Hydroxysafflor yellow A protects against thioacetamide-induced liver fibrosis in rats via suppressing proinflammatory/fibrogenic mediators and promoting hepatic stellate cell senescence and apoptosis

Abstract

Objective: To evaluate the effect of hydroxysafflor yellow A (HSYA) on thioacetamide-induced liver fibrosis. Methods: Thioacetamide was administered to rats intraperitoneally in doses of 200 mg/kg twice a week for 12 weeks. Thioacetamide-intoxicated rats were given silymarin (50 mg/kg) or HSYA (5 mg/kg) orally every day for 8 weeks. Liver enzymes, fibrosis markers, histological changes as well as immunohistochemistry of TNF-α, IL-6, p21, α-SMA, and caspase-3 were examined. The effect of HSYA on HSC-T6 activation/proliferation and apoptosis was also determined in vitro. Results: HSYA decreased liver enzymes, TNF-α, IL-6, and p21 expressions, hepatic PDGF-B, TIMP-1, TGF-β1, and hydroxyproline levels, as well as fibrosis score (S2 vs. S4) compared to the thioacetamide group. HSYA also downregulated α-SMA while increasing caspase-3 expression. Surprisingly, at 500 μg/mL, HSYA had only a slightly suppressive effect on HSC proliferation, with a 9.5% reduction. However, it significantly reduced TGF-β1, inhibited α-SMA expression, induced caspase-3 expression, and promoted cell senescence. Conclusions: HSYA may be a potential therapeutic agent for delaying and reversing the progression of liver fibrosis. More research on HSYA at higher doses and for a longer period is warranted.

Keywords

• hydroxysafflor yellow a; thioacetamide; hepatic stellate cells; inflammatory markers; liver fibrosis; p21; α-sma apoptosis