Features, Pharmacological Chemistry, Molecular Mechanism and Health Benefits of Lemon

Nitika       Singh; Nagendra    Sastry    Yarla; Nikhat    Jamal    Siddiqi; Maria       de Lourdes Pereira; Bechan       Sharma

Abstract

Background: Citrus limon, a Mediterranean-grown citrus species of plants belonging to the Rutaceae family, occupies a place of an impressive range of food and medicinal uses with considerable value in the economy of the fruit of the country. Citrus fruits are economically important with large-scale production of both the fresh fruits and industrially processed products. The extracts and phytochemicals obtained from all parts of C. limon have shown immense therapeutic potential because of their anticancer, anti-tumor and anti-inflammatory nature, and also serve as an important ingredient in the formulation of several ethnic herbal medicines. These properties are mediated by the presence of different phytochemicals, vitamins and nutrients in the citrus fruits.

Material and Methods: The methods involved in the preparation of the present article included the collection of information from various scientific databases, indexed periodicals, and search engines such as Medline Scopus google scholar PubMed, PubMed central web of science, and science direct.

Results: This communication presents an updated account of different pharmacological aspects of C. limon associated with its anti-oxidative, antiulcer, antihelmintic, insecticidal, anticancer, cytotoxic, and estrogenic activities. In addition, C. limon extracts possess hepatoprotective, anti-hyperglycemic, and antimicrobial properties. The present article includes the structure and function of different key chemical constituents from different parts of C. limon. Also, the possible molecular mechanisms of actions of bioactive compounds from C. limon are displayed.

Conclusion: The traditional and ethno-medicinal literature revealed that C. limon is very effective in different pathologies. Most of these compounds possessing antioxidant properties would be implicated in offering health benefits by acting as potential nutraceuticals to humans with special reference to disease management of health and disease.

Keywords: Citrus limon, pharmacochemistry, bioactive, health benefits, nutraceuticals, antioxidants.

Graphical Abstract

[1] 
Sofowora, A.; Ogunbodede, E.; Onayade, A. The role and place of medicinal plants in the strategies for disease prevention. Afr. J. Tradit. Complement. Altern. Med.,  2013, 10(5), 210-229.
[http://dx.doi.org/10.4314/ajtcam.v10i5.2] [PMID:  24311829] 
[2] 
Arias, B.A.; Ramón-Laca, L. Pharmacological properties of citrus and their ancient and medieval uses in the Mediterranean region. J. Ethnopharmacol.,  2005, 97(1), 89-95.
[http://dx.doi.org/10.1016/j.jep.2004.10.019] [PMID:  15652281] 
[3] 
Acar, A.; Erdoğan, İ.; Alan, Ş.; Pınar, M.N. Comparison of pollen protein patterns and pollen morphology of Taxus baccata L. and Cupressus arizonica Greene. Int. J. Nat. Life Sci.,  2017, 1, 83-88.
[4] 
Erdem, F.; Dogan, G.; Kiran, Y.; Evren, H. Morphological, anatomical, palynological and kary-ological characters of endemic Sideritis vulcanica (Lamiaceae) from Turkey. Int. J. Nat. Life Sci.,  2017, 1, 1-11.
[5] 
Yüce, B.E.; Bagc, E. Essential oil composition of Hypericum uniglandulosum Hausskn. ex Bornm. and Hypericum lydium Boiss. from Turkey. Int. J. Nat. Life Sci.,  2017, 1, 12-18.
[6] 
Erecevit, P.; Kırbağ, S. Determination of some biological properties over Kluyveromyces lactis 1 of Rheum ribes L. (Rhubarb) as a traditional medicinal and food plant. Int. J. Nat. Life Sci.,  2017, 1, 22-31.
[7] 
Baytop, T. Therapy with medicinal plants in turkey (Past and Present), Istanbul, Nobel Medicine Publication. Chin. Med.,  1999, 3, 179-204.
[8] 
Webber, H.J. History and Development of the Citrus Industry; University of California Division of Agricultural Sciences, 1967, pp. 307-444.
[9] 
González-Molina, E.; Domínguez-Perles, R.; Moreno, D.A.; García-Viguera, C. Natural bioactive compounds of Citrus limon for food and health. J. Pharm. Biomed. Anal.,  2010, 51(2), 327-345.
[http://dx.doi.org/10.1016/j.jpba.2009.07.027] [PMID:  19748198] 
[10] 
Joy, P.P.; Thomas, J.; Mathew, S.; Skaria, B.P. Medicinal plants; Aromatic and Medicinal Plants Research Station, 1998, pp. 1-189.
[11] 
Lv, X.; Zhao, S.; Ning, Z.; Zeng, H.; Shu, Y.; Tao, O.; Xiao, C.; Lu, C.; Liu, Y. Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health. Chem. Cent. J.,  2015, 9, 68.
[http://dx.doi.org/10.1186/s13065-015-0145-9] [PMID:  26705419] 
[12] 
Hojjati, M.; Barzegar, H. Chemical composition and biological activities of lemon (Citrus limon) leaf essential oil. Food Sci. Nutr.,  2017, 4, 15-24.
[13] 
Vijaylakshmi, P.; Radha, R. An overview: Citrus maxima. J. Phytopharmacol.,  2015, 4, 263-267.
[14] 
Favela-Hernández, J.M.J.; González-Santiago, O.; Ramírez-Cabrera, M.A.; Esquivel-Ferriño, P.C.; Camacho-Corona, M.R. Chemistry and pharmacology of Citrus sinensis. Molecules,  2016, 21, 247.
[http://dx.doi.org/10.3390/molecules21020247] 
[15] 
Makni, M.; Jemai, R.; Kriaa, W.; Chtourou, Y.; Fetoui, H. Citrus limon from Tunisia: phytochemical and physicochemical properties and biological activities. BioMed. Res. Int.,  2018, 2018, 6251546.
[16] 
Chaturvedi, D. Basketful benefits of Citrus limon. Int. Res. J. Pharm.,  2016, 7, 1-4.
[http://dx.doi.org/10.7897/2230-8407.07653] 
[17] 
Sanofer, A. Role of citrus fruits in health. J. Pharm. Sci. Res.,  2014, 6, 121-123.
[18] 
Davies, F.S.; Albrigo, L.G. Citrus; CAB International: Wallingford, 1994, p. 254.
[19] 
Udapurkar, P.P.; Bhusnure, O.G.; Kamble, S.R. Development and characterization of citrus limon phospholipid complex as an effective phytoconstituent delivery system. Int. J. Life Sci. Pharm. Res.,  2018, 8, 1-13.
[20] 
Khazir, J.; Mir, B.A.; Ahmad, S.; Cowan, D.A. Natural products as lead compounds in drug discovery J. Asian Nat. Prod. Res.,  2013, 15, 64-788.
[21] 
Sidana, J.; Saini, V.; Dahiya, S.; Nain, P.; Bala, S. A review on Citrus – The boon of nature. Int. J. Pharm. Sci. Rev. Res.,  2013, 18, 20-27.
[22] 
Liu, Y.; Ren, C.; Cao, Y.; Wang, Y.; Duan, W.; Xie, L.; Sun, C.; Li, X. Characterization and purification of bergamottin from Citrus grandis (L.) Osbeck cv. Yongjiazaoxiangyou and its antiproliferative activity and effect on glucose consumption in HepG2 cells. Molecules,  2017, 22(7), 1227.
[http://dx.doi.org/10.3390/molecules22071227] [PMID:  28726768] 
[23] 
Khaleel, C.; Tabanca, N.; Buchbauer, G. α-Terpineol, a natural monoterpene: A review of its biological properties. Open Chem.,  2018, 16, 349-361.
[http://dx.doi.org/10.1515/chem-2018-0040] 
[24] 
Kretschmar, J.A.; Baumann, T.W. Caffeine in Citrus flowers. Phytochemistry,  1999, 52, 19-23.
[http://dx.doi.org/10.1016/S0031-9422(99)00119-3] 
[25] 
Lou, S.N.; Ho, C.T. Phenolic compounds and biological activities of small-size citrus: Kumquat and calamondin. Yao Wu Shi Pin Fen Xi,  2017, 25(1), 162-175.
[http://dx.doi.org/10.1016/j.jfda.2016.10.024] [PMID:  28911534] 
[26] 
Dosoky, N.S.; Setzer, W.N. Biological activities and safety of citrus spp. essential oils. Int. J. Mol. Sci.,  2018, 19(7), 1-25.
[http://dx.doi.org/10.3390/ijms19071966] [PMID:  29976894] 
[27] 
Gualdani, R.; Cavalluzzi, M.M.; Lentini, G.; Habtemariam, S. The chemistry and pharmacology of Citrus Limonoids. Molecules,  2016, 21(11), E1530.
[http://dx.doi.org/10.3390/molecules21111530] [PMID:  27845763] 
[28] 
Janati, S.S.F.; Beheshti, H.R.; Feizy, J.; Fahim, N.K. Chemical composition of lemon and peels its considerations as animal food. Gida,  2012, 37, 267-271.
[29] 
Arteche García. Fitoterapia: Vademecum de Prescripcion; Mas-son: Barcelona, 1998. 
[30] 
Mehl, F.; Marti, G.; Boccard, J.; Debrus, B.; Merle, P.; Delort, E.; Baroux, L.; Raymo, V.; Velazco, M.I.; Sommer, H.; Wolfender, J.L.; Rudaz, S. Differentiation of lemon essential oil based on volatile and non-volatile fractions with various analytical techniques: a metabolomic approach. Food Chem.,  2014, 143, 325-335.
[http://dx.doi.org/10.1016/j.foodchem.2013.07.125] [PMID:  24054247] 
[31] 
Nasser, N.; Hossain, A.M.A. Comparative chemical composition and antimicrobial activity study of essential oils from two imported lemon fruits samples against pathogenic bacteria. J. Basic Appl. Sci.,  2014, 3, 247-253.
[32] 
Singh, N.; Kumar, A.; Gupta, V.K.; Sharma, B. Biochemical and molecular bases of lead-induced toxicity in mammalian systems and possible mitigations. Chem. Res. Toxicol.,  2018, 31(10), 1009-1021.
[http://dx.doi.org/10.1021/acs.chemrestox.8b00193] [PMID:  30178661] 
[33] 
Hajimahmoodi, M.; Aliabadipoor, M.; Moghaddam, G.; Sadeghi, N.; Oveisi, M.R.; Jannat, B. Evaluation of in vitro antioxidant activities of lemon juice for safety assessment. Am. J. Food Technol.,  2012, 7, 708-714.
[http://dx.doi.org/10.3923/ajft.2012.708.714] 
[34] 
Campêlo, L.M.; Gonçalves, F.C.; Feitosa, C.M.; de Freitas, R.M. Antioxidant activity of Citrus limon essential oil in mouse hippocampus. Pharm. Biol.,  2011, 49(7), 709-715.
[http://dx.doi.org/10.3109/13880209.2010.541924] [PMID:  21639684] 
[35] 
Castillo, S.; Dávila-Aviña, J.; Heredia, N.; Garcia, S. Antioxidant activity and influence of Citrus byproduct extracts on adherence and invasion of Campylobacter jejuni and on the relative expression of cadF and ciaB. Food Sci. Biotechnol.,  2017, 26(2), 453-459.
[http://dx.doi.org/10.1007/s10068-017-0062-x] [PMID:  30263564] 
[36] 
Al-Snafi, A.E. Nutritional value and pharmacological importance of citrus species grown in Iraq. IOSR J. Pharm. (IOSRPHR),  2016, 6, 76-108.
[http://dx.doi.org/10.9790/3013-0680176108] 
[37] 
Diab, K.A. In Vitro studies on phytochemical content, antioxidant, anticancer, immunomodulatory, and antigenotoxic activities of lemon, grapefruit, and mandarin Citrus peels. Asian Pac. J. Cancer Prev.,  2016, 17(7), 3559-3567.
[PMID: 27510009] 
[38] 
Rashmi, R.; Bojan Magesh, S.; Mohanram Ramkumar, K.; Suryanarayanan, S. Venkata SubbaRao, M. Antioxidant potential of naringenin helps to protect liver tissue from streptozotocin-induced damage. Rep. Biochem. Mol. Biol.,  2018, 7(1), 76-84.
[PMID: 30324121] 
[39] 
Bhavitavya, B.; Asdaq, S.M.B.; Asad, M.; Prasad, S. Antiulcer Activity of Lemon (Citrus limon) fruit juice and its interaction with conventionally used antiulcer drugs in rats. J. Nat. Prod.,  2012, 2, 61-68.
[40] 
Millet, F. Essential oils and lemon tree oil (Citrus limon (L.) Burm.). Phytotherapie,  2014, 12, 89.
[http://dx.doi.org/10.1007/s10298-014-0857-3] 
[41] 
Chaudhari, S.Y.; Ruknuddin, G.; Prajapati, P. Ethno medicinal values of Citrus genus: A review. J. Dr. D.Y. Patil Univ.,  2016, 9, 560-565.
[http://dx.doi.org/10.4103/0975-2870.192146] 
[42] 
Khatiwora, E. Citrus Limon leaves from north-eastern India: A potential source of anthelmintic agent against Eicinia Foetida. J. Drug Deliv. Ther.,  2018, 8, 55-57.
[http://dx.doi.org/10.22270/jddt.v8i3.1696] 
[43] 
Abdelqader, A.; Qarallah, B.; Al-Ramamneh, D.; Daş, G. Anthelmintic effects of citrus peels ethanolic extracts against Ascaridia galli. Vet. Parasitol.,  2012, 188(1-2), 78-84.
[http://dx.doi.org/10.1016/j.vetpar.2012.03.003] [PMID:  22463876] 
[44] 
Das, S.S.; Dey, M.; Ghosh, A.K. Determination of anthelmintic activity of the leaf and bark extract of tamarindus indica linn. Indian J. Pharm. Sci.,  2011, 73(1), 104-107.
[http://dx.doi.org/10.4103/0250-474X.89768] [PMID:  22131633] 
[45] 
Cirmi, S.; Maugeri, A.; Ferlazzo, N.; Gangemi, S.; Calapai, G.; Schumacher, U.; Navarra, M. Anticancer potential of Citrus Juices and their extracts: A systematic review of both preclinical and clinical studies. Front. Pharmacol.,  2017, 30, 420.
[46] 
Salehi, F.; Behboudi, H.; Kavoosi, G.; Ardestani, S.K. Oxidative DNA damage induced by ROS-modulating agents with the ability to target DNA: A comparison of the biological characteristics of citrus pectin and apple pectin. Sci. Rep.,  2018, 8(1), 13902.
[http://dx.doi.org/10.1038/s41598-018-32308-2] [PMID:  30224635] 
[47] 
Segun, P.A.; Ismail, F.M.D.; Ogbole, O.O.; Nahar, L.; Evans, A.R.; Ajaiyeoba, E.O.; Sarker, S.D. Acridone alkaloids from the stem bark of Citrus aurantium display selective cytotoxicity against breast, liver, lung and prostate human carcinoma cells. J. Ethnopharmacol.,  2018, 227, 131-138.
[http://dx.doi.org/10.1016/j.jep.2018.08.039] [PMID:  30189240] 
[48] 
Fidyt, K.; Fiedorowicz, A.; Strządała, L.; Szumny, A. β-caryophyllene and β-caryophyllene oxide-natural compounds of anticancer and analgesic properties. Cancer Med.,  2016, 5(10), 3007-3017.
[http://dx.doi.org/10.1002/cam4.816] [PMID:  27696789] 
[49] 
Kozioł, E.; Skalicka-Woźniak, K. Imperatorin-pharmacological meaning and analytical clues: profound investigation. Phytochem. Rev.,  2016, 15, 627-649.
[http://dx.doi.org/10.1007/s11101-016-9456-2] [PMID:  27453708] 
[50] 
Lee, J.; Lee, J.; Kim, M.; Kim, J.H. Fermented extraction of citrus unshiu peel inhibits viability and migration of human pancreatic cancers. J. Med. Food,  2018, 21(1), 5-12.
[http://dx.doi.org/10.1089/jmf.2017.3984] [PMID:  29346059] 
[51] 
Silalahi, J. Anticancer and health protective properties of Citrus fruit components. Asia Pac. J. Clin. Nutr.,  2002, 11(1), 79-84.
[http://dx.doi.org/10.1046/j.1440-6047.2002.00271.x] [PMID:  11890643] 
[52] 
Kumar, K.A.; Narayani, M.; Subanthini, A.; Jayakumar, M. Antimicrobial activity and phytochemical analysis of citrus fruit peels -utilization of fruit waste. Int. J. Eng. Sci. Technol.,  2011, 3, 5414-5421.
[53] 
Abu-shanab, B.; Adwan, G.; Abu-safiya, D.; Jarrar, N.; Adwan, K. Antibacterial activities of some plant extracts utilized in popular medicine in Palestine. Turk. J. Biol.,  2004, 28, 99-102.
[54] 
CDC NNIS System. National Nosocomial Infections Surveillance (NNIS) system report, data summary from January 1990-May 1999. Am. J. Infect. Control,  1999, 27, 520-532.
[PMID:  10586157] 
[55] 
Hindi, N.K.K.; Chabuck, Z.A.G. Antimicrobial activity of different aqueous lemon extracts. J. Appl. Pharmaceut. Sci.,  2013, 3, 074-078.
[56] 
Khan, Y.; Khan, R.A.; Afroz, S.; Siddiq, A. Evaluation of hypolipidemic effect of citrus lemon. J. Basic Appl. Sci.,  2010, 6, 39-43.
[57] 
Lee, H.; Woo, M.; Kim, M.; Noh, J.S.; Song, Y.O. Antioxidative and Cholesterol-Lowering Effects of Lemon Essential Oil in Hypercholesterolemia-Induced Rabbits. Prev. Nutr. Food Sci.,  2018, 23(1), 8-14.
[http://dx.doi.org/10.3746/pnf.2018.23.1.8] [PMID:  29662842] 
[58] 
Jing, L.; Zhang, Y.; Fan, S.; Gu, M.; Guan, Y.; Lu, X.; Huang, C.; Zhou, Z. Preventive and ameliorating effects of citrus D-limonene on dyslipidemia and hyperglycemia in mice with high-fat diet-induced obesity. Eur. J. Pharmacol.,  2013, 715(1-3), 46-55.
[http://dx.doi.org/10.1016/j.ejphar.2013.06.022] [PMID:  23838456] 
[59] 
Oshaghi, M.A.; Ghalandari, R.; Vatandoost, H.; Shayeghi, M.; Kamali-nejad, M.; Tourabi-Khaledi, H.; Abolhassani, M.; Hashemzadeh, M. Repellent effect of extracts and essential oils of Citrus limon (Rutaceae) and Melissa officinalis (Labiatae) against main malaria vector, Anopheles stephensi (Diptera: Culicidae). Iran. J. Public Health,  2003, 32, 47-52.
[60] 
Adusei-Mensah, F.; Inkum, I.E.; Agbale, C.M.; Eric, A. Comparative evaluation of the insecticidal and insect repellent properties of the volatile oils of Citrus Aurantifolia (Lime), Citrus Sinensis (Sweet Orange) and Citrus Limon (Lemon) on Camponotus Nearcticus (Carpenter Ants). Int. J. Novel Res. Interdiscipl. Stud.,  2014, 1, 19-25.
[61] 
Manimaran, A.; Cruz, M.J.; Muthu, C.; Vincent, S.; Ignacimuthu, S. Repellant activity of plant essential oils formulation against three disease causing mosquito vectors. J. Agri. Tech.,  2013, 9, 845-854.
[62] 
Albishi, T.; John, J.A.; Al-Khalifa, A.S.; Shahidi, F. Phenolic content and antioxidant activities of selected potato varieties and their processing byproducts. J. Funct. Foods,  2013, 5, 590-600.
[http://dx.doi.org/10.1016/j.jff.2012.11.019] 
[63] 
Ke, Z.L.; Pan, Y.; Xu, X.D.; Nie, C.; Zhou, Z.Q. Citrus flavonoids and human cancers. J. Food Nutr. Res.,  2015, 3, 341-351.
[http://dx.doi.org/10.12691/jfnr-3-5-9] 
[64] 
El-ghfar, A.A.; Ibrahim, H.M.; Hassan, I.M.; Fattah, A.A.; Mahmoud, M.H. Peels of lemon and orange as value-added ingredients: chemical and antioxidant properties. Int. J. Curr. Microbiol. Appl. Sci.,  2016, 5, 777-794.
[http://dx.doi.org/10.20546/ijcmas.2016.512.089] 
[65] 
Valgimigli, L.; Gabbanini, S.; Berlini, E.; Lucchi, E.; Beltramini, C.; Bertarelli, Y.L. Lemon (Citrus limon, Burm.f.) essential oil enhances the trans-epidermal release of lipid-(A, E) and water-(B6, C) soluble vitamins from topical emulsions in reconstructed human epidermis. Int. J. Cosmet. Sci.,  2012, 34(4), 347-356.
[http://dx.doi.org/10.1111/j.1468-2494.2012.00725.x] [PMID:  22515469] 
[66] 
Thomas, L.; Kamath, J.V. Anti-hyperglycemic activity of citrus limon leaves in streptozotocin induced diabetic rats. Indian Drug,  2017, 54, 74-80.
[67] 
Vasu, P.; Khan, N.D.; Khan, Z.H.; Mular, S.M. In vitro antidiabetic activity of methanolic extract of Citrus limon, Punicagranatum, Musa acuminata peel. Int. J. Appl. Res.,  2017, 3, 804-806.
[68] 
Verengai, W.; Chagonda, L.; Chitindingu, K.; Marume, A.; Taderera, T. An anti-diabetic poly-herbal medicine prepared from extracts of Annona Stenophylla, Citrus Limon and Zingiber Officinale. Int. J. Pharm. Sci. Res.,  2017, 8, 1048-1055.
[69] 
Akhila, S.; Bindu, A.R.; Bindu, K.; Aleykutty, N.A. Phytochemical and pharmacological evaluation of Citrus Limon peel. World J. Pharm. Pharm. Sci.,  2015, 4, 1128-1135.
[70] 
Bhavsar, S.K.P.; Joshi, M.B.; Santani, D.D. Investigation into hepatoprotective activity of Citrus limon. Pharm. Biol.,  2007, 45, 303-311.
[http://dx.doi.org/10.1080/13880200701214995] 
[71] 
Zhou, T.; Zhang, Z.; Xu, D.; Wang, F.; Zhou, Y.; Zheng, J.; Li, Y.; Zhang, J.; Li, H. Protective effects of lemon juice on alcohol-induced liver injury in mice. Biomed Res. Int.,  2017, 20177463571
[72] 
Bouzenna, H.; Dhibi, S.; Samout, N.; Rjeibi, I.; Talarmin, H.; Elfeki, A.; Hfaiedh, N. The protective effect of Citrus limon essential oil on hepatotoxicity and nephrotoxicity induced by aspirin in rats. Biomed. Pharmacother.,  2016, 83, 1327-1334.
[http://dx.doi.org/10.1016/j.biopha.2016.08.037] [PMID:  27571876] 
[73] 
Amorim, J.L.; Simas, D.L.R.; Pinheiro, M.M.G.; Moreno, D.S.A.; Alviano, C.S. Anti-inflammatory properties and chemical characterization of the essential oils of four Citrus Species. Plos One,  2016, 11(4), e0153643.
[74] 
Martins, H.B.; Selis, N.D.; Souza, C.L.S.; Nascimento, F.S.; de Carvalho, S.P.; Gusmão, L.D.; Nascimento, J.D.; Brito, A.K.; de Souza, S.I.; de Oliveira, M.V.; Timenetsky, J.; Yatsuda, R.; Uetanabaro, A.P.; Marques, L.M. Anti-inflammatory activity of the essential oil Citral in experimental infection with Staphylococcus aureus in a model air pouch. Evid. Based Complement. Alternat. Med.,  2017, 2017, 2505610.
[http://dx.doi.org/10.1155/2017/2505610] [PMID:  28316634] 
[75] 
Déciga-Campos, M.; Ortiz-Andrade, R.; Sanchez-Recillas, A.; Flores-Guido, J.S.; Ramírez Camacho, M.A. Antinociceptive and antihyperalgesic activity of a traditional maya herbal preparation composed of Pouteria Campechiana, Chrysophyllum Cainito, Citrus Limonum, and Annona Muricata. Drug Dev. Res.,  2017, 78(2), 91-97.
[http://dx.doi.org/10.1002/ddr.21378] [PMID:  28176363] 
[76] 
Chadwick, M.; Trewin, H.; Gawthrop, F.; Wagstaff, C. Sesquiterpenoids lactones: benefits to plants and people. Int. J. Mol. Sci.,  2013, 14(6), 12780-12805.
[http://dx.doi.org/10.3390/ijms140612780] [PMID:  23783276] 
[77] 
Nasri, H.; Baradaran, A.; Shirzad, H.; Rafieian-Kopaei, M. New concepts in nutraceuticals as alternative for pharmaceuticals. Int. J. Prev. Med.,  2014, 5(12), 1487-1499.
[PMID: 25709784] 
[78] 
Pan, S.Y.; Zhou, S.F.; Gao, S.H.; Yu, Z.L.; Zhang, S.F.; Tang, M.K.; Sun, J.N.; Ma, D.L.; Han, Y.F.; Fong, W.F.; Ko, K.M. New Perspectives on How to Discover Drugs from Herbal Medicines: CAM’s outstanding contribution to modern therapeutics. Evid. Based Complement. Alternat. Med.,  2013, 2013, 627375.
[http://dx.doi.org/10.1155/2013/627375] [PMID:  23634172] 
[79] 
Li, L.; Zhou, X.; Li, N.; Sun, M.; Lv, J.; Xu, Z. Herbal drugs against cardiovascular disease: traditional medicine and modern development. Drug Discov. Today,  2015, 20(9), 1074-1086.
[http://dx.doi.org/10.1016/j.drudis.2015.04.009] [PMID:  25956424] 
[80] 
Marı’n, F.R.; Martinez, M.; Uribesalgo, T.; Castillo, S.; Frutos, M.J. Changes in nutraceutical composition of lemon juices according to different industrial extraction systems. Food Chem.,  2002, 78, 319-324.
[http://dx.doi.org/10.1016/S0308-8146(02)00102-4] 
[81] 
Miyake, Y.; Yamamoto, K.; Osawa, T. Metabolism of antioxidant in lemon fruit (Citrus limon BURM. f.) by human intestinal bacteria. J. Agric. Food Chem.,  1997, 45, 3738-3742.
[http://dx.doi.org/10.1021/jf970403r] 
[82] 
Campêlo, L.M.L.; de Almeida, A.A.; de Freitas, R.L.; Cerqueira, G.S.; de Sousa, G.F.; Saldanha, G.B.; Feitosa, C.M.; de Freitas, R.M. Antioxidant and antinociceptive effects of Citrus limon essential oil in mice. J. Biomed. Biotechnol.,  2011, 2011, 678673.
[http://dx.doi.org/10.1155/2011/678673] [PMID:  21660140] 
[83] 
Tag, H.M.; Kelany, O.E.; Tantawy, H.M.; Fahmy, A. Potential anti-inflammatory effect of lemon and hot pepper extracts on adjuvant-induced arthritis in mice. J. Basic Appl. Zoology.,  2014, 67, 149-157.
[http://dx.doi.org/10.1016/j.jobaz.2014.01.003] 
[84] 
Ho, P.C.; Saville, D.J.; Coville, P.F.; Wanwimolruk, S. Content of CYP3A4 inhibitors, naringin, naringenin and bergapten in grapefruit and grapefruit juice products. Pharm. Acta Helv.,  2000, 74(4), 379-385.
[http://dx.doi.org/10.1016/S0031-6865(99)00062-X] [PMID:  10812937] 
[85] 
Harapu, C.D.; Miron, A.; Cuciureanu, M.; Cuciureanu, R. Flavonoids--bioactive compounds in fruits juice. Rev. Med. Chir. Soc. Med. Nat. Iasi,  2010, 114(4), 1209-1214.
[PMID:  21500482] 
[86] 
Suthutvoravut, S.; Kamyarat, O. Spermicidal effects of lemon juice and juices from other natural products. Agric. Nat. Resourc.,  2016, 50, 133-138.

Cite As

Medicinal Chemistry

Features, Pharmacological Chemistry, Molecular Mechanism and Health Benefits of Lemon

Abstract

Graphical Abstract