Garlic-derived S-allylmercaptocysteine is a hepato-protective agent in non-alcoholic fatty liver disease in vivo animal model

Abstract

PurposeTo investigate the hepato-protective properties and underlying mechanisms of SAMC in a non-alcoholic fatty liver disease (NAFLD) rat model.MethodsFemale rats were fed with a diet comprising highly unsaturated fat diet (30% fish oil) for 8 weeks to develop NAFLD with or without an intraperitoneal injection of 200 mg/kg SAMC three times per week. After euthanasia, blood and liver samples of rats were collected for histological and biochemical analyses.ResultsCo-treatment of SAMC attenuated NAFLD-induced liver injury, fat accumulation, collagen formation and free fatty acids (FFAs). At the molecular level, SAMC decreased the lipogenesis marker and restored the lipolysis marker. SAMC also reduced the expression levels of pro-fibrogenic factors and diminished liver oxidative stress partly through the inhibition in the activity of cytochrome P450 2E1-dependent pathway. NAFLD-induced inflammation was also partially mitigated by SAMC treatment via reduction in the pro-inflammatory mediators, chemokines and suppressor of cytokine signaling. The protective effect of SAMC is also shown partly through the restoration of altered phosphorylation status of FFAs-dependent MAP kinase pathways and diminished in the nuclear transcription factors (NF-κB and AP-1) activity during NAFLD development.ConclusionsSAMC is a novel hepato-protective agent against NAFLD caused by abnormal liver functions. Garlic or garlic derivatives could be considered as a potent food supplement in the prevention of fatty liver disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s00394-012-0301-0) contains supplementary material, which is available to authorized users.

Translational Implications of the Alcohol-Metabolizing Enzymes, Including Cytochrome P450-2E1, in Alcoholic and Nonalcoholic Liver Disease

“…It is well established that increased nitroxidative stress can be produced from impaired mitochondrial function (i.e., mitochondrial dysfunction), elevated levels of ethanol-inducible cytochrome P450-2E1 (CYP2E1) and other CYP isozymes, NADPH oxidases, inducible form of nitric oxide synthase (iNOS) and xanthine oxidase (XO) (Aubert, Begriche, Knockarert, Robin, & Fromenty, 2011;Lieber, 2004b;Spruss, Kanuri, Uebel, Bischoff, & Bergheim, 2011). On the other hand, the cellular levels of small-molecule antioxidants, such as glutathione (GSH), many vitamins including retinoic acid (vitamin A), thiamine (vitamin B1), ascorbic acid (vitamin C), and α-tocopherol (vitamin E), are known to be decreased following alcohol exposure (Cederbaum, 2012a;Leung & Nieto, 2013;Lieber, 1997;Nanji et al, 2003;Xiao et al, 2013) and/or under different pathophysiological conditions such as hypoxic liver injury and aging (Marí, Morales, Colell, García-Ruiz, & Fernández-Checa, 2009). Furthermore, recent data has shown that the activities of antioxidant enzymes such as glutathione peroxidase (Gpx), catalase, and superoxide dismutase (SOD) can be inhibited by alcohol and nonalcoholic substances (Abdelmegeed, Jang, Banerjee, Hardwick, & Song, 2013;Abdelmegeed, Moon, Chen, Gonzalez, & Song, 2010;Carmiel-Haggai, Cederbaum, & Nieto, 2005;Song et al, 2013).…”

Bee’s honey attenuates non-alcoholic steatohepatitis-induced hepatic injury through the regulation of thioredoxin-interacting protein–NLRP3 inflammasome pathway

“…Although some proposed pharmaceutical drugs have been extensively investigated in laboratory study, further tests and evaluations are necessary before applying clinically. In the past decades, several natural compounds are found to possess hepato-protective effects against the progression of NAFLD/NASH, including garlic [6], wolfberry [7], resveratrol [8], silibinin [9], coffee [10], and honey [11]. Due to their potent antioxidant and anti-inflammatory properties, these herbal derivatives hold promising prospects for future clinical application.…”

Allium sativum

“…Garlic-derived S-allylmercaptocysteine (SAMC) exhibited hepatoprotective effect in nonalcoholic fatty liver disease (NAFLD) in rats (Xiao et al 2013 ). Co-treatment of SAMC attenuated NAFLD-induced liver injury, fat accumulation, collagen formation and free fatty acids (FFAs).…”