Salvianolic acid B inhibits hepatic stellate cell activation and liver fibrosis by targeting PDGFR beta

Liver fibrosis is a reversible pathological process and a wound healing response to liver injury. As an early stage of various liver diseases, liver fibrosis can develop into cirrhosis, liver failure, and even liver cancer if not controlled in time. Salvia miltiorrhiza is a medicinal plant with hepatoprotective effects. Salvianolic acid B (Sal B) is the representative component of S. miltiorrhiza. Many studies have reported the anti-liver fibrosis effects and mechanisms of Sal B. However, the direct anti-fibrotic targets of Sal B have not yet been reported. Plateletderived growth factor receptor beta (PDGFR beta) is one of the most classical targets in liver fibrosis, which is closely related to hepatic stellate cells (HSCs) activated. Previously, we established and applied a PDGFR beta affinity chromatography model, and found that Sal B binds well to PDGFR beta. Therefore, this study aimed to investigate the direct targets of Sal B against liver fibrosis. We confirmed the binding ability of Sal B to PDGFR beta by molecular docking and a surface plasmon resonance biosensor. Our findings indicated that Sal B targeted PDGFR beta to inhibit the activation, migration and proliferation of HSCs and suppressed the PDGF-BB-induced PDGFR beta signaling pathway. Annexin V-FITC/PI assay showed that Sal B reversed the PDGF-BB-induced decrease in HSC apoptosis rate. In the mouse liver fibrosis model, Sal B inhibited the PDGFR beta signaling pathway, HSC activation and reduced inflammatory response, ultimately improved CCl4-induced liver fibrosis. In summary, the direct anti-fibrotic targets of Sal B may be PDGFR beta, and this study clarified the anti-liver fibrosis effects and mechanism of Sal B.

Automated summary

Liver fibrosis is a reversible pathological process that can lead to liver failure and cancer. Salvia miltiorrhiza is a medicinal plant with hepatoprotective effects, and its component Salvianolic acid B has been found to have anti-liver fibrosis effects. This study discovered that Sal B targets PDGFR beta to inhibit the activation, migration, and proliferation of hepatic stellate cells, which are closely related to liver fibrosis.