Baicalin protects against 17α-ethinylestradiol-induced cholestasis via Sirt1/HNF-1α/FXR pathway

OBJECTIVE Baicalin is a major flavonoid component of Scutellaria baicalensis, and has been used in the treatment of liver diseases for many years. However, the role of baicalin in estrogen-induced cholestasis(EIC) remains to be elucidated. This present study explored the protective effect of baicalin against estrogen-induced liver injury and further elucidated the mechanisms involved both in vivo and in vitro. METHODS We conducted a series of experiments using 17α-ethinylestradiol(EE) induced cholestatic rats and cultured HepG2 cells. Serum, bile, and liver samples were collected for biochemical and histological analyses. Bile acid composition in liver was analyzed by LC-MS/MS. The mechanisms underlying the hepatoprotective of baicalin were investigated by RT-PCR, Western blotting analyses and immunohistochemistry. RESULTS Baicalin showed obvious hepatoprotective effects in EIC rats by reducing serum biomarkers and increasing the bile flow rate, as well as by alleviating liver histology and restoring the abnormal composition of hepatic bile acids(BAs). In addition, baicalin protected against EE induced liver injury by up-regulation of the expression of hepatic efflux transporters and down-regulation of hepatic uptake transporters. Furthermore, baicalin increased the expression of hepatic BA synthase(CYP27 A1) and metabolic enzymes(Bal, Baat and Sult2 a1) in EIC rats. We showed that baicalin significantly inhibited hepatic inflammatory responses in EIC rats through reducing elevated levels of TNF-α, IL-1β, IL-6 and NF-κB. Finally, we confirmed that baicalin maintains BA homeostasis and alleviates inflammation through Sirt1/HNF-1α/FXR signaling pathway. CONCLUSION Baicalin protects against estrogen-induced cholestatic liver injury, and the underlying mechanism involved is related to activation of the Sirt1/HNF-1α/FXR signaling pathway.