Resveratrol Regulating SIRT1-NF-κB Signal Pathway in Intrahepatic Cholestasis of Pregnancy.
Hepatol Res. 2018 Jun 1. Epub 2018 Jun 1. PMID: 29855113
OBJECTIVE: 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 SIRT1-NF-κB signal pathway and bile acid biosynthesis in intrahepatic cholestasis of pregnancy.
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 condition before dealing these cells with resveratrol as an activator of SIRT1 and EX-57 as an inhibitor of SIRT1. We established ICP rats model to analyze the therapeutic effect of resveratrol.
RESULTS: The expression of SIRT1 protein in normal placenta tissues was higher than that in ICP, and the expression of NF-κB in normal group was lower than ICP group. SIRT1 was down-regulated, while NF-κB and TNF-α were up-regulated, in syncytiotrophoblast HTR-8 cells treated by TCA. This phenomenon could be reverted by resveratrol, and these effects could be blocked by Ex-527.
CONCLUSION: These data demonstrate that resveratrol may protect syncytiotrophoblast against TCA-induced inflammatory injury by up-regulation of SIRT1 and down-regulation of NF-κB and TNF-α. Resveratrol could be a potential therapeutic target for intrahepatic cholestasis of pregnancy.