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Sweet Lemon
C H A P T E R
45 Sweet Lemon Adan Iqbal1, Rasheed Ahmad Khera1, Muhammad Asif Hanif1, Muhammad Adnan Ayub2, Abdullah Mohammed Al-Sadi3 1
Department of Chemistry, University of Agriculture, Faisalabad, Pakistan; 2 Department of Chemistry, University of Okara, Okara, Pakistan; 3 Department of Crop Sciences, College of Agricultural and Marine Sciences, Sultan Qaboos University, Oman
O U T L I N E 1. Botany 1.1 Introduction 1.2 History/Origin 1.3 Demography/Location 1.4 Botany, Morphology, Ecology
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2. Chemistry
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3. Postharvest Technology
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4. Processing
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5. Value Addition
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6. Uses
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7. Pharmacological Uses 7.1 Antimicrobial Activity 7.2 Antioxidant Activity 7.3 Cardiovascular Diseases 7.4 Antiinflammatory Activity
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Medicinal Plants of South Asia https://doi.org/10.1016/B978-0-08-102659-5.00045-8
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Copyright © 2020 Elsevier Ltd. All rights reserved.
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7.5 7.6 7.7 7.8 7.9
Anticancer Potential Antidiabetic Effects Repellent/Larvicidal Activity Antiatherosclerotic Activity Dissolution of Gallstone
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8. Side Effects and Toxicity
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References
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1. BOTANY 1.1 Introduction Sweet lemon (Citrus limetta Risso) (Fig. 45.1) is a small evergreen tree with irregular branches. It is a member of the family Rutaceae. This family is found in temperate and tropical regions of the world and is economically very important due to its fruit usage. The Rutaceae family comprises 150 genera and 1600 species that are distributed worldwide. All these genera are closely related to one another due to interhybridization. Interhybridization seems to be possible between different citrus plants and those plants that are not categorized as citrus, results in generation of new varieties. Four taxa of the citrus fruits that include orange, lemon, grapefruit, and tangerine are in many cases propagated asexually, and this results in loss of their characteristic traits when bred. However, these hybrids are frequently produced, which makes the citrus family tree a complicated one. C. limetta is known by different common names in the world. It is known as sweet lemon, Mediterranean sweet lemon in English, and mittha in Pakistan. Limu Shirin is its name in Iran, kannada in India, and malta in Bangladesh. Although the most common citrus is sweet lemon (C. limetta), many other varieties and cultivars of this genus are available that vary in flavors, scents, and uses. The most common examples include lemon, grapefruit, pomelo, tangerine, and tangelo (Gulsen and Roose, 2001). C. limetta flavors can range from sweet to acidic, while all varieties possess a pleasant odor.
1.2 History/Origin The generic name citrus was derived from Latin, in which it was traditionally used to describe the species “Citron medica.” It originated, however, from the Greek word cedar. The exact origin of citrus fruits has not been clearly identified. Several hypotheses by different researchers
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Sweet lemon
FIGURE 45.1 Citrus limetta tree and fruit (Mousambi/Mittaha).
have been proposed. It was identified that the important centers of origin of citrus and its genera are subtropical and tropical regions of India, Southeast Asia and China. The evidence reporting the presence of citrus in China was presented in the book “Tribute of Yu,” during the kingdom of Ta Yu in 2205e2197 BC. Literature of the Chou dynasty 1027e256 BC and Chin and Han dynasties 202 BC 220 AD provides evidence regarding the presence of citrus fruits. In Chinese culture, citron was considered to be the hand of Buddha, and it was exchanged for good luck. Some historians consider that it was brought to Palestine by Jews upon their return from Babylonian exile in about 500 BC, while others think that it was brought by the return of Alexander from India in about 300 AD. With the conquest of Spain by the Moors, oranges were introduced there
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around 900 AD. The Spanish introduced citrus fruits to the modern world around the 16th century, and they propagated it to the Europe and North and South America, specifically Florida and Mexico, which are today considered the largest citrus orchards in the world. World citrus production started around the 19th century with the advent of railroads and steam ships.
1.3 Demography/Location Citrus fruits are found in a variety of environmental conditions and geographic regions. The most suitable conditions for their growth are considered to be found in tropical and subtropical regions. Sand, water, heat, and drought tolerance are major ecologic factors affecting their growth. They exhibit drought tolerance but no heat or water tolerance. C. limetta’s main production is seen in Pakistan, India, China, Philippines, Burma, Thailand, Indonesia, Guinea, Australia, Vietnam, Malaysia, Palestine, and Egypt. It is rare in Europe. FAO (2016) statistics showed that, worldwide, citrus species are grown in more than 140 countries, accounting for 124246.0 thousand tons of fruit that were produced in the year 2016. Among them, the largest producers of the citrus fruits (in thousand tons) are the China (32,705.9), Brazil (16555.1), the United States (7829.0), India (9755.8), Spain (6682.0), and Mexico (6634.0). Pakistan is among top 10 leading citrus-producing countries of world with a yearly production of 1907.4 thousand tons. FAO (2016) statistics showed that major lemon- and lime-producing countries (in thousand tons) are India (2613.8), China (2405.9), and Mexico (2270.0) (FAO, 2016).
1.4 Botany, Morphology, Ecology C. limetta is a small tree with irregular branches and numerous thorns that may reach up to 5e8 m in height at maturity. The leaf is of simple type with pinnate venation and alternate leaf arrangement. The leaf margins are crenate with glossy leaf texture, and the leaf possesses a pleasant odor. Leaves are oval and rounded. Flowers appear in the spring season, possess a pleasant smell, and are white in color. Flower size ranges from 1.5 to 3 cm. Petals are reflexed. The fruit is oval to pear shape and consists of a pericarp of green color initially, which changes to yellow at the end of the ripening season. The pulp is sweetish to slightly acidic in taste. An extensive root system of palisade form is found in which there is a central one around which develops many secondary roots (Cossmann, 1940). Production of fruit starts when the tree is 5e7 years old, and maximum production is achieved when it reaches the age of 10e20 years.
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Sweet limes are picked when they are ripened and achieve the size of a tennis ball, with a luster of greenish yellow, indicating the right picking season (Sharma et al., 2004).
2. CHEMISTRY C. limetta essential oil is extracted from the peel. The stages that contain the maximum amount of essential oil of C. limetta are stages one and two, in which a large number of glands are present for the production of essential oils. The essential oil contains several components, the most abundant of which is D-limonene, renowned for its antibacterial properties (Khan et al., 2016). Limonene is the most abundant and is present in concentrations of 45%e90% of the total essential oil, and it is responsible for the antimicrobial properties (Murdock and Allen, 1960). C. limetta contains a wide range of phytonutrients that include acetophenones, low molecular phenolic acids (hydroxy benzoic acid and hydroxyl cinnamic acids), flavonoids, terpenoids, and limonoids. The essential oil contains a low amount of fatty acids that typically include linoleic acid, palmitic acid, oleic acid, and stearic acid. C. limetta is a rich source of calories and other essential components that include minerals, proteins, and vitamins. It is considered to have a lower fat content, and this quality makes it an ideal food for weightreducing diets and for people suffering from heart, coronary, and cancer diseases (Khan et al., 2016). In general, one cup of fruit or 100% fruit juice, or ½ cup of dried fruit, can be considered one cup from the fruit group. One serving of sweet lemon fruit contains 43 calories, 0e0.3 g of fat, 9e9.3 mg of carbohydrates, 0e0.8 g of proteins, and 40e50 mg of vitamin C. Additionally, it also provides 480e490 mg of potassium, 0e0.7 mg iron, 30e40 mg calcium, and 25e30 mg phosphorus. It also serves as a source of vitamin A, flavonoids, limonoids, dietary fibers, and carotenoids (Okwu and Emenike, 2006). Chemical constituents of the fruits are affected by changes in climate, growing conditions, type of cultivar or rootstock used, and difference in maturity stage. The high nutritional content of C. limetta makes it beneficial for health and an ideal food. The most abundant terpenes found in C. limetta essential oil are monoterpenes such as D-limonene, known for its antibacterial activity and citral for antifungal applications. Linalool has fungistatic properties (Colecio-Jua´rez et al., 2012). Sweet lime is also a good source of flavonoids. Citrus essential oil can be utilized for edible applications, as pharmaceutical components, in nutritional supplements, in aromatherapy, and in the cosmetic industry. Safe, natural sources and wide acceptance by users are responsible for the use of the essential oils on a large scale. Citral, Dlimonene, and linalool are mainly present in lime essential oil (Fig. 45.2).
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H O
H
Citral
H O
Linalool
d-limonene
FIGURE 45.2
Structures of major chemical constituents of sweet lemon essential oil.
3. POSTHARVEST TECHNOLOGY The most appropriate season for the vegetative growth of sweet limes is the rainy season, which includes the months of July, August, and November. March is also considered a peak season for growth of other citrus varieties. Losses during fresh fruit handling range from 5% to 10% in most developed countries, but from 25% to 30% or more in developing countries. However, citrus fruits are nonclimacteric and have a relatively long shelf life compared to mangos, bananas, and other tropical fruits. The dry and hot climate in the most parts of the tropical world render fruit unsuitable for marketing if not properly handled and stored. Ethylene has a role in the ripening and abscission of citrus and needs to be used wisely to benefit consumers and handlers. Removing ethylene from the fruit storage environment is challenging; although, its removal extends shelf life. Other plant growth-regulating substances, such as cytokinins, auxins, gibberellins, and polyamines, also profoundly affect fruit quality. Understanding the mechanism of action and key processes regulated by the plant regulators and bioregulators may lead to generation of strategies for modifying fruit characteristics to improve quality and delay senescence.
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An ethylene inhibitor, 1-methyl cyclopropane (1-MCP), that apparently binds to the cellular ethylene receptor has been found to reduce chilling injury, stem-end rot, and volatile off flavor. This nontoxic, odorless compound also delays color development, so it has been recommended for use in green citrus fruits (Porat et al., 1999). During grading, immature, unripened, and decayed fruits are discarded by visual inspection, and fruits are packed, according to their size, in sacks or wooden or cardboard boxes before being sold as fresh fruits in local markets. To increase the shelf life to 25e26 days and to avoid postharvest damage even at room temperature, they can be treated with wax after harvesting the fruits. The shelf life can also be extended by wrapping the fruit with polythene sheets that are heat shrinkable. The coating process, using different types of waxes such as aqueous waxes, solvent-based waxes and wax solutions, reduces water loss and has been practiced for centuries to extend the storage life of citrus fruits. Nowadays, edible coatings, such as esters, lipids, sucrose, and cellulose enable the process of packaging without the use of hazardous chemicals (Krochta et al., 1994). The ideal storage temperature is 10e12 C with 90%e95% relative humidity. Local market transportation involves the use of cargo without refrigeration, and it often results in severe damage due to decay and fungal infections. For transportation of export quality, it is essential to regulate the temperature during storage and transport. This cool chain involves the presence of a cold store on the farm, in transportation vehicles, and at airports, etc. Citrus fruits are considered to be nonclimacteric, and they have a long shelf life. However, if they are not properly stored, postharvest damage can occur, such as the development of physiologic disorders, loss of taste, chilling injury, and various fungal diseases.
4. PROCESSING Citrus fruits are consumed either as fresh fruits or in the forms of their by-products that include juices, jams, marmalades, etc. Almost one-third of the total citrus fruit production includes its use in the form of processed products. Citrus juices are consumed either as fresh juice or ready-to-serve juices. Fresh juice involves freshly squeezed juice, traditionally used at home (Okwu and Emenike, 2007). The shelf life of frozen juice may be up to 6 months. For the preparation of ready-to-serve juices, juice is packed in glass or plastic containers or cardboard cartons. This juice has a shelf life depending on the pasteurization procedures used and is available in the market as a ready-to-serve source. Sweet lime itself remains fresh for about 2 weeks at room temperature and 4e8 weeks when refrigerated. Slices of fruit can also be stored when frozen by submerging the slices in sweet syrup within an airtight glass container. Without submerging, the limonoid
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content can cause the pulp to be bitter in taste. The essential oil is composed of volatile compounds and is typically extracted from citrus peel using various techniques such as hydro distillation, solvent extraction, peel pressing, cold pressing, steam distillation, and microwave-assisted hydro distillation, depending on yield and quality required. Other processing procedures involve the preparation of jams and marmalades. Jam is an intermediate-moisture food prepared by boiling fruit pulp with sugar (sucrose), pectin, acid, and other ingredients (preservative, coloring, and flavoring materials) to a reasonably thick consistency, firm enough to hold the fruit tissues in position (Baker, 1994; Barrett et al., 2004). As a result of processing, peel is discarded as waste material.
5. VALUE ADDITION It is used either as fresh fruit, in the form of pickles, eaten as a salad, as a flavoring in beverages, and foods, etc. (Ferguson, 1990). In cooking, lime is valued both for the acidity of its juice and the floral aroma of its zest. It is very commonly used in authentic Mexican, Southwestern US, Vietnamese, and Thai dishes. It is used as an ingredient in many cocktails because of its refreshing aroma. Traditionally, it is also used as a pickle and used in many countries, especially in India and Pakistan. The use of dry lime and loomi as a flavoring is typical of Persian and Iraqi cuisine as well as in Gulf style Baharat (a spice mixture that is also called kabsa or kebsa). Lime is an essential ingredient of any cuisine from India, and many varieties of lime dishes are made, such as sweetened lime pickle, salted pickle, and lime chutney. Lime is also used as an herb in south and east Asia, where it is used to add flavor to cold and hot water, tonics, and beverages. The pulp and peel are used as natural food additives, as consumer awareness toward chemical additives results in demand for natural food additives, and research regarding the use of C. limetta peel extract as a natural additive also proves it to possess in vitro antifungal activities against food-borne pathogens. In this way, it has proved itself to be an excellent food additive. In the traditional indigenous medicinal system, sweet lime juice is valued for curing fever, malaria, and jaundice (Cowan, 1999).
6. USES C. limetta contributes significantly in maintaining health and providing essential nutrients. C. limetta is a rich source of calories and has a low fat content. It contributes a lot to human health through its bioactive components, mineral contents, and dietary fibers. It is used a lot as a food
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additive, and its peel, a waste from processing, is also used for several purposes. The essential oil and extract of C. limetta have been screened for their potential uses as alternative remedies for the treatment of many infectious diseases, preservation of food, as a food flavoring agent, and as adsorbent in the perfume industry. In recent years, citrus processing waste has been used for the production of single cell protein, biohydrogen, bioethanol, and multiple enzymes. In India, sweet lime is used in tantara for removing evil spirits. It is also combined with Indian chilies to make a protective charm to protect from evil eye. Furthermore, it is believed that hanging lime over sick people cures them of all illness by removing all evils lurking inside the body.
7. PHARMACOLOGICAL USES 7.1 Antimicrobial Activity C. limetta peel oil showed significant antifungal and antibacterial activity against different food-borne pathogens including bacteria such as Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Lactobacillus acidophilus, Escherichia coli, and fungi including Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, and Aspergillus ficuum. These foodborne pathogens cause illness such as dysentery, pneumonia, food poisoning, whooping cough, and cholera. Higher contents of monoterpenoid hydrocarbon as a component of essential oil are usually considered to be the main reason for the antimicrobial activity (Shahzad et al., 2009).
7.2 Antioxidant Activity Methanolic extract of C. limetta fruit peel shows significant in vitro antioxidant activity against superoxide radicals, nitric oxide radicals, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging radicals, and it also results in inhibition of lipid peroxidase. DPHH radicals pair off by accepting hydrogen from the methanolic extract of C. limetta. This pairing results in the formation of stable DPHH. Nitric oxide radicals are generated endogenously and influence the function of vasodilation, synaptic plasticity, neurotransmission, and memory in the central nervous system. Superoxide radical formation occurs by activated phagocytes such as macrophages, monocytes, and eosinophils, when they attack bacteria and viruses (Halliwell and Gutteridge, 2015). Methanolic extract has also shown inhibition against ferrous and ferric ioneinduced lipid peroxidation.
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7.3 Cardiovascular Diseases Owing to the antihypertensive effect of flavonoids, hesperidin and naringin as components of peel, and inner parts of the C. limetta fruit, it antagonizes the effect of angiotensin II (Touyz and Schiffrin, 2000). Angiotensin II is a potent vasoconstrictor and is responsible for immediate elevation of blood pressure due to its peptide nature and is responsible for cardiovascular diseases such as heart attack and stroke by causing thrombosis (blood clotting). This antagonistic effect of C. limetta extract is considered to be a physiologic process, i.e., without antagonizing the effect of any specific binding receptor.
7.4 Antiinflammatory Activity The leaves, fruits, and peel of C. limetta extract, owing to xanthine oxidase activity, serve as a natural source to treat gout by stopping biosynthesis of uric acid, and they have fewer side effects compared to synthetic drugs. Potent xanthine oxidase inhibitors include polyphenols, flavonoids, coumarins, ellagic acid, valoneic acid, and dilactones, which are present in this medicinal plant.
7.5 Anticancer Potential C. limetta fruit peel significantly reduces the volume of tumor cells and results in a decrease of cancerous activity, i.e., abnormal cell division, as have been proven by the previous studies on rat and increase in hemoglobin content and number of red blood cells. Thus, the citrus peel is responsible for maintaining the hematologic profile. Citrus flavonoids can inhibit the invasion of chick heart fragments and syngeneic mice liver by malignant mouse tumor cells. Hesperidin and diosmin have been shown to exhibit anticarcinogenic activities in various in vivo studies. The polymethoxylated flavones have been shown in numerous in vitro studies to exert strong antiproliferative action against cancer cells (Yang et al., 1997), antigen-activated T lymphocytes, gastric cancer cells, prostate cancer cells (Hirano et al., 1995), and squamous cell carcinoma (Bracke et al., 1994), and antimetastatic actions against human breast cancer cells have also been observed with tangeretin. Naringin, hesperidin, nobiletin, and tangeretin inhibit the bacterial mutagenesis (Hirano et al., 1995). The medicinal value of C. limetta derives from the bioactive phytochemical constituents that are responsible for the significant physiologic effect on the human body. C. limetta plants are estimated to contain about 40 limonoids, of which limonin and nomilin are abundant. These limonoids are responsible for the bitter taste of citrus species. Limonoids are responsible for inhibiting tumor formation and show anticancer activity.
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This anticancer activity is attributed to the ability to stimulate the GST (Glutathione S-Transferase) enzyme. GST is responsible for catalyzing the reaction of dangerous electrophiles with glutathione and converting them to less toxic and hydrophilic substances, which are ultimately excreted from the body. In this way, they show anticancer activity (Okwu and Emenike, 2006).
7.6 Antidiabetic Effects Methanolic extract of C. limetta fruit peel showed antihyperglycemic activity in streptozotocin-induced diabetic rats (Arai et al., 2000). The fruit peel of C. limetta is rich in flavonoids such as hesperidin and naringin. Both of these flavonoids possess a potent hypoglycemic activity that is responsible for mediating glucose-regulating enzymes. Both hesperidin and naringin have significantly lowered the blood glucose level, partly by increasing glycolysis and glycogen concentration or by lowering the gluconeogenesis process in the liver. Thus, the presence of flavonoids in the peel extract of C. limetta might be responsible for the antihyperglycemic activity and prove it a safe antidiabetic agent. In another study, quercetin flavonoid was shown to stimulate the release of insulin and increase the uptake of calcium by the islet cell, suggesting a way for the treatment of noninsulin-dependent cells. The inhibitory effect of the aqueous C. limetta peel extract on the metabolism of carbohydrates was studied. The extract inhibited primarily the enzyme a-amylase by 49.6% at a concentration of 20 mg/mL and to a lesser extent the enzyme a-glucosidase with an inhibition of 28.2% at the same concentration. This inhibition was likely due to the high polyphenol content in the C. limetta peel (19.1 mg GAE/g).
7.7 Repellent/Larvicidal Activity C. limetta peel extract has been found to possess larvicidal activity against Aedes aegypti and Anopheles stephensi. C. limetta peel extract in hexane and petroleum ether solvent were found to be effective against malarial and dengue fever vectors. The extract of hexane possesses 1.9fold larvicidal potential compared to the extract using petroleum ether as solvent (Kumar et al., 2012). The repellent activity can be attributed to the active ingredients of alkaloids, flavonoids, saponins, and phenolics present in the extract of citrus peels that exert an inhibitory influence on the lactic acid receptor cells. These receptor cells are responsible for attracting the mosquito to bite and feed on the blood. Due to this inhibitory effect, the mosquitoes are no longer attracted to bite, and this blood feeding response is prevented.
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7.8 Antiatherosclerotic Activity C. limetta possesses antiatherosclerotic effects due to the flavonoids that exert influence on the arteries of the vascular system and can oxidize cholesterol of plaque due to its antioxidative property. In this way, it protects the body against coronary heart diseases. Research has shown that regular consumption of flavonoids can reduce the risk of death from coronary heart diseases (Okwu, 2005). There is a correlation between flavonoids and cholesterol concentration of plasma. High consumption of flavonoids results in a decrease in cholesterol concentration of plasma and ultimately reduced risk of mortality from coronary heart diseases. Oxidative damage has been suggested to be a contributory factor in the development and complication of thrombosis. Recently, the beneficial effects of antioxidants from citrus fruits against thrombosis have gained interest (Okwu, 2005). Cholesterol-lowering effects of C. limetta are produced by limonene. Furthermore, polymethoxylated flavones (PMFs) are present in citrus fruit peel, which can lower cholesterol more effectively than some prescription drugs, without showing any side effects. Among the variety of citrus fruits containing PMFs, the most common PMFs were tangeretin and nobiletin. PMFs work like statin drugs that inhibit the synthesis of cholesterol and triglycerides inside the liver.
7.9 Dissolution of Gallstone In C. limetta, the most abundant monoterpenoid, D-limonene (appears to be 45%e90% of the total), results in the dissolution of gallstones. Dlimonene is a clinically proven solvent of cholesterol-containing gall stones, and it can dissolve a human gall stone within 2 hours. In animals, D-limonene infusion in gall bladder results in dissolution and disintegration of gallstones that were extracted from the bile juice in the bile duct (Koyuncu et al., 1998). In postgallstone surgery, infusion of D-limonene in patients results in dissolutions of gallstones that were left during surgery. This dissolution occurs after three infusions of 20 mL of D-limonene. Citrus fruits are highly recommended for persons suffering from kidney stones, gout, and arthritis. Citrates (citric acid salts) with citrus juice, containing especially potassium citrate, prevent the formation of kidney stones and ease their dissolution.
8. SIDE EFFECTS AND TOXICITY There is no doubt lime juice carries plentiful health benefits; however, it may have a number of side effects that might cause health hazards like the decay of tooth enamel and ulcers within the stomach. Gastroesophageal
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reflux disorder is a digestive disorder triggered by limes or acidic foods. The vitamin C in lime juice, also called ascorbic acid, affects the absorption of iron in the body. Lime juice contains sulfites that can cause reactions and allergies in some people. Though lime juice helps treat kidney stones and is good for healthy kidneys, people suffering from kidney ailments should not consume lime juice because it might cause renal damage. Citrus fruits generally contain high potassium levels. This might be bad for those suffering from kidney disease. The diseased kidneys would not be able to maintain the electrolyte balance. This leads to abnormal levels of potassium, sodium, and phosphorous.
References Arai, Y., Watanabe, S., Kimira, M., Shimoi, K., Mochizuki, R., Kinae, N., 2000. Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. Journal of Nutrition 130, 2243e2250. Baker, R.A., 1994. Potential Dietary Benefits of Citrus Pectin and Fiber. Food technology, USA). Barrett, D.M., Somogyi, L., Ramaswamy, H.S., 2004. Processing Fruits: Science and Technology. CRC Press. Bracke, M., Bruyneel, E., Vermeulen, S.J., Vennekens, K.l., Vanmarck, V., Mareel, M., 1994. Citrus flavonoid effect on tumor invasion and metastasis. Food Technology 48, 121e124. ´ lvarez, J.E., Martı´nez-Gonza´lez, G.M., Colecio-Jua´rez, M.C., Rubio-Nu´n˜ez, R.E., Botello-A Navarrete-Bolan˜os, J.L., Jime´nez-Islas, H., 2012. Characterization of volatile compounds in the essential oil of sweet lime (Citrus limetta Risso). Chilean Journal of Agricultural Research 72, 275. Cossmann, K., 1940. Citrus roots: their anatomy, osmotic pressure and periodicity of growth. Palestine Journal of Botany 3, 65e104. Cowan, M.M., 1999. Plant products as antimicrobial agents. Clinical Microbiology Reviews 12, 564e582. FAO, 2016. Food and Agriculture Organization of the United Nations, Citrus Fruit e Fresh and Processed Statistical Bulletin. http://www.fao.org/economic/est/est-commodities/citrusfruit/en/1-63. Ferguson, U., 1990. Citrus Fruits Processing. Horticultural Science, Florida, pp. 117e118. Gulsen, O., Roose, M., 2001. Lemons: diversity and relationships with selected citrus genotypes as measured with nuclear genome markers. Journal of the American Society for Horticultural Science 126, 309e317. Halliwell, B., Gutteridge, J.M., 2015. Free Radicals in Biology and Medicine. Oxford University Press, USA. Hirano, T., Abe, K., Gotoh, M., Oka, K., 1995. Citrus flavone tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes. British Journal of Cancer 72, 1380. Khan, A.A., Mahmood, T., Siddiqui, H.H., Akhtar, J., 2016. Journal of Chemical and Pharmaceutical Research 8 (3), 555e563. Koyuncu, H., Berkarda, B., Baykut, F., Soybir, G., Alatli, C., Gu¨l, H., Altun, M., 1998. Preventive effect of hesperidin against inflammation in CD-1 mouse skin caused by tumor promoter. Anticancer Research 19, 3237e3241. Krochta, J.M., Baldwin, E.A., Nisperos-Carriedo, M.O., 1994. Edible Coatings and Films to Improve Food Quality. Technomic Publ. Co.
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Kumar, S., Warikoo, R., Mishra, M., Seth, A., Wahab, N., 2012. Larvicidal efficacy of the Citrus limetta peel extracts against Indian strains of Anopheles stephensi Liston and Aedes aegypti L. Parasitology Research 111, 173e178. Murdock, D., Allen, W., 1960. Germicidal effect of orange peel oil and D-limonene in water and orange juice. Food Technology 14, 441e445. Okwu, D., 2005. Phytochemicals, vitamins and mineral contents of two Nigerian medicinal plants. International Journal of Molecular Medicine and Advance Sciences 1, 375e381. Okwu, D., Emenike, I., 2006. Evaluation of the phytonutrients and vitamins content of citrus fruits. International Journal of Molecular Medicine and Advance Sciences 2, 1e6. Okwu, D., Emenike, I., 2007. Nutritive value and mineral content of different varieties of citrus fruits. Journal of Food Technology 5, 105e108. Porat, R., Weiss, B., Cohen, L., Daus, A., Goren, R., Droby, S., 1999. Effects of ethylene and 1methylcyclopropene on the postharvest qualities of ‘Shamouti’oranges. Postharvest Biology and Technology 15, 155e163. Shahzad, K., Nawaz, S., Ahmad, R., Mahmud, S., Iqbal, Z., Saeed, K., 2009. Evaluation of antioxidant and antimicrobial activity of essential oil of Tangerine fruit peel. Pakistan Journal of Biochemistry and Molecular Biology 42, 4e7. Sharma, B., Hore, D., Gupta, S., 2004. Genetic resources of citrus of North-Eastern India and their potential use. Genetic Resources and Crop Evolution 51, 411e418. Touyz, R.M., Schiffrin, E.L., 2000. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacological Reviews 52, 639e672. Yang, M., Tanaka, T., Hirose, Y., Deguchi, T., Mori, H., Kawada, Y., 1997. Chemopreventive effects of diosmin and hesperidin on N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary-bladder carcinogenesis in male ICR mice. International Journal of Cancer 73, 719e724.
45 Sweet Lemon Adan Iqbal1, Rasheed Ahmad Khera1, Muhammad Asif Hanif1, Muhammad Adnan Ayub2, Abdullah Mohammed Al-Sadi3 1
Department of Chemistry, University of Agriculture, Faisalabad, Pakistan; 2 Department of Chemistry, University of Okara, Okara, Pakistan; 3 Department of Crop Sciences, College of Agricultural and Marine Sciences, Sultan Qaboos University, Oman
O U T L I N E 1. Botany 1.1 Introduction 1.2 History/Origin 1.3 Demography/Location 1.4 Botany, Morphology, Ecology
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2. Chemistry
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3. Postharvest Technology
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4. Processing
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5. Value Addition
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6. Uses
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7. Pharmacological Uses 7.1 Antimicrobial Activity 7.2 Antioxidant Activity 7.3 Cardiovascular Diseases 7.4 Antiinflammatory Activity
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Medicinal Plants of South Asia https://doi.org/10.1016/B978-0-08-102659-5.00045-8
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Copyright © 2020 Elsevier Ltd. All rights reserved.
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7.5 7.6 7.7 7.8 7.9
Anticancer Potential Antidiabetic Effects Repellent/Larvicidal Activity Antiatherosclerotic Activity Dissolution of Gallstone
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8. Side Effects and Toxicity
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References
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1. BOTANY 1.1 Introduction Sweet lemon (Citrus limetta Risso) (Fig. 45.1) is a small evergreen tree with irregular branches. It is a member of the family Rutaceae. This family is found in temperate and tropical regions of the world and is economically very important due to its fruit usage. The Rutaceae family comprises 150 genera and 1600 species that are distributed worldwide. All these genera are closely related to one another due to interhybridization. Interhybridization seems to be possible between different citrus plants and those plants that are not categorized as citrus, results in generation of new varieties. Four taxa of the citrus fruits that include orange, lemon, grapefruit, and tangerine are in many cases propagated asexually, and this results in loss of their characteristic traits when bred. However, these hybrids are frequently produced, which makes the citrus family tree a complicated one. C. limetta is known by different common names in the world. It is known as sweet lemon, Mediterranean sweet lemon in English, and mittha in Pakistan. Limu Shirin is its name in Iran, kannada in India, and malta in Bangladesh. Although the most common citrus is sweet lemon (C. limetta), many other varieties and cultivars of this genus are available that vary in flavors, scents, and uses. The most common examples include lemon, grapefruit, pomelo, tangerine, and tangelo (Gulsen and Roose, 2001). C. limetta flavors can range from sweet to acidic, while all varieties possess a pleasant odor.
1.2 History/Origin The generic name citrus was derived from Latin, in which it was traditionally used to describe the species “Citron medica.” It originated, however, from the Greek word cedar. The exact origin of citrus fruits has not been clearly identified. Several hypotheses by different researchers
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Sweet lemon
FIGURE 45.1 Citrus limetta tree and fruit (Mousambi/Mittaha).
have been proposed. It was identified that the important centers of origin of citrus and its genera are subtropical and tropical regions of India, Southeast Asia and China. The evidence reporting the presence of citrus in China was presented in the book “Tribute of Yu,” during the kingdom of Ta Yu in 2205e2197 BC. Literature of the Chou dynasty 1027e256 BC and Chin and Han dynasties 202 BC 220 AD provides evidence regarding the presence of citrus fruits. In Chinese culture, citron was considered to be the hand of Buddha, and it was exchanged for good luck. Some historians consider that it was brought to Palestine by Jews upon their return from Babylonian exile in about 500 BC, while others think that it was brought by the return of Alexander from India in about 300 AD. With the conquest of Spain by the Moors, oranges were introduced there
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around 900 AD. The Spanish introduced citrus fruits to the modern world around the 16th century, and they propagated it to the Europe and North and South America, specifically Florida and Mexico, which are today considered the largest citrus orchards in the world. World citrus production started around the 19th century with the advent of railroads and steam ships.
1.3 Demography/Location Citrus fruits are found in a variety of environmental conditions and geographic regions. The most suitable conditions for their growth are considered to be found in tropical and subtropical regions. Sand, water, heat, and drought tolerance are major ecologic factors affecting their growth. They exhibit drought tolerance but no heat or water tolerance. C. limetta’s main production is seen in Pakistan, India, China, Philippines, Burma, Thailand, Indonesia, Guinea, Australia, Vietnam, Malaysia, Palestine, and Egypt. It is rare in Europe. FAO (2016) statistics showed that, worldwide, citrus species are grown in more than 140 countries, accounting for 124246.0 thousand tons of fruit that were produced in the year 2016. Among them, the largest producers of the citrus fruits (in thousand tons) are the China (32,705.9), Brazil (16555.1), the United States (7829.0), India (9755.8), Spain (6682.0), and Mexico (6634.0). Pakistan is among top 10 leading citrus-producing countries of world with a yearly production of 1907.4 thousand tons. FAO (2016) statistics showed that major lemon- and lime-producing countries (in thousand tons) are India (2613.8), China (2405.9), and Mexico (2270.0) (FAO, 2016).
1.4 Botany, Morphology, Ecology C. limetta is a small tree with irregular branches and numerous thorns that may reach up to 5e8 m in height at maturity. The leaf is of simple type with pinnate venation and alternate leaf arrangement. The leaf margins are crenate with glossy leaf texture, and the leaf possesses a pleasant odor. Leaves are oval and rounded. Flowers appear in the spring season, possess a pleasant smell, and are white in color. Flower size ranges from 1.5 to 3 cm. Petals are reflexed. The fruit is oval to pear shape and consists of a pericarp of green color initially, which changes to yellow at the end of the ripening season. The pulp is sweetish to slightly acidic in taste. An extensive root system of palisade form is found in which there is a central one around which develops many secondary roots (Cossmann, 1940). Production of fruit starts when the tree is 5e7 years old, and maximum production is achieved when it reaches the age of 10e20 years.
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Sweet limes are picked when they are ripened and achieve the size of a tennis ball, with a luster of greenish yellow, indicating the right picking season (Sharma et al., 2004).
2. CHEMISTRY C. limetta essential oil is extracted from the peel. The stages that contain the maximum amount of essential oil of C. limetta are stages one and two, in which a large number of glands are present for the production of essential oils. The essential oil contains several components, the most abundant of which is D-limonene, renowned for its antibacterial properties (Khan et al., 2016). Limonene is the most abundant and is present in concentrations of 45%e90% of the total essential oil, and it is responsible for the antimicrobial properties (Murdock and Allen, 1960). C. limetta contains a wide range of phytonutrients that include acetophenones, low molecular phenolic acids (hydroxy benzoic acid and hydroxyl cinnamic acids), flavonoids, terpenoids, and limonoids. The essential oil contains a low amount of fatty acids that typically include linoleic acid, palmitic acid, oleic acid, and stearic acid. C. limetta is a rich source of calories and other essential components that include minerals, proteins, and vitamins. It is considered to have a lower fat content, and this quality makes it an ideal food for weightreducing diets and for people suffering from heart, coronary, and cancer diseases (Khan et al., 2016). In general, one cup of fruit or 100% fruit juice, or ½ cup of dried fruit, can be considered one cup from the fruit group. One serving of sweet lemon fruit contains 43 calories, 0e0.3 g of fat, 9e9.3 mg of carbohydrates, 0e0.8 g of proteins, and 40e50 mg of vitamin C. Additionally, it also provides 480e490 mg of potassium, 0e0.7 mg iron, 30e40 mg calcium, and 25e30 mg phosphorus. It also serves as a source of vitamin A, flavonoids, limonoids, dietary fibers, and carotenoids (Okwu and Emenike, 2006). Chemical constituents of the fruits are affected by changes in climate, growing conditions, type of cultivar or rootstock used, and difference in maturity stage. The high nutritional content of C. limetta makes it beneficial for health and an ideal food. The most abundant terpenes found in C. limetta essential oil are monoterpenes such as D-limonene, known for its antibacterial activity and citral for antifungal applications. Linalool has fungistatic properties (Colecio-Jua´rez et al., 2012). Sweet lime is also a good source of flavonoids. Citrus essential oil can be utilized for edible applications, as pharmaceutical components, in nutritional supplements, in aromatherapy, and in the cosmetic industry. Safe, natural sources and wide acceptance by users are responsible for the use of the essential oils on a large scale. Citral, Dlimonene, and linalool are mainly present in lime essential oil (Fig. 45.2).
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H O
H
Citral
H O
Linalool
d-limonene
FIGURE 45.2
Structures of major chemical constituents of sweet lemon essential oil.
3. POSTHARVEST TECHNOLOGY The most appropriate season for the vegetative growth of sweet limes is the rainy season, which includes the months of July, August, and November. March is also considered a peak season for growth of other citrus varieties. Losses during fresh fruit handling range from 5% to 10% in most developed countries, but from 25% to 30% or more in developing countries. However, citrus fruits are nonclimacteric and have a relatively long shelf life compared to mangos, bananas, and other tropical fruits. The dry and hot climate in the most parts of the tropical world render fruit unsuitable for marketing if not properly handled and stored. Ethylene has a role in the ripening and abscission of citrus and needs to be used wisely to benefit consumers and handlers. Removing ethylene from the fruit storage environment is challenging; although, its removal extends shelf life. Other plant growth-regulating substances, such as cytokinins, auxins, gibberellins, and polyamines, also profoundly affect fruit quality. Understanding the mechanism of action and key processes regulated by the plant regulators and bioregulators may lead to generation of strategies for modifying fruit characteristics to improve quality and delay senescence.
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An ethylene inhibitor, 1-methyl cyclopropane (1-MCP), that apparently binds to the cellular ethylene receptor has been found to reduce chilling injury, stem-end rot, and volatile off flavor. This nontoxic, odorless compound also delays color development, so it has been recommended for use in green citrus fruits (Porat et al., 1999). During grading, immature, unripened, and decayed fruits are discarded by visual inspection, and fruits are packed, according to their size, in sacks or wooden or cardboard boxes before being sold as fresh fruits in local markets. To increase the shelf life to 25e26 days and to avoid postharvest damage even at room temperature, they can be treated with wax after harvesting the fruits. The shelf life can also be extended by wrapping the fruit with polythene sheets that are heat shrinkable. The coating process, using different types of waxes such as aqueous waxes, solvent-based waxes and wax solutions, reduces water loss and has been practiced for centuries to extend the storage life of citrus fruits. Nowadays, edible coatings, such as esters, lipids, sucrose, and cellulose enable the process of packaging without the use of hazardous chemicals (Krochta et al., 1994). The ideal storage temperature is 10e12 C with 90%e95% relative humidity. Local market transportation involves the use of cargo without refrigeration, and it often results in severe damage due to decay and fungal infections. For transportation of export quality, it is essential to regulate the temperature during storage and transport. This cool chain involves the presence of a cold store on the farm, in transportation vehicles, and at airports, etc. Citrus fruits are considered to be nonclimacteric, and they have a long shelf life. However, if they are not properly stored, postharvest damage can occur, such as the development of physiologic disorders, loss of taste, chilling injury, and various fungal diseases.
4. PROCESSING Citrus fruits are consumed either as fresh fruits or in the forms of their by-products that include juices, jams, marmalades, etc. Almost one-third of the total citrus fruit production includes its use in the form of processed products. Citrus juices are consumed either as fresh juice or ready-to-serve juices. Fresh juice involves freshly squeezed juice, traditionally used at home (Okwu and Emenike, 2007). The shelf life of frozen juice may be up to 6 months. For the preparation of ready-to-serve juices, juice is packed in glass or plastic containers or cardboard cartons. This juice has a shelf life depending on the pasteurization procedures used and is available in the market as a ready-to-serve source. Sweet lime itself remains fresh for about 2 weeks at room temperature and 4e8 weeks when refrigerated. Slices of fruit can also be stored when frozen by submerging the slices in sweet syrup within an airtight glass container. Without submerging, the limonoid
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content can cause the pulp to be bitter in taste. The essential oil is composed of volatile compounds and is typically extracted from citrus peel using various techniques such as hydro distillation, solvent extraction, peel pressing, cold pressing, steam distillation, and microwave-assisted hydro distillation, depending on yield and quality required. Other processing procedures involve the preparation of jams and marmalades. Jam is an intermediate-moisture food prepared by boiling fruit pulp with sugar (sucrose), pectin, acid, and other ingredients (preservative, coloring, and flavoring materials) to a reasonably thick consistency, firm enough to hold the fruit tissues in position (Baker, 1994; Barrett et al., 2004). As a result of processing, peel is discarded as waste material.
5. VALUE ADDITION It is used either as fresh fruit, in the form of pickles, eaten as a salad, as a flavoring in beverages, and foods, etc. (Ferguson, 1990). In cooking, lime is valued both for the acidity of its juice and the floral aroma of its zest. It is very commonly used in authentic Mexican, Southwestern US, Vietnamese, and Thai dishes. It is used as an ingredient in many cocktails because of its refreshing aroma. Traditionally, it is also used as a pickle and used in many countries, especially in India and Pakistan. The use of dry lime and loomi as a flavoring is typical of Persian and Iraqi cuisine as well as in Gulf style Baharat (a spice mixture that is also called kabsa or kebsa). Lime is an essential ingredient of any cuisine from India, and many varieties of lime dishes are made, such as sweetened lime pickle, salted pickle, and lime chutney. Lime is also used as an herb in south and east Asia, where it is used to add flavor to cold and hot water, tonics, and beverages. The pulp and peel are used as natural food additives, as consumer awareness toward chemical additives results in demand for natural food additives, and research regarding the use of C. limetta peel extract as a natural additive also proves it to possess in vitro antifungal activities against food-borne pathogens. In this way, it has proved itself to be an excellent food additive. In the traditional indigenous medicinal system, sweet lime juice is valued for curing fever, malaria, and jaundice (Cowan, 1999).
6. USES C. limetta contributes significantly in maintaining health and providing essential nutrients. C. limetta is a rich source of calories and has a low fat content. It contributes a lot to human health through its bioactive components, mineral contents, and dietary fibers. It is used a lot as a food
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additive, and its peel, a waste from processing, is also used for several purposes. The essential oil and extract of C. limetta have been screened for their potential uses as alternative remedies for the treatment of many infectious diseases, preservation of food, as a food flavoring agent, and as adsorbent in the perfume industry. In recent years, citrus processing waste has been used for the production of single cell protein, biohydrogen, bioethanol, and multiple enzymes. In India, sweet lime is used in tantara for removing evil spirits. It is also combined with Indian chilies to make a protective charm to protect from evil eye. Furthermore, it is believed that hanging lime over sick people cures them of all illness by removing all evils lurking inside the body.
7. PHARMACOLOGICAL USES 7.1 Antimicrobial Activity C. limetta peel oil showed significant antifungal and antibacterial activity against different food-borne pathogens including bacteria such as Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Lactobacillus acidophilus, Escherichia coli, and fungi including Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, and Aspergillus ficuum. These foodborne pathogens cause illness such as dysentery, pneumonia, food poisoning, whooping cough, and cholera. Higher contents of monoterpenoid hydrocarbon as a component of essential oil are usually considered to be the main reason for the antimicrobial activity (Shahzad et al., 2009).
7.2 Antioxidant Activity Methanolic extract of C. limetta fruit peel shows significant in vitro antioxidant activity against superoxide radicals, nitric oxide radicals, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging radicals, and it also results in inhibition of lipid peroxidase. DPHH radicals pair off by accepting hydrogen from the methanolic extract of C. limetta. This pairing results in the formation of stable DPHH. Nitric oxide radicals are generated endogenously and influence the function of vasodilation, synaptic plasticity, neurotransmission, and memory in the central nervous system. Superoxide radical formation occurs by activated phagocytes such as macrophages, monocytes, and eosinophils, when they attack bacteria and viruses (Halliwell and Gutteridge, 2015). Methanolic extract has also shown inhibition against ferrous and ferric ioneinduced lipid peroxidation.
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7.3 Cardiovascular Diseases Owing to the antihypertensive effect of flavonoids, hesperidin and naringin as components of peel, and inner parts of the C. limetta fruit, it antagonizes the effect of angiotensin II (Touyz and Schiffrin, 2000). Angiotensin II is a potent vasoconstrictor and is responsible for immediate elevation of blood pressure due to its peptide nature and is responsible for cardiovascular diseases such as heart attack and stroke by causing thrombosis (blood clotting). This antagonistic effect of C. limetta extract is considered to be a physiologic process, i.e., without antagonizing the effect of any specific binding receptor.
7.4 Antiinflammatory Activity The leaves, fruits, and peel of C. limetta extract, owing to xanthine oxidase activity, serve as a natural source to treat gout by stopping biosynthesis of uric acid, and they have fewer side effects compared to synthetic drugs. Potent xanthine oxidase inhibitors include polyphenols, flavonoids, coumarins, ellagic acid, valoneic acid, and dilactones, which are present in this medicinal plant.
7.5 Anticancer Potential C. limetta fruit peel significantly reduces the volume of tumor cells and results in a decrease of cancerous activity, i.e., abnormal cell division, as have been proven by the previous studies on rat and increase in hemoglobin content and number of red blood cells. Thus, the citrus peel is responsible for maintaining the hematologic profile. Citrus flavonoids can inhibit the invasion of chick heart fragments and syngeneic mice liver by malignant mouse tumor cells. Hesperidin and diosmin have been shown to exhibit anticarcinogenic activities in various in vivo studies. The polymethoxylated flavones have been shown in numerous in vitro studies to exert strong antiproliferative action against cancer cells (Yang et al., 1997), antigen-activated T lymphocytes, gastric cancer cells, prostate cancer cells (Hirano et al., 1995), and squamous cell carcinoma (Bracke et al., 1994), and antimetastatic actions against human breast cancer cells have also been observed with tangeretin. Naringin, hesperidin, nobiletin, and tangeretin inhibit the bacterial mutagenesis (Hirano et al., 1995). The medicinal value of C. limetta derives from the bioactive phytochemical constituents that are responsible for the significant physiologic effect on the human body. C. limetta plants are estimated to contain about 40 limonoids, of which limonin and nomilin are abundant. These limonoids are responsible for the bitter taste of citrus species. Limonoids are responsible for inhibiting tumor formation and show anticancer activity.
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This anticancer activity is attributed to the ability to stimulate the GST (Glutathione S-Transferase) enzyme. GST is responsible for catalyzing the reaction of dangerous electrophiles with glutathione and converting them to less toxic and hydrophilic substances, which are ultimately excreted from the body. In this way, they show anticancer activity (Okwu and Emenike, 2006).
7.6 Antidiabetic Effects Methanolic extract of C. limetta fruit peel showed antihyperglycemic activity in streptozotocin-induced diabetic rats (Arai et al., 2000). The fruit peel of C. limetta is rich in flavonoids such as hesperidin and naringin. Both of these flavonoids possess a potent hypoglycemic activity that is responsible for mediating glucose-regulating enzymes. Both hesperidin and naringin have significantly lowered the blood glucose level, partly by increasing glycolysis and glycogen concentration or by lowering the gluconeogenesis process in the liver. Thus, the presence of flavonoids in the peel extract of C. limetta might be responsible for the antihyperglycemic activity and prove it a safe antidiabetic agent. In another study, quercetin flavonoid was shown to stimulate the release of insulin and increase the uptake of calcium by the islet cell, suggesting a way for the treatment of noninsulin-dependent cells. The inhibitory effect of the aqueous C. limetta peel extract on the metabolism of carbohydrates was studied. The extract inhibited primarily the enzyme a-amylase by 49.6% at a concentration of 20 mg/mL and to a lesser extent the enzyme a-glucosidase with an inhibition of 28.2% at the same concentration. This inhibition was likely due to the high polyphenol content in the C. limetta peel (19.1 mg GAE/g).
7.7 Repellent/Larvicidal Activity C. limetta peel extract has been found to possess larvicidal activity against Aedes aegypti and Anopheles stephensi. C. limetta peel extract in hexane and petroleum ether solvent were found to be effective against malarial and dengue fever vectors. The extract of hexane possesses 1.9fold larvicidal potential compared to the extract using petroleum ether as solvent (Kumar et al., 2012). The repellent activity can be attributed to the active ingredients of alkaloids, flavonoids, saponins, and phenolics present in the extract of citrus peels that exert an inhibitory influence on the lactic acid receptor cells. These receptor cells are responsible for attracting the mosquito to bite and feed on the blood. Due to this inhibitory effect, the mosquitoes are no longer attracted to bite, and this blood feeding response is prevented.
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7.8 Antiatherosclerotic Activity C. limetta possesses antiatherosclerotic effects due to the flavonoids that exert influence on the arteries of the vascular system and can oxidize cholesterol of plaque due to its antioxidative property. In this way, it protects the body against coronary heart diseases. Research has shown that regular consumption of flavonoids can reduce the risk of death from coronary heart diseases (Okwu, 2005). There is a correlation between flavonoids and cholesterol concentration of plasma. High consumption of flavonoids results in a decrease in cholesterol concentration of plasma and ultimately reduced risk of mortality from coronary heart diseases. Oxidative damage has been suggested to be a contributory factor in the development and complication of thrombosis. Recently, the beneficial effects of antioxidants from citrus fruits against thrombosis have gained interest (Okwu, 2005). Cholesterol-lowering effects of C. limetta are produced by limonene. Furthermore, polymethoxylated flavones (PMFs) are present in citrus fruit peel, which can lower cholesterol more effectively than some prescription drugs, without showing any side effects. Among the variety of citrus fruits containing PMFs, the most common PMFs were tangeretin and nobiletin. PMFs work like statin drugs that inhibit the synthesis of cholesterol and triglycerides inside the liver.
7.9 Dissolution of Gallstone In C. limetta, the most abundant monoterpenoid, D-limonene (appears to be 45%e90% of the total), results in the dissolution of gallstones. Dlimonene is a clinically proven solvent of cholesterol-containing gall stones, and it can dissolve a human gall stone within 2 hours. In animals, D-limonene infusion in gall bladder results in dissolution and disintegration of gallstones that were extracted from the bile juice in the bile duct (Koyuncu et al., 1998). In postgallstone surgery, infusion of D-limonene in patients results in dissolutions of gallstones that were left during surgery. This dissolution occurs after three infusions of 20 mL of D-limonene. Citrus fruits are highly recommended for persons suffering from kidney stones, gout, and arthritis. Citrates (citric acid salts) with citrus juice, containing especially potassium citrate, prevent the formation of kidney stones and ease their dissolution.
8. SIDE EFFECTS AND TOXICITY There is no doubt lime juice carries plentiful health benefits; however, it may have a number of side effects that might cause health hazards like the decay of tooth enamel and ulcers within the stomach. Gastroesophageal
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reflux disorder is a digestive disorder triggered by limes or acidic foods. The vitamin C in lime juice, also called ascorbic acid, affects the absorption of iron in the body. Lime juice contains sulfites that can cause reactions and allergies in some people. Though lime juice helps treat kidney stones and is good for healthy kidneys, people suffering from kidney ailments should not consume lime juice because it might cause renal damage. Citrus fruits generally contain high potassium levels. This might be bad for those suffering from kidney disease. The diseased kidneys would not be able to maintain the electrolyte balance. This leads to abnormal levels of potassium, sodium, and phosphorous.
References Arai, Y., Watanabe, S., Kimira, M., Shimoi, K., Mochizuki, R., Kinae, N., 2000. Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. Journal of Nutrition 130, 2243e2250. Baker, R.A., 1994. Potential Dietary Benefits of Citrus Pectin and Fiber. Food technology, USA). Barrett, D.M., Somogyi, L., Ramaswamy, H.S., 2004. Processing Fruits: Science and Technology. CRC Press. Bracke, M., Bruyneel, E., Vermeulen, S.J., Vennekens, K.l., Vanmarck, V., Mareel, M., 1994. Citrus flavonoid effect on tumor invasion and metastasis. Food Technology 48, 121e124. ´ lvarez, J.E., Martı´nez-Gonza´lez, G.M., Colecio-Jua´rez, M.C., Rubio-Nu´n˜ez, R.E., Botello-A Navarrete-Bolan˜os, J.L., Jime´nez-Islas, H., 2012. Characterization of volatile compounds in the essential oil of sweet lime (Citrus limetta Risso). Chilean Journal of Agricultural Research 72, 275. Cossmann, K., 1940. Citrus roots: their anatomy, osmotic pressure and periodicity of growth. Palestine Journal of Botany 3, 65e104. Cowan, M.M., 1999. Plant products as antimicrobial agents. Clinical Microbiology Reviews 12, 564e582. FAO, 2016. Food and Agriculture Organization of the United Nations, Citrus Fruit e Fresh and Processed Statistical Bulletin. http://www.fao.org/economic/est/est-commodities/citrusfruit/en/1-63. Ferguson, U., 1990. Citrus Fruits Processing. Horticultural Science, Florida, pp. 117e118. Gulsen, O., Roose, M., 2001. Lemons: diversity and relationships with selected citrus genotypes as measured with nuclear genome markers. Journal of the American Society for Horticultural Science 126, 309e317. Halliwell, B., Gutteridge, J.M., 2015. Free Radicals in Biology and Medicine. Oxford University Press, USA. Hirano, T., Abe, K., Gotoh, M., Oka, K., 1995. Citrus flavone tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes. British Journal of Cancer 72, 1380. Khan, A.A., Mahmood, T., Siddiqui, H.H., Akhtar, J., 2016. Journal of Chemical and Pharmaceutical Research 8 (3), 555e563. Koyuncu, H., Berkarda, B., Baykut, F., Soybir, G., Alatli, C., Gu¨l, H., Altun, M., 1998. Preventive effect of hesperidin against inflammation in CD-1 mouse skin caused by tumor promoter. Anticancer Research 19, 3237e3241. Krochta, J.M., Baldwin, E.A., Nisperos-Carriedo, M.O., 1994. Edible Coatings and Films to Improve Food Quality. Technomic Publ. Co.
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Kumar, S., Warikoo, R., Mishra, M., Seth, A., Wahab, N., 2012. Larvicidal efficacy of the Citrus limetta peel extracts against Indian strains of Anopheles stephensi Liston and Aedes aegypti L. Parasitology Research 111, 173e178. Murdock, D., Allen, W., 1960. Germicidal effect of orange peel oil and D-limonene in water and orange juice. Food Technology 14, 441e445. Okwu, D., 2005. Phytochemicals, vitamins and mineral contents of two Nigerian medicinal plants. International Journal of Molecular Medicine and Advance Sciences 1, 375e381. Okwu, D., Emenike, I., 2006. Evaluation of the phytonutrients and vitamins content of citrus fruits. International Journal of Molecular Medicine and Advance Sciences 2, 1e6. Okwu, D., Emenike, I., 2007. Nutritive value and mineral content of different varieties of citrus fruits. Journal of Food Technology 5, 105e108. Porat, R., Weiss, B., Cohen, L., Daus, A., Goren, R., Droby, S., 1999. Effects of ethylene and 1methylcyclopropene on the postharvest qualities of ‘Shamouti’oranges. Postharvest Biology and Technology 15, 155e163. Shahzad, K., Nawaz, S., Ahmad, R., Mahmud, S., Iqbal, Z., Saeed, K., 2009. Evaluation of antioxidant and antimicrobial activity of essential oil of Tangerine fruit peel. Pakistan Journal of Biochemistry and Molecular Biology 42, 4e7. Sharma, B., Hore, D., Gupta, S., 2004. Genetic resources of citrus of North-Eastern India and their potential use. Genetic Resources and Crop Evolution 51, 411e418. Touyz, R.M., Schiffrin, E.L., 2000. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacological Reviews 52, 639e672. Yang, M., Tanaka, T., Hirose, Y., Deguchi, T., Mori, H., Kawada, Y., 1997. Chemopreventive effects of diosmin and hesperidin on N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary-bladder carcinogenesis in male ICR mice. International Journal of Cancer 73, 719e724.