Onion (Allium cepa) and its Main Constituents as Antidotes or Protective Agents against Natural or Chemical Toxicities: A Comprehensive Review

Document Type : Review Paper


1 Department of Pharmacognosy, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran.

2 Public Health Department, Nursing Faculty at Aja University of Medical Sciences, Tehran, Iran.

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

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


Onion (Allium cepa) is a member of the family Amaryllidaceae and one of the most widely cultivated species of the genus Allium. Onion has plentiful chemical compounds such as allicin, quercetin, fisetin, other sulphurous compounds: diallyl disulphide and diallyl trisulphide. Onion and its main components in specific doses have shown a lot of benefits including free-radical scavenging and antioxidant properties, anticholesterolemic, anti-heavy metals toxicity, antihyperuricemia, antimicrobial, anti-gastric ulcer, and anticancer. This study summarizes numerous in-vitro and animal studies on the protective effects of onion against natural and chemical toxicities.  Onion and its main components can ameliorate the toxicity of chemical agents in kidney, liver, brain, blood, heart, reproductive system, embryo, pancreas through reducing lipid peroxidation, antioxidant effect, radical-scavenging, anti-inflammatory, chelating agent, cytoprotective activities, increasing protein synthesis in damaged tissues, suppressing apoptosis, as well as modulation of PKC-𝜀/p38MAPK, Wnt/beta-Catenin, ERK, JNK, p38 MAPK, Bcl-2, Bax, and NF-κB signaling pathways.

Graphical Abstract

Onion (Allium cepa) and its Main Constituents as Antidotes or Protective Agents against Natural or Chemical Toxicities: A Comprehensive Review


(1)        Koneru M, Sahu BD, Kumar JM, Kuncha M, Kadari A, Kilari EK, and Sistla R. Fisetin protects liver from binge alcohol-induced toxicity by mechanisms including inhibition of matrix metalloproteinases (MMPs) and oxidative stress. J. Funct. Foods. (2016) 22: 588-601.
(2)        Lee BK and Jung YS. Allium cepa Extract and Quercetin Protect Neuronal Cells from Oxidative Stress via PKC-epsilon Inactivation/ERK1/2 Activation. Oxid. Med. Cell. Longev. (2016) 2016: 2495624.
(3)        Bilyk A, Cooper PL, and Sapers GM. Varietal differences in distribution of quercetin and kaempferol in onion (Allium cepa L.) tissue. J. Agr. Food Chem. (1984) 32: 274-6.
(4)        Izawa H, Kohara M, Aizawa K, Suganuma H, Inakuma T, Watanabe G, Taya K, and Sagai M. Alleviative effects of quercetin and onion on male reproductive toxicity induced by diesel exhaust particles. Biosci. Biotech. Bioch. (2008) 72: 1235-41.
(5)        Bystrická J, Musilová J, Vollmannová A, Timoracká M, and Kavalcová P. Bioactive components of onion (Allium cepa L.) - A Review. Acta Aliment. (2013) 42: 11-22.
(6)        Brodnitz MH, Pollock C, and Vallon P. Flavor components of onion oil. J. Agr. Food Chem. (1969) 17: 760-3.
(7)        Griffiths G, Trueman L, Crowther T, Thomas B, and Smith B. Onions--a global benefit to health. Phytother. Res. (2002) 16: 603-15.
(8)        Suru SM. Onion and garlic extracts lessen cadmium-induced nephrotoxicity in rats. Biometals. (2008) 21: 623-33.
(9)        Ola-Mudathir KF and Maduagwu EN. Antioxidant Effects of Methanol Extract of Allium cepa linn on Cyanide-induced Renal Toxicity in Male Wistar Rats. Niger. J. Physiol. Sci. (2014) 29: 147-51.
(10)      Mohammadi S, Lotfian N, Keshavarz P, Tavakkoli M, Mohammadi M, Tavakkoli Tabasi K, Delshad A, Karimi M, and Mohammadzadeh F. Protective effects of hydro-alcoholic extract of allium cepa on biochemical and morphometric parameters of mice kidneys exposed to formaldehyde. Sci. J. Kurdestan Med.  Sci. (2016) 21: 41-9.
(11)      Kim J, Seo Y, Park JH, and Noh SK. Protective effect of onion wine on alcoholic fatty liver in rats. J. Korean Soc. Food. Sci. Nutr. (2016) 45: 467-73.
(12)      Haddad Kashani H. Protective effect of Allium cepa (Onion) seeds (AC) extract on histopathology of testis in STZ-induced male rats. Int. J. Reprod. Biomed. (2017) 15: 92-3.
(13)      Brzóska MM, Borowska S, and Tomczyk M. Antioxidants as a potential preventive and therapeutic strategy for cadmium. Curr. Drug Targets. (2016) 17: 1350-84.
(14)      Zaki SM. Evaluation of antioxidant and anti-lipid peroxidation potentials of Nigella sativa and onion extract on nicotine-induced lung damage. Folia Morphol. (Warsz). (2018)
(15)      Rahmat A, Leng CY, Bakar FIA, and Bakar MFA. Effect of red onion (Allium Cepa var. Aggregatum g. don) on serum uric acid level and total antioxidant status in normal and induced hyperuricemic rats. Asian J. Pharm. Clin. Res. (2018) 11: 178-83.
(16)      Elhassaneen YA and Abd Elhady YA. Onion peel powder alleviate acrylamide-induced cytotoxicity and immunotoxicity in liver cell culture. Life Sci. (2014) 11: 381-8.
(17)      Sparnins VL, Barany G, and Wattenberg LW. Effects of organosulfur compounds from garlic and onions on benzo[a]pyrene-induced neoplasia and glutathione S-transferase activity in the mouse. Carcinogenesis. (1988) 9: 131-4.
(18)      Alpsoy S, Kanter M, Aktas C, Erboga M, Akyuz A, Akkoyun DC, and Oran M. Protective effects of onion extract on cadmium-induced oxidative stress, histological damage, and apoptosis in rat heart. Biol. Trace. Elem. Res. (2014) 159: 297-303.
(19)      Ola-Mudathir KF, Suru SM, Fafunso MA, Obioha UE, and Faremi TY. Protective roles of onion and garlic extracts on cadmium-induced changes in sperm characteristics and testicular oxidative damage in rats. Food Chem. Toxicol. (2008) 46: 3604-11.
(20)      Cho YH, Lee JW, Woo HD, Lee S, Kim YJ, Lee Y, Shin S, Joung H, and Chung HW. Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes. Int. J. Environ. Res. Public Health. (2016) 13: 227.
(21)      Guo C, Yang RJ, Jang K, Zhou XL, and Liu YZ. Protective Effects of Pretreatment with Quercetin Against Lipopolysaccharide-Induced Apoptosis and the Inhibition of Osteoblast Differentiation via the MAPK and Wnt/beta-Catenin Pathways in MC3T3-E1 Cells. Cell. Physiol. Biochem. (2017) 43: 1547-61.
(22)      Yang EJ, Kim GS, Kim JA, and Song KS. Protective effects of onion-derived quercetin on glutamate-mediated hippocampal neuronal cell death. Pharmacogn. Mag. (2013) 9: 302-8.
(23)      Reza Tamtaji O, Hosseinzadeh H, Talaei SA, Behnam M, Mahdi Takht Firoozeh S, Taghizadeh M, and Alipoor R. Protective Effects of Red Onion (Allium cepa) Ethanolic Extract on Learning and Memory Impairments in Animal Models of Diabetes. Galen Med. J. (2017) 6:249-57.
(24)      Tabeshpour J, Mehri S, Shaebani Behbahani F, and Hosseinzadeh H. Protective effects of Vitis vinifera (grapes) and one of its biologically active constituents, resveratrol, against natural and chemical toxicities: A comprehensive review. Phytother. Res. (2018) 32: 2164-90.
(25)      Hosseini A and Hosseinzadeh H. Antidotal or protective effects of Curcuma longa (turmeric) and its active ingredient, curcumin, against natural and chemical toxicities: A review. Biomed. Pharmacother. (2018) 99: 411-21.
(26)      Dorri M, Hashemitabar S, and Hosseinzadeh H. Cinnamon (Cinnamomum zeylanicum) as an antidote or a protective agent against natural or chemical toxicities: a review. Drug. Chem. Toxicol. (2018) 41: 338-51.
(27)      Mohammadzadeh N, Mehri S, and Hosseinzadeh H. Berberis vulgaris and its constituent berberine as antidotes and protective agents against natural or chemical toxicities. Iran J. Basic Med. Sci. (2017) 20: 538-51.
(28)      Tavakkoli A, Ahmadi A, Razavi BM, and Hosseinzadeh H. Black Seed (Nigella Sativa) and its Constituent Thymoquinone as an Antidote or a Protective Agent Against Natural or Chemical Toxicities. Iran J. Pharm. Res. (2017) 16: 2-23.
(29)      Rameshrad M, Razavi BM, and Hosseinzadeh H. Protective effects of green tea and its main constituents against natural and chemical toxins: A comprehensive review. Food Chem. Toxicol. (2017) 100: 115-37.
(30)      Hedayati N, Naeini MB, Nezami A, Hosseinzadeh H, Wallace Hayes A, Hosseini S, Imenshahidi M, and Karimi G. Protective effect of lycopene against chemical and natural toxins: A review. Biofactors. (2019) 45: 5-23.
(31)      Abdel-Wahhab MA and Aly SE. Antioxidants and radical scavenging properties of vegetable extracts in rats fed aflatoxin-contaminated diet. J. Agric. Food Chem. (2003) 51: 2409-14.
(32)      Koehler P, Beuchat L, and Chhinnan M. Influence of temperature and water activity on aflatoxin production by Aspergillus flavus in cowpea (Vigna unguiculata) seeds and meal. J. food prot. (1985) 48: 1040-3.
(33)      DE WIT JC, Notermans S, Gorin N, and Kampelmacher E. Effect of garlic oil or onion oil on toxin production by Clostridium botulinum in meat slurry. J. food prot. (1979) 42: 222-4.
(34)      Roshan N, Riley TV, Knight DR, and Hammer KA. Effect of natural products on the production and activity of Clostridium difficile toxins in-vitro. Sci. Rep. (2018) 8: 1-9.
(35)      Bin Asad MH, Tahir Razi M, Sabih D, Najamus-Saqib Q, Nasim J, Murtaza G, and Hussain I. Anti-venom potential of Pakistani medicinal plants: inhibition of anticoagulation activity of Naja naja karachiensis toxin. Curr. Sci. (2013) 105: 1419-24.
(36)      Asad MH, Durr ES, Yaqab T, Murtaza G, Hussain MS, Hussain MS, Nasir MT, Azhar S, Khan SA, and Hussain I. Phospholipases A2: enzymatic assay for snake venom (Naja naja karachiensis) with their neutralization by medicinal plants of Pakistan. Acta Pol. Pharm. (2014) 71: 625-30.
(37)      Bin Asad MH, Iqbal M, Akram MR, Khawaja NR, Muneer S, Shabbir MZ, Khan MS, Murtaza G, and Hussain I. 5′-nucleotidases of Naja naja karachiensis snake venom: Their determination, toxicities and remedial approach by natural inhibitors (medicinal plants). Acta Pol. Pharm. (2016) 73: 667-73.
(38)      Asad MH, Murtaza G, Ubaid M, Durr e S, Sajjad A, Mehmood R, Mahmood Q, Ansari MM, Karim S, Mehmood Z, and Hussain I. Naja naja karachiensis envenomation: biochemical parameters for cardiac, liver, and renal damage along with their neutralization by medicinal plants. Biomed. Res. Int. (2014) 2014: 970540.
(39)      Asad MHHBS, Durr e  Chaudhory, B. A. Ahmad, Iftikhar Hussain  Hussain, Muhammad Sikandar Izhar, Nasir  Akmal, Naim Shahzad, Abid Hussain Hussain, Iqbal Muhammad. Anti-hemolytic property of local medicinal plant(s) upon Pakistani cobra venom induced hemolysis. J. Anim. Plant Sci. (2014) 24: 1701-1708.
(40)      Çelıksoy MH, Sancak R, Söğüt A, Güner ŞN, and Korkmaz A. Characteristics of venom allergic reactions in Turkish beekeepers and alternative treatment modalities. Int. Forum Allergy Rh. (2014) 4: 555-8.
(41)      Jakaria M, Azam S, Cho D-Y, Haque M, Kim I-S, and Choi D-K. The Methanol Extract of Allium cepa L. Protects Inflammatory Markers in LPS-Induced BV-2 Microglial Cells and Upregulates the Antiapoptotic Gene and Antioxidant Enzymes in N27-A Cells. Antioxidants. (2019) 8: 348.
(42)      Bastaki SMA and Amir N. Effect of allylsulfide, allyldisulfide and quercetin on histamine-induced gastric acid secretion and alcohol-induced gastric ulcer in rats In-vivo. J.Gastroenterol. Hepatol. (2016) 31: 58-9.
(43)      Mehri S, Shahi M, Razavi BM, Hassani FV, and Hosseinzadeh H. Neuroprotective effect of thymoquinone in acrylamide-induced neurotoxicity in Wistar rats. Iran. J Basic Med. Sci. (2014) 17: 1007-11.
(44)      Mehri S, Abnous K, Khooei A, Mousavi SH, Shariaty VM, and Hosseinzadeh H. Crocin reduced acrylamide-induced neurotoxicity in Wistar rat through inhibition of oxidative stress. Iran J. Basic. Med. Sci. (2015) 18: 902-8.
(45)      Singh T and Goel RK. Neuroprotective effect of Allium cepa L. in aluminium chloride induced neurotoxicity. Neurotoxicology. (2015) 49: 1-7.
(46)      Ali HA, Afifi M, Abdelazim AM, and Mosleh YY. Quercetin and omega 3 ameliorate oxidative stress induced by aluminium chloride in the brain. J. Mol. Neurosci. (2014) 53: 654-60.
(47)      Yeh S-L, Yeh C-L, Chan S-T, and Chuang C-H. Plasma rich in quercetin metabolites induces G2/M arrest by upregulating PPAR-γ expression in human A549 lung cancer cells. Planta medica. (2011) 77: 992-8.
(48)      Ghosh A, Mandal AK, Sarkar S, and Das N. Hepatoprotective and neuroprotective activity of liposomal quercetin in combating chronic arsenic induced oxidative damage in liver and brain of rats. Drug Deliv. (2011) 18: 451-9.
(49)      Ahmed AF, Al-Yousef HM, Al-Qahtani JH, and Al-Said MS. A hepatonephro-protective phenolic-rich extract from red onion (Allium cepa L.) peels. Pak. J. Pharm. Sci. (2017) 30:
(50)      Hosseini SM, Taghiabadi E, Abnous K, Timcheh Hariri A, Pourbakhsh H, and Hosseinzadeh H. Protective effect of thymoquinone, the active constituent of Nigella sativa fixed oil, against ethanol toxicity in rats. Iran J. Basic Med. Sci. (2017) 20: 927-39.
(51)      Pourbakhsh H, Taghiabadi E, Abnous K, Hariri AT, Hosseini SM, and Hosseinzadeh H. Effect of Nigella sativa fixed oil on ethanol toxicity in rats. Iran J. Basic Med. Sci. (2014) 17: 1020-31.
(52)      Rezaee-Khorasany A, Razavi BM, Taghiabadi E, Tabatabaei Yazdi A, and Hosseinzadeh H. Effect of saffron (stigma of Crocus sativus L.) aqueous extract on ethanol toxicity in rats: A biochemical, histopathological and molecular study. J. Ethnopharmacol. (2019) 237: 286-99.
(53)      Edenharder R, Frangart J, Hager M, Hofmann P, and Rauscher R. Protective effects of fruits and vegetables against In-vivo clastogenicity of cyclophosphamide or benzo[a]pyrene in mice. Food Chem. Toxicol. (1998) 36: 637-45.
(54)      Ige SF, Olaleye SB, Akhigbe RE, Akanbi TA, Oyekunle OA, and Udoh U-AS. Testicular toxicity and sperm quality following cadmium exposure in rats: Ameliorative potentials of Allium cepa. J. Hum. Reprod. Sci. (2012) 5: 37.
(55)      Obioha UE, Suru SM, Ola-Mudathir KF, and Faremi TY. Hepatoprotective Potentials of Onion and Garlic Extracts on Cadmium-Induced Oxidative Damage in Rats. Biol. Trace Elem. Res. (2009) 129: 143-56.
(56)      Ola-Mudathir FK and Suru SM. Onion and garlic extracts as potential antidotes for cadmium-induced biochemical alterations in prostate glands of rats. Andrologia. (2015) 47: 1075-82.
(57)      Ige S and Akhigbe R. Common onion (Allium cepa) extract reverses cadmium-induced organ toxicity and dyslipidaemia via redox alteration in rats. Pathophysiology. (2013) 20: 269-74.
(58)      Piechowiak T and Balawejder M. Onion skin extract as a protective agent against oxidative stress in Saccharomyces cerevisiae induced by cadmium. J. Food Biochem. (2019) 43: e12872.
(59)      Tedesco I, Carbone V, Spagnuolo C, Minasi P, and Russo GL. Identification and quantification of flavonoids from two southern italian cultivars of Allium cepa L., Tropea (Red Onion) and Montoro (Copper Onion), and their capacity to protect human erythrocytes from oxidative stress. J. Agric. Food Chem. (2015) 63: 5229-38.
(60)      Platt KL, Edenharder R, Aderhold S, Muckel E, and Glatt H. Fruits and vegetables protect against the genotoxicity of heterocyclic aromatic amines activated by human xenobiotic-metabolizing enzymes expressed in immortal mammalian cells. Mutat. Res. (2010) 703: 90-8.
(61)      Kim YJ, Seo SG, Choi K, Kim JE, Kang H, Chung MY, Lee KW, and Lee HJ. Recovery effect of onion peel extract against H2O2-induced inhibition of gap-junctional intercellular communication is mediated through quercetin. J. Food Sci. (2014) 79: H1011-H7.
(62)      Fernández-Bedmar Z, Demyda-Peyrás S, Merinas-Amo T, and del Río-Celestino M. Nutraceutic potential of two allium species and their distinctive organosulfur compounds: a multi-assay evaluation. Foods. (2019) 8: 222.
(63)      Sajitha G, Augusti K, and Jose R. Prophylactic effects of garlic oil and onion oil fractions as compared to vitamin E on rats orally fed with lead acetate solution. Indian J. Clin. Biochem. (2016) 31: 260-9.
(64)      Tricker AR and Preussmann R. Carcinogenic N-nitrosamines in the diet: occurrence, formation, mechanisms and carcinogenic potential. Mutat. Res. Genet. Toxicol. Environ. Mutagen. (1991) 259: 277-89.
(65)      Martínez A, Cambero I, Ikken Y, Marín ML, Haza AI, and Morales P. Protective Effect of Broccoli, Onion, Carrot, and Licorice Extracts against Cytotoxicity of N-Nitrosamines Evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide Assay. J. Agric. Food Chem. (1998) 46: 585-9.
(66)      Takada N, Kitano M, Chen T, Yano Y, Otani S, and Fukushima S. Enhancing Effects of Organosulfur Compounds from Garlic and Onions on Hepatocarcinogenesis in Rats: Association with Increased Cell Proliferation and Elevated Ornithine Decarboxylase Activity. Japanese J. Cancer Res. (1994) 85: 1067-72.
(67)      Takada N, Matsuda T, Otoshi T, and Fukushima S. Enhancement by Organosulfur Compounds from Garlic and Onions of Diethylnitrosamine-induced Glutathione 5-Transferase Positive Foci in the Rat Liver. Cancer Res. (1994) 54: 2895-9.
(68)      Mete R, Oran M, Topcu B, Oznur M, Seber ES, Gedikbasi A, and Yetisyigit T. Protective effects of onion (Allium cepa) extract against doxorubicin-induced hepatotoxicity in rats. Toxicol. Ind. Health. (2016) 32: 551-7.
(69)      Chinnala KM, Achanta P, Vangala VL, and Elsani MM. Evaluation for nephroprotective activity of ethanolic extract of Allium cepa Linn. In gentamicin-induced nephrotoxicity in rats. Asian J. Pharm. Clin. Res. (2017) 10: 356-9.
(70)      Mehdizadeh R, Parizadeh MR, Khooei A-R, Mehri S, and Hosseinzadeh H. Cardioprotective effect of saffron extract and safranal in isoproterenol-induced myocardial infarction in wistar rats. Iran J. Basic .Med. Sci. (2013) 16: 56.
(71)      Peng D and Liu Q. Cardioprotective effect of cycloalliin in isoproterenol-induced myocardial infarction in albino rats: A mechanistic study. Arch. Biol. Sci.. (2016) 68: 789-93.
(72)      Reliene R and Schiestl RH. Glutathione depletion by buthionine sulfoximine induces DNA deletions in mice. Carcinogenesis. (2006) 27: 240-4.
(73)      Griffith OW. Mechanism of action, metabolism, and toxicity of buthionine sulfoximine and its higher homologs, potent inhibitors of glutathione synthesis. J Biol Chem. (1982) 257: 13704-12.
(74)      Lee BK and Jung Y-S. Allium cepa extract and quercetin protect neuronal cells from oxidative stress via PKC-ε inactivation/ERK1/2 activation. Oxid. med. cell. longev.. (2016) 2016:
(75)      Eleazu CO, Eleazu KC, Chukwuma S, and Essien UN. Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. J. Diabetes Metab. Disord. (2013) 12: 60.
(76)      Hosseini S, Imenshahidi M, Hosseinzadeh H, and Karimi G. Effects of plant extracts and bioactive compounds on attenuation of bleomycin-induced pulmonary fibrosis. Biomed. Pharmacother. (2018) 107: 1454-65.
(77)      Roldan-Marin E, Krath BN, Poulsen M, Binderup ML, Nielsen TH, Hansen M, Barri T, Langkilde S, Cano MP, Sanchez-Moreno C, and Dragsted LO. Effects of an onion by-product on bioactivity and safety markers in healthy rats. Br. J. Nutr. (2009) 102: 1574-82.
(78)      Adeoye OJ, Olayinka OA, Bernard SA, Sikiru OA, Kofoworola OI, Olufemi OJ, and Adekunle AA. Testicular and spermatotoxic potential of methanol extract of red cultivar Allium cepa in rats. J Complement. Integr. Med. (2018) 15:
(79)      Parton K. Onion toxicity in farmed animals. New Zealand veterinary journal. (2000) 48: 89-.
(80)      Tang X, Xia Z, and Yu J. An experimental study of hemolysis induced by onion (Allium cepa) poisoning in dogs. J. Vet. Pharmacol. Ther. (2008) 31: 143-9.
(81)      Votto AP, Domingues BS, de Souza MM, da Silva Júnior FM, Caldas SS, Filgueira D, Clementin RM, Primel EG, Vallochi AL, and Furlong EB. Toxicity mechanisms of onion (Allium cepa) extracts and compounds in multidrug resistant erythroleukemic cell line. Biological. research. (2010) 43: 429-37.
(82)      Kojima T, Tanaka T, Mori H, Kato Y, and Nakamura M. Acute and subacute toxicity tests of onion coat, natural colorant extracted from onion (Allium cepa L.), in (C57BL/6× C3H) F1 mice. J. Toxicol. Environ. Health Part A. (1993) 38: 89-101.