s-allylmercaptocysteine and Non-alcoholic-Fatty-Liver-Disease

To investigate the novel molecular mechanisms of the antioxidant and anti-inflammatory properties of S-allylmercaptocysteine (SAMC) based on a transcriptomic study in a nonalcoholic steatohepatitis (NASH) rat model METHODS: NASH was induced in Sprague-Dawley rats by feeding with a high fat diet (HFD) for 12 weeks. 200 mg/kg SAMC was fed by oral gavage for 4 weeks from 9 to 12 week.. SAMC co-administration attenuated HFD-induced liver injury, including the increased serum ALT, hepatic oxidative stress and inflammation. Transcriptomic analysis revealed that SAMC dramatically induced the XRE- and ARE-driven drug metabolising enzymes (DMEs) including Akr7a3, Akr1b8, and Nqo1. The nuclear translocation of the upstream regulator of xenobiotics metabolism, AHR, and regulator of antioxidant responses, NRF2, were significantly increased by SAMC treatment. Furthermore, SAMC counteracted the effects of HFD on NF-κB/IκB and NLRP3/6 pathways with decreasing protein levels of ASC, cleaved caspase-1, IL-18, and IL-1β. These results were further verified in another mice NASH model induced by an MCD diet with SAMC co-administration.. We propose that SAMC triggers AHR/NRF2-mediated antioxidant responses which may further suppress the NLRP3/6 inflammasome pathway and NF-κB activation, contributing to the improvement of NASH.

Topics: Animals; Cysteine; Inflammation; Liver; Mice; NF-E2-Related Factor 2; NF-kappa B; NF-KappaB Inhibitor alpha; NLR Family, Pyrin Domain-Containing 3 Protein; Non-alcoholic Fatty Liver Disease; Pharmaceutical Preparations; Rats; Rats, Sprague-Dawley

To investigate the hepato-protective properties and underlying mechanisms of SAMC in a non-alcoholic fatty liver disease (NAFLD) rat model.. Female 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.. Co-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.. SAMC 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.

Topics: Animals; Blotting, Western; Cysteine; Cytochrome P-450 CYP2E1; Cytochrome P-450 CYP2E1 Inhibitors; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Fatty Liver; Female; Garlic; Inflammation; Lipogenesis; Liver; MAP Kinase Signaling System; NF-kappa B; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Phosphorylation; Plant Extracts; Rats; Rats, Sprague-Dawley; Transcription Factor AP-1