Asperuloside, an iridoid glycoside found in Rubiaceae plants for attenuating fibrogenesis and inflammation in hepatic fibrosis.

Asperuloside (ASP) exhibits a broad range of biological and pharmaceutical activities. The purpose of this study was to investigate the hepatoprotective effects of ASP and its potential mechanisms in suppressing hepatic fibrosis. RNA sequencing revealed significant alterations in the SIRT6/Toll-like receptor pathway in TAA-induced mice. SIRT6 deficiency attenuated the effect of ASP on the expression of α-SMA, TLR2, TLR4, and IRAK4 in activated LX-2 cells. ASP reduced serum levels of ALT, AST, and TBil, ameliorated histopathological changes in the liver, and suppressed extracellular matrix (ECM) accumulation in TAA-induced hepatic fibrosis. Additionally, ASP downregulated inflammatory factors such as TLR2 and TLR4, while enhancing SIRT6 expression in TAA-induced mice. ASP alleviated hepatic inflammation and fibrogenesis in TAA-induced hepatic fibrosis and reversed the activation of HSCs. Collectively, these findings support the potential of ASP as a novel therapeutic option for hepatic fibrosis.