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.