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Hepatoprotection of Yangonin Against Hepatic Fibrosis in Mice via Farnesoid X Receptor Activation

Hepatoprotection of Yangonin Against Hepatic Fibrosis in Mice via Farnesoid X Receptor Activation

Xiaohui Wang, Ting Fu, Junqiao Wang, Changyuan Wang, Kexin Liu, Jingjing Wu, Huijun Sun, Xiaodong Ma, Pengyuan Sun, Qiang Meng

Int Immunopharmacol. 2019 Oct;75:105833.

PMID: 31450152

Abstract:

Hepatic fibrosis is a reversible would-healing response following chronic liver injury of different aetiologies and represents a major worldwide health problem. Up to date, there is no satisfactory drugs treated for liver fibrosis. The present study was to investigate hepatoprotection of yangonin against liver fibrosis induced by thioacetamide (TAA) in mice and further to clarify the involvement of farnesoid X receptor (FXR) in vivo and in vitro. Yangonin treatment remarkably ameliorated TAA-induced liver injury by reducing relative liver weight, as well as serum ALT and AST activities. Moreover, yangonin alleviated TAA-induced accumulation of bile acids through increasing the expression of bile acid efflux transporters such as Bsep and Mrp2, and reducing hepatic uptake transporter Ntcp expression, all of these are FXR-target genes. The liver sections stained by H&E indicated that the histopathological change induced by TAA was improved by yangonin. Masson and Sirius red staining indicated the obvious anti-fibrotic effect of yangonin. The mechanism of anti-fibrotic effect of yangonin was that yangonin reduced collagen content by regulating the genes involved in hepatic fibrosis including COL1-α1 and TIMP-1. Besides, yangonin inhibited hepatic stellate cell activation by reducing TGF-β1 and α-SMA expression. In addition, yangonin protected against TAA-induced hepatic inflammation via its inhibition of NF-κB and TNF-α. These hepatoprotective effects of yangonin were abrogated by guggulsterone which is a FXR antagonist. In vitro experiment further demonstrated dose-dependent activation of FXR by yangonin using dual-luciferase reporter assay. In summary, yangonin produces hepatoprotection against TAA-induced liver fibrosis via FXR activation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP500629	Yangonin		500-62-9	Price

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