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Didymin Alleviates Hepatic Fibrosis Through Inhibiting ERK and PI3K/Akt Pathways via Regulation of Raf Kinase Inhibitor Protein

Didymin Alleviates Hepatic Fibrosis Through Inhibiting ERK and PI3K/Akt Pathways via Regulation of Raf Kinase Inhibitor Protein

Xing Lin, Faicheng Bai, Jinlan Nie, Shengjuan Lu, Chunyuang Lu, Xunshuai Zhu, Jinbin Wei, Zhongpeng Lu, Quanfang Huang

Cell Physiol Biochem. 2016;40(6):1422-1432.

PMID: 27997902

Abstract:

Background:
Didymin has been reported to have anti-cancer potential. However, the effect of didymin on liver fibrosis remains illdefined.
Methods:
Hepatic fibrosis was induced by CCl4 in rats. The effects of didymin on liver pathology and collagen accumulation were observed by hematoxylin-eosin and Masson's trichrome staining, respectively. Serum transaminases activities and collagen-related indicators levels were determined by commercially available kits. Moreover, the effects of didymin on hepatic stellate cell apoptosis and cell cycle were analyzed by flow cytometry. Mitochondrial membrane potential was detected by using rhodamine-123 dye. The expression of Raf kinase inhibitor protein (RKIP) and the phosphorylation of the ERK/MAPK and PI3K/Akt pathways were assessed by Western blot.
Results:
Didymin significantly ameliorated chronic liver injury and collagen deposition. It strongly inhibited hepatic stellate cells proliferation, induced apoptosis and caused cell cycle arrest in G2/M phase. Moreover, didymin notably attenuated mitochondrial membrane potential, accompanied by release of cytochrome C. Didymin significantly inhibited the ERK/MAPK and PI3K/Akt pathways. The effects of didymin on the collagen accumulation in rats and on the biological behaviors of hepatic stellate cells were largely abolished by the specific RKIP inhibitor locostatin.
Conclusion:
Didymin alleviates hepatic fibrosis by inhibiting ERK/MAPK and PI3K/Akt pathways via regulation of RKIP expression.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP14259473	Didymin		14259-47-3	Price

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