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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

An Up-to-Date Review on Citrus Flavonoids: Chemistry and Benefits in Health and Diseases

Author(s): Osama M. Ahmed*, Sameh F. AbouZid, Noha A. Ahmed, Mohamed Y. Zaky and Han Liu

Volume 27, Issue 4, 2021

Published on: 27 November, 2020

Page: [513 - 530] Pages: 18

DOI: 10.2174/1381612826666201127122313


Flavonoids, the main class of polyphenols, are characterized by the presence of 2-phenyl-benzo-pyrane nucleus. They are found in rich quantities in citrus fruits. Citrus flavonoids are classified into flavanones, flavones, flavonols, polymethoxyflavones and anthocyanins (found only in blood oranges). Flavanones are the most abundant flavonoids in citrus fruits. In many situations, there are structure-function relationships. Due to their especial structures and presence of many hydroxyls, polymethoxies and glycoside moiety, the flavonoids have an array of multiple biological and pharmacological activities. This article provides an updated overview of the differences in chemical structures of the classes and members of citrus flavonoids and their benefits in health and diseases. The review article also sheds light on the mechanisms of actions of citrus flavonoids in the treatment of different diseases, including arthritis, diabetes mellitus, cancer and neurodegenerative disorders as well as liver, kidney and heart diseases. The accumulated and updated knowledge in this review may provide useful information and ideas in the discovery of new strategies for the use of citrus flavonoids in the protection, prevention and therapy of diseases.

Keywords: Citrus flavonoids, chemistry, benefits in health, benefits in diseases, polymethoxies, glycoside moiety.

Mahato N, Sinha M, Sharma K, Koteswararao R, Cho MH. Modern Extraction and Purification Techniques for Obtaining High Purity Food-Grade Bioactive Compounds and Value-Added Co-Products from Citrus Wastes. Foods 2019; 8(11): 523.
[] [PMID: 31652773]
Weisskopf A, Fuller DQ. Citrus Fruits: Origins and Development. New York, NY, USA: Springer 2014.
Wu J, Zhao YM, Deng ZK. Tangeretin ameliorates renal failure via regulating oxidative stress, NF-κB-TNF-α/iNOS signalling and improves memory and cognitive deficits in 5/6 nephrectomized rats. Inflammopharmacol 2018; 26(1): 119-32.
[] [PMID: 28871498]
Sharma K, Mahato N, Lee YR. Extraction, characterization and biological activity of citrus flavonoids. Rev Chem Eng 2018; 35: 265-84.
FAO. Market and policy analysis of raw materials, horticulture and tropical (RAMHOT) products team. Rome, Italy: Food and Agriculture Organization of the United Nations 2017. Available at:
Cirmi S, Ferlazzo N, Lombardo GE, et al. Neurodegenerative diseases: Might Citrus flavonoids play a protective role? Molecules 2016; 21(10): 1312.
[] [PMID: 27706034]
Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci 2016; 5.
[] [PMID: 28620474]
Hodek P, Trefil P, Stiborová M. Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chem Biol Interact 2002; 139(1): 1-21.
[] [PMID: 11803026]
Matheyambath AC, Padmanabham P. Pallyath Citrus fruitsEncyclopedia of Food and Health Walthan, MA 02451. USA: Academic Press, Elsevier LTd 2016; pp. 136-40.
Ortuno A, Arcas M, Benavente-Garcıa O, et al. Evolution of polymethoxy flavones during development of tangelo Nova fruits. Food Chem 1999; 66: 217-20.
Del Rıo J, Fuster M, Gómez P, et al. Citrus limon: a source of flavonoids of pharmaceutical interest. Food Chem 2004; 84: 457-61.
Hertog MG, Kromhout D, Aravanis C, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 1995; 155(4): 381-6.
[] [PMID: 7848021]
Knekt P, Kumpulainen J, Järvinen R, et al. Flavonoid intake and risk of chronic diseases. Am J Clin Nutr 2002; 76(3): 560-8.
[] [PMID: 12198000]
Le Marchand L. Cancer preventive effects of flavonoids-a review. Biomed Pharmacother 2002; 56(6): 296-301.
[] [PMID: 12224601]
Yi L, Ma S, Ren D. Phytochemistry and bioactivity of Citrus flavonoids: a focus on antioxidant, anti-inflammatory, anticancer and cardiovascular protection activities. Phytochem Rev 2017; 16: 479-511.
Ahmed OM, Ashour MB, Abd El-Fattah AS. The Preventive effects of navel orange peel ethanolic extract and naringin on doxorubicin-induced nephrocardiotoxicity in male albino rats. Indo Am J Pharmaceut Res 2017; 7(07): 109-17.
Ahmed O, Fahim H, Mahmoud A, Eman Ahmed EA. Bee venom and hesperidin effectively mitigate complete Freund’s adjuvant-induced arthritis via immunomodulation and enhancement of antioxidant defense system. Arch Rheumatol 2017; 33(2): 198-212.
[] [PMID: 30207564]
Ahmed OM, Mohamed T, Moustafa H, Hamdy H, Ahmed RR, Aboud E. Quercetin and low level laser therapy promote wound healing process in diabetic rats via structural reorganization and modulatory effects on inflammation and oxidative stress. Biomed Pharmacother 2018; 101: 58-73.
[] [PMID: 29477473]
Ahmed OM, Ashour MB, Fahim HI, et al. Citrus limon and paradisi fruit peel hydroethanolic extracts prevent the progress of complete Freund’s adjuvant-induced arthritis in male Wistar rats. Adv Anim Vet Sci 2018; 6(10): 443-55.
Ahmed OM, Ashour MB, Fahim HI, et al. The role of Th1/Th2/Th17 cytokines and antioxidant defense system in mediating the effects of lemon and grapefruit peel hydroethanolic extracts An Up-to-Date Review on Citrus Flavonoids: Chemistry and Benefits in Health and Diseases Current Pharmaceutical Design, 2021, Vol. 27, No. 4 525 on adjuvant-induced arthritis. J App Pharm Sci 2018; 8(10): 069-81.
Ahmed OM, Fahim HI, Ahmed HY, Mahmoud B, Aljohani SAS, Abdelazeem WH. The nephropreventive and antioxidant effects of navel orange peel hydroethanolic extract, naringin and naringenin in n-acetyl-p-aminophenol-administered Wistar rats. Adv Anim Vet Sci 2019; 7(2): 96-105.
Ahmed OM, Fahim HI, Ahmed HY, et al. The preventive effects and the mechanisms of action of navel orange peel hydroethanolic extract, naringin, and naringenin in N-Acetyl-p-aminophenol-induced liver injury in Wistar rats. Oxid Med Cell Longev 2019. Article ID 2019; 2745352: 1-19.
Zaky MY, Ahmed OM, Ahmed AA, et al. Naringenin and quercetin inhibit the instigating effects of diethylnitrosamine /acetylaminofluorene on cardiac function, oxidative stress and inflammation. Biocell 2019; 43(2-1): 29-40.
Barreca D, Gattuso G, Bellocco E, et al. Flavanones: Citrus phytochemical with health-promoting properties. Biofactors 2017; 43(4): 495-506.
[] [PMID: 28497905]
Peterson J, Dwyer J. Flavonoids: dietary occurrence and biochemical activity. Nutr Res 1998; 18: 1995-2018.
Middleton E Jr. Effect of plant flavonoids on immune and inflammatory cell function. Adv Exp Med Biol 1998; 439: 175-82.
[] [PMID: 9781303]
Nogata Y, Sakamoto K, Shiratsuchi H, Ishii T, Yano M, Ohta H. Flavonoid composition of fruit tissues of citrus species. Biosci Biotechnol Biochem 2006; 70(1): 178-92.
[] [PMID: 16428836]
Gandhi GR, Vasconcelos ABS, Wu DT, et al. Citrus flavonoids as promising phytochemicals targeting diabetes and related complications: A systematic review of in vitro and in vivo studies. Nutrients 2020; 12(10): 2907.
[] [PMID: 32977511]
Castillo J, Benavente O, Del Río JA. Naringin and neohesperidin levels during development of leaves, flower buds, and fruits of Citrus-aurantium. Plant Physiol 1992; 99(1): 67-73.
[] [PMID: 16668885]
Mir IA, Tiku AB. Chemopreventive and therapeutic potential of “naringenin,” a flavanone present in citrus fruits. Nutr Cancer 2015; 67(1): 27-42.
[] [PMID: 25514618]
Iwashina T. Flavonoid properties of five families newly incorporated into the order Caryophyllales. Bull Natl Mus Nat Sci 2013; 39: 25-51.
Tomas-Barberam FA, Ferrers F, Gil MI. Antioxidant and Phenolic Metabolite from fruits, vegetables and changes during postharvest storage and processing.Studies in natural products chemistry Bioactive Natural Products (Part D). Amsterdam. In: Switherland: Elsevier. 2000; 23: pp. 739-96.
Marhuenda J, Cerdá B, Villaño D, et al. Citrus and health Citrus-health benefits and production technology. IntechOpen 2018.
Urpi-Sarda M, Rothwell J, Morand C, et al. Bioavailability of flavanones. New York, NY, USA: CRC Press 2012.
Ahmed OM, Hassan MA, Abdel-Twab SM, Abdel Azeem MN. Navel orange peel hydroethanolic extract, naringin and naringenin have anti-diabetic potentials in type 2 diabetic rats. Biomed Pharmacother 2017; 94: 197-205.
[] [PMID: 28759757]
Ahmed OM, Ahmed AA, Fahim HI, Zaky MY. Quercetin and naringenin abate diethylnitrosamine/acetylaminofluorene-induced hepatocarcinogenesis in Wistar rats: the roles of oxidative stress, inflammation and cell apoptosis. Drug Chem Toxicol 2019. In press
[] [PMID: 31665932]
Mahmoud H, Ahmed OM, Fahim HI, et al. Effects of rutin and quercetin on doxorubicin-induced renocardiotoxicity in male wistar rats. Adv Anim Vet Sci 2020; 8(4): 370-84.
Jiang N, Doseff AI, Grotewold E. Flavones: From biosynthesis to health benefits. Plants (Basel) 2016; 5(2): 27.
[] [PMID: 27338492]
López-Lázaro M. Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem 2009; 9(1): 31-59.
[] [PMID: 19149659]
Adamczak A, Ożarowski M, Karpiński TM. Antibacterial activity of some flavonoids and organic acids widely distributed in plants. J Clin Med 2019; 9(1): 109.
[] [PMID: 31906141]
Choi EJ. Hesperetin induced G1-phase cell cycle arrest in human breast cancer MCF-7 cells: involvement of CDK4 and p21. Nutr Cancer 2007; 59(1): 115-9.
[] [PMID: 17927510]
Sultana B, Anwar F. Flavonols (kaempeferol, quercetin, myricetin) contents of selected fruits, vegetables and medicinal plants. Food Chem 2008; 108(3): 879-84.
[] [PMID: 26065748]
Salvamani S, Gunasekaran B, Shaharuddin NA, Ahmad SA, Shukor MY. Antiartherosclerotic effects of plant flavonoids. BioMed Res Int 2014; 2014
[] [PMID: 24971331]
Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn Rev 2016; 10(20): 84-9.
[] [PMID: 28082789]
Ahmed OM, Abdel-Moneim A, Abulyazid E, et al. Antihyperglycemic, antihyperlipidemic and antioxidant effects and the probable mechanisms of action of Ruta graveolens infusion and rutin in nicotinamide-streptozotocin-induced diabetic rats. Diabetol Croat 2010; 39(1): 15-35.
Al-Dhabi NA, Arasu MV, Park CH, Park SU. An up-to-date review of rutin and its biological and pharmacological activities. EXCLI J 2015; 14: 59-63.
[PMID: 26535031]
Niture NT, Ansari AA, Naik SR. Anti-hyperglycemic activity of rutin in streptozotocin-induced diabetic rats: an effect mediated through cytokines, antioxidants and lipid biomarkers. Indian J Exp Biol 2014; 52(7): 720-7.
[PMID: 25059040]
Yang J, Lee H, Sung J, Kim Y, Jeong HS, Lee J. Conversion of rutin to Quercetin by acid treatment in relation to biological activities. Prev Nutr Food Sci 2019; 24(3): 313-20.
[] [PMID: 31608257]
Zhang Y, Chen AY, Li M, Chen C, Yao Q. Ginkgo biloba extract kaempferol inhibits cell proliferation and induces apoptosis in pancreatic cancer cells. J Surg Res 2008; 148(1): 17-23.
[] [PMID: 18570926]
Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev 2014; 8(16): 122-46.
[] [PMID: 25125885]
Shields M. ChemotherapeuticsPharmacognosy fundamentals, applications and strategies. Elsevier Inc 2017; pp. 295-313.
Li S, Pan M-H, Lo C-Y, et al. Chemistry and health effects of polymethoxyflavones and hydroxylated polymethoxyflavones. J Funct Foods 2009; 1: 2-12.
Nielsen SE, Breinholt V, Cornett C, Dragsted LO. Biotransformation of the citrus flavone tangeretin in rats. Identification of metabolites with intact flavane nucleus. Food Chem Toxicol 2000; 38(9): 739-46.
[] [PMID: 10930694]
Li S, Wang H, Guo L, et al. Chemistry and bioactivity of nobiletin and its metabolites. J Funct Foods 2014; 6: 2-10.
Mizuno H, Yoshikawa H, Usuki T. Extraction of nobiletin and tangeretin from peels of shekwasha and ponkan using [C2mim] [(MeO)(H)PO2] and centrifugation. Nat Prod Communicat 2019; 1-6.
Bracke ME, Bruyneel EA, Vermeulen SJ, et al. Citrus flavonoid effect on tumor invasion and metastasis. Food Technol 1994; 48: 121-4.
Benavente-García O, Castillo J. Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity. J Agric Food Chem 2008; 56(15): 6185-205.
[] [PMID: 18593176]
Liu LL, Li FH, Zhang Y, Zhang XF, Yang J. Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice. Braz J Med Biol Res 2017; 50(8)
[] [PMID: 28746467]
Eun SH, Woo JT, Kim DH. Tangeretin inhibits IL-12 expression and NF-kappaB activation in dendritic cells and attenuates colitis in mice. Planta Med 2017; 83(6): 527-33.
[PMID: 27806407]
Periyasamy K, Baskaran K, Ilakkia A, Vanitha K, Selvaraj S, Sakthisekaran D. Antitumor efficacy of tangeretin by targeting the oxidative stress mediated on 7,12-dimethylbenz(a) anthracene-induced proliferative breast cancer in Sprague-Dawley rats. Cancer Chemother Pharmacol 2015; 75(2): 263-72.
[] [PMID: 25431347]
Li YR, Li S, Ho CT, et al. Tangeretin derivative, 5-acetyloxy-6,7,8,4′-tetramethoxyflavone induces G2/M arrest, apoptosis and autophagy in human non-small cell lung cancer cells in vitro and in vivo. Cancer Biol Ther 2016; 17(1): 48-64.
[] [PMID: 26569090]
Miyata Y, Tanaka H, Shimada A, et al. Regulation of adipocytokine secretion and adipocyte hypertrophy by polymethoxyflavonoids, nobiletin and tangeretin. Life Sci 2011; 88(13-14): 613-8.
[] [PMID: 21295043]
Tominari T, Hirata M, Matsumoto C, Inada M, Miyaura C. Polymethoxy flavonoids, nobiletin and tangeretin, prevent lipopolysaccharide-induced inflammatory bone loss in an experimental model for periodontitis. J Pharmacol Sci 2012; 119(4): 390-4.
[] [PMID: 22850615]
Huang H, Li L, Shi W, et al. The multifunctional effects of nobiletin and its metabolites in vivo and in vitro. Evid Based Complement Alternat Med 2016; 14.
Goulas V, Vicente AR, Manganaris GA. Structural diversity of anthocyanins in fruitsAnthocyanins: structure, biosynthesis and health benefits. NY, USA: Nova Science Publishers Inc 2012.
Pervaiz T, Songtao J, Faghihi F, et al. Naturally occurring anthocyanin, structure, functions and biosynthetic pathway in fruit plants. J Plant Biochem Physiol 2017; 5: 187.
Butelli E, Garcia-Lor A, Licciardello C, et al. Changes in anthocyanin production during domestication of citrus. Plant Physiol 2017; 173(4): 2225-42.
[] [PMID: 28196843]
Tsai T-C, Huang H-P, Chang Y-C, Wang CJ. An anthocyanin-rich extract from Hibiscus sabdariffa linnaeus inhibits N-nitrosomethylurea-induced leukemia in rats. J Agric Food Chem 2014; 62(7): 1572-80.
[] [PMID: 24471438]
Das AB, Goud VV, Das C. 9 - Phenolic compounds as functional ingredients in beverages. Value-added ingredients and enrichment of beverages.The Science of beverages series Book Copyright © 2019 Elsevier Inc. In: Grumezescu, AM. 2019; 14: pp. 285-323.
Adel Abdel-Moneim A, Ahmed OM, Fahim HI, et al. Ameliorative effects of quercetin and naringenin on diethylnitrosamine/2-acetyl aminoflourene-induced nephrotoxicity in male Wistar rats. Am J Biochem 2016; 6(5): 113-21.
Di Majo D, Giammanco M, La Guardia M, Tripoli E, Giammanco S, Finotti E. Flavanones in Citrus fruit: Structure-antioxidant activity relationships. Food Res Int 2005; 38: 1161-6.
Calabrò ML, Galtieri V, Cutroneo P, Tommasini S, Ficarra P, Ficarra R. Study of the extraction procedure by experimental design and validation of a LC method for determination of flavonoids in Citrus bergamia juice. J Pharm Biomed Anal 2004; 35(2): 349-63.
[] [PMID: 15063468]
Hirata T, Fujii M, Akita K, et al. Identification and physiological evaluation of the components from citrus fruits as potential drugs for anti-corpulence and anticancer. Bioorg Med Chem 2009; 17(1): 25-8.
[] [PMID: 19054677]
Theodoratou E, Kyle J, Cetnarskyj R, et al. Dietary flavonoids and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 2007; 16(4): 684-93.
[] [PMID: 17416758]
Saraf S, Ashawat MS, Saraf S. Flavonoids: A nutritional protection against oxidative and UV induced cellular damages. Pharmacogn Rev 2007; 1: 30-40.
Dhiman A, Nanda A, Ahmad S. A quest for staunch effects of flavonoids: Utopian protection against hepatic ailments. Arab J Chem 2016; 9: S1813-23.
Halliwell B. How to characterize an antioxidant: an update. Biochem Soc Symp 1995; 61: 73-101.
[] [PMID: 8660405]
Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001; 74(4): 418-25.
[] [PMID: 11566638]
Sichel G, Corsaro C, Scalia M, Di Bilio AJ, Bonomo RP. In vitro scavenger activity of some flavonoids and melanins against O2-. Free Radic Biol Med 1991; 11(1): 1-8.
[] [PMID: 1657731]
Tripoli E. guardia M La, S Giammanco, majo D, Di. Citrus flavonoids: Molecular structure, biological activity and nutritional properties: A review. Food Chem 2007; 104: 466-79.
Miyake Y, Shimoi K, Kumazawa S, Yamamoto K, Kinae N, Osawa T. Identification and antioxidant activity of flavonoid metabolites in plasma and urine of eriocitrin-treated rats. J Agric Food Chem 2000; 48(8): 3217-24.
[] [PMID: 10956094]
Madeswaran A, Umamaheswari M, Asokkumar K, et al. In-silico docking studies of lipoxygenase inhibitory activity of commercially available flavonoids. J Comput Method Mol Des 2011; 1: 65-72.
Manthey JA, Grohmann K, Guthrie N. Biological properties of citrus flavonoids pertaining to cancer and inflammation. Curr Med Chem 2001; 8(2): 135-53.
[] [PMID: 11172671]
Lv X, Zhao S, Ning Z, et al. Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health. Chem Cent J 2015; 9: 68.
[] [PMID: 26705419]
Sridharan B, Mehra Y, Ganesh RN, Viswanathan P. Regulation of urinary crystal inhibiting proteins and inflammatory genes by lemon peel extract and formulated citrus bioflavonoids on ethylene glycol induced urolithic rats. Food Chem Toxicol 2016; 94: 75-84.
[] [PMID: 27241030]
Wu L-H, Lin C, Lin H-Y, et al. Naringenin suppresses neuroinflammatory responses through inducing suppressor of cytokine signaling 3 expression. Mol Neurobiol 2016; 53(2): 1080-91.
[] [PMID: 25579382]
Vafeiadou K, Vauzour D, Lee HY, Rodriguez-Mateos A, Williams RJ, Spencer JP. The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury. Arch Biochem Biophys 2009; 484(1): 100-9.
[] [PMID: 19467635]
Choi JS, Yokozawa T, Oura H. Antihyperlipidemic effect of flavonoids from Prunus davidiana. J Nat Prod 1991; 54(1): 218-24.
[] [PMID: 2045817]
Lai C-S, Li S, Chai C-Y, et al. Inhibitory effect of citrus 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone on 12-O-tetradecanoylphorbol 13-acetate-induced skin inflammation and tumor promotion in mice. Carcinogenesis 2007; 28(12): 2581-8.
[] [PMID: 17962218]
Wu X, Song M, Wang M, et al. Chemopreventive effects of nobiletin and its colonic metabolites on colon carcinogenesis. Mol Nutr Food Res 2015; 59(12): 2383-94.
[] [PMID: 26445322]
Akachi T, Shiina Y, Ohishi Y, et al. Hepatoprotective effects of flavonoids from shekwasha (Citrus depressa) against D-galactosamine-induced liver injury in rats. J Nutr Sci Vitaminol (Tokyo) 2010; 56(1): 60-7.
[] [PMID: 20354348]
Kim WR, Brown RS Jr, Terrault NA, El-Serag H. Burden of liver disease in the United States: summary of a workshop. Hepatology 2002; 36(1): 227-42.
[] [PMID: 12085369]
Srivastava JK, Gupta S. Health promoting benefits of chamomile in the elderly population Complementary and Alternative Therapies and the Aging Population. Oxford, UK: Elsevier 2009.
Choe S-C, Kim H-S, Jeong T-S, Bok S-H, Park Y-B. Naringin has an antiatherogenic effect with the inhibition of intercellular adhesion molecule-1 in hypercholesterolemic rabbits. J Cardiovasc Pharmacol 2001; 38(6): 947-55.
[] [PMID: 11707699]
Alvarez MA, Debattista NB, Pappano NB. Antimicrobial activity and synergism of some substituted flavonoids. Folia Microbiol (Praha) 2008; 53(1): 23-8.
[] [PMID: 18481214]
Lee EY, Kim SH, Chang SN, et al. Efficacy of polymethoxylated flavonoids from Citrus depressa extract on alcohol-induced liver injury in mice. Biotechnol Bioproc E 2019; 24: 907-14.
Smith SC Jr, Collins A, Ferrari R, et al. World Heart Federation; American Heart Association; American College of Cardiology Foundation; European Heart Network; European Society of Cardiology. Our time: a call to save preventable death from cardiovascular disease (heart disease and stroke). J Am Coll Cardiol 2012; 60(22): 2343-8.
[] [PMID: 22995536]
Toh JY, Tan VM, Lim PC, Lim ST, Chong MF. Flavonoids from fruit and vegetables: a focus on cardiovascular risk factors. Curr Atheroscler Rep 2013; 15(12): 368.
[] [PMID: 24091782]
Yamada M, Tanabe F, Arai N, et al. Bioavailability of glucosyl hesperidin in rats. Biosci Biotechnol Biochem 2006; 70(6): 1386-94.
[] [PMID: 16794318]
Mink PJ, Scrafford CG, Barraj LM, et al. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr 2007; 85(3): 895-909.
[] [PMID: 17344514]
Li C, Schluesener H. Health-promoting effects of the citrus flavanone hesperidin. Crit Rev Food Sci Nutr 2017; 57(3): 613-31.
[] [PMID: 25675136]
Roohbakhsh A, Parhiz H, Soltani F, Rezaee R, Iranshahi M. Molecular mechanisms behind the biological effects of hesperidin and hesperetin for the prevention of cancer and cardiovascular diseases. Life Sci 2015; 124: 64-74.
[] [PMID: 25625242]
Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 1993; 342(8878): 1007-11.
[] [PMID: 8105262]
Naderi GA, Asgary S, Sarraf-Zadegan N, Shirvany H. Anti-oxidant effect of flavonoids on the susceptibility of LDL oxidation. Mol Cell Biochem 2003; 246(1-2): 193-6.
[] [PMID: 12841362]
Whitman SC, Kurowska EM, Manthey JA, Daugherty A. Nobiletin, a citrus flavonoid isolated from tangerines, selectively inhibits class A scavenger receptor-mediated metabolism of acetylated LDL by mouse macrophages. Atherosclerosis 2005; 178(1): 25-32.
[] [PMID: 15585197]
Wu M, Zhang H, Zhou C, Jia H, Ma Z, Zou Z. Identification of the chemical constituents in aqueous extract of Zhi-Qiao and evaluation of its antidepressant effect. Molecules 2015; 20(4): 6925-40.
[] [PMID: 25913931]
Hwang SL, Yen GC. Neuroprotective effects of the citrus flavanones against H2O2-induced cytotoxicity in PC12 cells. J Agric Food Chem 2008; 56(3): 859-64.
[] [PMID: 18189359]
Hwang SL, Yen GC. Modulation of Akt, JNK, and p38 activation is involved in citrus flavonoid-mediated cytoprotection of PC12 cells challenged by hydrogen peroxide. J Agric Food Chem 2009; 57(6): 2576-82.
[] [PMID: 19222219]
Ayaz M, Sadiq A, Junaid M, et al. Flavonoids as Prospective Neuroprotectants and Their Therapeutic Propensity in Aging Associated Neurological Disorders. Front Aging Neurosci 2019; 11: 155.
[] [PMID: 31293414]
Li Y-J, Zhang T, Tu J-X, et al. Tangeretin inhibits IL-1beta induced proliferation of rheumatoid synovial fibroblasts and the production of COX-2, PGE2 and MMPs via modulation of p38 MAPK/ERK/JNK pathways. Bangladesh J Pharmacol 2015; 10: 714-25.
Seki T, Kamiya T, Furukawa K, et al. Nobiletin-rich Citrus reticulata peels, a kampo medicine for Alzheimer’s disease: a case series. Geriatr Gerontol Int 2013; 13(1): 236-8.
[] [PMID: 23286569]
Okuyama S, Shimada N, Kaji M, et al. Heptamethoxyflavone, a citrus flavonoid, enhances brain-derived neurotrophic factor production and neurogenesis in the hippocampus following cerebral global ischemia in mice. Neurosci Lett 2012; 528(2): 190-5.
[] [PMID: 22985518]
Shih P-H, Chan Y-C, Liao J-W, Wang MF, Yen GC. Antioxidant and cognitive promotion effects of anthocyanin-rich mulberry (Morus atropurpurea L.) on senescence-accelerated mice and prevention of Alzheimer’s disease. J Nutr Biochem 2010; 21(7): 598-605.
[] [PMID: 19443193]
Kim HG, Ju MS, Shim JS, et al. Mulberry fruit protects dopaminergic neurons in toxin-induced Parkinson’s disease models. Br J Nutr 2010; 104(1): 8-16.
[] [PMID: 20187987]
Gutierres JM, Carvalho FB, Schetinger MRC, et al. Neuroprotective effect of anthocyanins on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia in rats. Int J Dev Neurosci 2014; 33: 88-97.
[] [PMID: 24374256]
Mandalari G, Bennett RN, Bisignano G, et al. Antimicrobial activity of flavonoids extracted from bergamot (Citrus bergamia Risso) peel, a byproduct of the essential oil industry. J Appl Microbiol 2007; 103(6): 2056-64.
[] [PMID: 18045389]
Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: promising natural compounds against viral infections. Arch Virol 2017; 162(9): 2539-51.
[] [PMID: 28547385]
Middleton E Jr, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000; 52(4): 673-751.
[PMID: 11121513]
De Meyer N, Haemers A, Mishra L, et al. 4′-Hydroxy-3-methoxyflavones with potent antipicornavirus activity. J Med Chem 1991; 34(2): 736-46.
[] [PMID: 1847431]
Manthey JA, Grohmann K, Montanari A, Ash K, Manthey CL. Polymethoxylated flavones derived from citrus suppress tumor necrosis factor-α expression by human monocytes. J Nat Prod 1999; 62(3): 441-4.
[] [PMID: 10096854]
Kawaguchi K, Kikuchi S, Hasunuma R, Maruyama H, Yoshikawa T, Kumazawa Y. A citrus flavonoid hesperidin suppresses infection-induced endotoxin shock in mice. Biol Pharm Bull 2004; 27(5): 679-83.
[] [PMID: 15133244]
Araruna MK, Brito SA, Morais-Braga MF, et al. Evaluation of antibiotic & antibiotic modifying activity of pilocarpine & rutin. Indian J Med Res 2012; 135: 252-4.
[PMID: 22446871]
Dubey S, Ganeshpurkar A, Bansal D, et al. Experimental studies on bioactive potential of rutin. Chron Young Sci 2013; 4: 153-7.
Dubey S, Ganeshpurkar A, Shrivastava A, Bansal D, Dubey N. Rutin exerts antiulcer effect by inhibiting the gastric proton pump. Indian J Pharmacol 2013; 45(4): 415-7.
[] [PMID: 24014928]
Johann S, Mendes BG, Missau FC, de Resende MA, Pizzolatti MG. Antifungal activity of five species of Polygala. Braz J Microbiol 2011; 42(3): 1065-75.
[] [PMID: 24031724]
Ganeshpurkar A, Saluja AK. The pharmacological potential of rutin. Saudi Pharm J 2017; 25(2): 149-64.
[] [PMID: 28344465]
Yap HY, Tee SZ, Wong MM, Chow SK, Peh SC, Teow SY. Pathogenic role of immune cells in rheumatoid arthritis: implications in clinical treatment and biomarker development. Cells 2018; 7(10): 161.
[] [PMID: 30304822]
Chow Y, Chi K-Y. The Role of inflammation in the pathogenesis of osteoarthritis. Mediators of Inflamm 2020; 19.
Lee JH, Kim GH. Evaluation of antioxidant and inhibitory activities for different subclasses flavonoids on enzymes for rheumatoid arthritis. J Food Sci 2010; 75(7): H212-7.
[] [PMID: 21535545]
Pannu A, Goyal RK, Ojha S, et al. Naringenin: A promising flavonoid for herbal treatment of rheumatoid arthritis and associated inflammatory disordersBioactive food as dietary interventions for arthritis and related inflammatory diseases. London: Elsevier 2019.
Ostrakhovitch EA, Afanas’ev IB. Oxidative stress in rheumatoid arthritis leukocytes: suppression by rutin and other antioxidants and chelators. Biochem Pharmacol 2001; 62(6): 743-6.
[] [PMID: 11551519]
Guardia T, Rotelli AE, Juarez AO, Pelzer LE. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Farmaco 2001; 56(9): 683-7.
[] [PMID: 11680812]
Han Y. Rutin has therapeutic effect on septic arthritis caused by Candida albicans. Int Immunopharmacol 2009; 9(2): 207-11.
[] [PMID: 19041425]
Horcajada MN, Sanchez C, Membrez Scalfo F, et al. Oleuropein or rutin consumption decreases the spontaneous development of osteoarthritis in the Hartley guinea pig. Osteoarthritis Cartilage 2015; 23(1): 94-102.
[] [PMID: 25219641]
Liu Z, Guo S, Dong Q. Nobiletin suppresses IL-21/IL-21 receptor-mediated inflammatory response in MH7A fibroblast-like synoviocytes (FLS): An implication in rheumatoid arthritis. Eur J Pharmacol 2020; 875.
[] [PMID: 31978425]
Liu J-w, Hao C-w, Wang Z-h, et al. Nobiletin inhibits expression of inflammatory mediators and regulates JNK/ERK/p38 MAPK and PI3K/Akt pathways in human osteoarthritic chondrocytes. Trop J Pharm Res 2016; 15: 535-45.
Lin N, Sato T, Takayama Y, et al. Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages. Biochem Pharmacol 2003; 65(12): 2065-71.
[] [PMID: 12787887]
Ho S-C, Kuo C-T. Hesperidin, nobiletin, and tangeretin are collectively responsible for the anti-neuroinflammatory capacity of tangerine peel (Citri reticulatae pericarpium). Food Chem Toxicol 2014; 71: 176-82.
[] [PMID: 24955543]
Li T, Zhang J, Zhu H, et al. Proteomic analysis of differentially expressed proteins involved in peel senescence in harvested mandarin fruit. Front Plant Sci 2016; 7: 725.
[] [PMID: 27303420]
Diabetes. World Health Organization 2020. Available at:
Shen W, Xu Y, Lu YH. Inhibitory effects of Citrus flavonoids on starch digestion and antihyperglycemic effects in HepG2 cells. J Agric Food Chem 2012; 60(38): 9609-19.
[] [PMID: 22958058]
Akiyama S, Katsumata S, Suzuki K, Ishimi Y, Wu J, Uehara M. Dietary hesperidin exerts hypoglycemic and hypolipidemic effects in streptozotocin-induced marginal type 1 diabetic rats. J Clin Biochem Nutr 2010; 46(1): 87-92.
[] [PMID: 20104270]
Annadurai T, Muralidharan AR, Joseph T, Hsu MJ, Thomas PA, Geraldine P. Antihyperglycemic and antioxidant effects of a flavanone, naringenin, in streptozotocin-nicotinamide-induced experimental diabetic rats. J Physiol Biochem 2012; 68(3): 307-18.
[] [PMID: 22234849]
Fallahi F, Roghani M, Moghadami S. Citrus flavonoid naringenin improves aortic reactivity in streptozotocin-diabetic rats. Indian J Pharmacol 2012; 44(3): 382-6.
[] [PMID: 22701251]
Sundaram R, Nandhakumar E, Haseena Banu H. Hesperidin, a citrus flavonoid ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Toxicol Mech Methods 2019; 29(9): 644-53.
[] [PMID: 31345080]
Srirangam R, Majumdar S. Passive asymmetric transport of hesperetin across isolated rabbit cornea. Int J Pharm 2010; 394(1-2): 60-7.
[] [PMID: 20438820]
Sharma M, Akhtar N, Sambhav K, Shete G, Bansal AK, Sharma SS. Emerging potential of citrus flavanones as an antioxidant in diabetes and its complications. Curr Top Med Chem 2015; 15(2): 187-95.
[] [PMID: 25547100]
Judy W, Stogsdill W, Judy D, et al. Efficacy of Diabetinol™ on glycemic control in insulin resistant hamsters and subjects with impaired fasting glucose-a pilot study. J Funct Foods 2010; 2: 171-8.
Sharma AK, Bharti S, Ojha S, et al. Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes. Br J Nutr 2011; 106(11): 1713-23.
[] [PMID: 21736771]
Singh Z, Sharma S, Kaur A. Ameliorative nature of flavonoid naringin: A comprehensive review of antitoxic effects. Trends Phytochem Res 2019; 3: 67-76.
Pari L, Srinivasan S. Antihyperglycemic effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. Biomed Pharmacother 2010; 64(7): 477-81.
[] [PMID: 20362409]
Jain D, Bansal MK, Dalvi R, Upganlawar A, Somani R. Protective effect of diosmin against diabetic neuropathy in experimental rats. J Integr Med 2014; 12(1): 35-41.
[] [PMID: 24461593]
Stewart LK, Wang Z, Ribnicky D, Soileau JL, Cefalu WT, Gettys TW. Failure of dietary quercetin to alter the temporal progression of insulin resistance among tissues of C57BL/6J mice during the development of diet-induced obesity. Diabetologia 2009; 52(3): 514-23.
[] [PMID: 19142628]
Koolaji N, Shammugasamy B, Schindeler A, et al. Citrus peel flavonoids as potential cancer prevention agents. Curr Dev Nutr 2020; 4(5)
Park KI, Park HS, Nagappan A, et al. Induction of the cell cycle arrest and apoptosis by flavonoids isolated from Korean Citrus aurantium L. in non-small-cell lung cancer cells. Food Chem 2012; 135(4): 2728-35.
[] [PMID: 22980865]
Nagappan A, Lee HJ, Saralamma VVG, et al. Flavonoids isolated from Citrus platymamma induced G2/M cell cycle arrest and apoptosis in A549 human lung cancer cells. Oncol Lett 2016; 12(2): 1394-402.
[] [PMID: 27446443]
Kim D-I, Lee S-J, Lee S-B, Park K, Kim WJ, Moon SK. Requirement for Ras/Raf/ERK pathway in naringin-induced G1-cell-cycle arrest via p21WAF1 expression. Carcinogenesis 2008; 29(9): 1701-9.
[] [PMID: 18296682]
Cayrol C, Knibiehler M, Ducommun B. p21 binding to PCNA causes G1 and G2 cell cycle arrest in p53-deficient cells. Oncogene 1998; 16(3): 311-20.
[] [PMID: 9467956]
Iwase Y, Takemura Y, Ju-ichi M, et al. Cancer chemopreventive activity of 3,5,6,7,8,3′,4′-heptamethoxyflavone from the peel of citrus plants. Cancer Lett 2001; 163(1): 7-9.
[] [PMID: 11163102]
Mori A, Nishino C, Enoki N, et al. Cytotoxicity of plant flavonoids against HeLa cells. Phytochemistry 1988; 27: 1017-20.
Hosokawa N, Hirayoshi K, Nakai A, et al. Flavonoids inhibit the expression of heat shock proteins. Cell Struct Funct 1990; 15(6): 393-401.
[] [PMID: 2085852]
Scambia G, Ranelletti FO, Panici PB, et al. Inhibitory effect of quercetin on OVCA 433 cells and presence of type II oestrogen binding sites in primary ovarian tumours and cultured cells. Br J Cancer 1990; 62(6): 942-6.
[] [PMID: 2257224]
Huang YT, Hwang JJ, Lee PP, et al. Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on cell growth and metastasis-associated properties in A431 cells overexpressing epidermal growth factor receptor. Br J Pharmacol 1999; 128(5): 999-1010.
[] [PMID: 10556937]
Castillo MH, Perkins E, Campbell JH, et al. The effects of the bioflavonoid quercetin on squamous cell carcinoma of head and neck origin. Am J Surg 1989; 158(4): 351-5.
[] [PMID: 2802040]
Lee L-T, Huang Y-T, Hwang J-J, et al. Transinactivation of the epidermal growth factor receptor tyrosine kinase and focal adhesion kinase phosphorylation by dietary flavonoids: effect on invasive potential of human carcinoma cells. Biochem Pharmacol 2004; 67(11): 2103-14.
[] [PMID: 15135307]
Liao C-Y, Lee C-C, Tsai C-C, et al. Novel investigations of flavonoids as chemopreventive agents for hepatocellular carcinoma. BioMed Res Int 2015; 2015
[] [PMID: 26858957]
Alonso-Castro AJ, Domínguez F, García-Carrancá A. Rutin exerts antitumor effects on nude mice bearing SW480 tumor. Arch Med Res 2013; 44(5): 346-51.
[] [PMID: 23867787]
Chen H, Miao Q, Geng M, et al. Anti-tumor effect of rutin on human neuroblastoma cell lines through inducing G2/M cell cycle arrest and promoting apoptosis. ScientificWorldJournal 2013; 2013
[] [PMID: 24459422]
Araújo JR, Gonçalves P, Martel F. Chemopreventive effect of dietary polyphenols in colorectal cancer cell lines. Nutr Res 2011; 31(2): 77-87.
[] [PMID: 21419311]
Kandaswami C, Perkins E, Soloniuk DS, Drzewiecki G, Middleton E Jr. Antiproliferative effects of citrus flavonoids on a human squamous cell carcinoma in vitro. Cancer Lett 1991; 56(2): 147-52.
[] [PMID: 1998943]
Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M. Antiproliferative activity of flavonoids on several cancer cell lines. Biosci Biotechnol Biochem 1999; 63(5): 896-9.
[] [PMID: 10380632]
Surichan S, Androutsopoulos VP, Sifakis S, et al. Bioactivation of the citrus flavonoid nobiletin by CYP1 enzymes in MCF7 breast adenocarcinoma cells. Food Chem Toxicol 2012; 50(9): 3320-8.
[] [PMID: 22743247]
Rawson NE, Ho C-T. LI S. Efficacious anti-cancer property of flavonoids from citrus peels. Food Sci Hum Wellness 2014; 3: 104-9.
Suzuki R, Kohno H, Murakami A, et al. Citrus nobiletin inhibits azoxymethane-induced large bowel carcinogenesis in rats. Biofactors 2004; 22(1-4): 111-4.
[] [PMID: 15751122]
Kunimasa K, Ikekita M, Sato M, et al. Nobiletin, a citrus polymethoxyflavonoid, suppresses multiple angiogenesis-related endothelial cell functions and angiogenesis in vivo. Cancer Sci 2010; 101(11): 2462-9.
[] [PMID: 20670297]
Yoshimizu N, Otani Y, Saikawa Y, et al. Anti-tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: antiproliferative effects, induction of apoptosis and cell cycle deregulation. Aliment Pharmacol Ther 2004; 20(Suppl. 1): 95-101.
[] [PMID: 15298613]
Tundis R, Acquaviva R, Bonesi M, et al. Citrus FlavanonesHandbook of dietary phytochemicals. Springer Nature Singapore Pte Ltd. 2020; pp. 1-30.
Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Sci World J 2013; 16.
Wyss-Coray T. Ageing, neurodegeneration and brain rejuvenation. Nature 2016; 539(7628): 180-6.
[] [PMID: 27830812]
Letenneur L, Proust-Lima C, Le Gouge A, Dartigues JF, Barberger-Gateau P. Flavonoid intake and cognitive decline over a 10-year period. Am J Epidemiol 2007; 165(12): 1364-71.
[] [PMID: 17369607]
Kesse-Guyot E, Fezeu L, Andreeva VA, et al. Total and specific polyphenol intakes in midlife are associated with cognitive function measured 13 years later. J Nutr 2012; 142(1): 76-83.
[] [PMID: 22090468]
Manach C, Williamson G, Morand C, Scalbert A, Rémésy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 2005; 81(1)(Suppl.): 230S-42S.
[] [PMID: 15640486]
Hwang SJ, Kim YW, Park Y, Lee HJ, Kim KW. Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells. Inflamm Res 2014; 63(1): 81-90.
[] [PMID: 24127072]
Antunes MS, Goes ATR, Boeira SP, Prigol M, Jesse CR. Protective effect of hesperidin in a model of Parkinson’s disease induced by 6-hydroxydopamine in aged mice. Nutrition 2014; 30(11-12): 1415-22.
[] [PMID: 25280422]
Heo HJ, Kim DO, Shin SC, Kim MJ, Kim BG, Shin DH. Effect of antioxidant flavanone, naringenin, from Citrus junoson neuroprotection. J Agric Food Chem 2004; 52(6): 1520-5.
[] [PMID: 15030205]
Prakash A, Shur B, Kumar A. Naringin protects memory impairment and mitochondrial oxidative damage against aluminum-induced neurotoxicity in rats. Int J Neurosci 2013; 123(9): 636-45.
[] [PMID: 23510099]
Khan MM, Raza SS, Javed H, et al. Rutin protects dopaminergic neurons from oxidative stress in an animal model of Parkinson’s disease. Neurotox Res 2012; 22(1): 1-15.
[] [PMID: 22194158]
Onozuka H, Nakajima A, Matsuzaki K, et al. Nobiletin, a citrus flavonoid, improves memory impairment and Abeta pathology in a transgenic mouse model of Alzheimer’s disease. J Pharmacol Exp Ther 2008; 326(3): 739-44.
[] [PMID: 18544674]
Nakajima A, Aoyama Y, Nguyen TT, et al. Nobiletin, a citrus flavonoid, ameliorates cognitive impairment, oxidative burden, and hyperphosphorylation of tau in senescence-accelerated mouse. Behav Brain Res 2013; 250: 351-60.
[] [PMID: 23714077]
Nakajima A, Ohizumi Y. Potential benefits of nobiletin, a citrus flavonoid, against Alzheimer’s disease and Parkinson’s disease. Int J Mol Sci 2019; 20(14): 3380.
[] [PMID: 31295812]
Yasuda N, Ishii T, Oyama D, et al. Neuroprotective effect of nobiletin on cerebral ischemia-reperfusion injury in transient middle cerebral artery-occluded rats. Brain Res 2014; 1559: 46-54.
[] [PMID: 24534366]
Matsuzaki K, Yamakuni T, Hashimoto M, et al. Nobiletin restoring beta-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer’s disease model rats. Neurosci Lett 2006; 400(3): 230-4.
[] [PMID: 16581185]
Yang JS, Wu XH, Yu HG, Teng LS. Tangeretin inhibits neurodegeneration and attenuates inflammatory responses and behavioural deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease dementia in rats. Inflammopharmacology 2017; 25(4): 471-84.
[] [PMID: 28577132]
Braidy N, Behzad S, Habtemariam S, et al. Neuroprotective effects of citrus fruit-derived flavonoids, nobiletin and tangeretin in Alzheimer’s and Parkinson’s disease. CNS Neurol Disord Drug Targets 2017; 16(4): 387-97.
[] [PMID: 28474543]
Testai L, Calderone V. Nutraceutical value of citrus flavanones and their implications in cardiovascular disease. Nutrients 2017; 9(5): 502.
[] [PMID: 28509871]
Hollman PC, Geelen A, Kromhout D. Dietary flavonol intake may lower stroke risk in men and women. J Nutr 2010; 140(3): 600-4.
[] [PMID: 20089788]
Gan Y, Tong X, Li L, et al. Consumption of fruit and vegetable and risk of coronary heart disease: a meta-analysis of prospective cohort studies. Int J Cardiol 2015; 183: 129-37.
[] [PMID: 25662075]
Orhan IE, Nabavi SF, Daglia M, Tenore GC, Mansouri K, Nabavi SM. Naringenin and atherosclerosis: a review of literature. Curr Pharm Biotechnol 2015; 16(3): 245-51.
[] [PMID: 25483717]
Adebiyi OA, Adebiyi OO, Owira PM. Naringin reduces hyperglycemia-induced cardiac fibrosis by relieving oxidative stress. PLoS One 11(3)e0149890
Adil M, Kandhare AD, Ghosh P, Venkata S, Raygude KS, Bodhankar SL. Ameliorative effect of naringin in acetaminophen-induced hepatic and renal toxicity in laboratory rats: role of FXR and KIM-1. Ren Fail 2016; 38(6): 1007-20.
[] [PMID: 27050864]
Kwatra M, Kumar V, Jangra A, et al. Ameliorative effect of naringin against doxorubicin-induced acute cardiac toxicity in rats. Pharm Biol 2016; 54(4): 637-47.
[] [PMID: 26471226]
Demonty I, Lin Y, Zebregs YE, et al. The citrus flavonoids hesperidin and naringin do not affect serum cholesterol in moderately hypercholesterolemic men and women. J Nutr 2010; 140(9): 1615-20.
[] [PMID: 20660284]
Sundaram R, Shanthi P, Sachdanandam P. Tangeretin, a polymethoxylated flavone, modulates lipid homeostasis and decreases oxidative stress by inhibiting NF-κB activation and proinflammatory cytokines in cardiac tissue of streptozotocin-induced diabetic rats. J Funct Foods 2015; 2015: 315-33.
Sangpheak W, Kicuntod J, Schuster R, et al. Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin. Beilstein J Org Chem 2015; 11: 2763-73.
[] [PMID: 26877798]
Kuntić V, Brborić J, Holclajtner-Antunović I, Uskoković-Marković S. Evaluating the bioactive effects of flavonoid hesperidin-a new literature data survey. Vojnosanit Pregl 2014; 71(1): 60-5.
[] [PMID: 24516992]
Salehi B, Fokou PVT, Sharifi-Rad M, et al. The therapeutic potential of naringenin: A review of clinical trials. Pharmaceuticals (Basel) 2019; 12(1): 1-18.
[] [PMID: 30634637]
Seo E-K, Silva GL, Chai H-B, et al. Cytotoxic prenylated flavanones from Monotes engleri. Phytochemistry 1997; 45(3): 509-15.
[] [PMID: 9190085]
Wang YC, Huang KM. In vitro anti-inflammatory effect of apigenin in the Helicobacter pylori-infected gastric adenocarcinoma cells. Food Chem Toxicol 2013; 53: 376-83.
[] [PMID: 23266501]
Ozçelik B, Kartal M, Orhan I. Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids. Pharm Biol 2011; 49(4): 396-402.
[] [PMID: 21391841]
Yan X, Qi M, Li P, Zhan Y, Shao H. Apigenin in cancer therapy: anti-cancer effects and mechanisms of action. Cell Biosci 2017; 7: 50.
[] [PMID: 29034071]
Xu L, Zhang Y, Tian K, et al. Apigenin suppresses PD-L1 expression in melanoma and host dendritic cells to elicit synergistic therapeutic effects. J Exp Clin Cancer Res 2018; 37(1): 261.
[] [PMID: 30373602]
Sudhakaran M, Sardesai S, Doseff AI. Flavonoids: New Frontier for Immuno-Regulation and Breast Cancer Control. Antioxidants 2019; 8(4)
[] [PMID: 30995775]
Kakar M, Amin MU, Alghamdi S, et al. Antimicrobial, cytotoxic, and antioxidant potential of a novel flavone “6,7,4′-trimethyl flavone” isolated from Wulfenia amherstiana. In: Evidence-Based Complementary and Alternative Medicine. In: 2020; p. 12.
Javed H, Khan MM, Ahmad A, et al. Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type. Neuroscience 2012; 210(17): 340-52.
[] [PMID: 22441036]
Richetti SK, Blank M, Capiotti KM, et al. Quercetin and rutin prevent scopolamine-induced memory impairment in zebrafish. Behav Brain Res 2011; 217(1): 10-5.
[] [PMID: 20888863]
Bakir S, Catalkaya G, Ceylan FD, et al. Role of dietary antioxidants in neurodegenerative diseases: Where are we Standing? Curr Pharm Des 2020; 26(7): 714-29.
[] [PMID: 31914905]

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