s-allylmercaptocysteine and Inflammation

SAMC (S-allylmercaptocysteine) possesses significant anti-tumor effects and is proven to inhibit inflammation in chronic obstructive pulmonary disease. The potential to regulate the immune system of SAMC inspired us to detect whether SAMC can promote anti-tumor immunity. Here we found that SAMC inhibits tumor development and progression by boosting CD8

Topics: Apoptosis; B7-H1 Antigen; Cell Line, Tumor; Humans; Inflammation

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

The garlic-derived organosulfur compound S-allylmercaptocysteine (SAMC) has been reported to exhibit anti-inflammatory and anti-oxidative activities, whereas its potential therapeutic effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) is unknown. In this study, we focused on exploring the therapeutic effects of SAMC on LPS-induced ALI mice and the involvement of underlying molecular mechanisms. BalB/c mice were treated with SAMC (10, 30 and 60 mg/kg) or positive control N-acetylcysteine (NAC, 500 mg/kg) by gavage after intratracheal instillation of LPS for 30 min and were sacrificed 24 h after LPS administration. Our results indicate that the treatment with SAMC not only ameliorated the histological changes but also decreased LPS-triggered lung edema. Moreover, SAMC displayed an anti-inflammatory effect through reducing inflammatory cells infiltration, myeloperoxidase (MPO) formation and inhibiting pro-inflammatory cytokines/mediator production including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) via suppressing the activation of nuclear factor-kappaB (NF-κB) signaling pathway. Furthermore, SAMC attenuated oxidative stress evoked by LPS via diminishing malondialdehyde (MDA) formation and reversing glutathione (GSH) and superoxide dismutase (SOD) depletion. Meanwhile, SAMC up-regulated expressions of endogenous antioxidant/detoxifying proteins including heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1(NQO1) through reversing the suppression of Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway. Our results demonstrate that SAMC effectively attenuated LPS-induced ALI which was largely dependent upon inhibition of inflammation and oxidative stress via NF-κB and Keap1/Nrf2 signaling pathways.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Cysteine; Cytokines; Humans; Inflammation; Inflammation Mediators; Kelch-Like ECH-Associated Protein 1; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Signal Transduction; Superoxide Dismutase

Cisplatin is a potent chemotherapeutic agent, but its clinical usage is limited by nephrotoxicity. S-allylmercaptocysteine (SAMC), one of the water-soluble organosulfur garlic derivatives, has antioxidant and anti-inflammatory properties and plays an important role in protecting cells from apoptosis. This study aims to examine the protective effects of SAMC on cisplatin nephrotoxicity and to explore the mechanism of its renoprotection. Rats were treated with cisplatin with or without pre-treatment with SAMC. Renal function, histological change, oxidative stress markers and antioxidant enzyme activities were investigated. Apoptotic marker, nuclearfactor (NF)-κB activity, expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1) and inflammatory cytokines were also examined. The effect of SAMC on cell viability and apoptosis was examined in cultured human kidney (HK-2) cells. SAMC was confirmed to significantly attenuate cisplatin-induced renal damage by using histological pathology and molecular biological method. Pre-treatment with SAMC reduced NF-κB activity, up-regulated Nrf2 and NQO1 expression and down-regulated inflammatory cytokine levels after cisplatin administration. Cisplatin-induced apoptosis in HK-2 cells was significantly attenuated by SAMC. Thus our results suggest that SAMC could be a potential therapeutic agent in the treatment of the cisplatin-induced nephrotoxicity through its anti-apoptotic, anti-oxidant and anti-inflammatory effects.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Biomarkers; Cell Line, Tumor; Cell Survival; Cisplatin; Cysteine; Down-Regulation; Humans; Inflammation; Interleukin-1beta; Kidney; Male; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Up-Regulation

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

To study the protective effects and underlying molecular mechanisms of SAMC on carbon tetrachloride (CCl4)-induced acute hepatotoxicity in the mouse model.. Mice were intraperitoneally injected with CCl4 (50 μl/kg; single dose) to induce acute hepatotoxicity with or without a 2-h pre-treatment of SAMC intraperitoneal injection (200 mg/kg; single dose). After 8 h, the blood serum and liver samples of mice were collected and subjected to measurements of histological and molecular parameters of hepatotoxicity.. SAMC reduced CCl4-triggered cellular necrosis and inflammation in the liver under histological analysis. Since co-treatment of SAMC and CCl4 enhanced the expressions of antioxidant enzymes, reduced the nitric oxide (NO)-dependent oxidative stress, and inhibited lipid peroxidation induced by CCl4. SAMC played an essential antioxidative role during CCl4-induced hepatotoxicity. Administration of SAMC also ameliorated hepatic inflammation induced by CCl4 via inhibiting the activity of NF-κB subunits p50 and p65, thus reducing the expressions of pro-inflammatory cytokines, mediators, and chemokines, as well as promoting pro-regenerative factors at both transcriptional and translational levels.. Our results indicate that SAMC mitigates cellular damage, oxidative stress, and inflammation in CCl4-induced acute hepatotoxicity mouse model through regulation of NF-κB. Garlic or garlic derivatives may therefore be a potential food supplement in the prevention of liver damage.

Topics: Alanine Transaminase; Animals; Antioxidants; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Cysteine; Female; Inflammation; Lipid Peroxidation; Liver; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; NF-kappa B; Nitric Oxide; Oxidative Stress