Salvianolic acid B ameliorates hepatic fibrosis via inhibiting p300/CBP.

Salvianolic acid B (Sal B), an active ingredient extracted from Salvia miltiorrhiza Bunge, has shown hepatic anti-fibrotic activity. Hepatic stellate cells (HSCs) activation is considered the determining event in liver fibrogenesis. E1A binding protein p300 (p300)/CREB binding protein (CBP) is an attractive target for inhibiting HSCs activation. But whether Sal B inhibits hepatic fibrosis through suppressing p300/CBP is unknown. We used DEN/CCl/CHOH to establish a mouse model of hepatic fibrosis and detect the effects of Sal B on liver function, pathological alterations, and p300/CBP expression. TGF-β1 was used to induce LX-2 cells for in vitro experimental validation. Additionally, the effects of Sal B on LX-2 activation were explored using the p300/CBP activator CTB, and molecular docking was used to predict the interaction between Sal B and p300. The in vivo results demonstrated that Sal B improved liver function, reversed pathological changes, reduced collagen synthesis, and downregulated the protein levels of p300 and CBP in DEN/CCl/CHOH-induced hepatic fibrosis mice. The in vitro results showed that Sal B inhibited LX-2 cells activation and decreased both the mRNA and protein levels of p300 and CBP. Furthermore, the p300/CBP activator CTB reversed the inhibitory effect of Sal B on LX-2 cells activation. Molecular docking showed that Sal B bound well to p300 with a high degree of match and a binding energy of -14.859 kcal/mol. Our study revealed that Sal B ameliorates hepatic fibrosis, which likely via inhibition of p300/CBP. However, the specific binding site deserves further exploration.