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Abstract Title:

Liquiritigenin inhibits hepatic fibrogenesis and TGF-β1/Smad with Hippo/YAP signal.

Abstract Source:

Phytomedicine. 2018 Dec 10 ;62:152780. Epub 2018 Dec 10. PMID: 31121384

Abstract Author(s):

Eun Hye Lee, Kwang-Il Park, Kwang-Youn Kim, Ju-Hee Lee, Eun Jeong Jang, Sae Kwang Ku, Sang Chan Kim, Ho Young Suk, Ji Young Park, Su Youn Baek, Young Woo Kim

Article Affiliation:

Eun Hye Lee

Abstract:

BACKGROUND: Recent reports highlighted the possibility that Yes-associated protein (YAP) and transforming growth factor-β1 (TGF-β1) can act as critical regulators of hepatic stellate cells (HSCs) activation; therefore, it is natural for compounds targeting Hippo/YAP and TGF-β1/Smad signaling pathways to be identified as potential anti-fibrotic candidates.

PURPOSE: Liquiritigenin (LQ) is an aglycone of liquiritin and has been reported to protect the liver from injury. However, its effects on the Hippo/YAP and TGF-β1/Smad pathways have not been identified to date.

METHODS: We conducted a series of experiments using CCl-induced fibrotic mice and cultured LX-2 cells.

RESULT: LQ significantly inhibited liver fibrosis, as indicated by decreases in regions of hepatic degeneration, inflammatory cell infiltration, and the intensity ofα-smooth muscle actin (α-SMA) staining in mice. Moreover, LQ blocked the TGF-β1-induced phosphorylation of Smad 3, and the transcript levels of plasminogen activator inhibitor-1 (PAI-1) and matrix metalloproteinase-2 (MMP-2) in LX-2 cells, which is similar with resveratrol and oxyresveratrol (positive controls). Furthermore, LQ increased activation of large tumor suppressor kinase 1 (LATS1) with the induction of YAP phosphorylation, thereby preventing YAP transcriptional activity and suppressing the expression of exacerbated TGF-β1/Smad signaling molecules.

CONCLUSION: These results clearly show that LQ ameliorated experimental liver fibrosis by acting on the TGF-β1/Smad and Hippo/YAP pathways, indicating that LQ has the potential for effective treatment of liver fibrosis.

Study Type : Animal Study
Additional Links
Pharmacological Actions : Anti-Fibrotic : CK(924) : AC(463)

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Sayer Ji
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