Resveratrol regulates the silent information regulator 1-nuclear factor-κB signaling pathway in intrahepatic cholestasis of pregnancy.

ABSTRACT

AIM: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease characterized by raised serum bile acids and adverse fetal outcomes. In this study, we aimed to explore the molecular and biochemical mechanism of resveratrol in regulating the silent information regulator 1-nuclear factor-κB (SIRT1-NF-κB) signaling pathway and bile acid biosynthesis in ICP. METHODS: We analyzed serum and placenta samples from 30 normal and ICP pregnancy women. Then we treated HTR-8/SVneo cells with taurocholic acid (TCA) to mimic ICP conditions before treating these cells with resveratrol, as an activator of SIRT1, and EX-57, as an inhibitor of SIRT1. We established an ICP rat model to analyze the therapeutic effect of resveratrol. RESULTS: The expression of SIRT1 protein was higher in normal placenta tissues than in ICP, and the expression of NF-κB was lower in the normal group than in the ICP group. We found that SIRT1 was downregulated, whereas NF-κB and tuor necrosis factor-α (TNF-α) were upregulated, in syncytiotrophoblast HTR-8 cells treated with TCA. This phenomenon could be reversed by resveratrol, and these effects could be blocked by Ex-527. CONCLUSION: These data indicate that resveratrol might protect syncytiotrophoblast against TCA-induced inflammatory injury by upregulation of SIRT1 and downregulation of NF-κB and TNF-α. Resveratrol could be a potential therapeutic target for ICP.