The effects of Allium cepa L. (onion) and its active constituents on metabolic syndrome: A review

Document Type : Review Article

Authors

1 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

4 Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

5 3 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Metabolic syndrome as a clustering disorder includes excess abdominal fat distribution, abnormal insulin and glucose metabolism, disturbed blood lipids, pro-inflammatory state, and hypertension. Regarding to the adverse effects of synthetic medicines, the identification of appropriate healthcare approaches, such as herbal medicines, with fewer side effects is more favorable. Allium cepa L. (onion) is a culinary and medicinal herb belonging to the family of Amaryllidaceae. Flavonoids such as quercetin and kaempferol, alk(en)yl cysteine sulfoxides including S-methyl cysteine sulfoxide and S-propyl cysteine sulfoxide, cycloalliin, thiosulfinates, and sulfides are main compounds existing in the plant. A. cepa and its pharmacologically active constituents display broad-spectrum activities including anti-oxidant, anti-inflammatory, lipid-modifying, anti-obesity, antihypertensive, and antidiabetic effects. Our objective in this review was to find out the role of A. cepa and its bioactive phytochemicals as cardiovascular protective agents in different metabolic syndrome risk factors, including hyperlipidemia, high blood glucose, obesity, and hypertension.

Keywords


1. Samson SL, Garber AJ. Metabolic syndrome. Endocrinol Metab Clin North Am 2014; 43:1-23.
2. Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol 2010; 56:1113-1132.
3. GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392:1736-1788.
4. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112:2735-2752.
5. Ekor M. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol 2014; 4:177.
6. Teshika JD, Zakariyyah AM, Zaynab T, Zengin G, Rengasamy KR, Pandian SK, et al. Traditional and modern uses of onion bulb (Allium cepa L.): a systematic review. Crit Rev Food Sci Nutr 2019; 59:S39-S70.
7. Upadhyay RK. Nutraceutical, pharmaceutical and therapeutic uses of Allium cepa: a review. Int J Green Pharm 2016; 10:S46-S64.
8. Ahmed N, Mahmood A, Ashraf A, Bano A, Tahir SS, Mahmood A. Ethnopharmacological relevance of indigenous medicinal plants from district Bahawalnagar, Punjab, Pakistan. J Ethnopharmacol 2015; 175:109-123.
9. Josabad Alonso-Castro A, Jose Maldonado-Miranda J, Zarate-Martinez A, Jacobo-Salcedo Mdel R, Fernandez-Galicia C, Alejandro Figueroa-Zuniga L, et al. Medicinal plants used in the Huasteca Potosina, Mexico. J Ethnopharmacol 2012; 143:292-298.
10. Ayyanar M, Ignacimuthu S. Ethnobotanical survey of medicinal plants commonly used by Kani tribals in Tirunelveli hills of Western Ghats, India. J Ethnopharmacol 2011; 134:851-864.
11. Prakash D, Singh BN, Upadhyay G. Anti-oxidant and free radical scavenging activities of phenols from onion (Allium cepa). Food Chem 2007; 102:1389-1393.
12. Breu W. Allium cepa L. (onion) Part 1: Chemistry and analysis. Phytomedicine 1996; 3:293-306.
13. Lee B, Jung JH, Kim HS. Assessment of red onion on anti-oxidant activity in rat. Food ChemToxicol 2012; 50:3912-3919.
14. Ren KW, Li YH, Wu G, Ren JZ, Lu HB, Li ZM, et al. Quercetin nanoparticles display antitumor activity via proliferation inhibition and apoptosis induction in liver cancer cells. Int J Oncol 2017; 50:1299-1311.
15. Wang R, Yang L, Li S, Ye D, Yang L, Liu Q, et al. Quercetin inhibits breast cancer stem cells via downregulation of aldehyde dehydrogenase 1A1 (ALDH1A1), chemokine receptor type 4 (CXCR4), mucin 1 (MUC1), and epithelial cell adhesion molecule (EpCAM). Med Sci Monit 2018; 24:412-420.
16. Draelos ZD. The ability of onion extract gel to improve the cosmetic appearance of postsurgical scars. J Cosmet Dermatol 2008; 7:101-104.
17. Peng Z, Gong X, Yang Y, Huang L, Zhang Q, Zhang P, et al. Hepatoprotective effect of quercetin against LPS/d-GalN induced acute liver injury in mice by inhibiting the IKK/NF-kappaB and MAPK signal pathways. Int Immunopharmacol 2017; 52:281-289.
18. Ro JY, Ryu JH, Park HJ, Cho HJ. Onion (Allium cepa L.) peel extract has anti-platelet effects in rat platelets. Springerplus 2015; 4:17.
19. Lee SM, Moon J, Chung JH, Cha YJ, Shin MJ. Effect of quercetin-rich onion peel extracts on arterial thrombosis in rats. Food Chem Toxicol 2013; 57:99-105.
20. Kumar VP, Venkatesh YP. Alleviation of cyclophosphamide-induced immunosuppression in Wistar rats by onion lectin (Allium cepa agglutinin). J Ethnopharmacol 2016; 186:280-288.
21. Khajah MA, Orabi KY, Hawai S, Sary HG, El-Hashim AZ. Onion bulb extract reduces colitis severity in mice via modulation of colonic inflammatory pathways and the apoptotic machinery. J Ethnopharmacol 2019; 241:112008.
22. Reddy RRL, Srinivasan K. Dietary fenugreek and onion attenuate cholesterol gallstone formation in lithogenic diet-fed mice. Int J Exp Pathol 2011; 92:308-319.
23. Singh T, Goel RK. Neuroprotective effect of Allium cepa L. in aluminium chloride induced neurotoxicity. Neurotoxicology 2015; 49:1-7.
24. Kim JH. Antibacterial action of onion (Allium cepa L.) extracts against oral pathogenic bacteria. J Nihon Univ Sch Dent 1997; 39:136-141.
25. Shams-Ghahfarokhi M, Shokoohamiri MR, Amirrajab N, Moghadasi B, Ghajari A, Zeini F, et al. In vitro antifungal activities of Allium cepa, Allium sativum and ketoconazole against some pathogenic yeasts and dermatophytes. Fitoterapia 2006; 77:321-323.
26. Kaiser P, Youssouf MS, Tasduq SA, Singh S, Sharma SC, Singh GD, et al. Anti-allergic effects of herbal product from Allium cepa (bulb). J Med Food 2009; 12:374-382.
27. Oliveira TT, Campos KM, Cerqueira-Lima AT, Cana Brasil Carneiro T, da Silva Velozo E, Ribeiro Melo IC, et al. Potential therapeutic effect of Allium cepa L. and quercetin in a murine model of Blomia tropicalis induced asthma. Daru 2015; 23:18.
28. Haidari F, Rashidi MR, Keshavarz SA, Mahboob SA, Eshraghian MR, Shahi MM. Effects of onion on serum uric acid levels and hepatic xanthine dehydrogenase/xanthine oxidase activities in hyperuricemic rats. Pak J Biol Sci 2008; 11:1779-1784.
29. Samad N, Saleem A. Administration of Allium cepa L. bulb attenuates stress-produced anxiety and depression and improves memory in male mice. Metab Brain Dis 2018; 33:271-281.
30. Jain S, Buttar HS, Chintameneni M, Kaur G. Prevention of cardiovascular diseases with anti-inflammatory and anti- oxidant nutraceuticals and herbal products: An overview of pre-clinical and clinical studies. Recent Pat Inflamm Allergy Drug Discov 2018; 12:145-157.
31. Tang GY, Meng X, Li Y, Zhao CN, Liu Q, Li HB. Effects of vegetables on cardiovascular diseases and related mechanisms. Nutrients 2017; 9:857.
32. Thomson M, Alnaqeeb MA, Bordia T, Al-Hassan JM, Afzal M, Ali M. Effects of aqueous extract of onion on the liver and lung of rats. J Ethnopharmacol 1998; 61:91-99.
33. Ebrahimi-Mamaghani M, Saghafi-Asl M, Pirouzpanah S, Asghari-Jafarabadi M. Effects of raw red onion consumption on metabolic features in overweight or obese women with polycystic ovary syndrome: A randomized controlled clinical trial. J Obstet Gynaecol Res 2014; 40:1067-1076.
34. Kim J, Cha YJ, Lee KH, Park E. Effect of onion peel extract supplementation on the lipid profile and antioxidative status of healthy young women: a randomized, placebo-controlled, double-blind, crossover trial. Nutr Res Practice 2013; 7:373-379.
35. Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care 2013; 40:195-211.
36. Srinivasan K. Dietary spices as beneficial modulators of lipid profile in conditions of metabolic disorders and diseases. Food  Funct 2013; 4:503-521.
37. Han SY, Hu Y, Anno T, Yanagita T. S-propyl cysteine reduces the secretion of apolipoprotein B100 and triacylglycerol by HepG2 cells. Nutrition 2002; 18:505-509.
38. Lee YG, Cho J, Hwang EJ, Jeon T, Moon J. Glu-Phe from onion (Allium Cepa L.) attenuates lipogenesis in hepatocytes. Biosci Biotechnol Biochem 2017; 81:1409-1416.
39. Sun L, Li E, Wang F, Wang T, Qin Z, Niu S, et al. Quercetin increases macrophage cholesterol efflux to inhibit foam cell formation through activating PPARγ-ABCA1 pathway. Int J Clin Exp Pathol 2015; 8:10854-10860.
40. Arteaga E, Villaseca P, Rojas A, Marshall G, Bianchi M. Phytoestrogens possess a weak anti-oxidant activity on low density lipoprotein in contrast to the flavonoid quercetin in vitro in postmenopausal women. Climacteric 2004; 7:397-403.
41. Bordia A, Arora SK, Kothari LK, Jain KC, Rathore BS, Rathore AS, et al. The protective action of essential oils of onion and garlic in cholesterol-fed rabbits. Atherosclerosis 1975; 22:103-109.
42. Vidyavati HG, Manjunatha H, Hemavathy J, Srinivasan K. Hypolipidemic and anti-oxidant efficacy of dehydrated onion in experimental rats. J Food SciTechnol 2010; 47:55-60.
43. Kang HJ, Pichiah BT, Abinaya RV, Sohn HS, Cha YS. Hypocholesterolemic effect of quercetin-rich onion peel extract in C57BL/6J mice fed with high cholesterol diet. Food Sci Biotechnol 2016; 25:855-860.
44. Jaiswal N, Rizvi SI. Onion extract (Allium cepa L.), quercetin and catechin up-regulate paraoxonase 1 activity with concomitant protection against low-density lipoprotein oxidation in male Wistar rats subjected to oxidative stress. J Sci Food Agr 2014; 94:2752-2757.
45. De Boer VCJ, Van Schothorst EM, Dihal AA, Van Der Woude H, Arts ICW, Rietjens IMCM, et al. Chronic quercetin exposure affects fatty acid catabolism in rat lung. Life Sci 2006; 63:2847-2858.
46. Yanagita T, Han S, Wang YM, Tsuruta Y, Anno T. Cycloalliin, a cyclic sulfur imino acid, reduces serum triacylglycerol in rats. Nutrition 2003; 19:140-143.
47. Kumari K, Augusti KT. Lipid lowering effect of S-methyl cysteine sulfoxide from Allium cepa Linn in high cholesterol diet fed rats. J Ethnopharmacol 2007; 109:367-371.
48. Emamat H, Foroughi F, Eini-Zinab H, Hekmatdoost A. The effects of onion consumption on prevention of nonalcoholic fatty liver disease. Indian J Clin Biochem 2018; 33:75-80.
49. Emamat H, Foroughi F, Eini-Zinab H, Taghizadeh M, Rismanchi M, Hekmatdoost A. The effects of onion consumption on treatment of metabolic, histologic, and inflammatory features of nonalcoholic fatty liver disease. J Diabetes Metab Dis 2016; 15:25.
50. Lu TM, Chiu HF, Shen YC, Chung CC, Venkatakrishnan K, Wang CK. Hypocholesterolemic efficacy of quercetin rich onion juice in healthy mild hypercholesterolemic adults: A pilot study. Plant Foods Human Nutr 2015; 70:395-400.
51. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet 2017; 390:2627-2642.
52. Joo JK, Lee KS. Pharmacotherapy for obesity. J Menopausal Med 2014; 20:90-96.
53. Marrelli M, Amodeo V, Statti G, Conforti F. Biological properties and bioactive components of Allium cepa L.: Focus on potential benefits in the treatment of obesity and related comorbidities. Molecules 2018; 24:119.
54. Williams DJ, Edwards D, Hamernig I, Jian L, James AP, Johnson SK, et al. Vegetables containing phytochemicals with potential anti-obesity properties: A review. Food Res Int 2013; 52:323-333.
55. Funakoshi T, Kanzaki N, Otsuka Y, Izumo T, Shibata H, Machida S. Quercetin inhibits adipogenesis of muscle progenitor cells in vitro. Biochem Biophys Rep 2018; 13:39-44.
56. Bae CR, Park YK, Cha YS. Quercetin-rich onion peel extract suppresses adipogenesis by down-regulating adipogenic transcription factors and gene expression in 3T3-L1 adipocytes. J Sci Food Agr 2014; 94:2655-2660.
57. Seo MJ, Lee YJ, Hwang JH, Kim KJ, Lee BY. The inhibitory effects of quercetin on obesity and obesity-induced inflammation by regulation of MAPK signaling. J Nutr Biochem 2015; 26:1308-1316.
58. Eseberri I, Miranda J, Lasa A, Churruca I, Portillo MP. Doses of quercetin in the range of serum concentrations exert delipidating effects in 3t3-l1 preadipocytes by acting on different stages of adipogenesis, but not in mature adipocytes. Oxid Med Cell Longev 2015; 2015.
59. Yoshinari O, Shiojima Y, Igarashi K. Anti-Obesity Effects of Onion Extract in Zucker Diabetic Fatty Rats. Nutrients 2012; 4:1518-1526.
60. Forney LA, Lenard NR, Stewart LK, Henagan TM. Dietary quercetin attenuates adipose tissue expansion and inflammation and alters adipocyte morphology in a tissue-specific manner. Int J Mol Sci 2018; 19:895.
61. Pangeni R, Kang SW, Oak M, Park EY, Park JW. Oral delivery of quercetin in oil-in-water nanoemulsion: In vitro characterization and in vivo anti-obesity efficacy in mice. J Funct Foods 2017; 38:571-581.
62. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009; 360:1509-1517.
63. Lee SG, Parks JS, Kang HW. Quercetin, a functional compound of onion peel, remodels white adipocytes to brown-like adipocytes. J Nutr Biochem 2017; 42:62-71.
64. Lee JS, Cha YJ, Lee KH, Yim JE. Onion peel extract reduces the percentage of body fat in overweight and obese subjects: a 12-week, randomized, double-blind, placebo-controlled study. Nutr ResPractice 2016; 10:175-181.
65. Kim KA, Yim JE. The effect of onion peel extract on inflammatory mediators in korean overweight and obese women. Clin Nutr Res 2016; 5:261-269.
66. Blacher J, Levy BI, Mourad JJ, Safar ME, Bakris G. From epidemiological transition to modern cardiovascular epidemiology: hypertension in the 21st century. Lancet 2016; 388:530-532.
67. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 2016; 387:957-967.
68. Aslam M, Ahmad M, Mobasher F. Efficacy and tolerability of antihypertensive drugs in diabetic and nondiabetic patients. J Pharm Bioallied Sci 2017; 9:56-65.
69. Chen ZY, Peng C, Jiao R, Wong YM, Yang N, Huang Y. Anti-hypertensive nutraceuticals and functional foods. J Agr Food Chem 2009; 57:4485-4499.
70. Oboh G, Ademiluyi AO, Agunloye OM, Ademosun AO, Ogunsakin BG. Inhibitory effect of garlic, purple onion, and white onion on key enzymes linked with type 2 diabetes and hypertension. J Diet Suppl 2018:1-14.
71. Muhammad SA, Fatima N. In silico analysis and molecular docking studies of potential angiotensin-converting enzyme inhibitor using quercetin glycosides. Pharmacogn Mag 2015; 11:S123-S126.
72. Monori-Kiss A, Monos E, Nádasy GL. Quantitative analysis of vasodilatory action of quercetin on intramural coronary resistance arteries of the rat in vitro. PLoS ONE 2014; 9 :e105587.
73. Lodi F, Jimenez R, Moreno L, Kroon PA, Needs PW, Hughes DA, et al. Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasorelaxant effects in rat aorta. Atherosclerosis 2009; 204:34-39.
74. Brankovic S, Radenkovic M, Kitic D, Veljkovic S, Ivetic V, Pavlovic D, et al. Comparison of the hypotensive and bradycardic activity of ginkgo, garlic, and onion extracts. Clin Exp Hypertension 2011; 33:95-99.
75. Naseri MKG, Arabian M, Badavi M, Ahangarpour A. Vasorelaxant and hypotensive effects of Allium cepa peel hydroalcoholic extract in rat. Pakistan J Biol Sci 2008; 11:1569-1575.
76. Kawamoto E, Sakai Y, Okamura Y, Yamamoto Y. Effects of boiling on the antihypertensive and anti-oxidant activities of onion. J Nutr Sci Vitaminol 2004; 50:171-176.
77. Sakai Y, Murakami T, Yamamoto Y. Antihypertensive effects of onion on NO synthase inhibitor-induced hypertensive rats and spontaneously hypertensive rats. Biosci Biotechnol Biochem 2003; 67:1305-1311.
78. Kivirantat J, Huovinen K, Seppänen‐Laakso T, Hiltunen R, Karppanen H, Kilpeläinen M. Effects of onion and garlic extracts on spontaneously hypertensive rats. Phytother Res 1989; 3:132-135.
79. Brull V, Burak C, Stoffel-Wagner B, Wolffram S, Nickenig G, Muller C, et al. Acute intake of quercetin from onion skin extract does not influence postprandial blood pressure and endothelial function in overweight-to-obese adults with hypertension: a randomized, double-blind, placebo-controlled, crossover trial. Eur J Nutr 2017; 56:1347-1357.
80. Perez A, Gonzalez-Manzano S, Jimenez R, Perez-Abud R, Haro JM, Osuna A, et al. The flavonoid quercetin induces acute vasodilator effects in healthy volunteers: Correlation with beta-glucuronidase activity. Pharmacol Res 2014; 89:11-18.
81. Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T. Quercetin reduces blood pressure in hypertensive subjects. J Nutr 2007; 137:2405-2411.
82. Kalus U, Pindur G, Jung F, Mayer B, Radtke H, Bachmann K, et al. Influence of the onion as an essential ingredient of the Mediterranean diet on arterial blood pressure and blood fluidity. Drug Res 2000; 50:795-801.
83. Egert S, Boesch-Saadatmandi C, Wolffram S, Rimbach G, Müller MJ. Serum lipid and blood pressure responses to quercetin vary in overweight patients by apolipoprotein E genotype. J Nutr 2010; 140:278-284.
84. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet 2016; 387:1513-1530.
85. American Diabetes Association. Microvascular complications and foot care: standards of medical care in diabetes. Diabetes Care 2019; 42:S124.
86. Kim HY, Kim K. Protein glycation inhibitory and antioxidative activities of some plant extracts in vitro. J Agr Food Chem 2003; 51:1586-1591.
87. Jaiswal N, Rizvi SI. Amylase inhibitory and metal chelating effects of different layers of onion (Allium cepa L.) at two different stages of maturation in vitro. Ann Phytomed Int J2017; 6:45-50.
88. Kim SH, Jo SH, Kwon YI, Hwang JK. Effects of Onion (Allium cepa L.) Extract administration on intestinal alpha-glucosidases activities and spikes in postprandial blood glucose levels in SD rats model. Int J Mol Sci 2011; 12:3757-3769.
89. Schulze C, Bangert A, Schwanck B, Vollert H, Blaschek W, Daniel H. Extracts and flavonoids from onion inhibit the intestinal sodium-coupled glucose transporter 1 (SGLT1) in vitro but show no anti-hyperglycaemic effects in vivo in normoglycaemic mice and human volunteers. J Funct Foods 2015; 18:117-128.
90. Gautam S, Pal S, Maurya R, Srivastava AK. Ethanolic extract of Allium cepa stimulates glucose transporter typ 4-mediated glucose uptake by the activation of insulin signaling. Planta Med 2015; 81:208-214.
91. Augusti KT. Effect of alloxan diabetes of allyl propyl disulphide obtained from onion. Naturwissenschaften 1974; 61:172-173.
92. Augusti KT, Roy VCM, Semple M. Effect of allyl propyl disulphide isolated from onion (Allium cepa L.) on glucose tolerance of alloxan diabetic rabbits. Experientia 1974; 30:1119-1120.
93. Jain RC, Vyas CR. Letter: Hypoglycaemia action of onion on rabbits. Br Med J 1974; 2:730.
94. Karawya MS, Abdel Wahab SM, El-Olemy MM, Farrag NM. Diphenylamine, an antihyperglycemic agent from onion and tea. J Nat Prod 1984; 47:775-780.
95. Kumari K, Augusti KT. Antidiabetic effects of s-methylcysteine sulfoxide on alloxan diabetes. Planta Med 1995; 61:72-74.
96. Ikechukwu OJ, Ifeanyi OS. The Antidiabetic effects of the bioactive flavonoid (Kaempferol-3-O-beta-D-6{P- Coumaroyl} Glucopyranoside) isolated from Allium cepa. Recent Pat Antiinfect Drug Discov 2016; 11:44-52.
97. Kook S, Kim GH, Choi K. The antidiabetic effect of onion and garlic in experimental diabetic rats: Meta-analysis. J Med Food 2009; 12:552-560.
98. Devarshi PP, Jones AD, Taylor EM, Stefanska B, Henagan TM. Quercetin and quercetin-rich red onion extract alter Pgc-1 alpha promoter methylation and splice variant expression. PPAR Res 2017 ;2017:3235693.
99. Snyder SM, Zhao B, Luo T, Kaiser C, Cavender G, Hamilton-Reeves J, et al. Consumption of quercetin and quercetin- containing apple and cherry extracts affects blood glucose concentration, hepatic metabolism, and gene expression patterns in obese C57BL/6J high fat-fed mice. J Nutr 2016; 146:1001-1007.
100. Kaur G, Invally M, Chintamaneni M. Influence of piperine and quercetin on antidiabetic potential of curcumin. J Complement Integr Med 2016; 13:247-255.
101. Al-Malki AL. inhibition of alpha-glucosidase by thiosulfinate as a target for glucose modulation in diabetic rats. Evid Based Complement Altern Med 2016; 2016:7687915.
102. Thomas S, Senthilkumar GP, Sivaraman K, Bobby Z, Paneerselvam S, Harichandrakumar KT. Effect of S-Methyl-L-cysteine on oxidative stress, inflammation and insulin resistance in male Wistar rats fed with high fructose diet. Iran J Med Sci 2015; 40:45-50.
103. Gomes IBS, Porto ML, Santos MCLFS, Campagnaro BP, Pereira TMC, Meyrelles SS, et al. Renoprotective, anti-oxidative and anti-apoptotic effects of oral low-dose quercetin in the C57BL/6J model of diabetic nephropathy. Lipids Health Dis 2014; 13.
104. Jung YS, Kim MH, Lee SH, Baik EJ, Park SW, Moon CH. Antithrombotic effect of onion in streptozotocin-induced diabetic rat. Prostag Leukotr Ess 2002; 66:453-458.
105. Fallah V, Mahabadi JA, Mahabadi MY, Kashani HH, Nikzad H. Protective effect of Allium cepa (Onion) seeds (AC) extract on histopathology of testis in STZ-induced male rats. Int J Morphol 2017; 35:1517-1524.
106. Bhanot A, Shri R. A comparative profile of methanol extracts of Allium cepa and Allium sativum in diabetic neuropathy in mice. Pharmacognosy Res 2010; 2:374-384.
107. Jafarpour-Sadegh F, Montazeri V, Adili A, Esfehani A, Rashidi MR, Pirouzpanah S. Consumption of fresh yellow onion ameliorates hyperglycemia and insulin resistance in breast cancer patients during doxorubicin-based chemotherapy: A randomized controlled clinical trial. Integr Cancer Ther 2017; 16:276-289.
108. Taj Eldin IM, Ahmed EM, Elwahab HMA. Preliminary study of the clinical hypoglycemic effects of Allium cepa (red onion) in type 1 and type 2 diabetic patients. Environ Health Insights 2010; 4:71-77.
109. Hoffman R, Ranjbar G, Madden AM. Inhibition of the glycaemic response by onion: A comparison between lactose-tolerant and lactose-intolerant adults. Eur J Clin Nutr 2016; 70:1089-1091.
110. Lee SM, Moon J, Cho Y, Chung JH, Shin MJ. Quercetin up-regulates expressions of peroxisome proliferator-activated receptor γ, liver X receptor α, and ATP binding cassette transporter A1 genes and increases cholesterol efflux in human macrophage cell line. Nutr Res 2013; 33:136-143.
111. Jung H, Wee JH, Kim K, Sung H, Shin H. Effect of onion (Allium cepa) ultra-high pressure processing and hot water extracts on the serum cholesterol level in high cholesterol-fed rats. Food Sci Biotechnol 2015; 24:287-294.
112. Lata S, Saxena KK, Bhasin V, Saxena RS, Kumar A, Srivastava VK. Beneficial effects of Allium sativum, Allium cepa and Commiphora mukul on experimental hyperlipidemia and atherosclerosis-a comparative evaluation. J Postgrad Med 1991; 37:132-135.
113. Guan L, Chung HY, Su YL, Jiao R, Peng C, Chen ZY. Hypocholesterolemic activity of onion is mediated by enhancing excretion of fecal sterols in hamsters. Food  Funct 2010; 1:84-89.
114. Sikder K, Das N, Kesh SB, Dey S. Quercetin and beta-sitosterol prevent high fat diet induced dyslipidemia and hepatotoxicity in Swiss albino mice. Indian J Exp Biol 2014; 52:60-66.
115. Moon J, Do HJ, Kim OY, Shin MJ. Antiobesity effects of quercetin-rich onion peel extract on the differentiation of 3T3-L1 preadipocytes and the adipogenesis in high fat-fed rats. Food Chem Toxicol 2013; 58:347-354.
116. Henagan TM, Cefalu WT, Ribnicky DM, Noland RC, Dunville K, Campbell WW, et al. In vivo effects of dietary quercetin and quercetin-rich red onion extract on skeletal muscle mitochondria, metabolism, and insulin sensitivity. Genes Nutr 2015; 10:451.
117. Arias N, Picó C, Teresa Macarulla M, Oliver P, Miranda J, Palou A, et al. A combination of resveratrol and quercetin induces browning in white adipose tissue of rats fed an obesogenic diet. Obesity 2017; 25:111-121.
118. Vazquez-Prieto MA, Rodriguez Lanzi C, Lembo C, Galmarini CR, Miatello RM. Garlic and onion attenuates vascular inflammation and oxidative stress in fructose-fed rats. J Nutr Metab 2011; 2011:475216.
119. Gonzalez-Pena D, Angulo J, Vallejo S, Colina-Coca C, de Ancos B, Sanchez-Ferrer CF, et al. High-cholesterol diet enriched with onion affects endothelium-dependent relaxation and NADPH oxidase activity in mesenteric microvessels from Wistar rats. Nutr Metab 2014; 11:57.
120. Jalili T, Carlstrom J, Kim S, Freeman D, Jin HF, Wu TC, et al. Quercetin-supplemented diets lower blood pressure and attenuate cardiac hypertrophy in rats with aortic constriction. J Cardiovasc Pharmacol 2006; 47:531-541.
121. Wu HR, Xu BJ. Inhibitory effects of onion against α-glucosidase activity and its correlation with phenolic anti-oxidants. Int J Food Prop 2014; 17:599-609.
122. Ozougwu JC. Anti-diabetic effects of Allium cepa (onions) aqueous extracts on alloxan-induced diabetic Rattus novergicus. J Med Plants Res 2011; 5:1134-1139.
123. Babu PS, Srinivasan K. Influence of dietary capsaicin and onion on the metabolic abnormalities associated with streptozotocin induced diabetes mellitus. Mol Cell Biochem 1997; 175:49-57.
124. El-Soud NA, Khalil M. Antioxidative effects of Allium cepa essential oil in streptozotocin induced diabetic rats. Macedonian J Med Sci 2010; 3:344-351.
125. Ogunmodede OS, Saalu LC, Ogunlade B, Akunna GG, Oyewopo AO. An evaluation of the hypoglycemic, anti-oxidant and hepatoprotective potentials of onion (Allium cepa L.) on alloxan-induced diabetic rabbits. Int J Pharmacol 2012; 8:21-29.
126. Jung JY, Lim Y, Moon MS, Kim JY, Kwon O. Onion peel extracts ameliorate hyperglycemia and insulin resistance in high fat diet/streptozotocin-induced diabetic rats. Nutr Metab 2011; 8:18.
127. Arias N, MacArulla MT, Aguirre L, Martínez-Castaño MG, Portillo MP. Quercetin can reduce insulin resistance without decreasing adipose tissue and skeletal muscle fat accumulation. Genes Nutr 2014; 9:361.
128. Anhê GF, Okamoto MM, Kinote A, Sollon C, Lellis-Santos C, Anhê FF, et al. Quercetin decreases inflammatory response and increases insulin action in skeletal muscle of ob/ob mice and in L6 myotubes. Eur J Pharmacol 2012; 689:285-293.
129. Shetty AK, Rashmi R, Rajan MGR, Sambaiah K, Salimath PV. Antidiabetic influence of quercetin in streptozotocin-induced diabetic rats. Nutr Res 2004; 24:373-381.
130. Khaki A, Fathiazad F, Ahmadi-Ashtiani HR, Rezazadeh S, Rastegar H, Imani AM. Compartments of quercetin & Allium cepa (onion) on blood glucose in diabetic rats. J MedPlants 2010; 9:107-112.
131. G PS, Thomas S, K S, Sankar P, Bobby Z. Study the effect of s-methyl L-cysteine on lipid metabolism in an experimental model of diet induced obesity. J Clin Diagn Res 2013; 7:2449-2451.
132. Choi EY, Lee H, Woo JS, Jang HH, Hwang SJ, Kim HS, et al. Effect of onion peel extract on endothelial function and endothelial progenitor cells in overweight and obese individuals. Nutrition 2015; 31:1131-1135.
133. Khorshidi M, Moini A, Alipoor E, Rezvan N, Gorgani-Firuzjaee S, Yaseri M, et al. The effects of quercetin supplementation on metabolic and hormonal parameters as well as plasma concentration and gene expression of resistin in overweight or obese women with polycystic ovary syndrome. Phytother Res 2018; 32:2282-2289.
134. Brull V, Burak C, Stoffel-Wagner B, Wolffram S, Nickenig G, Muller C, et al. No effects of quercetin from onion skin extract on serum leptin and adiponectin concentrations in overweight-to-obese patients with (pre-)hypertension: a randomized double-blinded, placebo-controlled crossover trial. Eur J Nutr 2017; 56:2265-2275.
135. Nishimura M, Muro T, Kobori M, Nishihira J. Effect of daily ingestion of quercetin-rich onion powder for 12 weeks on visceral fat: A randomised, double-blind, placebo-controlled, parallel-group study. Nutrients 2019; 12.
136. Bruell V, Burak C, Stoffel-Wagner B, Wolffram S, Nickenig G, Mueller C, et al. Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-) hypertension: a randomised double-blinded placebo-controlled cross-over trial. British J Nutr 2015; 114:1263-1277.
137. Lee KH, Park E, Lee HJ, Kim MO, Cha YJ, Kim JM, et al. Effects of daily quercetin-rich supplementation on cardiometabolic risks in male smokers. Nutr Res Practice 2011; 5:28-33.
138. Rezvan N, Moini A, Gorgani-Firuzjaee S, Hosseinzadeh-Attar MJ. Oral quercetin supplementation enhances adiponectin receptor transcript expression in polycystic ovary syndrome patients: A randomized placebo-controlled double-blind clinical trial. Cell J 2018; 19:627-633.