ReferenceID 2969
Tectorigenin alleviates intrahepatic cholestasis by inhibiting hepatic inflammation and bile accumulation via activation of PPARγ
Br J Pharmacol
BACKGROUND AND PURPOSE: Increasing evidence suggests that human cholestasis is closely associated with the accumulation and activation of hepatic macrophages. Research indicates that activation of PPARgamma exerts liver
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- Reference Id
- 2969
- Evidence Id
- 19559
- Core Evidence Id
- 19559
- Source Reference Id
- 5937
- Herb2 Reference Id
- HBREF006734
- Subject Paper Key
- HBIN045833_33661551
- Pubmed Id
- 33661551
- Doi
- 10.1111/bph.15429
- Paper Title
- Tectorigenin alleviates intrahepatic cholestasis by inhibiting hepatic inflammation and bile accumulation via activation of PPARγ
- Paper Abstract
- BACKGROUND AND PURPOSE: Increasing evidence suggests that human cholestasis is closely associated with the accumulation and activation of hepatic macrophages. Research indicates that activation of PPARgamma exerts liver protective effects in cholestatic liver disease (CLD), particularly by ameliorating inflammation and fibrosis, thus limiting disease progression. However, existing PPARgamma agonists, such as troglitazone and rosiglitazone, have significant side effects that prevent their clinical application in the treatment of CLD. In this study, we found that tectorigenin alleviates intrahepatic cholestasis in mice by activating PPARgamma. EXPERIMENTAL APPROACH: Wild-type mice were intragastrically administered alpha-naphthylisothiocyanate (ANIT) or fed a diet containing 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to simultaneously establish an experimental model of intrahepatic cholestasis and tectorigenin intervention, followed by determination of intrahepatic cholestasis and the mechanisms involved. In addition, PPARgamma-deficient mice were administered ANIT and/or tectorigenin to determine whether tectorigenin exerts its liver protective effect by activating PPARgamma. KEY RESULTS: Treatment with tectorigenin alleviated intrahepatic cholestasis by inhibiting the recruitment and activation of hepatic macrophages and by promoting the expression of bile transporters via activation of PPARgamma. Furthermore, tectorigenin increased expression of the bile salt export pump (BSEP) through enhanced PPARgamma binding to the BSEP promoter. In PPARgamma-deficient mice, the hepatoprotective effect of tectorigenin during cholestasis was blocked. CONCLUSION AND IMPLICATIONS: In conclusion, tectorigenin reduced the recruitment and activation of hepatic macrophages and enhanced the export of bile acids by activating PPARgamma. Taken together, our results suggest that tectorigenin is a candidate compound for cholestasis treatment.
- Journal
- Br J Pharmacol
- Publish Year
- 2021
- Experiment Subject
- mouse; human
- Experiment Type
- Animal Experiment
- Phenotype Related
- Cholestasis; Inflammation; Cholestatic Liver Disease; Fibrosis; Intrahepatic Cholestasis
- Paper Title Cn
- Paper Title En
- Tectorigenin alleviates intrahepatic cholestasis by inhibiting hepatic inflammation and bile accumulation via activation of PPARγ
- Bilingual Status
- semi_complete