S-allyl-cysteine attenuates carbon tetrachloride-induced liver fibrosis in rats by targeting STAT3/SMAD3 pathway

S-allyl-cysteine (SAC) is one of the major compounds in aged garlic extract, and has been proved to be an endogenous donor of hydrogen sulfide (H₂S), which plays emerging roles in the gastrointestinal tract and liver. In this study, Sprague-Dawley rats were intraperitoneally injected with a mixture of carbon tetrachloride (CCl₄, 1 mL/kg body weight) and olive oil (1:1 v/v) every other day for 8 weeks to induce liver fibrosis. Treatment of SAC (50 mg/kg/day) could attenuate CCl₄-induced liver fibrosis, with improved semi-quantitative scores of fibrosis severity based on the staining of H&E, Oil Red O, and Sirius Red. SAC attenuated CCl₄-induced transaminase elevation in the plasma of the rats. In the liver, SAC could reduce the mRNA expression of inflammatory and fibrogenic cytokines, including interleukin 6, interferon γ, tumor necrosis factor α, and transforming growth factor β (TGFβ), as well as induce the mRNA expression of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. The mRNA expression of biomarkers of liver fibrosis, including α-smooth muscle actin, fibronectin and collagen I, were also decreased after SAC treatment. In addition, SAC reduced the phosphorylation of SMAD3 and signal transducers and activators of transcription 3, and further inhibited their binding ability to transcription promoters. Taken together, SAC attenuated CCl₄-induced liver fibrosis in rats with anti-oxidant, anti-inflammatory and anti-fibrotic effects, and targeted STAT3/SMAD3 pathway to inhibit gene transcription.