Salvianolic acid B blocks hepatic stellate cell activation via FGF19/FGFR4 signaling

Introduction and objectives: The activation of hepatic stellate cells (HSCs) is the main cause of liver fibrosis. The beneficial effects of fibroblast growth factor (FGF) 19 on liver fibrosis were recently reported. The S. miltiorrhiza as well as S. miltiorrhiza derived bioactive chemical components has shown prominent antifibrotic effects in liver fibrosis but the mechanism is still not fully understood. We aimed to investigate the bioactive compounds derived from S. miltiorrhiza which exerts antifibrotic effects in HSCs via regulating FGF19. Materials and methods: FGF19 level in culture media was determined by enzyme-linked immunosorbent assay. Cell proliferation was measured by Cell Counting Kit-8 assay. Further, mRNA and protein expressions were assessed by quantitative polymerase chain reaction and western blotting, respectively. Knocking down of FGF receptor 4 (FGFR4) by transfection with siRNA was used to confirm the role of FGF19/FGFR4 signaling. Results: Using the human HSC cell line LX-2, we screened several natural products and found that bioactive compounds isolated from Salvia miltiorrhiza, particularly salvianolic acid B, strongly upregulated FGF19 secretion by LX-2 cells. We further showed that salvianolic acid B inhibited lipopolysaccharide (LPS)induced HSC proliferation and activation. LPS treatment may also reduce the mRNA and protein levels of FGF19 and its receptor FGFR4. Salvianolic acid B treatment restored the impaired expressions of FGF19 and FGFR4. Finally, FGFR4 knockdown abolished the antifibrotic effects of salvianolic acid B in the LPS-induced HSC activation model. Conclusions: Salvianolic acid B prevented LPS-induced HSC proliferation and activation by enhancing antifibrotic FGF19/FGFR4 signaling. (C) 2020 Fundaci 6n Cl ' nica Medica Sur, A.C. Published by Elsevier Espaa, S.L.U. This is an open access article under the CC BY-NC-ND license.

Automated summary

This study identified that salvianolic acid B derived from Salvia miltiorrhiza can inhibit the proliferation and activation of hepatic stellate cells (HSCs) by regulating the FGF19/FGFR4 signaling pathway, demonstrating its anti-fibrotic effects in liver fibrosis.