Converting cork by-products to ecofriendly cork bioactive ingredients: Novel pharmaceutical and cosmetics applications

Industrial Crops & Products 125 (2018) 72–84

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Converting cork by-products to ecofriendly cork bioactive ingredients: Novel pharmaceutical and cosmetics applications C. Carriçoa, H.M. Ribeirob, J. Martob, a b

T

⁎

Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

A R T I C LE I N FO

A B S T R A C T

Keywords: Cork By-products Pharmaceutical Cosmetics Topical application Sustainability

Quercus suber forests are very important, both economically and ecologically, in countries from the Mediterranean basin. Quercus suber bark or cork is obtained from the outer bark of this tree and it is the base of many commercial and profitable products. The industry around cork extraction and transformation leads to the production of considerable amounts of by-products, some of them considered as waste. Cork and its by-products can be an important source of multiple bioactive components, such as phenolic acids, terpenoids and tannins. These natural products present a wide variety of relevant properties, namely antioxidant, anti-inflammatory, antiaging, radical scavenger and depigmenting activity. Thus, cork and its by-products can be reused as promising ingredients in topical products. They may be used in different pharmaceutical and cosmetic applications, such as skin ageing prevention and skin depigmenting activity or as complements in acne treatment and skin inflammatory processes. The heterogeneity of its chemical composition and its extraordinary properties make cork a material with a lot of potential and considerable importance. Reusing and valorising cork by-products in the cosmetic field fits with the current sustainable perspective. In this literature review, the different cork byproducts and their bioactive compounds are presented and the promising application of these wastes as cosmetic and pharmaceutical ingredients is analysed.

1. Introduction Presently, with the growing environmental protection awareness, there is a strong market trend to formulate green and natural products. Sustainability is the new goal, increasingly pursued by professionals and consumers alike (Rastogi et al., 1996; Mestre and Gil, 2011; Gil, 2014; Csorba and Boglea, 2011). The aim is to reduce the environmental impact of products by creating value and rationally using the resources (Mestre and Gil, 2011; Sierra-Pérez et al., 2015). Customers are always demanding better, more sustainable alternatives and are actively seeking a more natural and healthy lifestyle. There is also an increased interest in biological activity of natural products (Rastogi et al., 1996; Batista et al., 2015; Silva et al., 2005; Nohynek et al., 2010). This way, companies are motivated to develop innovative products based on material derived from plants or microorganisms, that is, renewable resources. Moreover, it is suggested that bioactive ingredients from natural sources have greater biocompatibility when compared with to synthetic substances. Consequently, products that are natural or organic are regarded as healthy (Rastogi et al., 1996; Csorba

and Boglea, 2011; Batista et al., 2015; Gonçalves et al., 2015; Philippe et al., 2012; Cervellon et al., 2011). The increasing use of natural plant ingredients in cosmetic products raised new safety issues that require novel approaches to their safety evaluation. Pragmatic approaches for quality and safety standards of botanical ingredients are needed (Antignac et al., 2011). Quercus suber bark, commonly known as cork, is a natural material obtained from the outer bark of the oak tree Quercus suber L. (Jové et al., 2011; Gil, 2015). There are around 2 million hectares of cork forest in the western Mediterranean basin. Q. suber acts as a buffer to soil erosion, its forests avoid desertification and have a massive social and economic importance in their region. Portugal has 32% of cork forests and is the leading producer and exporter of cork, followed by Spain (Pereira, 2011; Parsons, 1962; González-García et al., 2013). Cork is a renewable and non-toxic material, used since ancient Egypt in multiple applications (Gil, 2014; Silva et al., 2005; Gil, 2015). The bark is obtained from the tree without endangering it, since the stripping process only means that the tree will rebuild a new cork layer (Jové et al., 2011; Gil, 2015).

⁎ Corresponding author at: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal. E-mail address: jmmarto@ff.ulisboa.pt (J. Marto).

https://doi.org/10.1016/j.indcrop.2018.08.092 Received 17 June 2018; Received in revised form 13 August 2018; Accepted 31 August 2018 0926-6690/ © 2018 Elsevier B.V. All rights reserved.

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2010; Leist et al., 2012). Nowadays, there is a huge preoccupation with skin ageing, skin pathologies, such as skin cancer and acne, or any kind of skin imperfections. Some of these concerns are related to sun exposure due to the UV radiation. Its absorption by the skin originates reactive oxygen species (ROS), causing “oxidative damage” to cellular components (Mukherjee et al., 2011; Marto et al., 2016; Matsuoka et al., 2006; Leyden, 1997). UV radiation is carcinogenic and accelerates skin ageing and photodermatoses (Nohynek et al., 2010). Besides UV radiation, other environmental factors, like pollution, also promote skin ageing. These factors lead to the formation of free radicals that polymerize collagen and reduce skin elasticity and skin capacity to hold water, causing wrinkles (Mukherjee et al., 2011; Momtaz and Abdollahi, 2012). Acne vulgaris, also mentioned, affects a great number of people and their quality of life. This pathology involves excessive amounts of sebum and inflammatory lesions that can seriously affect the appearance of the skin (González-García et al., 2013; Gil, 1997). Taking this into account, it is easy to understand the importance of cosmetic products. Particularly, natural products lead to an ample variety of phytomolecules, with properties like scavenging free radicals from skin cells, preventing trans-epidermal water loss, inhibiting lipogeneses and preventing wrinkles (Mukherjee et al., 2011). Q. suber bark is one of such products. It is a multifunctional ingredient full of relevant properties that together with its by-products, can be used as a constituent of skin care products (e.g. cork granulates can be used as exfoliant particles and cork extracts as antioxidant and antiaging agents). In this review, the possible new applications of Q. suber by-products as bioactive ingredients for cosmetic and topical pharmaceutical products were discussed, analysing the main compounds responsible for their activity and evidencing their effects on skin.

Cork goes through different transformation processes and can originate several high added-value products for different fields’ applications (Silva et al., 2005; Gonçalves et al., 2015). This makes it a very promising area of study (Mestre and Gil, 2011; Gil, 2014). Cork is a light weight material, impermeable to liquids, a good thermal insulator, resistant to microbial activity, with high friction coefficient. Its bestknown use is as stoppers for wine bottles, which has the greatest economic impact, despite the severe competition from substitutes and synthetic materials (Parsons, 1962; Pereira et al., 1987; Bejarano et al., 2015). However, cork products and the waste from its production have a lot of potential and can be used in innovative ways (Parsons, 1962; Cordeiro et al., 1998). During the production processes, by-products of cork are originated. Ideally, all these by-products would be reused or valued in some way, consolidating their sustainable nature. For example, cork powder is nowadays burned to produce energy. New derivative cork products are used in different fields, such as the construction industry, and its diversity of uses is likely to increase due to its multiple by-products and attractive properties. The future holds many possibilities for this multifunctional material (Gil, 2015; Sousa et al., 2006). There is a need and an opportunity to rethink and upgrade the by-products applications and value them further as important sources of oleochemicals (Pereira, 1988). Cosmetic and topical pharmaceutical application could be a new way to reuse Q. suber by-products. Cork consists essentially of suberin, lignin and cellulose, containing also smaller amounts of extractives, fatty acids, terpenes, long chain aliphatic compounds and saccharides. The presence of several extractable phenolic acids was also identified. The interest on these natural phenolic compounds relies on the wide variety of relevant properties shown by this family, namely, their antioxidant, antiinflammatory, radical scavenger, enzyme inhibitor and antimicrobial properties. Several studies demonstrate that the extracts obtained from Q. suber bark have in fact antioxidant, antiaging, anti-inflammatory and anti-fungal properties all from a naturally occurring and sustainable material (Fernandes et al., 2011; Santos et al., 2010). The heterogeneity of chemical composition and its extraordinary properties make cork a material with a lot of potential and considerable importance in several industries, namely in the cosmetic and pharmaceutical field (Santos et al., 2010; Castola et al., 2005; Subhashini et al., 2016; Khennouf et al., 2003). Cosmetics are a common type of product that people apply on the skin. Cosmetics do not penetrate through the deeper layers of the skin, meaning there is no significant systemic exposure. However, it cannot be excluded that, in some circumstances, its components might cause a reaction (Nohynek et al., 2010). Consequently, before placing a cosmetic product on the market, a safety assessment must be performed, because as stated in the European legislation, cosmetic products must be safe for the consumer. Cosmetic products follow the requirements of the EC Cosmetics Regulation 1223/2009, where product exposure estimates and toxicological evaluation are essential for the safety assessment, as well as skin compatibility studies (EC, 2009). In particular, it is possible to assess the safety of pharmaceutic, cosmetic and other chemical products, using literature data, in vitro studies, computational approaches and human tests, since animal testing is no longer permitted by European legislation (SCCS et al., 2010; Domingo et al., 2016; Villaverde et al., 2017). It is expected that the right balance of in vivo, in vitro and computational toxicology predictions applied as early as possible will help to reduce the number of safety issues. Many computational approaches are available to predict the toxicity induced by a small molecule from its chemical drawing. In silico techniques like knowledge-based expert systems (quantitative) structure activity relationship tools and modeling approaches may therefore help to predict adverse reactions in preclinical studies. In the future the overall hazard and risk assessment strategy will likely include the standardization of analytical approaches, more complete and reliable data collection methods, and a better understanding of toxicity mechanisms (Merlot,

2. Quercus suber bark and its by-products 2.1. Characterizing cork Q. suber, commonly known as cork oak, belongs to the Fagaceae family (Parsons, 1962; González-García et al., 2013). It has a narrow geographical range, growing in the Western part of the Mediterranean basin and along the Atlantic coast of North Africa and South-Western Europe, mainly in the Iberian Peninsula (Mestre and Gil, 2011; SierraPérez et al., 2015; Pereira, 2011; Lumaret et al., 2005). These regions have ideal weather conditions, with dry summers and mild winters, for oak trees’ growth (Jové et al., 2011; Touati et al., 2015). Q. suber can grow to 15–20 m height and live 200–250 years (González-García et al., 2013; Touati et al., 2015). Its forests are very important, both economically and ecologically, in countries from the Mediterranean basin (Mestre and Gil, 2011; Santos et al., 2013). Cork is the suberose parenchyma from the outer bark of Q. suber, obtained both from the trunk and branches of the tree. The tree has the ability to regenerate it, by producing a suberose thick layer from its inner bark. This bark tissue is formed by the phellogen of the cork oak, responsible for the formation of new cells due to its meristematic nature, which means cell generation ability (Mestre and Gil, 2011; Silva et al., 2005; Pereira et al., 1987; Pereira, 1988). As such, the cork itself can be extracted without endangering biodiversity or causing damage to the tree. In other words, it is a natural, recyclable, non-toxic, renewable resource with high environmental qualities that plays a relevant role in sustainability (Sierra-Pérez et al., 2015; Pereira, 2011; González-García et al., 2013; Touati et al., 2015). Its forests play a key role in ecological processes and its use remotes to Antiquity, to times before Egyptian, Greek and Roman civilisations, where it was firstly used in fishing floats and other maritime devices (Mestre and Gil, 2011; Pereira, 2011; Santos et al., 2013). Q. suber outer bark is a barrier between the cortex of the tree and the atmosphere. It is elastic, light, impermeable to liquids and gases, it does not absorb water and can absorb energy, showing chemical and 73

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1988). Life span for stripping the bark is between 150 and 200 years, equivalent to 13–18 extractions (Mestre and Gil, 2011; Jové et al., 2011). There are 2 main products that result from cork harvest: virgin cork or “desbóia” and reproduction cork or “amandia”, obtained from the 3rd collection onwards and the main source of economic income. The first corresponds to the first cork layer ever removed from the oak, when the tree is about 20 or 30 years old. This uneven outer bark is usually of poor quality and used only in granulated form, latter transformed in agglomerates, to produce corkboards for insulation, decorative purposes or shoe soles. The original outer bark of the tree is rough, full of cavities, with irregular surface, density and thickness. Afterwards, a new layer of regenerated cork grows but it is still of low quality. Reproduction cork is the name given to the successive cork layers that are harvested at 9-years intervals and have approximated thickness of 2–5 cm. These layers are, on the contrary, smooth, finegrained and have high quality. They are essentially used for production of cork stoppers (Mestre and Gil, 2011; Silva et al., 2005; Parsons, 1962; González-García et al., 2013; Pereira et al., 1987). After extracting the cork, it stabilizes in the forest, being equilibrated by leaving it under ambient air conditions until its moisture is 6–10%, which normally occurs approximately 21 days after stripping. Then it is transported to a preparation factory where the slabs are boiled and selected to manufacture cork stoppers and agglomerated cork products (Sierra-Pérez et al., 2015; González-García et al., 2013). Selection is done by hand, dividing cork into groups according to thickness, quality and size. Cork to be used for stoppers is selected based on external surface analysis (Silva et al., 2005). Summarizing, cork industry has 5 branches of activity: Production, that involves planting, preserving and stripping the trees; Preparation, where the cork is selected, boiled, marked, cut and packed; Transformation, that basically consists on washing and drying the cork, resulting in the production of natural cork products, like stoppers; Granulating the cork waste of an inferior quality, triturating and classifying based on granulometry; and finally Agglomerating, to create cork agglomerates from production residues previously granulated (Mestre and Gil, 2011).

biological stability. Cork can be compressed and has very low thermal and electric conductivity, making it a good insulator. Furthermore, it is innocuous, resistant and can be used as acoustic and vibration absorber, as well as a dielectric material (Mestre and Gil, 2011; Pereira, 2011; Parsons, 1962; Bejarano et al., 2015; Santos et al., 2013; Gil, 2009). Cork is composed of dead cells that have lost their internal content and have several wall layers (González-García et al., 2013; Gil, 2009; Aroso et al., 2015). Macroscopically, cork presents layers of alveolate cells that confer it important physical and mechanical properties (Mestre and Gil, 2011). Hooke was the first to observe cork under the microscope. The researcher analysed the cellular structure of Q. suber bark in 1664, contributing to the knowledge of plant and wood anatomy (Silva et al., 2005; Pereira, 2011; Pereira et al., 1987; Pereira, 1988). Later, the observations were confirmed by Leeuwenhoek (1704) in the Netherlands and by Natividade (1938) in Portugal. Q. suber bark is a homogenous tissue of thin-walled prism-shaped cells, regularly arranged, without intercellular spaces. While the cells do not communicate with each other, they are stacked in columns and their most usual shapes are heptagonal, hexagonal or pentagonal, although the average number of sides is six. Scanning microscopy showed that the cell walls are heavily, but irregularly, corrugated. This happens because of compression during bark growth (Silva et al., 2005; Pereira, 2011; Pereira et al., 1987). Additionally, cork cells are filled of lenticular channels (radial and oriented pores) that allow oxygenation of meristematic tissue and influence cork porosity and therefore its quality (Silva et al., 2005; Pereira et al., 1987). Cork cells contain a gas like air in their interior, responsible for important properties. Q. suber bark density varies with the age of the tree, but is usually low due to the high content of gas in the cells. This also implies a very poor heat and sound transfer, giving rise to cork’s good insulation properties (Silva et al., 2005; Pereira, 2011). 2.2. The cork industry There is a significant industry developed around cork and its production. More than 85% of the global cork production happens in Portugal, Spain, France and Italy (Gil, 2014; Sierra-Pérez et al., 2015; Pereira, 2011; Pereira et al., 1987). About 70% of cork production translates in wine bottling industry and 22% of cork is used in the building industry (Mestre and Gil, 2011; Gil, 2014.). For the last 300 years cork has been used as stopper for bottled wine and its large scale commercial exploitation started due to that industry. Cork stoppers are used because they are impermeable to liquid and air, preventing oxidation, and also because they are resilient and compressible (Silva et al., 2005). Furthermore, some studies concluded that wines are positively affected by contact with the cork stopper, since some components can migrate from it into the wine (Gil, 2014; Conde et al., 1997, 1998a). From 1960 it began to be used more frequently for other purposes, like aeronautics and construction (Mestre and Gil, 2011; Gil, 2009). In 1892, it was discovered that low quality cork and cork waste could be used to produce composition cork and corkboards. These cork sub-products are used presently for thermal and acoustic insulation (Parsons, 1962). In Portugal, the extraction of cork, called stripping, happens once every 9 years, the legal time interval. After 9 years the bark is ready to be harvested again without harming the oak tree or the environment (Mestre and Gil, 2011; Jové et al., 2011). Cork layer is harvested from trunk and branches of Q. suber L., usually in the summer, after the tree reaches approximately 70 cm of circumference and 1,3 m height (Parsons, 1962; González-García et al., 2013). The oak cannot be completely stripped of its bark, however (Mestre and Gil, 2011). The extraction is made in the form of tubular pieces mainly by a manual process, although mechanical processes exist nowadays (Mestre and Gil, 2011). Stripping the tree promotes the same to produce the new bark layer, so there is an increase in cork production due to its extraction (Gil, 2015; Pereira, 2011; González-García et al., 2013; Pereira,

2.3. Sustainability and by-products Cork is a sustainable and eco-efficient material and a renewable source with high environmental advantages. Cork regenerates after each stripping and the tree survives the loss of more than 50% of its outer bark. This is one of the main reasons for its sustainable nature (Gil, 2014; Sierra-Pérez et al., 2015). Besides this, Q. suber L. forests are important for ecological processes, like water retention, soil conservation and carbon storage. Cork oak forests regulate water cycle, by promoting infiltration of rain, and prevent soil erosion, helping soil conservation. These forests combat desertification and, being the home of many animal and plant species, promote biodiversity (Mestre and Gil, 2011; Sierra-Pérez et al., 2015). Cork products store carbon for extended periods of time and delay its return to the atmosphere. This way, cork oak forests reduce carbon dioxide emissions by CO2 fixation, countering world’s pollution. Since cork extraction promotes the tree to produce more cork and the CO2 is fixed in that bark layer, the harvesting process decreases the CO2 in the atmosphere (Mestre and Gil, 2011; Gil, 2014; González-García et al., 2013). This reinforces the environmental importance of cork and its contribution to a sustainable world (Gil, 2014). The production of cork planks (extracted pieces of cork produced after boiling, stabilization and selection processes) originates a lot of waste. As does the production of cork stoppers or cork products for other uses. In truth, the annual production of cork waste reaches 50,000 tons (Jové et al., 2011; Gil, 1997). But the industry’s residues can be valued in several applications (Silva et al., 2005; Santos et al., 2013; Gil, 2009). Fig. 1 shows various by-products, that result from the 74

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be used as a filling agent, in agriculture and explosives manufacture. Also as a source of chemical components (Gil, 1997; Santos et al., 2013; Aroso et al., 2015). Cork extracts are another Q. suber sub-product full of potential, since they are a source of important bioactive components. They can be obtained from different cork products, such as natural cork, cork powder and black condensate, originating phenolic extracts and aliphatic extracts. The composition of the extract depends on the solvent used for their extraction. Solvents, such as water, methanol, dichloromethane, propyleneglycol, ethanol, have been used for cork products extraction. These extracts contain several substances, cork extractives, with a lot of potential for new applications, like bioactive ingredients for cosmetic and topical pharmaceutical formulations (Santos et al., 2013; Aroso et al., 2015). Santos et al. (Santos et al., 2010) obtained promising results with high extraction yields for cork extraction, using water as solvent. In addition, a new cork hydroglycolic extract was patented recently. It was obtained by extracting from cork granulates its bioactive compounds using a mixture of water:propyleneglycol. This solvent proved to have excellent properties and selectivity to extract bioactive compounds from cork (Batista et al., 2015). An additional residue that results from cork stoppers production is cooking wastewaters. These brown liquid substances are released when cork is boiled, for stoppers production, and they contain high quantities of phenolic components but no suberin (Sousa et al., 2006; Silvestre et al., 2008; Madureira et al., 2012). Another example is the wood obtained from Q. suber, usually used for heating purposes (GonzálezGarcía et al., 2013; Igueld et al., 2015). Even though there are several examples of cork sub-products, they are not exploited to their full potential (Gil, 2009). Several studies have been developed recently to discover new applications for cork and its by-products. It is important nowadays to promote valorisation of forest by-products as emerging alternatives to petrochemical derivatives and as a source of important chemicals (Santos et al., 2013; Silvestre et al., 2008). Recently, there has been increasing innovation in the development of new cork materials, like composites, high-performance insulators, space vehicles, complex structures under vibration and dynamic loads, as well as other high-tech applications (Pereira, 2011). Another one is the use of cork as a promising biosorbent for organic pollutants. Cork has a heterogeneous chemical composition, which provides a lot of bonding sites for a variety of pollutants. For this reason, it has high adsorption capacity (Jové et al., 2011). In summary, this material has enormous potential for new applications (Sierra-Pérez et al., 2015; Gil, 2009; Fernandes et al., 2009).

Fig. 1. Cork by-products.

transformation processes, like cork granulates, composition cork and expanded cork agglomerates (Mestre and Gil, 2011; Gil, 2015). Granulates are manly used as raw material for the manufacture of agglomerates. They are the result of grinding parings, virgin cork, scraps, cork pieces and stopper’s production waste. In other words, cork waste from the cutting stage and material rejected at the selection stage. Expanded cork agglomerates or black agglomerates result from agglutinating granulates without using any synthetic agents to bind them. The transformation of cork raw material in expanded cork agglomerates with cork resins, using superheated steam fuel produced with cork waste is a perfect example of a sustainable by-product (Mestre and Gil, 2011; Gil, 2015; Santos et al., 2013; Gil, 2009). They have a higher extractive level and can be used in multiple applications like thermal insulation or as a source of bioactive compounds (Mestre and Gil, 2011). The invention of mixing cork granulates with other materials happen in 1909 by Charles McManus. Composition cork is the result of binding cork granulates with natural or synthetic resins. With the existence of different binding agents and chemical additives, it is possible to adapt the composite to user or purpose requirements. This material is a great opportunity to reuse cork products or recycle them, since it maintains all the great properties of cork and of all the other materials used (Mestre and Gil, 2011; Gil, 2009). Another by-product originated from insulation corkboard industry, during the formation of black agglomerate, is black condensate. Black agglomerate production involves the treatment of cork particles at elevated temperatures (250–500 °C) without adding any adhesive. This leads to the formation of vapours that condensate in the autoclave pipes, forming the black condensate, which is used to produce energy by burning it (Sousa et al., 2006; Santos et al., 2013; Silvestre et al., 2008). Cork powder is also a residue from the industrial transformation of cork. It has high heating value and it is currently used for combustion and energy production. Chemical components may be obtained from cork powder extract (Mestre and Gil, 2011; Touati et al., 2015; Santos et al., 2013; Silvestre et al., 2008). This by-product is the major waste from cork industry, originating from grinding, cutting and finishing processes. It is the sum of all cork wastes including raw cork impurities, cork material powder, cork particles < 0.5 mm (low granulometry fraction not used for agglomerates), that include outer layers of the tree and mineral particles. Cork particles not suitable for granulates are removed by granulometric separation. Usually cork powder is composed by particles with sizes inferior to 0.25 mm and it is produced during all phases of industrial cork production. In cork stopper production, cork powder corresponds to 25–30% of the raw material. It can

3. Chemical composition of cork The properties of a material depend on the chemical characteristics of its components. Cork chemical composition is quite complex and it includes a large variety of molecules. Fig. 2 shows a simplified version of that composition emphasising the most relevant parts.

Fig. 2. Quercus suber bark composition. 75

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Graça and Pereira (2000) performed a depolymerization and subsequent analysis of cork suberin from the outer bark of Q. suber, using a simplified methanolysis method and quantifying glycerol and longchain monomers by gas chromatography. The results suggest that glycerol is a significant component of suberin (14%) (Silvestre et al., 2008; Graça and Pereira, 1997, 2000). Studies revealed an ordered arrangement of aliphatic esterified layers, alternating with layers rich in esterified coumarates and glycerol (Gandini et al., 2006). This supports the idea that suberin has a polymeric structure where its monomers suffer successive esterification. Besides the mentioned monomers, Q. suber suberin is composed by an epoxide ring in mid-chain position. The epoxyacids represent around 30% of the total suberin. Two of the main long-chain aliphatic monomers are 9-epoxyoctadecanoic acid and 9-epoxy-18-hydroxyoctadecanoic acid (Silvestre et al., 2008; Graça and Pereira, 2000). Silvestre et al. compiled the information from several studies and, despite significative percentage variations, concluded that the main components of suberin are ω-hydroxyfatty acids or hydroxyalkanoic acids (26–62%), followed by α,ω-dicarboxylic acids or alkanedioic acids (6–53%) and fatty acids (1–15%). Also present, but in lower concentrations, are aromatic compounds (0.1–7.9%) and aliphatic alcohols (0.4–8.3%). The 18 and 22 chains lengths of carbon atoms are the dominant ones, representing 75% of all monomers, and ferulic acid is the main component from aromatic domain (Silvestre et al., 2008; Bento et al., 2001; Gandini et al., 2006). These results were confirmed by other studies, where monomeric suberin composition was studied, most of the times, using gas chromatography combined with mass spectrometry (Cordeiro et al., 1998; Bento et al., 2001; Lopes et al., 2000; Holloway, 1972; Graça, 2015; Coquet et al., 2008). Suberin is a promising ingredient that can be valued in new applications, like industrial development as a source of new macromolecular materials. Its monomers are ideal for use as building blocks for polymers. Depolymerized suberin monomers have been used for synthesis of polyurethanes and polyesters (Santos et al., 2013; Silvestre et al., 2008; Gandini et al., 2006; Sousa et al., 2008). Suberin main components like ω-hydroxyfatty and α,ω-dicarboxylic acids, are not very abundant in nature, rendering suberin exploitation paramount for the synthesis of polymeric materials (polyols) (Silvestre et al., 2008; Pinto et al., 2009; Gandini et al., 2006). Regarding cork’s by-products, Silva et al. (2005), observed that virgin cork, usually discarded for having low quality, contains more suberin and has a higher extractable content than reproduction cork. Although different authors defend that reproduction cork has more suberin (Pereira, 2011, 1988). Natural cork has a higher amount of suberin than cork powder. However, cork powder can be a source of more than 16,000 ton of suberin per year. This could be a way to increase valorisation of cork powder as a source of suberin. Overall it can be concluded that cork by-products are a valuable resource to produce new macromolecular materials, particularly in the valorisation of its

It is consensual that natural cork contains suberin (≈40%), lignin (≈25%), polysaccharides (≈20%) and extractives (≈15%). Its exact chemical composition, however, depends on climatic and soil conditions, geographic origin, tree dimensions, its age and growth conditions (Silva et al., 2005; Sousa et al., 2006; Pereira, 1988; Santos et al., 2013; Pinto et al., 2009). Jové et al. (2011) and Pereira (2011) observed that cork also contains ash or inorganic components (0.4–3.3%). 3.1. Suberin The main structural components of cork’s cell walls are suberin, lignin and cellulose (Silva et al., 2005; Pereira et al., 1987; Pereira, 1988; Conde et al., 1998b; Lopes et al., 1998). The most abundant one is suberin and it represents a source of important chemicals for the production of new cork derivate materials (Pereira, 1988; Santos et al., 2010; Silvestre et al., 2008; Bento et al., 2001). Suberized cell wall structure attracted the interest of many researchers over the years and its exact composition remains a matter of debate (Cordeiro et al., 1998; Silvestre et al., 2008; Bento et al., 2001; Gandini et al., 2006; Sousa et al., 2008; Lopes et al., 2000; Holloway, 1972; Rocha et al., 2001; Graça and Pereira, 1997). Suberin functions as a protective barrier between the plant and the environment, being responsible for cells impermeability (González-García et al., 2013). It is found in the cell walls of external tissues of plants, mainly in the outer bark of trees (Graça, 2015). However, only a restricted number of species has a justifiable amount for its exploitation. One of these species is Quercus suber, more accurately its bark. It is the only tree in the world that produces such a thick layer of suberose tissue (Silvestre et al., 2008; Pinto et al., 2009; Gandini et al., 2006). Cork suberin is characterized by a polyester structure. It is made of long-chain fatty components, glycerol, hydroxyfatty and phenolic acids, linked by ester groups (Silva et al., 2005; Jové et al., 2011; Gandini et al., 2006; Graça and Pereira, 1997). Being a renewable source of chemicals and more specifically macromonomers (Silvestre et al., 2008; Gandini et al., 2006), several studies use depolymerised suberin, by cleaving the ester bonds, to analyse its monomeric subunits (Silva et al., 2005; Cordeiro et al., 1998; Silvestre et al., 2008; Bento et al., 2001). Ester cleavage through alkaline methanolysis, using methanolic sodium methoxide as reagent, is the most common depolymerization method to investigate suberin monomers (Silvestre et al., 2008; Gandini et al., 2006; Rocha et al., 2001). Suberin is composed of different molecular species, more specifically polyphenolic and polyaliphatic components, meaning it has an aromatic and an aliphatic domain. The first is structurally similar to lignin, whilst the latter is composed of long-chain ω-hydroxyfatty acids and α,ω-dicarboxylic acids connected by glycerol groups (Silva et al., 2005; Silvestre et al., 2008; Bento et al., 2001; Gandini et al., 2006; Graça, 2015). The aromatic domain of suberin is more complex than the aliphatic one (Silvestre et al., 2008; Gandini et al., 2006; Marques et al., 1994). Table 1 Monomeric composition of suberin from Q. suber. Monomers

Formula

Relative abundance (%)

References

Glycerol 1-Alkanols

CH2OHCHOHCH2OH CH3(CH2)nCH2OH

4.3–14.2 0.4–8.3

Alkanoic acids

CH3(CH2)nCOOH

1.0–14.9

α,ω-diacids (Saturated and Substituted) ω-hydroxyacids (Saturated and Substituted) Ferulic acid (aromatic compounds) Others and unidentified

COOH(CH2)nCOOH

6.1–53.3

COOH (CH2)nCOOH

24.8–61.7

C10H10O4

0.4–7.9

–

10.4–22.0

Pereira (2011), Bento et al. (2001) and Graça and Pereira (2000) Pereira (2011), Silvestre et al. (2008), Bento et al. (2001), Gandini et al. (2006), Lopes (2000), Graça (2015), Graça and Pereira (2000) and Coquet et al. (2008) Pereira (2011), Silvestre et al. (2008), Bento et al. (2001), Gandini et al. (2006), Lopes (2000), Graça (2015) and Graça and Pereira (2000) Pereira (2011), Silvestre et al. (2008), Bento et al. (2001), Gandini et al. (2006), Lopes (2000) and Graça and Pereira (2000) Pereira (2011), Silvestre et al. (2008), Bento et al. (2001), Gandini et al. (2006), Lopes (2000) and Graça and Pereira (2000) Pereira (2011), Silvestre et al. (2008), Bento et al. (2001), Gandini et al. (2006), Lopes (2000) and Graça and Pereira (2000) Pereira (2011), Gandini et al. (2006), Graça (2015) and Graça and Pereira (2000)

76

et al. et al. et al. et al. et al.

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2009). Cork extractives are usually classified in two main groups: aliphatics or waxes – extracted with low-polarity solvents like hexane, dichloromethane and chloroform – and phenolics, solubilized with ethanol and water (Silva et al., 2005; Jové et al., 2011; Pereira, 2011; Santos et al., 2010; Touati et al., 2015).

highly hydrophobic characteristics (Table 1) (Silvestre et al., 2008; Pinto et al., 2009; Gandini et al., 2006; Sousa et al., 2008). 3.2. Lignin Another significant component from Q. suber bark is lignin (Pereira, 2011; Lopes et al., 1998; Marques et al., 1994). Lignin is a heterogenous polymer, composed of strong covalent bonds, that assures mechanical support and rigidity to cork cell walls (Pereira, 2011). Lopes et al. (1998) used permanganate oxidation method to study the structure and proportions of the condensed and non-condensed units of lignin in the hope of deepening the knowledge of the nature of this aromatic polymer. The results supported the idea that lignin represents the main aromatic fraction of cork and that the aromatic domain of suberin has a similar structure to lignin (Lopes et al., 1998; Marques et al., 1994). According to Pereira H., 1988’s observations, cork cell walls are lignified in a manner similar to other wood or bark materials. They further state that cork cell walls are divided in three layers: primary thin wall, rich in lignin; secondary thick wall, made of suberin and waxes, but speculated to be also lignified; tertiary wall, a thin lignin and polysaccharides layer. The alkaline oxidation of cork lignin produces vanillin or vanillic acid (Jové et al., 2011). Regarding by-products, cork powder is known to contain higher quantities of lignin. Pinto et al. (2009) claims that this results from the enrichment of the inner and outer surfaces of the cork planks, from where powder is obtained. This is particularly true for the outer surface, prevalent in the powder, thanks to environmental exposure. The concertation of lignin in cork powder can even exceed the one in the original cork, thus rendering the powder as an excellent source for this aromatic.

3.5. Waxes Waxes represent the lipophilic fraction and a third of all cork extractives. They are made of aliphatic and aromatic components and are responsible for cork impermeability, along with suberin. Around half of these components are triterpenes (Silva et al., 2005; Pereira, 1988; Fernandes et al., 2009). The other half are n-alkanes, n-alkanols and fatty acids (Pereira, 2011; Touati et al., 2015; Fernandes et al., 2009). Triterpenic compounds are lipophilic extractives of cork with promising applications as bioactive ingredients. They include cerin, friedelin, betulin and betulinic acid, lupane derivatives (lupeol) as well as sterols (Pereira, 2011; Sousa et al., 2006; Santos et al., 2010; Touati et al., 2015; Fernandes et al., 2009). Cork cells contain cerin crystals in significant amount (Silva et al., 2005). Friedelin, in particular, also abundant in cork cells, has important properties (Silva et al., 2005; Touati et al., 2015; Santos et al., 2013) and applications that will be further discussed in the next chapter. A study on qualitative and quantitative composition of cork triterpenic fraction revealed: friedelin (49.5–79.7%); betulin (5.1–21.5%); betulinic acid (5.4–35.6%); β-sitosterol (3.2–9.0%); sitos-4-en-3-one (2.6–7.5%) and 3-α-hydroxyfriedelan-2-one (12.6–29.6%) (Castola et al., 2002). Castola et al. (Castola et al., 2005) used two methods of extraction to study triterpenoids and sterols present in cork aliphatic extracts. A traditional method, using dichloromethane as extraction solvent, and an innovative one, using supercritical CO2 as solvent. Both extracts confirmed that friedelin is the main component and the presence of betulin, betulinic acid, β-amyrin and steroids (β-sitosterol, sitos-4-en-3one and campesterol) (Castola et al., 2005, 2002). The results also showed that the innovative method of extraction originated more sterols than the one using dichloromethane. In another research work, Pinto et al. (2009) concluded that the major components from dichloromethane and methanol cork extracts are triterpenoids: cerin and friedelin in natural cork and betulinic acid in cork powder. Sousa et al. (2006) studied the lipophilic extractives of cork by-products. Using gas chromatography-mass spectrometry, they confirmed that the main triterpene from cork powder is betulinic acid and added that the main one from black condensate is friedelin. Moreover, extractive yields of black condensate are higher than those of cork powder. This shows the promise of cork by-products as sources of bioactive components. In addition, this study compared the total content of lipophilic extractives from inner cork and outer cork fractions and it was concluded that the concentration of extractives is higher in the inner surface. The lower values from the outer layer can be explained by the high environmental exposure.

3.3. Polysaccharides Suberin and lignin are hydrophobic biopolymers, but cork has hydrophilic polysaccharides (hemicellulose and cellulose) as well (Jové et al., 2011). Polysaccharides are low molecular weight components with average values between 528–968 g/mol, that give structural rigidity to cells and are present in smaller amounts. In cork, they are cellulose and hemicellulose, composed by different monosaccharides, such as glucose, xylose, arabinose, galactose and mannose (Silva et al., 2005). Pereira H. studied the chemical composition of virgin cork and verified that there are differences between Q. suber L. and other plant barks in the content of polysaccharides. Glucose represents about 50% of all monosaccharides, xylose 35% and arabinose 7%, a higher percentage than usually seen in other species. These results suggest that cellulose represents only about half of total polysaccharides, which means it accounts for approximately 9% of cork cell wall material. Contrary to other woods and barks, where it represents roughly 50% of cell wall material, in cork, cellulose does not play such a crucial role (Pereira, 1988).

3.6. Phenolics 3.4. Extractives The phenolic fraction of Q. suber bark can be extracted by polar solvents and represents 6 to 9% of cork (Pereira, 2011). Phenolic compounds are common components from plants and have a potential biological activity. The phenolic composition of cork has been intensively studied (Fernandes et al., 2011; Touati et al., 2015; Conde et al., 1997, 1998a). They include phenolic acids, phenolic aldehydes, coumarins, tannins and flavonoids (Silva et al., 2005; Bejarano et al., 2015; Touati et al., 2015; Fernandes et al., 2009). Table 2 summarizes the analysis of cork extractives from several sources. Q. suber L. has a tannin-rich inner bark replete of important properties for the review at hand, which will be discussed in the following chapter (Parsons, 1962; Fernandes et al., 2011; Santos et al., 2013). Tannins can be monomeric or polymeric and condensed or hydrolysable

Perhaps most valued due to their attractive and multifunctional properties, cork has a large variety of extractable components, such as alkanes, alkanols, waxes, triterpenes, fatty acids, glycerides, sterols, phenols and polyphenols (Jové et al., 2011; Pereira, 2011). The fraction of cork extractives is composed of low molecular weight molecules that are not covalently bonded to the structural elements of the cell wall, like suberin and lignin, and therefore can be easily extracted using solvents (Bejarano et al., 2015; Conde et al., 1998a). Their relative abundance varies even amongst trees in the same region (Fernandes et al., 2011). Some of these components can be responsible for a few organoleptic properties of wine, as a result of cork being used as a bottle stopper (Fernandes et al., 2011; Conde et al., 1997; Fernandes et al., 77

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Table 2 Analysis of cork phenolic extractives and HPLC quantitative evaluation. Compounds

Formula

Type of component

Extraction solvent

Quantity (μg/g dry cork)

References

Gallic acid

C7H6O5

Phenolic acid

MeOH:H2O; ether fraction

12.6–22.1 30.6–241.6 931.0 118.5–736.5 60–100

Conde et al. (1997) Santos et al. (2010) Touati et al. (2015) Santos et al. (2013) Batista et al. (2015)

22.7–64.8 6.0–126.0 17.5–118.3 79.3 1414.5 100–130

Conde et al. (1997) Conde et al. (1998a) Santos et al. (2010) Santos et al. (2013) Touati et al. (2015) Batista et al. (2015)

7.4–18.5 3.0–50.0 19.6 9.0–19.8 1.0–22.0 57.6 112.1

Conde et al. (1997) Conde et al. (1998a) Touati et al. (2015) Conde et al. (1997) Conde et al. (1998a) Santos et al. (2010) Touati et al. (2015)

162.5–307.0 111.0–327.0 1060.5 2031.5 1246.5 6800–8200

Conde et al., 1997 Conde et al. (1998a) Touati et al. (2015) Santos et al. (2010) Santos et al. (2013) Batista et al. (2015)

23.1–33.7 6.0–44.0 67.7 8.7–15.7 4.0–16.0 6.2–9.3 3.0–9.0 4.9

Conde et al. (1997) Conde et al. (1998a) Touati et al. (2015) Conde et al. (1997) Conde et al. (1998a) Conde et al. (1997) Conde et al. (1998a) Santos et al. (2010)

C3H8O2:H2O Protocatechuic acid

C7H6O4

Phenolic acid

MeOH:H2O; ether fraction

C3H8O2:H2O Ferulic acid

C10H10O4

Phenolic acid

MeOH:H2O; ether fraction

Caffeic acid

C9H8O4

Phenolic acid

MeOH:H2O; ether fraction

Ellagic acid

C14H6O8

Phenolic acid

MeOH:H2O; ether fraction

C3H8O2:H2O Vanillic acid

C8H8O4

Phenolic acid

MeOH:H2O; ether fraction

Scopoletin

C10H8O4

Coumarin

MeOH:H2O; ether fraction

Aesculetin

C9H6O4

Coumarin

MeOH:H2O; ether fraction

Coniferaldehyde

C10H10O3

Phenolic aldehyde

MeOH:H2O; ether fraction

9.6–12.5 14.0–22.0 194.3

Conde et al. (1997) Conde et al. (1998a) Santos et al. (2013)

Vanillin

C8H8O3

Phenolic aldehyde

MeOH:H2O; ether fraction

15.5–16.9 7.0–28.0 14.3 42.3

Conde et al. (1997) Conde et al. (1998a) Santos et al. (2010) Touati et al. (2015)

Sinapaldehyde

C11H12O4

Phenolic aldehyde

MeOH:H2O; ether fraction

3.7–5.0 1.0–3.0

Conde et al. (1997) Conde et al. (1998a)

Protocatechuic aldehyde

C7H6O3

Phenolic aldehyde

MeOH:H2O; ether fraction

5.2–9.5 3.0–22.0

Conde et al. (1997) Conde et al. (1998a)

Roburin A

C82H50O50

Ellagitannin

MeOH:H2O; water fraction

16.0–75.0 46.0–59.0

Conde et al. (1998a) Cadahía et al. (1998)

Roburin E

C46H34O30

Ellagitannin

MeOH:H2O; water fraction

32.0–145.0 108.0–137.0

Conde et al. (1998a) Cadahía et al. (1998)

Grandinin

C46H34O30

Ellagitannin

MeOH:H2O; water fraction

47.0–309.0

Conde et al. (1998a)

Ellagitannin

C3H8O2:H2O

500–3200

Batista et al. (2015)

Castalagin Roburin E

C41H26O26

Ellagitannin

MeOH:H2O; water fraction C3H8O2:H2O

82.0–709.0 1800–2100

Conde et al. (1998a) Batista et al. (2015)

Vescalagin

C41H26O26

Ellagitannin

MeOH:H2O; water fraction C3H8O2:H2O

14.0–124.0 800–1900

Conde et al. (1998a) Batista et al. (2015)

Ellagitannin

MeOH:H2O; water fraction

490.9

Touati et al. (2015)

Roburin A + Roburin E + Grandinin

Vescalagin + Castalagin

cork extract. Besides tannins, the other phenolic compounds present in cork are ellagic acid, gallic acid, protocatechuic acid, vanillic acid, caffeic acid and ferulic acid (phenolic acids); aesculetin and scopoletin (coumarins); protocatechuic aldehyde, vanillin, coumaric acid, coniferaldehyde and sinapaldehyde (Silva et al., 2005; Fernandes et al., 2011; Santos et al., 2010; Conde et al., 1997, 1998a). Cork polyphenolic composition was determined by Conde et al. (1998a), using HPLC. In this study, reproduction cork was extracted with methanol:water solvent, originating an ether fraction, composed

(Fernandes et al., 2009). The latter are the most relevant ones. Cork tannins are mostly ellagitannins – castalagin, grandinin, roburins A and E and vascalagin (Silva et al., 2005; Bejarano et al., 2015; Fernandes et al., 2011; Santos et al., 2010; Conde et al., 1998a). These compounds are very prominent in cork extracts. HPLC quantitative evaluation concluded that castalagin is the most abundant ellagitannin (Conde et al., 1998a). Ellagitannins can play a key role in wine oxidation processes and wine ageing. Fernandes et al. (Fernandes et al., 2011) also identified mongolicain, a flavanoellagitanin, as part of phenolic 78

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4. Application and properties of cork and its by-products as ingredients in medicines and cosmetics

of low molecular weight polyphenolic compounds, and an aqueous fraction, composed of polymeric polyphenols, specially tannins. The results, confirmed by similar studies, showed that the most abundant phenolic compound in cork extracts is ellagic acid, followed by protocatechuic acid, and that phenolic acids are the main low molecular weight polyphenols in cork, while aldehydes and coumarins are minor components (Santos et al., 2013; Conde et al., 1997, 1998a). It was also evident that the age of the oak and the distance of the collected sample from the base of the tree can influence the composition of the extracts obtained (Conde et al., 1998a). The phenolic composition of cork was confirmed by HPLC-DAD/ ESI-MS, performed by Fernandes et al. (2011), evidencing the importance of tannins and wide variety of low molecular weight phenols. The chemical composition of some of these components can be influenced by the industrial processing (Conde et al., 1997). The new cork hydroglycolic extract mention before is composed of gallic acid, protocatechuic acid, ellagic acid, roburin, grandinin, castalagin and vescalagin, also identified using HPLC-DAD/MS. The major components are ellagic acid and ellagitannins (Batista et al., 2015). Water and ethanol cork extracts are composed of phenolic acids, ellagitannins and flavonoids. In the case of cork extracted by water, it has molecules of higher polarity than those obtained with ethanol (Aroso et al., 2015). A new component was identified in water extract: hydroxybenzoic acid. Santos et al. (2010) performed different extractions: methanol/water extraction followed by ethyl ether fractionation (a) and sequential extraction with methanol (b) and water (c). The results showed that, by using different solvents, the total extracted phenolic content was different, as well as some of the components identified. For example, the total phenolic content was pointedly higher in water extract (c), presenting a higher extraction yield. This shows that it is possible to use water to extract phenolic fraction of cork instead of more harmful solvents. However, several components did not appear with this solvent’s extraction, like aesculetin, vanillin, vanillic acid, coumaric acid and ferulic acid and some, such as ellagic acid, appeared in much smaller concentrations. The attention payed to phenolic compounds resides on their properties: antioxidant, anti-inflammatory, radical scavenger, antiallergic, anticancer, antimicrobial, antiaging, depigmenting and anti-acne. The interest in these natural components for cosmetic applications has increased in the last few years because of their properties (Batista et al., 2015; Santos et al., 2010). Some phenolic compounds can be found in cork powder as well (Silva et al., 2005). Cork powder is composed by 12% extractives, 33% suberin and 25% lignin. The rest are polysaccharides and inorganic fractions (Aroso et al., 2015). Santos et al. (2013) compared the phenolic compositions of natural cork extract, cork powder extract and black condensate extract. There was a higher value of extraction yield from natural cork, followed by cork powder. Black condensate yield was smaller due to its volatile nature. The total phenolic content was also higher in natural cork extract. The extraction was made with methanol:water mixture, at mild conditions. The main components identified in phenolic natural cork, cork powder and black condensate extracts were ellagic acid, gallic acid, quinic acid, protocatechuic acid and aesculetin. Besides these components, it was observed that black condensate extract had coumaric acid, vanillin, coniferaldehyde and hydroxyphenyllactic acid. Cork powder extract presented ferulic acid, contrary to natural cork and black condensate extracts. Another cork by-product with phenolic compounds in its composition is cork cooking wastewater. Studies suggest that the major phenolic acids in these wastewaters are gallic, protocatechuic, ferulic and ellagic acids (Madureira et al., 2012). This way, it is possible to conclude that phenolic, aliphatic and triterpenic compounds can be found in cork and its by-products (Bejarano et al., 2015). These studies promote the valorisation of cork industry by-products and could broad the type of markets and clients for the cork sector.

4.1. Antioxidant activity Antioxidants are substances that delay oxidation of other molecules by inhibiting the oxidation chain reactions. They can be endogenous and exogenous molecules (Gonzalez-Burgos and Gomez-Serranillos, 2012; Lee et al., 2004; Rodrigues et al., 2015). Reactive oxygen species (ROS) appear during metabolic processes and are involved in these reactions. In small concentrations, ROS play an important role in intracellular functions, but when there is an imbalance between these species and antioxidants it results in oxidative stress (Gonzalez-Burgos and Gomez-Serranillos, 2012; Rodrigues et al., 2015). In this scenario, ROS may cause oxidative damages that are involved in the development of several diseases as well as in skin ageing process. These free radicals react with important molecules in connective tissue and cell membranes, modifying them. Lipids, proteins and DNA can be a target of intracellular ROS (Batista et al., 2015; Gonzalez-Burgos and GomezSerranillos, 2012; Lee et al., 2004). Antioxidant molecules prevent these damages, acting as free radical scavengers and modulating the endogenous antioxidant system (Gonzalez-Burgos and GomezSerranillos, 2012; Lee et al., 2004). At the skin level, UV rays are widely known to be the cause of premature photoaging, immune dysfunction and some types of skin cancer, contributing to long term skin damage. The ROS formation caused by exposure to UV radiation is a key contributing factor to these damages (Rodrigues et al., 2015). Thus, antioxidants that can protect the skin from the oxidative stress, can prevent mutagenesis, carcinogenesis and skin ageing. The skin uses endogenous antioxidants in that protective process, but not without suffering depletion in the process (Rodrigues et al., 2015). So, it makes sense that antioxidants can be used as ingredients for topical applications. Following the trend of natural products, antioxidants from plant sources can be a valued ingredient in cosmetic formulations (Igueld et al., 2015; Lee et al., 2004; Wojdyło et al., 2007; Kahkonen et al., 1999). Bioassays of plant compounds and extracts have been showing that antioxidant capacity (Rodrigues et al., 2015). The bark of Q. suber is definitely a candidate, being a rich source of bioactive compounds with antioxidant capacity, such as phenolic acids, tannins and flavonoids (Batista et al., 2015; Igueld et al., 2015; Fernandes et al., 2009; Lee et al., 2004; Kahkonen et al., 1999). In particular, phenolic components are known to have strong radical scavenging properties and the ability to decrease oxidative stress in skin cells, which makes them rather interesting for the cosmetic industry (Silva et al., 2005). They have been the focus of intense scrutiny due to their powerful antioxidant activity, both in vitro and in vivo studies (Batista et al., 2015; Bejarano et al., 2015; Santos et al., 2010; Santos et al., 2013; Lee et al., 2004; Rodrigues et al., 2015). This activity is due to their redox properties. They act like reducing agents, hydrogen or electron donators and singlet oxygen quenchers, inhibiting oxidative enzymes (Touati et al., 2015; Kahkonen et al., 1999; Shan et al., 2005; Noferi et al.,1997; Rice-Evans et al., 1997). Table 3 summarizes some of these studies and others on alternative extractives. Several studies confirmed that phenolic acids present in cork, such as caffeic acid, gallic acid, ellagic acid, ferulic acid, vanillic acid and protocatechuic acid, are powerful antioxidants (Touati et al., 2015; Lee et al., 2004; Rodrigues et al., 2015; Kahkonen et al., 1999). Rice-Evans et al. (1997); Wojdyło et al. (2007) and Kikuzaki et al. (2002), using different methods, determined that ferulic acid and caffeic acid have significant antioxidant activity. The antioxidant capacity of gallic acid was confirmed by DPPH· free radical assay and revealed a dose-dependent relation in its effectiveness against oxidative stress. This natural plant-based polyphenol exhibited free radical scavenging effects and hydrophobicity (Lu et al., 2006). Other studies confirmed the strong antioxidant activity of gallic acid (Fernandes et al., 2009; 79

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Table 3 Cork components with antioxidant activity. Components

Molecular family

Method %

Results

References

Ellagic acid

Phenolic acid

DPPH LP

Radical scavenging activity < 75% LP inhibition 55–88%

Han et al. (2006)

Gallic acid

Phenolic acid

DPPH% DPPH% OSI BML

IC50 (μM) 6.0 ± 0.1 Radical scavenging activity (%) 75.7 ± 1.1 Induction period (h) 9.44 ± 0.93 No reported values

Lu et al. (2006) Kikuzaki et al. (2002)

Caffeic acid

Phenolic acid

TEAC DPPH· OSI BML

1.3 ± 0.01 mM of TEAC Radical scavenging activity (%) 49.6 ± 0.6 Induction period (h) 17.64 ± 3.50 No reported values

Rice-Evans et al. (1997) Kikuzaki et al. (2002)

Protocatechuic acid

Phenolic acid

FRAP DPPH% ABTS%+ O2−

IC50(Trolox)/IC50(PCA) = 3.7 IC50(Trolox)/IC50(PCA) = 2.8 IC50(Trolox)/IC50(PCA) = 2.3 IC50(Trolox)/IC50(PCA) = 4.2

Li et al. (2011)

Ferulic acid

Phenolic acid

DPPH O2− NO− DPPH% OSI BML TEAC

IC50 (μM) 4.14 ± 0.38 IC50 (μM) 33.06 ± 0.45 IC50 (μM) 4.56 ± 0.12 Radical scavenging activity (%) 27.3 ± 0.8 Induction period (h) 2.97 ± 0.11 No reported values 1.9 ± 0.02 mM of TEAC

Lee et al. (2004)

DPPH% FRAP LP

15 μM Equiv. Trolox 35 μM Equiv. Trolox LP inhibition 53-55%

Fernandes et al. (2009)

Castalagin

Ellagitannin

%

Kikuzaki et al. (2002)

Rice-Evans et al. (1997)

Khennouf et al. (2003)

Mongolicain

Flavanoellagitannin

DPPH FRAP

27 μM Equiv. Trolox 25 μM Equiv. Trolox

Fernandes et al. (2009)

Betulinic acid

Triterpene

DPPH% ABTS%+ ORAC

No reported values

Gonzalez-Burgos and Gomez-Serranillos (2012)

β-sitosterol

Triterpene

DPPH% ABTS%+ ORAC

No reported values

Gonzalez-Burgos and Gomez-Serranillos (2012)

Lupeol

Triterpene

DPPH% ABTS%+ ORAC

No reported values

Gonzalez-Burgos and Gomez-Serranillos (2012)

Vanillin

Phenolic aldehyde

ORAC ABTS%+

No reported values 19.4 μM of vanillin quenched 50 μM of ABTS%+

Tai et al. (2011)

ABTS%+ – 2,2-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid)); BML – Autoxidation of Bulk Methyl Linoleate; DPPH% – 2,2-diphenyl-2-picrylhydrazyl radical; FRAP – Ferric Reducing/Antioxidant Power; LP – Lipid peroxidation; NO− – Nitric Oxide Radical; PCA – Protocatechuic acid; ORAC – Oxygen Radical Absorbance Capacity; OSI – Omnion Oxidative Stability Instrument; O2− – Superoxide Radical; TEAC – Trolox Equivalent Antioxidant Activity.

et al., 2015). Santos et al. (2010) studied cork’s antioxidant property. Cork extract showed antioxidant capacity in the same range of ascorbic acid, a known powerful antioxidant. Another author, Batista et al. (2015), after confirming that cork extract is not cytotoxic to skin cells, by testing its compatibility with keratinocytes, demonstrated that increasing the cells’ contact-time with the extract, the inhibition of ROS also increases. This shows that cork has a DNA protection effect and antioxidant bioactivity. Research by Touati et al. (2015), using DPPH% and ABTS%+ assays and FRAP method, studied the antioxidant potential of methanol:water cork extract. Results suggest that this extract has high antioxidant activity, which can be explained by its high content of phenolic compounds. As observed by Santos et al. (2013), black condensate extract has also a very high antioxidant capacity, even higher than ascorbic acid. A similar claim can be said about cork powder extract (Aroso et al., 2015), in this case determined by DPPH· radical scavenger and oxygen reactive absorbance capacity assays. Ethanol cork powder extract was the most effective as thermo-oxidative stabilizer (Aroso et al., 2015). Even cork cooking wastewater presents antioxidant compounds, namely phenolic acids and tannins. Madureira et al. (2012) measured the antioxidant activity of this cork by-product by FRAP assay and proved this activity. For all the mentioned reasons, it is possible to conclude that cork and its by-products can be an important source of antioxidant species

Wojdyło et al., 2007; Kahkonen et al., 1999; Golumbic and Mattill, 1942). Hydrolysable tannins from cork, namely ellagitannins, are also powerful antioxidant agents. They have a large number of hydroxyl groups, especially galloyl groups, which increase the radical scavenging activity (Touati et al., 2015; Fernandes et al., 2009; Noferi et al., 1997). Mongolicain B, a flavanoellagitannin, and castalagin, both present in cork, have strong antiradical and ion-reducing capacity (Fernandes et al., 2009). Khennouf et al. (2003) studied the gastroprotective effects of acetone extract of Q. suber and its derivate tannins, using an ethanolinduced gastric ulcer model in mice. The extract and its tannin fraction strongly inhibited the lipid peroxidation, suggesting that the gastroprotective effect shown is related to tannins’ anti-peroxidant activity. This confirms antioxidant properties of tannins. Other natural bioactive components of cork showed antioxidant activity, namely vanillin and friedelin (Silva et al., 2005; Rodrigues et al., 2015). Triterpenes present in cork, like betulinic acid, lupeol and β-sitosterol, also show antioxidant activity (Gonzalez-Burgos and Gomez-Serranillos, 2012). Cork extracts themselves show antioxidant activity proven by several studies, using different methods, such as ORAC, HORAC, HOSC, DPPH·, ABTS·+, FRAP and O2− (Batista et al., 2015; Bejarano et al., 2015; Santos et al., 2010; Touati et al., 2015; Santos et al., 2013; Aroso 80

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improved skin roughness. The results showed that cork extract has significantly high tensor, brightening and smoothing effects on the skin and, consequently, an immense potential for antiaging skin care products (Coquet et al., 2008, 2004). A German brand called Birkenstock that produces cork-based cosmetic products, claims that the suberin in their composition has a proven lifting effect. Additionally, an in vivo study confirmed that cork extract, as part of a facial cosmetic product, decreased the deformation of the skin after suction and increased the viscoelastic recuperation of skin structure. The results suggest that cork extracts improve skin firmness (Batista et al., 2015). Thus, adding to the potential of cork as a valued cosmetic ingredient, that would prevent oxidative stress and decrease skin flaccidity and wrinkles.

and, consequently, be valued as ingredients in cosmetic and topical pharmaceutical products, namely in sunscreens or wrinkle preventing products, discussed in the next section. 4.2. Use as a sunscreen ingredient Many natural sunscreens have good antioxidant properties. Due to its phenolic structure, lignin is an excellent light absorber. It absorbs UVB radiation and because of this it can be used as a natural UV protective material in sunscreens (Sadeghifar et al., 2017). 4.3. Skin ageing prevention Skin ageing is a major concern nowadays. Therefore, one of the main goals of the cosmetic field is the development of antiaging products (Mukherjee et al., 2011; Rodrigues et al., 2015). Environmental aggressors, such as pollution and prolonged UV exposure, can lead to premature skin ageing. This happens because of cells’ exposure to oxidative stress, which causes accumulation of cellular damages, promoting the appearance of wrinkles (Rodrigues et al., 2015; Karim et al., 2014). Photoaging leads to the loss of structural integrity and physiological functions of the skin, resulting in epidermal thickness, disorganization of collagen and histological changes. This leads to wrinkled skin, by depletion of elastin, hyaluronan and collagen fibres. A wide variety of new cosmetics can prevent skin ageing and reduce the decrease of collagen and elastin (Mukherjee et al., 2011; Rodrigues et al., 2015). The degradation of elastin and collagen is promoted by elastase and collagenase, enzymes produced in normal conditions by the human body. An excessive amount of ROS increases elastase and collagenase, leading to premature skin ageing. As stated in the previous section, the antioxidant activity of cork extractives can be very relevant in preventing ROS formation. Furthermore, studies showed that extracts containing gallic, protocatechuic and caffeic acids inhibit collagenase and elastase activity. Also, terpenoid compounds are elastase inhibitors, preventing the degradation of elastin fibrous structure in the dermal matrix (Mukherjee et al., 2011; Karim et al., 2014). Additionally, flavanols show strong inhibitory activity towards collagenase enzyme, decreasing collagen degradation and wrinkles’ formation (Mandrone et al., 2015). This shows that several phenolic components present in cork have collagenase and elastase inhibitory activity (Karim et al., 2014). Metalloproteinases (MMP) are a group of enzymes responsible for the destruction of the extracellular matrix components and basal membranes. MMP degrade collagen, fibronectin, laminin and proteoglycan. MMP-1, -3 and -9 cause the degradation of collagen and elastin, leading to an increase in wrinkles formation and decrease of skin elasticity. In normal conditions, the basal concentration of MMP is low, but again, the overproduction of ROS and pro-inflammatory mediators, caused by UV radiation, results in MMP activation (Batista et al., 2015; Rodrigues et al., 2015). For this reason, inhibitors of MMP activity can be excellent ingredients in antiaging cosmetics. Cork extract’s capacity to inhibit MMP was confirmed. It is based on cork extract’s ability to block MMP substrate cleavage. Studies show that this antiaging activity is dose-dependent and is more evident for the inhibition of MMP-9. This way, cork extract can prevent skin ageing, wrinkles and loss of elasticity by preventing the degradation of collagen and elastin (Batista et al., 2015). Moreover, gallic acid, present in cork composition, exhibited MMP-1 inhibitory activity (Mukherjee et al., 2011). Other cork components have confirmed antiaging properties, namely friedelin and suberin. As mention before, hydroxycarboxylic acids are the main components of suberin. These compounds have smoothing antiwrinkle effect over the skin. Coquet et al. (2004) performed an in vivo double-blind clinical study to confirm this antiaging capacity of suberin cork extract. The skin application of this extract

4.4. Skin depigmenting activity Melanin, produced in epidermis’ cells called melanocytes, is the main substance responsible for skin pigmentation. It plays an important role in protecting the skin from damages caused by UV radiation. However, an excessive accumulation of melanin can cause irregular skin hyperpigmentation and aesthetic problems, such as freckles, age spots and melasma. It is important to control melanogenesis, to avoid its excessive accumulation (Batista et al., 2015; No et al., 2004; Kim, 2007; Ando et al., 2007). Tyrosinase is a key enzyme in melanin biosynthesis (Karim et al., 2014; Kim, 2007; Chang, 2009) and UV radiation and the presence of ROS promote its activity (Karim et al., 2014; No et al., 2004; Gillbro and Olsson, 2011). This enzyme directly regulates the amount of melanin produced, being involved in the formation of intermediates of the melanogenesis process, such as L-Dopa and dopaquinone (Batista et al., 2015; Gillbro and Olsson, 2011; Passi and Nazzaro‐Porro, 1981). Inhibition of tyrosinase activity decreases melanin production and deposition (Ando et al., 2007; Chang, 2009; Venditti et al., 2013). There is a great demand for cosmetic products that will uniformize skin pigmentation and help correct hyperpigmented dermatological imperfections. This way, there is an interest in tyrosinase inhibitors from natural sources for depigmenting or skin-lightening effect (Batista et al., 2015; No et al., 2004; Gillbro and Olsson, 2011). Phenolic components may act as depigmenting agents, functioning as alternative substrates or inhibitors of tyrosinase (Passi and Nazzaro‐Porro, 1981). Due to these properties, they can be used in cosmetic products (Yoshimura et al., 2005). Several cork components, such as flavanols and phenolic acids, are known tyrosinase inhibitors (Karim et al., 2014). In vivo and in vitro studies show that they have effect on melanocytes as inhibitors or alternative substrates of tyrosinase (Passi and Nazzaro‐Porro, 1981). Ellagitannins and ellagic acid inhibit the activity of tyrosinase (Ando et al., 2007; Yoshimura et al., 2005). When applied topically, these components suppressed UV induced skin pigmentation. Ellagic acid showed depigmenting activity in an in vitro study with mushroom tyrosinase. This phenolic acid inhibits the proliferation of melanocytes and melanin synthesis (Yoshimura et al., 2005). Another study using mushroom-derived tyrosinase concluded that protocatechuic aldehyde has a potent tyrosinase inhibitory effect, acting as a competitive or alternative substrate (No et al., 2004; Kim, 2007). Gallic acid can inhibit melanogenesis as well (Kim, 2007; Chang, 2009). It has a strong antityrosinase activity, which can be the result of its phenolic structure. This compound’s antioxidant activity may be related to its capacity to inhibit melanogenesis. You-Jung’s study (Kim, 2007) showed that there was a dose-dependent inhibition of melanin synthesis in B16 cells when in the presence of gallic acid. Cork extract itself showed very positive results in skin melasma whitening, meaning it has a great depigmenting activity. This is the result of cork extract potential to inhibit tyrosinase activity, consequently inhibiting melanin production in cells (Batista et al., 2015). In consequence, it is possible to conclude that cork can be an important 81

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neurodegenerative afflictions have in common an inflammation state. This leads to upregulation of different enzymes, pro-inflammatory mediators and signalization proteins in affected cells. Nitric oxide (NO) is a substance produced during inflammatory processes. It is a very reactive radical that originates an aggressive oxidant for our body. By inhibiting the production of nitrites, we can prevent cellular damages. Cork extract showed a good ability to inhibit NO in the presence of a pro-inflammatory stimulus (Batista et al., 2015). The same study observed decrease of iNOS levels, an enzyme directly involved in NO production during an inflammatory process. Cork extract was shown to also inhibit the activation of transcription factor NF-kB. NF-kB plays an important part in the activation of genes that encode proteins related to the inflammatory response. In addition, cork extract decreases the levels of cytokines like IL-6, TNF-α and CCL5, that are mediators present in inflammatory response. It is save to conclude then that cork extract revealed anti-inflammatory properties (Batista et al., 2015). Several other studies showed the anti-inflammatory activity of cork components. Polysaccharides, suberin, triterpenes, such as friedelin, and phenolic compounds, such as polyphenols, ellagitannins and gallic acid, all have anti-inflammatory properties (Batista et al., 2015; Silva et al., 2005; Santos et al., 2010; Mukherjee et al., 2011; Fernandes et al., 2009; Kahkonen et al., 1999). This could be a new path of addedvalue for the application of these products in health and cosmetic industries.

ingredient in skin depigmenting cosmetics. 4.5. Anti-acne properties Acne is a very common dermatological condition with a multifactorial etiology, that can involve inflammatory and bacterial processes (Saviuc et al., 2017; Lee et al., 2017; Sinha et al., 2014). An excessive amount of sebum production by the sebaceous glands is considered one of the main factors that leads to acne (Batista et al., 2015; Lee et al., 2017). Nowadays, the products used to control this skin disorder are based on mechanisms to control lipogenesis. Studies show that in the presence of cork extract there is an inhibition of lipids’ accumulation on keratinocytes and that the extract inhibits SREBP-1 gene expression (Batista et al., 2015). This transcription factor directly upregulates enzymes that promote lipogenesis and is responsible for synthesis of cholesterol and fatty acids (Batista et al., 2015; Lee et al., 2017). Polyphenols, in particular, have an inhibitory effect on lipid production and expression of SREBP-1 (Lee et al., 2017). Phenolic compounds, such as tannins, also have anti-acne activity (Saviuc et al., 2017). This means that cork and its components may be useful to regulate sebum production and can be used as cosmetic ingredients for anti-acne products. In addition, a study showed that cork powder has properties of biosorbent and can remove pollutants and oil substances by biosorption (Pintor et al., 2012). A new application for cork powder, as part of a cosmetic formulation, could be as an oiliness absorbent for an anti-acne product. Propionibacterium acnes is an anaerobic skin pathogen that plays an important role in acne vulgaris. Ellagic acid exhibited potent bacteriostatic effect against P. acnes. Lipases inhibition may also be important for anti-acne products since it reduces fatty acids and the inflammatory process. Gallic acid exhibited lipase inhibitory activity and potential as an anti-acne agent (Sinha et al., 2014; Muddathir et al., 2013).

4.7.2. Antimicrobial activity Q. suber species has bioactive components in its composition that have antimicrobial activity (Subhashini et al., 2016; Deryabin and Tolmacheva, 2015). Cork antibacterial properties have been confirmed by several studies (Gonçalves et al., 2015; Subhashini et al., 2016; Wojdyło et al., 2007). Methanol:water cork extract revealed antibacterial and antifungal capacity by disc diffusion method (Subhashini et al., 2016). A study showed that this phenolic extract is effective against Staphylococcus aureus and Pseudomonas aeruginosa but not against Escherichia coli and Listeria innocua (Touati et al., 2015). However, in another example, cork displayed high antimicrobial activity against Staphylococcus aureus and Escherichia coli. In general, cork has shown to be more effective against Gram positive bacteria (Gonçalves et al., 2015). This activity may be due to high content of phenolic compounds in cork, known to have antibacterial capacity (Gonçalves et al., 2015; Santos et al., 2010; Touati et al., 2015; Chanwitheesuk et al., 2007). Phenolic compounds, such as tannins, protocatechuic and gallic acids, are known antimicrobial agents (Santos et al., 2010; Touati et al., 2015; Chanwitheesuk et al., 2007). Gallic acid, for instance, shows antimicrobial activity against Salmonella typhi and Staphylococcus aureus (Subhashini et al., 2016; Chanwitheesuk et al., 2007). Ellagitannins also have antimicrobial activity, including several mechanisms against extracellular microbial enzymes, microbial metabolism and inhibition of oxidative phosphorylation. They show activity against fungi and bacteria (Fernandes et al., 2009; Scalbert, 1991).

4.6. Use as exfoliant particles Exfoliation can be important in skin care. The desquamation of the epidermal tissue promotes the accumulation of dead skin cells and other impurities on the surface of the skin. Regular removal of these layers of dead cells can improve the health and appearance of the skin and help promote renewal of the epidermis (Lee and Serridge, 2001; Matjuskova et al., 2015). Moreover, the accumulation of dead cells in the stratum corneum often affects cosmetics’ performance (Lee and Serridge, 2001). There are chemical and mechanical exfoliating processes (Matjuskova et al., 2015). However, frequently, sensitive skin does not tolerate chemical exfoliators, as they may cause redness, discomfort, dryness and irritation (Pons‐Guiraud, 2004). Therefore, in these cases, the use of gentle physical exfoliators might be more advisable. Mechanical exfoliation involves the physical removal of dead skin cells using abrasive or granular materials (Matjuskova et al., 2015). Their level of exfoliation depends on the size, shape and hardness of the exfoliant particles and they can have a stronger or weaker abrasive effect (Aubrun-Sonneville, Bordeaux, 2007). Cork granulates have been used as exfoliant particles by Amorim group. They claim it can be used as a gentle exfoliation ingredient for sensitive skin. Due to their morphology and properties, cork granulates are composed of extremely effective yet soft particles ideal for sensitive and delicate skins. Furthermore, low volume is required in the cosmetic formulations due to the material’s low density (Amorim Cork Composites Technical Bulletin, 2013).

4.7.3. Anti-cancer potential Presently, skin cancer has become one of the most frequent neoplastic diseases, probably due to human behaviour and greater UV radiation exposure. Studies have shown that the polyphenols present in cork lead to pro-apoptosis in cancerous cells, showing anticancer bioactivity (Bejarano et al., 2015; Fernandes et al., 2009). Cork phenolic components exhibited a dose-dependent growth inhibitory effect on human tumour cell lines (Fernandes et al., 2009). Bejarano et al. (2015), concluded that phenolic compounds, like ellagitannins, have the ability to induce apoptosis in tumour cells. Castalagin and vescalagin showed inhibitory properties in colon cancer, and castalagin exhibited cytotoxic effects in leukaemia cells (Bejarano et al., 2015; Fernandes et al., 2009). Ellagitannins and ellagic acid inhibited the proliferation of cells by stopping cell cycle and inducing apoptosis of

4.7. Other properties 4.7.1. Anti-inflammatory properties Skin ageing, acne and diseases like cancer, cardiovascular and 82

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cancerous cells (Bejarano et al., 2015; Fernandes et al., 2009). Gallic acid also revealed cytotoxic activity inhibiting cell growth and cell proliferation in a dose-dependent manner and altered the pathway of cell apoptosis (Fernandes et al., 2009; Maurya et al., 2010). Other potent inducers of apoptosis are caffeic acid and protocatechuic acid (Bejarano et al., 2015; Fiuza et al., 2004). Cork extracts show toxic effect on human myeloid leukaemia cells (Bejarano et al., 2015). Triterpenic compounds, like friedelin and its derivatives, also have anticancer properties (Silva et al., 2005; Fernandes et al., 2009). Betulinic acid is used in prevention and treatment of cancer (Silva et al., 2005). This shows that cork components have anticancer activity.

Dermatol. 127, 751–761. Antignac, E., Nohynek, G.J., Re, T., Clouzeau, J., Toutain, H., 2011. Safety of botanical ingredients in personal care products/cosmetics. Food Chem. Toxicol. 49, 324–341. Aroso, I.M., Fernandes, E.M., Pires, R.A., Mano, J.F., Reis, R.L., 2015. Cork extractives exhibit thermo-oxidative protection properties in polypropylene–cork composites and as direct additives for polypropylene. Polym. Degrad. Stab. 116, 45–52. Aubrun-Sonneville, O., Bordeaux, D., 2007. Soluble Article for Exfoliating the Skin. EP1795173A1. . Batista, M., Rosete, M., Ferreira, I., Ferreira, J., Duarte, C., Matias, A., 2015. Extracto hidro-glicólico de cortiça, processo para a sua preparação, formulações compreendendo o referido extracto e sua utilização. WO2015152746A1. Bejarano, I., Godoy-Cancho, B., Franco, L., Martínez-Cañas, M.A., Tormo, M.A., 2015. Quercus suber L. cork extracts induce apoptosis in human myeloid leukaemia HL-60 cells. Phytother. Res. 29, 1180–1187. Bento, M.F.S., Pereira, H., Cunha, M.Á., Moutinho, A., Van den Berg, K., Boon, J., 2001. A study of variability of suberin composition in cork from Quercus suber L. using thermally assisted transmethylation GC–MS. J. Anal. Appl. Pyrol. 57, 45–55. Cadahía, E., Conde, E., Fernández de Simón, B., García-Vallejo, M.C., 1998. Changes in tannic composition of reproduction cork Quercus suber throughout industrial processing. J. Agric. Food Chem. 46, 2332–2336. Castola, V., Bighelli, A., Rezzi, S., Melloni, G., Gladiali, S., Desjobert, J.M., Casanova, J., 2002. Composition and chemical variability of the triterpene fraction of dichloromethane extracts of cork (Quercus suber L.). Ind. Crops Prod. 15, 15–22. Castola, V., Marongiu, B., Bighelli, A., Floris, C., Laı ̈, A., Casanova, J., 2005. Extractives of cork (Quercus suber L.): chemical composition of dichloromethane and supercritical CO 2 extracts. Ind. Crops Prod. 21, 65–69. Cervellon, M.C., Rinaldi, M.J., Wernerfelt, A.S., 2011. How Green is Green? Consumers’ understanding of green cosmetics and their certifications. 10th International Marketing Trends Conference. Chang, T.S., 2009. An updated review of tyrosinase inhibitors. Int. J. Mol. Sci. 10, 2440–2475. Chanwitheesuk, A., Teerawutgulrag, A., Kilburn, J.D., Rakariyatham, N., 2007. Antimicrobial gallic acid from Caesalpinia mimosoides Lamk. Food Chem. 100, 1044–1048. Conde, E., Cadahía, E., García-Vallejo, M.C., Fernández de Simón, B., González-Adrados, J.R., 1997. Low molecular weight polyphenols in cork of Quercus suber. J. Agric. Food Chem. 45, 2695–2700. Conde, E., Cadahía, E., García-Vallejo, M.C., Fernández de Simón, B., 1998a. Polyphenolic composition of Quercus suber cork from different Spanish provenances. J. Agric. Food Chem. 46, 3166–3171. Conde, E., Cadahía, E., Garcia-Vallejo, M.C., Gonźalez-Adrados, J.R., 1998b. Chemical characterization of reproduction cork from Spanish Quercus suber. J. Wood Chem. Technol. 18, 447–469. Coquet, C., Bauza, E., Oberto, G., Berghi, A., Farnet, A.M., Ferré, E., Peyronel, D., Dal Farra, C., Domloge, N., 2004. Quercus suber cork extract displays a tensor and smoothing effect on human skin: an in vivo study. Drugs Exp. Clin. Res. 31, 89–99. Coquet, C., Ferré, E., Peyronel, D., Dal Farra, C., Farnet, A.M., 2008. Identification of new molecules extracted from Quercus suber L. cork. C. R. Biol. 331, 853–858. Cordeiro, N., Belgacem, M., Silvestre, A., Neto, C.P., Gandini, A., 1998. Cork suberin as a new source of chemicals: 1. Isolation and chemical characterization of its composition. Int. J. Biol. Macromol. 22, 71–80. Csorba, L.M., Boglea, V.A., 2011. Sustainable cosmetics: a major instrument in protecting the consumer’s interest. Reg. Bus. Stud. 3. Deryabin, D.G., Tolmacheva, A.A., 2015. Antibacterial and anti-quorum sensing molecular composition derived from quercus cortex (oak bark) extract. Molecules 20, 17093–17108. Domingo, L.R., Ríos-Gutiérrez, M., Pérez, P., 2016. Applications of the conceptual density functional theory indices to organic chemistry reactivity. Molecules 21, 748. EC, 2009. Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products. EC, Editor. Off. J. Eur. Union. Fernandes, A., Fernandes, I., Cruz, L., Mateus, N., Cabral, M., de Freitas, V., 2009. Antioxidant and biological properties of bioactive phenolic compounds from Quercus suber L. J. Agric. Food Chem. 57, 11154–11160. Fernandes, A., Sousa, A., Mateus, N., Cabral, M., de Freitas, V., 2011. Analysis of phenolic compounds in cork from Quercus suber L. by HPLC–DAD/ESI–MS. Food Chem. 125, 1398–1405. Fiuza, S., Gomes, C., Teixeira, L.J., Girão da Cruz, M.T., Cordeiro, M.N., Milhazes, N., Borges, F., Marques, M.P., 2004. Phenolic acid derivatives with potential anticancer properties––a structure–activity relationship study. Part 1: methyl, propyl and octyl esters of caffeic and gallic acids. Bioorg. Med. Chem. 12, 3581–3589. Gandini, A., Neto, C.P., Silvestre, A.J., 2006. Suberin: a promising renewable resource for novel macromolecular materials. Prog. Polym. Sci. 31, 878–892. Gil, L., 1997. Cork powder waste: an overview. Biomass Bioenergy 13, 59–61. Gil, L., 2009. Cork composites: a review. Materials 2, 776–789. Gil, L., 2014. Cork: a strategic material. Front. Chem. 2. Gil, L., 2015. Cork: sustainability and new applications. Front Mater. 1, 38. Gillbro, J., Olsson, M., 2011. The melanogenesis and mechanisms of skin‐lightening agents–existing and new approaches. Int. J. Cosmet. Sci. 33, 210–221. Golumbic, C., Mattill, H., 1942. The antioxidant properties of gallic acid and allied compounds. J. Am. Oil Chem. Soc. 19, 144–145. Gonçalves, F., Correia, P., Silva, S.P., Almeida-Aguiar, C., 2015. Evaluation of antimicrobial properties of cork. FEMS Microbiol. Lett. 363, 231. Gonzalez-Burgos, E., Gomez-Serranillos, M., 2012. Terpene compounds in nature: a review of their potential antioxidant activity. Curr. Med. Chem. 19, 5319–5341. González-García, S., Dias, A.C., Arroja, L., 2013. Life-cycle assessment of typical Portuguese cork oak woodlands. Sci. Total Environ. 452, 355–364. Graça, J., 2015. Suberin: the biopolyester at the frontier of plants. Front. Chem. 3, 62. Graça, J., Pereira, H., 1997. Cork suberin: a glyceryl based polyester. Holzforschung 51, 225–234. Graça, J., Pereira, H., 2000. Methanolysis of bark suberins: analysis of glycerol and acid

5. Conclusion and future perspectives This work presented a literature review of Q. suber bark properties and its applications to the cosmetic and pharmaceutical industry. The importance of cork as an economical asset in the Mediterranean basin countries was made clear, as well as the ecological nature of its exploitation. To supplement this sustainability facet, it was pointed out the potential reuse of cork’s by-products and wastes. The chemical composition of cork was then discriminated, evidencing the properties of its bioactive components. An emphasis was given to suberin and cork extractives, namely phenolic acids, tannins and triterpenes. This rich composition and its potential use in many diversified fields became obvious, and thus it is no surprise the uprising interest of the academic and research community, as well as the industry, in cork and its by-products. Finally, attention was given to cork’s and cork by-products’ properties that render them relevant as cosmetics’ ingredients. There is a huge preoccupation with skin appearance and skin care products with formulations targeting antioxidant, antiaging, anti-acne and depigmenting effects are increasingly popular. Combining that with consumers’ demand for natural products, makes cork a tempting material. Studies show it decreases ROS formation, inhibits the enzymes responsible for collagen and elastin degradation, controls lipogenesis and inhibits tyrosinase. More concrete studies using cork powder, granulates, wastewaters and black condensate, as part of skin care products, are required. For example, cork by-products depigmenting and anti-acne activity, especially when incorporated in topical formulations, should be clarified. Also, the use of cork granulates as exfoliant particles needs to be further explored. In vivo studies could be an important addition. Concerning the dermatological toxicity, no specific studies have been performed yet. Safety assessment analysis should be done as well as in vivo compatibility assays. Since many properties of cork and its by-products are shown by extracts, solvents that show greater biocompatibility, such as water, should be tested and more sustainable extraction methods should be developed. Further away from the key focus of this work, the pharmacological potential of cork and its by-products could also be explored in the future. Declaration of interest The authors state no conflict of interest and have received no payment in preparation of this manuscript. Acknowledgment This work was supported by the Fundação para a Ciência e a Tecnologia, Portugal (UID/DTP/04138/2013 to iMed.ULisboa). References Amorim Cork Composites Technical Bulletin. 2013. Ando, H., Kondoh, H., Ichihashi, M., Hearing, V.J., 2007. Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase. J. Invest.

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tyrosinase by protocatechuic aldehyde. Am. J. Chin. Med. 32, 97–103. Noferi, M., Masson, E., Merlin, A., Pizzi, A., Deglise, X., 1997. Antioxidant characteristics of hydrolysable and polyflavonoid tannins: an ESR kinetics study. J. Appl. Polym. Sci. 63, 475–482. Nohynek, G.J., Antignac, E., Re, T., Toutain, H., 2010. Safety assessment of personal care products/cosmetics and their ingredients. Toxicol. Appl. Pharmacol. 243, 239–259. Parsons, J.J., 1962. The cork oak forests and the evolution of the cork industry in southern Spain and Portugal. J. Econ. Geogr. 38, 195–214. Passi, S., Nazzaro‐Porro, M., 1981. Molecular basis of substrate and inhibitory specificity of tyrosinase: phenolic compounds. Br. J. Dermatol. 104, 659–665. Pereira, H., 1988. Chemical composition and variability of cork from Quercus suber L. Wood Sci. Technol. 22, 211–218. Pereira, H., 2011. Cork: Biology, Production and Uses, first ed. Elsevier Science. Pereira, H., Rosa, M.E., Fortes, M., 1987. The cellular structure of cork from Quercus suber L. J. IAWA 8, 213–218. Philippe, M., Didillon, B., Gilbert, L., 2012. Industrial commitment to green and sustainable chemistry: using renewable materials & developing eco-friendly processes and ingredients in cosmetics. Green Chem. 14, 952–956. Pinto, P.C., Sousa, A.F., Silvestre, A.J., Neto, C.P., Gandini, A., Eckerman, C., 2009. Quercus suber and Betula pendula outer barks as renewable sources of oleochemicals: a comparative study. Ind. Crops Prod. 29, 126–132. Pintor, A.M., Ferreira, C.I., Pereira, J.C., Correia, P., Silva, S.P., Vilar, V.J., Botelho, C.M., Boaventura, R.A., 2012. Use of cork powder and granules for the adsorption of pollutants: a review. Water Res. 46, 3152–3166. Pons‐Guiraud, A., 2004. Sensitive skin: a complex and multifactorial syndrome. J. Cosmet. Dermatol. 3, 145–148. Rastogi, S.C., Johansen, J.D., Menne, T., 1996. Natural ingredients based cosmetics. Contact Dermat. 34, 423–426. Rice-Evans, C., Miller, N., Paganga, G., 1997. Antioxidant properties of phenolic compounds. Trends Plant Sci. 2, 152–159. Rocha, S.M., Goodfellow, B.J., Delgadillo, I., Neto, C.P., Gil, A.M., 2001. Enzymatic isolation and structural characterisation of polymeric suberin of cork from Quercus suber L. Int. J. Biol. Macromol. 28, 107–119. Rodrigues, F., Pimentel, F.B., Oliveira, M.B.P., 2015. Olive by-products: challenge application in cosmetic industry. Ind. Crops Prod. 70, 116–124. Sadeghifar, H., Venditti, R., Jur, J., Gorga, R.E., Pawlak, J.J., 2017. Cellulose-lignin biodegradable and flexible UV protection film. ACS Sustain. Chem. Eng. 5, 625–631. Santos, S.A., Pinto, P.C., Silvestre, A.J., Neto, C.P., 2010. Chemical composition and antioxidant activity of phenolic extracts of cork from Quercus suber L. Ind. Crops Prod. 31, 521–526. Santos, S.A., Villaverde, J.J., Sousa, A.F., Coelho, J.F., Neto, C.P., Silvestre, A.J., 2013. Phenolic composition and antioxidant activity of industrial cork by-products. Ind. Crops Prod. 47, 262–269. Saviuc, C., Ciubucă, B., Dincă, G., Bleotu, C., Drumea, V., Chifiriuc, M.C., Popa, M., Pircalabioru, G.G., Marutescu, L., Lazăr, V., 2017. Development and sequential analysis of a new multi-agent, anti-acne formulation based on plant-derived antimicrobial and anti-inflammatory compounds. Int. J. Mol. Sci. 18, 175. Scalbert, A., 1991. Antimicrobial properties of tannins. Phytochemistry 30, 3875–3883. SCCS, The SCCS’s Notes of Guidance for the Testing of Cosmetic Ingredients and Their Safety Evaluation. 2010, European Commision Directorate-General for Health & Consumers Scientific Committee on Consumer Safety (SCCS). Shan, B., Cai, Y.Z., Sun, M., Corke, H., 2005. Antioxidant capacity of 26 spice extracts and characterization of their phenolic constituents. J. Agric. Food Chem. 53, 7749–7759. Sierra-Pérez, J., Boschmonart-Rives, J., Gabarrell, X., 2015. Production and trade analysis in the Iberian cork sector: economic characterization of a forest industry. Resour. Conserv. Recycl. 98, 55–66. Silva, S., Sabino, M., Fernandes, E., Correlo, V., Boesel, L., Reis, R., 2005. Cork: properties, capabilities and applications. Int. Mater. Rev. 50, 345–365. Silvestre, A.J., Neto, C.P., Gandini, A., 2008. Cork and suberins: major sources, properties and applications. Monomers, Polymers and Composites from Renewable Resources, first ed. pp. 305. Sinha, P., Srivastava, S., Mishra, N., Yadav, N.P., 2014. New perspectives on antiacne plant drugs: contribution to modern therapeutics. Biomed. Res. Int. 2014, 301304. Sousa, A.F., Pinto, P.C., Silvestre, A.J., Pascoal-Neto, C., 2006. Triterpenic and other lipophilic components from industrial cork byproducts. J. Agric. Food Chem. 54, 6888–6893. Sousa, A.F., Gandini, A., Silvestre, A.J., Pascoal, N.C., 2008. Synthesis and characterization of novel biopolyesters from suberin and model comonomers. ChemSusChem 1, 1020–1025. Subhashini, S., Begum, S.M., Rajesh, G., 2016. Antimicrobial characterisation combining spectrophotometric analysis of different oak species. Int. J. Herb. Med. 4, 32–35. Tai, A., Sawano, T., Yazama, F., Ito, H., 2011. Evaluation of antioxidant activity of vanillin by using multiple antioxidant assays. Biochim. Biophys. Acta 1810, 170–177. Touati, R., Santos, S.A., Rocha, S.M., Belhamel, K., Silvestre, A.J., 2015. The potential of cork from Quercus suber L. grown in Algeria as a source of bioactive lipophilic and phenolic compounds. Ind. Crops Prod. 76, 936–945. Venditti, A., Mandrone, M., Serrilli, A.M., Bianco, A., Iannello, C., Poli, F., Antognoni, F., 2013. Dihydroasparagusic acid: antioxidant and tyrosinase inhibitory activities and improved synthesis. J. Agric. Food Chem. 61, 6848–6855. Villaverde, J.J., Sevilla-Morán, B., López-Goti, C., Alonso-Prados, J.L., Sandín-España, P., 2017. Computational methodologies for the risk assessment of pesticides in the European Union. J. Agric. Food Chem. 65, 2017–2018. Wojdyło, A., Oszmiański, J., Czemerys, R., 2007. Antioxidant activity and phenolic compounds in 32 selected herbs. Food Chem. 105, 940–949. Yoshimura, M., Watanabe, Y., Kasai, K., Yamakoshi, J., Koga, T., 2005. Inhibitory effect of an ellagic acid-rich pomegranate extract on tyrosinase activity and ultraviolet-induced pigmentation. Biosci. Biotechnol. Biochem. 69, 2368–2373.

monomers. Phytochem. Anal. 11, 45–51. Han, D.H., Lee, M.J., Kim, J.H., 2006. Antioxidant and apoptosis-inducing activities of ellagic acid. Anticancer Res. 26, 3601–3606. Holloway, P., 1972. The composition of suberin from the corks of Quercus suber L. and Betula pendula Roth. Chem. Phys. Lipids 9, 158–170. Igueld, S.B., Abidi, H., Trabelsi-Ayadi, M., Chérif, J.K., 2015. Study of physicochemicals characteristics and antioxidant capacity of cork oak acorns (Quercus suber L.) grown in three regions in Tunisia. J. Appl. Pharm. Sci. 5, 26–32. Jové, P., Olivella-Costa, À., Cano, L., 2011. Study of the variability in chemical composition of bark layers of Quercus suber L. from different production areas. BioResources 6, 1806–1815. Kahkonen, M.P., Hopia, A.I., Vuorela, H.J., Rauha, J.P., Pihlaja, K., Kujala, T.S., Heinonen, M., 1999. Antioxidant activity of plant extracts containing phenolic compounds. J. Agric. Food Chem. 47, 3954–3962. Karim, A.A., Azlan, A., Ismail, A., Hashim, P., Gani, S.S.A., Zainudin, B.H., Abdullah, N.A., 2014. Phenolic composition, antioxidant, anti-wrinkles and tyrosinase inhibitory activities of cocoa pod extract. BMC Complement. Altern. Med. 14, 381. Khennouf, S., Benabdallah, H., Gharzouli, K., Amira, S., Ito, H., Kim, T.H., 2003. Effect of tannins from Quercus suber and Quercus coccifera leaves on ethanol-induced gastric lesions in mice. J. Agric. Food Chem. 51, 1469–1473. Kikuzaki, H., Hisamoto, M., Hirose, K., Akiyama, K., Taniguchi, H., 2002. Antioxidant properties of ferulic acid and its related compounds. J. Agric. Food Chem. 50, 2161–2168. Kim, Y.J., 2007. Antimelanogenic and antioxidant properties of gallic acid. Biol. Pharm. Bull. 30, 1052–1055. Lee, J.Y., Yoon, J.W., Kim, C.T., Lim, S.T., 2004. Antioxidant activity of phenylpropanoid esters isolated and identified from Platycodon grandiflorum A. DC. Phytochemistry 65, 3033–3039. Lee, K.E., Youm, J.K., Lee, W.J., Kang, S., Kim, Y.J., 2017. Polyphenol‐rich apple extract inhibits dexamethasone‐induced sebaceous lipids production by regulating SREBP1 expression. Exp. Dermatol. 26, 958–996. Lee, R.S., Serridge, D., 2001. Method of exfoliating skin. Official Gazette of the United States Patent & Trademark Office Patents 1250(4). Leeuwenhoek, A., 1704. A Letter from Mr Anthony Van Leeuwenhoek, FRS concerning the Barks of Trees. Philos. Trans. 24, 1843–1855. Leist, M., Lidbury, B.A., Yang, C., Hayden, P.J., Kelm, J.M., Ringeissen, S., Detroyer, A., Meunier, J.R., Rathman, J.F., Jackson, G.R., Stolper, G., Hasiwa, N., 2012. Novel technologies and an overall strategy to allow hazard assessment and risk prediction of chemicals, cosmetics, and drugs with animal-free methods. ALTEX 29, 373–388. Leyden, J.J., 1997. Therapy for acne vulgaris. New Engl. J. Med. 336, 1156–1162. Li, X., Wang, X., Chen, D., Chen, S., 2011. Antioxidant activity and mechanism of protocatechuic acid in vitro. Funct. Foods Health Dis. 1, 232–244. Lopes, M., Pascoal-Nero, C., Evtuguin, D., Silvestre, A., Gil, A., Cordeiro, N., 1998. Products of the permanganate oxidation of Cork, desuberized Cork, suberin and lignin from Quercus suber L. Holzforschung 52, 146–148. Lopes, M.H., Gel, A.M., Silvestre, A.J.D., Pascoal, N.C., 2000. Composition of suberin extracted upon gradual alkaline methanolysis of Quercus suber L. cork. J. Agric. Food Chem. 48, 383–391. Lu, Z., Nie, G., Belton, P.S., Tang, H., Zhao, B., 2006. Structure–activity relationship analysis of antioxidant ability and neuroprotective effect of gallic acid derivatives. Neurochem. Int. 48, 263–274. Lumaret, R., Tryphon-Dionnet, M., Michaud, H., Sanuy, A., Ipotesi, E., Born, C., 2005. Phylogeographical variation of chloroplast DNA in cork oak (Quercus suber). Ann. Bot. 96, 853–861. Madureira, J., Melo, R., Botelho, M., Leal, J., Fonseca, I., 2012. Effect of ionizing radiation on antioxidant compounds present in cork wastewater. Water Sci. Technol. 67, 374–379. Mandrone, M., Lorenzia, B., Venditti, A., Guarcini, L., Bianco, A., Sanna, C., Ballero, M., Poli, F., Antognoni, F., 2015. Antioxidant and anti-collagenase activity of Hypericum hircinum L. Ind. Crops Prod. 76, 402–408. Marques, A., Pereira, H., Meier, D., Faix, O., 1994. Quantitative analysis of cork (Quercus suber L.) and milled cork lignin by FTIR spectroscopy, analytical pyrolysis, and total hydrolysis. Holzforschung 48, 43–50. Marto, J., Gouveia, L., Gonçalves, L., Chiari-Andréo, B., Isaac, V., Pinto, P., 2016. Design of novel starch-based Pickering emulsions as platforms for skin photoprotection. J. Photochem. Photobiol. B 162, 56–64. Matjuskova, N., et al., 2015. An Abrasive Ingredient for Exfoliating Cosmetic Compositions. EP 2878340A1. . Matsuoka, Y., Yoneda, K., Sadahira, C., Katsuura, J., Moriue, T., Kubota, Y., 2006. Effects of skin care and makeup under instructions from dermatologists on the quality of life of female patients with acne vulgaris. J. Dermatol. 33, 745–752. Maurya, D.K., Nandakumar, N., Devasagayam, T.P., 2010. Anticancer property of gallic acid in A549, a human lung adenocarcinoma cell line, and possible mechanisms. J. Clin. Biochem. Nutr. 48, 85–90 33. Merlot, C., 2010. Computational toxicology—a tool for early safety evaluation Drug Discovery Today. Drug Discov. Today 15, 16–22. Mestre, A., Gil, L., 2011. Cork for sustainable product design. Ciência e Tecnologia dos Materiais 52–63. Momtaz, S., Abdollahi, M., 2012. A comprehensive review of biochemical and molecular evidences from animal and human studies on the role of oxidative stress in aging: an epiphenomenon or the cause. Asian J. Anim. Vet. Adv. 7, 1–19. Muddathir, A.M., Yamauchi, K., Mitsunaga, T., 2013. Anti-acne activity of tannin-related compounds isolated from Terminalia laxiflora. J. Food Sci. 59, 426–431. Mukherjee, P.K., Maity, N., Nema, N.K., Sarkar, B.K., 2011. Bioactive compounds from natural resources against skin aging. Phytomedicine 19, 64–73. Natividade, J., 1938. O que é cortiça. Boletim da Junta Nacional da Cortiça 1, 13–21. No, J.K., Kim, M.S., Kim, Y.J., Bae, S.J., Choi, J.S., Chung, H.Y., 2004. Inhibition of

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