where Lentinus edodes, Pleurotus ostreatus, Volvariella vovlaca, Flammulina
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velutipes, Hericium erinaceus, Auricularia auricula, Tremella fuciformis, Grifola
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frondosa, Pleurotus eryngii, Agaricus bisporus, and Agrocybe cylindracea are the
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major species (Hua et al, 2018; Wang et al, 2017). In 2013, edible fungus production
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in China reached 31.4 million tons according to Chinese Edible Fungi Association,
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with a value of more than 26 billion US dollars (Zhuang et al, 2015). Edible fungi are
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also considered as a healthy food because they are rich in bioactive compounds
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including polysaccharides (e.g. α- and β-glucan), proteins, peptides, polyphenols,
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terpenoids, vitamins and dietary fiber (Yan et al, 2018; Asaduzzaman et al, 2012; Reis
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et al, 2012). It has been reported that the fungus β-glucan has a broad spectrum of
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biological activity (Xu et al, 2014; Moradali, et al, 2007), and terpenoids and sterol
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compounds have antibacterial, antiviral and antioxidant activities (Kim et al, 2010;
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Mori et al, 2008; Zhang et al, 2013). Currently, edible fungues components of
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polysaccharide, saponin, triterpene, adenosine and flavonoids are the top five efficacy
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components in the approved health foods (Gu et al, 2016). Ganoderma lucidum,
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caterpillar fungus and poria cocos account for 68%, 15% and 10% of the total
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approved health food of edible fungus in China. Their attractive flavor/taste, high
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nutritional value and potential biological functions have made edible fungi not only
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popular in China and Asia, but also around the world.
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The health food can be classified into three generations according to the product
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characteristics and marketing time in China (Zhuang et al, 2015). The first generation
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products refer to health food by enhanced nutrition elements and active ingredients.
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For example, a health food is added with external components of calcium, magnesium,
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iron, zinc, selenium, vitamin, beta-carotene, folic acid, amino acids, and dietary fiber.
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The second generation products must have some specific physiological functions
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through strict animal and human study. This generation products are the majority of
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generation of health products not only needs to pass the above animal and human
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clinical study, but also know the functional components, their chemical structure and
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human health mechanisms. Therefore, understand the functional factors/constitues
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and their efficacy mechanisms of edible fungi are very important in development of
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this group of functional foods.
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How effectively destroy the cell wall to release the intracellular material is a
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main problem of obtaining active constituents from edible fungi. Conventional
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extraction methods usually involve large amounts of organic solvent and long
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extraction time, which are high cost and time consuming, have negative environment
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impact, and may result in the degradation and coagulation of active constituents. To
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alleviate these disadvantages, some new extraction methods have been developed (Yin
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et al, 2018; Yan et al, 2018; Chen et al, 2018). Efficient physical extraction techniques
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usually refers to the processing of cell disruption by physical means to increase the
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extraction yield and improve product quality (López et al, 2018; Milad et al, 2019;
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Münevver et al, 2019; Pataro et al, 2018). These technologies are energy efficient and
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environmentally friendly, showing the great potential for health care medicine and
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foods of active constituents. This review focuses on the recent developments in
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application of the efficient physical extraction techniques (UAE, MAE, SFE, UPE and
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PEF) to obtain active constituents from edible fungus and their potential applications
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in functional foods.
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2. Efficient physical extraction of active constituents from edible
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fungi
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2.1 Ultrasound-assisted extraction (UAE)
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In the process of ultrasound extraction, the crushed sample was dissolved in
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appropriate solvent and put into the ultrasonic bath, where the extraction temperature
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and extraction time are set already (Klejdusa et al., 2009). The ultrasound frequencies
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(greater than 20 kHz) can promote the hydration of edible fungi which cause the
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increase of the cell walls pores, lead to cell wall rupture. Therefore, the extraction
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(Golmohamadi et al., 2013; Huie, 2002; Cintas et al., 1999). Compared with
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conventional extraction techniques, utilization of ultrasound to assist the extraction of
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active constituents from edible fungi have numerous advantages. Firstlt, the UAE
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techniques can overcome the major limitations of the conventional extraction process
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for long extraction time and numerous solvent dosage. Secondly, the bioactivity
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preservation of extract products are higher due to lower extraction temperatures.
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Finally, the UAE process have lesser energy consumption and higher yield of
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production (Vinatoru et al., 2001; Rombaut et al., 2014; Alzorqi and Manickam, 2015).
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The ultrasound to assist extraction have demonstrated the improvements in extraction
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yield ranging from 6 to 35% in both aqueous and solvent extraction systems (Vilkhu
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et al., 2008).
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The application of ultrasound as a technique for assisting extraction of active
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constituents from edible fungi has been widely reported (Qiao et al., 2012; Chen et al.,
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2014a). In some studies, quadratic regression models have been used to optimize
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UAE of polysaccharides from edible fungi (Clemente et al., 2014; Yan et al., 2016).
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The polysaccharide extraction yield from Agaricus bisporus was approximately 5.5 %
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with ultrasound assisted water extraction by applying the response surface
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experiments (Tian et al., 2012; Chen et al., 2014a,b). Cheung et al (2013) extracted
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the polysaccharide from Grifola. Frondosa and Lentinus edodes with UAE, the
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polysaccharides yield was 0.05 %, and 0.13 % respectively after 60 min extraction
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and the edible fungus have loose particle structure.
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The highest polysaccharides yield from Agaricus bisporus of 6.02% was
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obtained under the optimized condition of ultrasonic power 230 W, extraction
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temperature 70 °C, extraction time 62 min, and solid-liquid ratio (W/M ratio) 30 ml/g
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(Tian et al. 2012). Under the ultrasonic power 30W, W/M ratio 40 ml/g, extraction
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time 8 h, polysaccharide extraction yield from Yunzhi mushroom was 5.95% (Pan et
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al., 2010). By using UAE, the polysaccharide yield from Lentinus edodes was around
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14.39 % under ultrasound power 340 W, water-material ratio 30:1 (ml:g), and
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ultrasound treatment time 14 min, which was obviously higher than water heating
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Tricholoma matsutake using UAE and response surface of quadratic regression design,
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the polysaccharide extraction yield was 7.97% under ultrasonic power 365W, W/M
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ratio 53.5ml/g, and extraction time 160 s. In a recent study, three extraction methods
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have been used to the extraction of β-D-glucan polysaccharides from cultivated
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mushroom by Alzorqi et al. (2017). The UAE extraction resulted in a higher yield of
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polysaccharides with higher content of β-D-glucan at shorter extraction time, and
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more importantly the extraction process in a state of low temperature all the time as
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compared to the conventional extraction methods of hot water extraction (HWE) and
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Soxhlet extraction (SE). The amount of β-D-glucan by UAE extraction (44.42 mg/g)
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was remarkably higher than HWE (37.73 mg/g) and SE (25.03 mg/g) respectively.
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Ingrid et al. (2017) applied the ultrasound to assist the extraction of polysaccharides
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from edible fungi by-products, and the extraction yields of 4.70 and 4.35% were
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obtained under the condition of ultrasonic amplitudes 100 mum and treatment times
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15 min after precipitation times of 1 h and 18 h, respectively.
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2.2 Microwave-assisted extraction (MAE)
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Microwave-assisted extraction (MAE) is a quickly and efficiently extraction
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technique that uses microwaves to evenly heat both solvent and material to facilitate
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the extraction of target components. The microwave is a non-ionizing electromagnetic
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wave with the frequency between 300 MHz and 300 GHz and is positioned between
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X-ray and infrared rays in the electromagnetic spectrum (Ajila et al., 2011). Recently,
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MAE has been applied in extraction of active constituents from soil, plant, and food
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matrices as it is more effective compared with conventional solvent extraction method
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(Mandal et al., 2007). The principle of MAE is that when hydrated biomaterial tissues
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cells are heated, water absorbs energy, evaporates and generates high pressures in the
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cells. The high pressures pushes the cell walls from within the cell and leads to cell
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rupture, therefore, the active constituents released into the extracellular solvents.
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(Letellier and Budzinski, 1999; Wang and Weller, 2006; Garofulic et al., 2013). This
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technique have several advantages over conventional heating extraction, including
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required shorter extraction time, less solvent amount and reduced energy consumption
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ACCEPTED MANUSCRIPT (Armenta et al., 2008; Garofulic et al., 2013). In addition, the enhancement of active
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constituents diffusion form intracellular to solvent increases the extraction yield
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(Armenta et al., 2008; Garofulic et al., 2013; Liazid et al., 2011). The effect of the
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microwave extraction is affected by microwave power, solvent-to-solid ratio, and
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extraction time. The choice of solvent is the other important factors for MAE which
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depends on the solubility of the active compounds and the microwave absorbing
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properties of the solvent (Antonietta et al., 2016).
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A study showed that tiny amounts of Agaricomycetes material and shorter time
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were required in MAE extraction of DNA for subsequent DNA PCR amplifications
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(Dornte et al., 2013). This technique had high reliability (about 90 %) and was
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suitable for fresh and aged fungal cultures, avoiding specific expensive and dangerous
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chemicals for cell lysis and reagent residual used in conventional extraction
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technology. The MAE technique was also used in isolating fungal metabolite
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ergosterol from Agaricus bisporus and compared the difference of ergosterol from
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MAE and classical solvent extraction (Young et al., 1995). However, the MAE
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process is simple, fast, reliable, and economical with respect to amounts of solvent
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required, especially when compared with traditional solvent methods (Elena et al.,
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2016).
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Ahmad et al. (2014) applied MAE to extract natural dyes from Pycnoporus
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sanguineus mushroom, and the results indicated that it is an attractive alternative to
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conventional boiling water extraction method. Fhernanda et al. (2017) reported that
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both MAE and pressurized solvent extraction are easy, rapid and efficient approaches
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to extract edible fungi polysaccharides. Heleno et al. (2016) observed that the
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extraction temperature, extraction time, microwave power and solid to liquid ratio had
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significant effects on the ergosterol extraction yield from Agaricus bisporus L. By
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using distilled water as solvent at microwave power of 400 W, temperature (132.8 °C)
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and solid-liquid ratio (1.6 g/L) for 19.4 min, about 556 mg ergosterol/100g dw edible
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fungi was obtained. Maeng et al. (2017) extracted the total phenolic constituent from
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Coriolus versicolor mushroom, 40% ethanol concentration, 125 W microwave power
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and 3.8 min extraction time were found to be the optimal conditions. However for
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phenolic content was achieved at extraction temperature 80 °C, extraction time 5 min,
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and ethanol concentration 80% (Mustafa et al. 2014). These studies indicate that MAE
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conditions should be optimized for extraction of different active constituent from
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different edible fungi species.
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2.3 Supercritical fluid extraction (SFE)
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Supercritical fluid extraction (SFE) is a modern technique that supercritical
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fluids are used to extract the active constituents from a solid or even liquid material.
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(Junior et al., 2010). The traditional solvent extraction is based on the diffusion
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process, solvent must be spread to the edible fungi tissue and active constituents
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dissolving out to solvent. The diffusivities of supercritical fluid are much faster than
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in liquids and therefore extraction time is more shorter. In addition, there is no surface
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tension between fluid and material, and the viscosity of supercritical fluid is lower
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than liquids. For the same extraction process, organic solvent extraction requires
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several hours whereas SFE only take 10 to 60 minutes (Antonietta et al, 2016; Skoog,
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2006). Fig. 1 is a laboratory-scale SEF extraction plant, where the system contains a
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pump for the gas cylinder, a pressure cell to contain the sample, a means of
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maintaining pressure in the system, and a collecting vessel. In operation, the fluid
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(usually carbon dioxide) is heated to supercritical condition, and then it quickly
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diffuses into the material internal and dissolve target active constituents in the
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extraction container. The dissolved active constituents is separated at lower pressure
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separator. The supercritical fluid after extraction can be cooled, re-compressed and
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recycling, or emissions into the atmosphere (Antonietta et al, 2016). Compared with
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the traditional method, the SFE technology presents various advantages, such as
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reduce energy consumption, operating under low temperature and high product
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quality with no solute in the solvent phase. However, this technology application is
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limited because of its scope of the only extraction low or medium polar active
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constituents and its production costs are the major drawback of this approach
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(Garcia-Salas et al., 2010; Silva et al., 2017; Kitzberger et al., 2009).
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Generally, carbon dioxide (CO2) have the particular characteristics of moderate
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supercritical fluid to extracts nonpolar compounds. For polar molecules extraction
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(such as anthocyanins), a polar solvent such as ethanol or methanol must also be
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added to supercritical fluid. Therefore the choice of the polar solvent may play an
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important part for the success of the extraction process. Due to ethanol and water are
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nontoxic, availability, and chemically inert (Ghafoor et al., 2014). The water/ethanol
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fraction are soluble in supercritical CO2 (scCO2) at the pressure and temperature, so
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the mixture can be considered supercritical (Ghafoor et al., 2014; Herrero et al., 2006).
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Consequently the CO2, ethanol and water were mixed according to the different
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proportions as the supercritical fluid is the most common method (Ghafoor et al.,
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2014; Junior et al., 2010).
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Simone et al. (2012) studied the extraction of antioxidant and antimicrobial
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compounds from Agaricus brasiliensis using SFE technology. The results showed that
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the optimal conditions of SFE were at temperature of 50 °C and 30 MPa in the
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presence of 10% ethanol, at which the extraction yields were reached 4.2%. The
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results were similar to that reported by Li et al. (2016) for the extraction from
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Ganoderma lucidum spores, and those reported by Kitzberger et al. (2007) for the
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extraction from Lentinula edodes, where 20 MPa and 40 °C with 15% aqueous
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ethanol as a co-solvent were used. It is not common to extract heat sensitive active
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compounds such as anthocyanins use temperatures above 40 °C, but the extraction of
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other phenolic constituents need higher temperatures. Diego et al. (2017) extracted
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vitamin D-enriched compounds from Shiitake mushrooms (Lentinula edodes) by
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supercritical fluid extraction combined with UV-irradiation. Fractions containing up to
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18% (w/w) ergosterol and other ergosterol derivatives (provitamin D2) was obtained,
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and they can be partially transformed into vitamin D2 by UV-light irradiation.
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The subcritical carbon dioxide extraction is a process that consists in using
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carbon dioxide under high pressure to maintain it in the liquid state. In the process of
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the extraction, the subcritical state can be reached under the critical temperature and
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pressure. With the development of extraction technology, supercritical extraction and
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subcritical extraction technology gradually replaced the traditional extraction
ACCEPTED MANUSCRIPT technology, which widely used in active constituents extraction. Senka et al. (2011)
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compared the efficacy of subcritical against supercritical carbon dioxide extraction of
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fatty acids from Boletus edulis. They found that increasing operational pressure and
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extraction time leads to increases in extraction yield in both subcritical and
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supercritical carbon dioxide extraction. An extraction yield of around 2.4% was
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achieved using subcritical extraction at the conditions of 27 °C, 344 bar and 3.6 h,
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whereas an extraction yield of 2.1% was obtained for supercritical extraction at the
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conditions of 40 °C, 238 bar and 4.8 h. The results suggest that both methods are
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effective on the extraction of fatty acids from Boletus edulis and the selection of
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which method could be depended on the availability of facilities and operational cost.
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2.4 Ultrahigh pressure-assisted extraction (UPE)
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The ultrahigh pressure-assisted extraction (UPE) is a developing rapidly novel
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technology in recent years to enhance extraction of active component from edible
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fungi. The extract solvent rapidly permeated to the plant internal vascular bundles and
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glandular cell under ultra high pressure, causing the volume change of cell and
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promoting the moving of chemical equilibrium (Ji et al., 2011; Zhang et al., 2012a;
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Zhu et al., 2012; Liu et al., 2013a,b). Pressure relief are usually performed in a few
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seconds, the pressure of the tissue cells from a few hundred MPa quickly reduced to
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atmospheric pressure (Xi et al., 2013). In the opposite direction of pressure, the cell
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wall and cell membrane are strongly impacted leding to the distortion, the solvent
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dissolved active component in cells rapidiy transfer to the outside of the cell under
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high osmotic pressure to achieve the extraction (Xi, et al., 2010; Joo et al., 2012). A
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laboratory-scale batch type prototype of UPE system (pressure 100 to 500 MPa;
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temperature 20-50 °C) is shown in Fig. 2 (Xi et al., 2011b; Chen et al., 2009a,b). The
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general procedures of UPE are illustrated in Figure 3 and were discussed
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systematically by Xi (2017). Briefly, dried edible fungi pulverized materials are mixed
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with the suitable solvent according to the similar dissolve mutually theory in the
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germfree storage bags. Then put the bag into a pressure vessel after ruling out the air
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in the bag, the pressure and temperature are controled by pressure vessel (Prasad et al.,
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2009; Lee et al., 2011). The pressure vessel is pressurized with the fluid (usually water)
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centrifuged (4,000 up to 8,000 rpm for 10-15 minutes), the filtered supernatant liquid
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is usually evaporated by a rotary evaporator under vacuum at 45-65 °C, and then
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stored at 4 °C in refrigerator (Xi, 2017). Thus, the edible fungus extracts that contain
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active compounds are obtained.
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The properties of water is hardly affected by the pressure, as long as it remained
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in the liquid state. However, higher pressure helps water into the sample tissue rapidly,
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resulting in improved mass transfer rate and extraction efficiency. The ultrahigh
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pressure-assisted extraction can be effectively used to extract the thermolabile active
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component (vitamins, anthocyanins) because of the mild processing temperature (Lee
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et al., 2011; Zhang et al., 2011a,b). The UPE improve the extraction rate by rupturing
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the cellular wall (Xi et al., 2011a; Chen et al., 2009a, b), membrane and organelles to
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reduced treatment time and solvent dosage. The UPE has been widely used to the
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extraction of plant active component in recent years (Xi et al., 2011b; Joo et al., 2011;
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Altuner et al., 2012; Guo et al., 2012; Joo et al., 2012; Xi and Wang, 2013), as can be
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deduced from a great mass of papers published dealing with this subject based on the
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publications available in web of knowledge since 2011. This technique has become
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relatively mature and can be effectively used for extraction of active constituents from
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edible fungi.
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Jiang (2011) studied the extraction of Lentinus edodes polysaccharide with UPE,
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the cell tissue were observed. Fig. 4 reveals that the Lentinus edodes tissues of the
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untreated samples (a,b) were basically intact, compared with the structures of the
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samples treated with UPE (c,d). Fig 4 shown that the cell structure of the untreated
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samples had a certain degree of damage through smash and homogeneous, but there
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are still large particles and cellular structure was not destroyed completely. After 140
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MPa of ultrahigh pressure treatment, the cellular structure has obvious changes which
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larger particles were broken, it has been difficult to observe the cellular structure
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significantly. Compared with control group, UPE treatment can further destroy the
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cellular structure and reduce the mass transfer resistance to improve the efficiency of
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extraction (Chen et al., 2009a,b). In addition, similar study results have also been
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reported by Chen et al. (2014a), who reported that UPE treatment could result in the
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disruption of the Cordyceps militaris tissue, which enhanced the mass transfer of the
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solvents into the edible fungi materials and the soluble active component into the
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solvents. Chen et al. (2015) extracted polysaccharides from Cordyceps militaris under the
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optimal UPE conditions. At the pressure of 300 MPa, solid–liquid ratio 1:40, and 2
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min of extraction time at 70 °C, a maximum polysaccharide yield 9.33% was obtained.
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A polysaccharide extraction yield of 2.762% was achieved when the mushroom of
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Ganoderma lucidum was extracted at the pressure 400 MPa, temperature 50 °C,
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material (g) to solvent (ml) ratio 1:40, and extraction time 6 min, which was 37.1%
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higher than that of water extraction (Du et al., 2009). It was also reported that the
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polysaccharide extraction yield from dried fruit bodies of Lentinus edodes was 8.96%
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at the optimal conditions of extraction time 4 min, extraction temperature 55 °C,
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pressure 350 MPa, and solid-liquid ratio 1:35. This was 2.23 times higher than that by
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water extraction, and 48.8% higher than that by ultrasonic combined with enzymatic
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hydrolysis extraction.
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2.5 Pulsed electric field extraction (PEF)
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Pulsed electric field (PEF) technology is used to extract intracellular active
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component as a non-thermal technique, the principle is requiring placement of target
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material between the poles in a batch or continuous treatment chamber and using short
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pulses of high voltage to promote polar material high speed move to the direction of
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electrode under the effect of electric field. The tissue cells was irreversible damaged
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because of cell membrane electroporation lead to the dissolution of bioactive
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substances (Antonietta and Matteo, 2016; Vorobiev and Lebovka, 2010). Used as
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intensification pretreatment, PEF has shown great potential to replace conventional
336
extraction technology as a moderate effective extraction technology (Donsi et al.,
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2010) and improve the extraction yields of bioactive component.
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A laboratory-scale prototype of PEF extraction system is represented in Fig. 5. It
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has three main components: a pulse generator, a treatment chamber and a pumping
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system. Material in the treatment chamber under high voltage (up to 40 kV) pulse
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the electrode will be corrosion and material be electrolysis. Therefore, the electrode
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surface should smooth as far as possibles to reduce the escape of the electron, the
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circular electrode was used to avoid electric field transition concentration and provide
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a uniform high voltage pulse electric field for materials when designing treatment
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chamber (Barba et al., 2015). The system is generally monitored and controlled by a
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computer and an oscilloscope. The effect of PEF-assisted extract mainly has been
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influenced by two aspects: on the one hand is the physicochemical properties of the
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material. The conductivity and resistance are determined by different material types
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and cell size, the greater the volume of the cell is sensitive to the pulsed electric field;
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On the other hand, extraction effect is influenced by temperature, pH, conductivity
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and viscosity (Elena et al., 2016; Vorobiev et al., 2010). In PEF-assisted extraction
353
process, the electric field strength is the decisive factor, pulse width, treatment time,
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number of pulses and energy density affect the extraction effect indirectly. The total
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specific energy are principally impacted by the applied voltage, the treatment time,
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and the resistance of the treatment chamber. (Elena et al., 2016; Puertolas et al.,
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2012).
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PEF technology is widely used in the extraction of active compounds from edible
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fungi, many studies have been reported by different authors. For instance, Yin et al.
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(2008) extracted polysaccharides from inonotus obliquus by PEF technology, the
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extraction yield of polysaccharide reached 49.8% which is 1.67 times of hot alkali
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extraction under the best optimize extraction conditions of 30 kV/cm field intensity,
363
pulse number 6, liquor ratio 25 mg/mL, pH 10. Compared with the traditional
364
extraction method, PEF have short extraction time (12 µs), high extraction efficiency
365
and less impurity in the extract. Zhang et al. (2011c) found that PEF technology
366
enhanced exopolysaccharides (EPS) extraction yield from Tibetan spiritual
367
mushrooms significantly. The EPS extraction yield was increased by 84.3% under the
368
conditions of number of pulses 8, electric field intensity 40 kV/cm and pH 7. Li et al.
369
(2013) compared the efficiency of PEF, ultrasonic and microwave assisted methods on
370
extraction of active components (fungal polysaccharide) from Auricularia auricula,
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and the highest yield of anti-coagulant activity fungal polysaccharide was obtained by
372
using PEF method under field strength of 24 kV/cm. In other study, PEF (100-1000 V/cm)-assisted pressure technique was used to
374
extract polysaccharide, proteins, and terpenoids from Agaricus bisporus. Parniakov et
375
al (2014) used PEF-assisted pressure technique and solvent technique to extract
376
proteins from Agaricus bisporus under electric field strength 800 V/cm. The
377
maximum protein extraction yield approximately was 0.26 under the condition of
378
pressure extraction (PE) alone. Combined with PEF-assisted extraction, the highest
379
extraction yield of 0.42 was achieved approximately. In addition, the protein extracts
380
from water extraction under 70 °C for 2 h and ethanol extraction under 25 °C for 24 h
381
were cloudy and their extract have impurities, whereas the extracts from PE+PEF was
382
clear. In addition, another study reported that combination of PEF with pressure
383
extraction allowed production of edible fungus extracts with higher extraction yield of
384
polysaccharides and proteins compared with pressure extraction alone (Elena et al.,
385
2016). The above studies show that PEF technology is an effective extraction method
386
which can improve the dissolution rate of active constituent in different materials by
387
controlling the PEF treatment conditions and the molecular structure of the natural
388
active constituent is not easy to be damaged.
389
2.6 Advantages and disadvantages of different technologies
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According to the existing researches, the UAE, MAE, SFE, UPE and PEF are all
391
fast and efficient for extracting active constituents from edible fungi. These physical
392
extraction techniques decrease the extraction time greatly because of working at
393
elevated pressure or/and temperature. Each technology has its own advantages and
394
disadvantages, which are listed in Table 1. According to the target extracting active
395
constituents, a suitable technology can be chosen.
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Compared with the traditional extraction technology, the UAE and MAE
397
operation are easier in many cases, almost no pollution to the environment, low cost
398
and relatively accurate results, which opens up a new research for the extraction of
399
active
400
ultrasonic-microwave synergistic extraction makes full use of the cavitation effect of
ingredients
from
edible
fungi.
The
innovation
technology
of
ACCEPTED MANUSCRIPT ultrasonic vibration and the high energy effect of microwave, complementing the
402
disadvantages of single UAE and MAE technology (Yin et al., 2018). The high
403
efficiency extraction for solid samples at low temperature and atmospheric pressure
404
are achieved. Cell wall is mainly composed of cellulose, hemicellulose and lignin.
405
The combination of ultrasound and microwave can change the size of cellulose
406
crystallization zone, reduce its crystallinity, and partially degrade lignin and
407
hemicellulose, so that solvent can quickly enter cells, which can effectively shorten
408
the extraction time and improve the extraction rate. In addition, the technology is
409
conducive to extracting components with poor polarity and thermal stability, and can
410
avoid decomposition caused by long time extraction under high temperature and
411
pressure, so that the molecular structure of the extract can not be destroyed.
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Supercritical CO2 is a common supercritical fluid, which is safe, non-toxic,
413
cheap and recyclable. However, supercritical CO2 extraction has a long time, high
414
extraction pressure and temperature, especially for solid materials, it is not only
415
inefficient but also has many cycles, so the large-scale application of supercritical
416
CO2 extraction technology is limited. In view of these shortcomings of supercritical
417
CO2 extraction, researchers at home and abroad have carried out extensive research on
418
ultrasound-enhanced supercritical CO2 extraction (Chemat et al., 2017; Wei et al.,
419
2016). Ultrasound-enhanced supercritical CO2 extraction technology refers to the
420
traditional supercritical CO2 extraction technology strengthened by external
421
ultrasound field to reduce the extraction temperature and pressure, as well as the
422
amount of entrainer, which can shorten the extraction time, improve the extraction
423
rate, while maintaining the unchanged structure of the extraction object.
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The cells are broken through membrane perforation produced by high-voltage
425
pulses during the process of PEF extraction, which can break cells in an instant and
426
take less time (Liu et al., 2018a,b). Compared with SFE and SCFE, PEF has lower
427
cost and higher universality of equipment, the heating process can be saved due to
428
rapid increase of temperature in the breaking process. However, there are still a series
429
of problems to be solved urgently in the application of PEF technology in industrial
430
production. PEF system should be standardized, including the structure of treatment
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room, operation mode and construction materials. Then perfect control system should
432
be designed to avoid changes caused by secondary effects. In addition electrochemical
433
reactions in the process of treatment should be considered to avoid the production of
434
toxic substances. The cell structure is changed by ultra-high pressure (reach up to 700 MPa), the
436
contact area with the solvent is increased and the mass transfer resistance is lowered,
437
causing the active ingredient dissolved quickly, and the extraction efficiency can be
438
significantly improved. UPE can be carried out at near room temperature, which not
439
result in structural changes and physiological activity reduction of small molecule
440
substances caused by thermal effects. Compared with traditional thermal extraction,
441
the volume of liquid decreases in the process of UPE, and there is no energy
442
consumption for solvent phase transformation. At the same time, the heat exchange
443
between the system and the external environment is also less because of the little
444
change of temperature in the extraction process. Therefore, only the volume
445
compression process of extracting solvent consumes part of the energy in the boosting
446
stage, and the energy loss of the whole process is very low. UPE technology has the
447
advantages of high efficiency and purity in the extraction of natural active ingredients
448
(Chen et al., 2014a). Especially, the extraction process can be carried out at room
449
temperature, avoiding the damage of thermal effect to natural active ingredients,
450
which has been affirmed by many researchers. Although UPE technology has many
451
unique advantages in extraction, in order to promote this new technology from
452
laboratory research to large-scale industrial production, the following aspects are
453
needed to continue to develop. The UPE equipment should be improved, such as
454
installation of real-time temperature monitoring equipment, in order to control
455
temperature more accurately. The synergistic extraction of natural active ingredients
456
by UPE technology and other technologies should be studied, such as the combination
457
of UPE technology and homogenization, enzyme-assisted UPE.
458
3. Bioactivities of edible fungi active constituents
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3.1 Research and application of active constituents
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3.1.1 Polysaccharide The active constituents such as polysaccharides, glycoprotein, peptides,
462
terpenoids and ergosterol derived from cultured mycelia, fruiting bodies, and filtrates
463
of edible fungi have displayed strong antitumor activities. Chihara (1969) assessed the
464
antitumor activities of extracted polysaccharides from edible fungi for the first in the
465
1960s. Since then, the fungal polysaccharide antitumor activity and its mechanisms of
466
action have been extensively investigated. The structural diversified polysaccharides
467
from edible fungi have been isolated by numerous researchers who proved the strong
468
antitumor activity (Yan et al., 2018; Ren et al., 2012; Zong et al., 2012; Chen et al.,
469
2011). Compared with the traditional antitumor drugs, the antitumor activities of
470
polysaccharides obtained from edible fungi exhibit several mechanisms of action,
471
which
472
(immune-enhancing activity); and (2) direct antitumor activity by inhibiting growth of
473
various types of tumor cells and tumor metastasis in the body, inducing apoptosis of
474
tumor cells (direct tumor inhibition activity) (Yan et al., 2018; Zhang et al., 2011d;
475
Wasser, 2002; Zhang et al., 2007).
(1)
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against
bearing
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Fig. 6 illustrates the mechanisms of antitumor activity of polysaccharides from
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Lentinus edodes. Lentinan is a β-(1→3)-D-glucan isolated from Lentinus edodes,
478
which can activate many immune cells to regulate the release cell signal
479
semiochemicals such as cytokines for the indirect immunostimulatory anti-cancer. The
480
increase of cytokine secretion in immune system have been observed in a mass of
481
research (Hou et al, 2008 a,b; Lull et al, 2005; Shin et al., 2003). Moreover, treatment
482
with lentinan can destroy cancer cells migration by increasing the phagocytosis of
483
immune cells in the human body and increase the production of chemical messengers
484
such as nitric oxide (NO) and hydrogen peroxideto (H2O2) to stimulate the immune
485
system. (Hou et al, 2008 a,b). In addition, hormonal factors play an important role in
486
cancer growth, which may be related to the immune-activating ability of lentinan.
487
These researches suggested that lentinan have the effect of inhibit the growth and
488
even kill cancer cells directly through a variety of pathways, human immune system
489
ars activated by different mechanisms such as the various immune cells stimulation
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ACCEPTED MANUSCRIPT and the cell signal messengers production. (Zhang et al., 2011d). Hamuro et al (1994)
491
demonstrated that the combination of cytokine interleukin IL-2 (a cell signaling
492
molecule) and lentinan for the reduction of lung metastasis colony numbers expressed
493
a synergistic effect which the reduction reach to 85%, the reduction reach to 28.4% or
494
7.1% reduction respectively when IL-2and lentinan alone. Drandarska et al (2005)
495
found that the combination of vaccine with lentinan can enhance against tuberculosis
496
by inducing the activation of immune cells in the lung tissue causing immune
497
response in lung and reduce its side effects. Moreover, better clinical results could be
498
obtained for cancer patients when lentinan is added to chemotherapy, the immune
499
responses was improved by regressing the lesions or tumors to prolongate the in
500
patients life (Zhang et al., 2011d).
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As the antineoplastic mechanism research, numerous encouraging clinical studies
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results from all over the world have been reported. Kosaka et al (1995) displayed that
503
the mixture of lentinan with hormonal therapy was more effective for the
504
enhancement of hormonal parameters such as follicle-stimulating hormone, serum
505
levels of estradiol, luteinizing hormone, and prolactin compare to hormonal therapy
506
alone. Fujimoto et al (2006) utilized adaptive immunotherapy and lentinan to treated a
507
case of recurrent ovarian cancer successfully. Zhang et al (2011d) have displayed the
508
potential anti-HIV activity of lentinan by clinical experiments. A Chinese patent
509
which applied the lentinan as orally or intravenously medicinal and as health-care
510
products have been registered (Jin et al., 2007).
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Fig. 7 are the mechanisms of antitumor activity of polysaccharides from
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Phellinus s. l. species. An acidic glycoprotein was isolated by Kim et al. (2003a,b)
513
from the fruiting body of Phellinus, demonstrated that not only selectively stimulates
514
proliferation of murine peritoneal macrophages in vitro but also markedly improved
515
the production of semiochemicals (NO and H2O2) for antitumor activity. Kim et al.
516
(2006) also demonstrated that a polysaccharide-protein clathrate extracted from the
517
fruiting body of Phellinus significantly increased B-cell proliferation, stimulated
518
macrophages to release the cytokines and semiochemicals NO in vitro. Moreover, a
519
proteoglycan extracted from the submerged fermentation mycelium of Phellinus
ACCEPTED MANUSCRIPT exhibited antitumor activity in vivo by enhancing lymphocytes proliferation and
521
increasing production of cytokines TNF-α and semiochemicals NO (Li et al., 2011;
522
Song et al., 2011; Xue et al., 2011; Liu et al., 2009). The results consistent with Li et
523
al. (2008). Li et al. (2004) found that a glycoprotein from Phellinus inhibited the
524
proliferation of SW480 colon cancer cells by induction of apoptosis. Polysaccharide
525
were extracted with different concentrations of ethanol (30%, 50% and 70% ethanol)
526
from Phellinus baumii showed higher macrophages stimulation activities (Li et al.,
527
2015). The fruiting body (or fungal mycelium) of Phellinus linteus is shown in Figure
528
8 and it has been commercially developed as Phellinus health food and cosmetic
529
products, mainly by using its polysaccharides and protein-bound polysaccharides.
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In addition, a novel polysaccharide is the mainly active component extracted
531
from Ganoderma atrum namely PSG-1 which markedly inhibited growth of CT26
532
tumor from tumor-bearing mice by causing apoptosis of CT26 cells (Hsiao et al., 2008;
533
Ma et al., 2011; Zeng et al., 2012). Moreover, PSG-1 enhanced the levels of cytokine
534
in serum and promoted the proliferation of lymphocyte as well as immune organ
535
index. Shi et al (2013) fractionated an acidic polysaccharide fraction with a molecular
536
weight of 3.68×105 Da from the fruiting bodies of Pleurotus abalonus, was the most
537
active in inhibiting MCF-7 cancer cells with an IC50 of 193 mg/mL. Ma et al (2015)
538
showed that a novel polysaccharide (namely GFP-A) with molecular mass of 889 kDa
539
from Grifola frondosa can significantly abate the inhibition of immune responses
540
induced by cyclophosphamide in vivo.
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edible fungi are studied more mature, bioactivities of other edible fungi active
543
component is also studied. The hypoglycemic activity of polysaccharide from three
544
fruiting bodies of Coprinus comatus (CC30, CC60, and CC80) was investigated by
545
Zhou et al (2015), the results showed the polysaccharide from CC60 can significantly
546
inhibit the promotion of blood glucose concentration when administered orally at a
547
dosage of 1000 mg/kg for 120 min. It also presents a long-term hypoglycemic effect
548
during 21 days of injection at the same dosage. Based on these results, polysaccharide
549
from CC60 has potential applications in diabetes patients as a natural medicine with
ACCEPTED MANUSCRIPT hypoglycemic activity. The antioxidant activity of polysaccharide from fruiting bodies
551
of Tricholoma lobayense was investigated by Ding et al (2016), the results showed
552
that polysaccharide not only could improve the cell viability, reduce the production of
553
reactive oxygen species (ROS) and inhibit oxidative damage, but also markedly
554
inhibite the formation of malondialdehyde (MDA) and improve the activities of
555
superoxide dismutase (SOD) and catalase (CAT) in mice liver and serum.
556
Furthermore, the antioxidant activity of polysaccharide from fruiting bodies of wild
557
Russula griseocarnosa was also investigated by Yuan et al (2017), the antioxidant
558
activities proved by reducing power to scavenge the DPPH, ABTS, superoxide radical
559
and hydroxyl radical.
560
3.1.2 Protein
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There are many kinds of active proteins in edible fungi, the most common of
562
which are agglutinin and fungal immunomodulatory proteins (FIP). FIP is a small
563
molecular protein with molecular weight ranging from 12 kD to 15 kD, while lectin
564
has molecular weight ranging from 12 kD to 190 kD, most of which are
565
macromolecular proteins, composed of four subunits. In different edible fungi, FIP
566
contains at least one α-helix and seven β-folds, and the amino acid sequences of these
567
proteins are highly homologous. Due to the differences in structure, edible fungus
568
proteins are involved in regulating various physiological functions such as anti-cancer,
569
anti-virus, anti-bacterial and immune regulation. In addition, antiviral proteins,
570
ribosomal inactivating proteins, laccase and other active proteins are also found in
571
edible fungi, which are different in molecular weight and structure (Ditamo et al.,
572
2015; Gao et al., 2013; Singe et al., 2010).
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FIP is a protein extracted from edible fungi or fungal fruiting bodies, which is
574
similar to the structure and function of immunoglobulin (Ig). There are mainly
575
Flammulina velutipes fungal immunomodulatory proteins (FIP-fve) and Volvariella
576
volvacea immunomodulatory proteins (FIP-vvo). FIP stimulates antigen presenting
577
cell (APC) to release cytokines of NO and IL-12 by combined with TLRs, which can
578
activate and promote the proliferation and differentiation of T cells (Th0) to form Th1
579
and Th2 cells, further activate macrophages and B cells, and producing a variety of
ACCEPTED MANUSCRIPT cytokines (Fig. 9). This process involves the phosphorylation of p38/MAPK and the
581
activation of nuclear transcription factor NF-κB. Therefore, the immune mechanism
582
of edible fungi immunoregulatory protein can be summarized as the activation of
583
p38/MAPK and NF-κB signaling pathways after combined with TLRs. Studies have
584
shown that FIP-fve can up-regulate the expression of intercellular adhesion
585
molecule-1 (ICAM-1) by phosphorylating p38/MAPK, and activate Th1 cells to
586
promote the production of IL-2 and IFN-γ, thus which played an immunoregulatory
587
role. FIP-vvo can not only activate Th1 cells and enhance the transcriptional
588
expression of IL-2, TNF-α and IFN-γ, but also induce Th2 cells to produce IL-4 and
589
further differentiate B cells, which can promote immunoglobulin transformation and
590
produce Ig E antibody. Sheu et al. showed that Pleurotus citrinopileatus
591
immunomodulatory protein (PCi P) activated macrophages to produce NO and TNF-α,
592
stimulated spleen cells to release IFN-γ, and speculated that this regulation process
593
was related to TLRs signaling pathway. In addition, studies have shown that
594
p38/MAPK and NF-κB are activated by FIP through TLRs, PI3K/Akt signaling
595
pathway is activated by Ganoderma tsugae fungal immunomodulatory protein
596
(FIP-gts) which stimulating human peripheral blood monocytes to produced IFN-γ.
597
Sun et al. (2017) investigated that the polypeptide from Pleurotus eryngii mycelium
598
inhibited the proliferation of cancer cells (cervical, breast, and stomach cancer cells),
599
but promoted the proliferation of macrophages (Ana-1 cell), TNF-α and IL-6 secretion,
600
TLR2 and TLR4 expression and increased macrophage phagocytic ability through NO
601
and H2O2 release.
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Edible fungus agglutinin is a bioactive protein or glycoprotein, which can induce
603
cell agglutination and participate in various physiological processes, such as
604
anti-cancer, anti-virus, immune regulation. Lectins can cross-link carbohydrates on
605
the cell surface and agglutinate red blood cells, which can activate cell signal
606
transduction pathways by binding to glycosylation receptors on the cell surface.
607
Clitocybe nebularis lectin (CNL) regulates p65 through TLR-4 signaling pathway,
608
stimulates the transcriptional expression of NF-κB, promotes the maturation of
609
dendritic cells, mediates T cells to produce IL-4, IL-6, IFN-γ and other cytokines, and
ACCEPTED MANUSCRIPT participates in the immune response (Svajger et al., 2011). Pleurotus ostreatus
611
agglutinin as an immunoadjuvant can stimulate DC maturation, promote IFN-γ
612
production in Th2 and Tc1 cells, and enhance the immunogenicity of hepatitis B virus
613
DNA vaccine. Agaricus bisporus lectin (ABL) inhibits NO production by M1
614
macrophages through TLR/Akt signaling pathway. It can be seen that the immune
615
regulation mechanism of edible fungus agglutinin is mainly through TLRs signaling
616
pathway, stimulating the proliferation and differentiation of macrophages, DC and
617
other immune cells, activating the production of cytokines by NF-κB (Pohleven et al.,
618
2012; Pushparajah et al., 2016).
619
3.1.3 Polyphenols and terpenes
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Polyphenols in edible fungi are a class of important natural antioxidants, which
621
can scavenge free radicals and quench reactive oxygen species, mainly including
622
phenolic acids, flavonoids, tannins and anthocyanins and other plant secondary
623
metabolites. Palacios et al (2011) found that the content of phenolic substances in the
624
edible fungi of Agaricus bisporus, A. sinensis, Chanterelle, Pine mushroom,
625
Pleurotus ostreatus were 1~6mg/g, The content of flavonoids was 0.9~3.0mg/g,
626
which all showed inhibition of linoleic acid autooxidation. Terpenoids in edible fungi
627
are mostly sesquiterpenoids, diterpenoids and triterpenoids. Most of them have
628
anti-inflammatory, anti-bacterial and anti-oxidative biological activities. Ganoderma
629
lucidum acid, a common triterpenoid compound in Ganoderma lucidum, is an
630
important active substance, more than 100 species were isolated from Ganoderma
631
lucidum.
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The antioxidant mechanisms of edible fungi mainly include free radical
633
scavenging, lipid oxidation inhibition, chelating transition metal ions and activating
634
antioxidant-related enzymes in vivo. Free radicals are metabolites of normal
635
physiological activities of cells, which mainly include hydroxyl radicals (·OH),
636
superoxide anion radicals (O2-), lipid peroxide, hydrogen peroxide and singlet oxygen.
637
Hydroxyl radicals can produce very strong oxidation, which are the main free radicals
638
causing protein and polysaccharide decomposition, lipid peroxidation and nucleic acid
639
breakdown. Superoxide anion free radicals can induce lipid peroxidation in vivo,
ACCEPTED MANUSCRIPT accelerate the aging of the body, and cause a series of diseases such as cancer and
641
cardiovascular diseases. Flavonoids and polyphenols in edible fungi can directly
642
quench singlet oxygen, prevent free radical chain reaction and lipid peroxidation to
643
avoid oxidative damage. Jayakumar et al. (2009) found that the clearance rate of
644
ethanol extracts from 10 mg/mL of Pleurotus ostreatus to O2- reached 60.02%.
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Oxygen free radical reaction and lipid peroxidation are in a dynamic equilibrium
646
state in the process of metabolism, maintaining many normal biochemical reactions
647
and immune reactions. Once the balance is unbalanced, oxygen radical chain reaction
648
is induced to form lipid peroxide (LPO), malondialdehyde (MDA) and 4-hydroxy
649
nonanenoic acid (HNE), which changed the fluidity and permeability of cell
650
membranes. Terpenoids and flavonoids in edible fungi can react with intermediates of
651
lipid chain oxidation (lipid free radicals or lipid oxygen free radicals), terminating the
652
chain reaction and inhibiting lipid oxidation. Wang et al. (2012a,b) isolated several
653
sesquiterpenoids from Flammulina velutipes with antioxidant, antitumor and
654
antimicrobial activities. The lipid peroxidation can be avoided by complexing ·OH on
655
polyphenol rings with Fe2+ or Cu2+, thus inhibiting the production of oxygen free
656
radicals. Yaltirak et al. (2009) demonstrated that the chelating ability of ethanol
657
extract of Russula edodes reached 58% at the concentration of 5 mg/mL. Gursoy et al.
658
(2009) showed that the chelating ability of methanol extracts from seven different
659
Morchella species for transition metal ions increased with the increase of extract
660
concentration.
661
3.2 Potential applications of active ingredients
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Fluorescence imaging is an important disease diagnosis technology, which has
663
outstanding advantages of high sensitivity and adjustable fluorescence characteristics
664
compared with radiography, magnetic resonance imaging, Raman imaging and
665
ultrasound imaging. The inorganic nanoparticles include semiconductor quantum dots,
666
metal nanoclusters, rare metal doped nanoparticles, carbon quantum dots and silicon
667
quantum dots and organic nanoparticles, such as organic dyes, conjugated polymers
668
and aggregation-induced emission are fluorescent imaging materials (Liu et al., 2016;
669
Huang et al., 2018). Compared with inorganic nanoparticles, organic nanomaterials
ACCEPTED MANUSCRIPT have attracted much attention, especially in the field of bioimaging, due to the
671
characteristic of adjustable molecular structure, biodegradability and low toxicity.
672
Therefore, the development of new fluorescent organic nanoparticles has always been
673
a hot research topic. Zhang et al. (2012b) prepared polydopamine fluorescent organic
674
nanoparticles for the first time and successfully applied them to bioimaging. The
675
co-assembly of dopamine with other functional molecules can further enrich the
676
structure and function of dopamine-based nanomaterials. The active ingredients of
677
edible fungi have unique physicochemical properties and functionality, such as
678
universal adhesion, excellent biocompatibility and biodegradability, which can be
679
considered to be used in fluorescent nanomaterials. In addition, polysaccharides and
680
proteins from edible fungi can be considered for drug delivery and controlled release
681
because of their structural diversity and easy surface modification of functional
682
molecules. The preparation, stability and biodegradability of active ingredient
683
nanomaterials of edible fungi were studied in order to better control the morphology
684
and function of nanomaterials. Structuring functional nano-platform based on active
685
ingredient materials, integrating the functions of bioimaging, drug delivery and cancer
686
treatment, will greatly bring the advantages of nano-materials into play.
687
4. Conclusion and future outlook
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This paper has systematically reviewed efficient physical technologies in
689
extraction of bioactive compounds from edible fungi which have potential antitumor
690
and antioxidant activities. These physical technologies including UAE, MAE, SFE,
691
UPE and PEF can greatly increase the extraction yield, reduce energy and solvent
692
consumption, and also improve the quality of the extracted compounds. However,
693
some extraction processes are complex and may have negative effect on the
694
bioactivity of the constituent. Consequently, it is important to create a database
695
including the optimal conditions to extract different active constituent with the
696
corresponding technology for specific edible fungus. Last but not least, further
697
progress in terms of the efficacy, legislation, cost-effectiveness ratio and convenient
698
manipulation of these efficient physical technologies should also be highlighted in the
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future works. Most of bioactive compounds from edible fungi have been proven to have the
701
potential for the prevention and treatment of diseases, mainly due to their antioxidant
702
activity, immune activity and antitumor activity. Although the bioactivity and
703
mechanisms of bioactive compounds from edible fungi have been largely reported, it
704
is necessary to study the structure-activity relationship between structure parameters
705
and biological activity. On the other hand, application of some bioactive compounds
706
is still in an early stage of development and only exists at the laboratory research level.
707
This requires extensive trials at pilot scale and industrial scale in the future work.
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Acknowledgments
709
This work was financially supported by China State Key Research Program (Contract
710
No. 2017YFD0400901), Jiangsu Province Key Agricultural Project (Contract No.
711
BE2016362), Jiangsu Province Collaborative Innovation Center for Food Safety and
712
Quality Control “Industry Development Program”, Jiangsu Province Infrastructure
713
Project (Contract No. BM2014051).
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Fig. 1. Laboratory-scale SEF extraction plant
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Fig. 2. Schematic representation of a laboratory-scale prototype of an UPE system.
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Fig. 3. Schematic procedures of UPE processing
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Fig. 4. SEM images of the control group (a,b), ×400&×l500; SE Mimages of the test
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Fig. 5. Schematic representation of a pulsed electric field (PEF) system
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Fig. 6. Mechanisms of antitumor activity of lentinan as a β-D-glucan.
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Fig. 7. Summary of mechanisms of antitumor activity of polysaccharides from
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Phellinus s. l. species.
Fig. 8. The fruiting body (or fungal mycelium) of Phellinus linteus and commercial
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Fig. 9. Immunomodulatory mechanism of edible mushroom proteins.
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Fig. 1. Laboratory-scale SEF extraction plant
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1. Gas cylinder 2. Cooling circulating water bath 3. CO2 pump 4. Air compressor 5. CO2 preheater
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6. Buffer tank 7. Extraction kettle 8. Micro valve 9. Collection bottle 10. Wet gas flowmeter
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Fig. 2. Schematic representation of a laboratory-scale prototype of an UPE system.
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Fig. 3. Schematic procedures of UPE processing
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Fig. 4. SEM images of the control group (a,b), ×400&×l500; SE Mimages of the test group (c,d),
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Fig. 5. Schematic representation of a pulsed electric field (PEF) system (Elena et al., 2016)
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Fig. 6. Mechanisms of antitumor activity of lentinan as a β-D-glucan. (Moradali et al., 2007)
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Fig. 7. Summary of mechanisms of antitumor activity of polysaccharides from Phellinus s. l.
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Fig. 8. The fruiting body (or fungal mycelium) of Phellinus linteus and commercial Phellinus
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Table 1 The advantages and disadvantages of each technology Characteristics
Advantages
Disadvantages
Conventional extraction methods
Solvent-assisted (water or organic solvents)extraction is a widely employed technique
An economic method, and does not requires any special equipment
Ultrasound-as sisted extraction
Edible fungus cells are disrupted by shock waves from cavitation bubbles, thus facilitating mass transfer hence an increase in the extraction yield
Microwave-as sisted extraction
A process that includes heating the material causing moisture to evaporate, which generates tremendous pressure, and the rupture of cells facilitates the release of the desired intracellular contents The density of a supercritical fluid is similar to a liquid and its viscosity is similar to a gas, its diffusivity is intermediate between the two states, thus favoring the extraction of intracellular compounds. Works under a super-high pressure ranging from 100 to 500 MPa and temperature of 20-50°C
An inexpensive and simple method which can be combined with solvent extraction methods and allows to decrease the extraction time and the temperature of the extraction Suitable for extraction of bioactive compounds; rapid sample preparation with reduced solvent usage Shorter extraction time and high separation efficiency; improved product purity
longer extraction times, lower yields, more organic solvent consumption, and poor extraction efficiency, which incorporate risk of thermal degradation of thermolabile active compounds Long ultrasonic time may cause fracture of functional structure and reduce extraction rate
Pulsed electric field extraction
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Technologies
The technique requires placement of food between two electrodes in a batch or continuous treatment chamber and its exposure to a pulsed voltage (typically, 0.1–5 kV/cm with pulses of 10–1000 μs for electroporation of plant cells). The duration and number of pulses should be limited to reduce the temperature increase, which is generally of no more than 3–5°C
Shorter extraction time, decreased solvent consumption, increased extraction yields, lower operating temperature, allowing the extraction of thermolabile compounds, fewer impurities Possible continuous operation; very short treatment times and suitable for thermolabile compounds extraction.
Uneven heating uniformity
High capital cost
the UPE requires the higher investment costs, such as, the elevated pressure needs expensive equipments；an additional filtration or centrifugation is necessary to remove the solid residue during UPE High capital cost
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Efficient physical extraction of active constituents from
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edible fungi and their potential bioactivities: A review
Highlights
Bullet point 1: Five efficient physical extraction technologies (UAE, MAE, SFE, UPE
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technologies are discussed.
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Bullet point 2: The advantages and disadvantages over conventional extraction
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Bullet point 3: The potential bioactivities of active constituents are also mentioned.