期刊
PHYTOTHERAPY RESEARCH
卷 35, 期 1, 页码 452-462出版社
WILEY
DOI: 10.1002/ptr.6824
关键词
apoptosis; GSK3 beta; hepatic stellate cells; honokiol; liver fibrosis; Wnt3a/beta-catenin
资金
- Korea Science and Engineering Foundation [2017R1A2A1A17069297]
The study found that honokiol can exert apoptotic and antifibrotic effects by activating GSK3 beta and inhibiting the Wnt3a/beta-catenin signaling pathway.
Though honokiol, derived from the Magnolia tree, was known to suppress renal fibrosis, pulmonary fibrosis, non-alcoholic steatoheptitis, inflammation and cancers, the underlying antifibrotic mechanisms of honokiol are not fully understood in hepatic stellate cells until now. Thus, in the present study, inhibitory mechanism of honokiol on liver fibrosis was elucidated mainly in hepatic stellate cells (HSCs) by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle analysis and western-blotting. Honokiol exerted cytotoxicity in LX-2, HSC-T6 and Hep-G2 cells. Honokiol increased sub G1 population and activated caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP) in HSCs. Moreover, honokiol attenuated the expression of alpha smooth muscle actin (alpha-SMA), transforming growth factor beta 1 (TGF-beta 1), phospho-Smad3, phospho-AKT, cyclin D1, c-Myc, Wnt3a, beta-catenin, and activated phosphorylation of glycogen synthase kinase 3 beta (GSK3 beta) in HSCs. Conversely, GSK3 beta inhibitor SB216763 reversed the effect of honokiol on PARP, alpha-SMA, phospho-GSK3 beta, beta-catenin and sub G1 population in LX-2 cells. Overall, honokiol exerts apoptotic and antifibrotic effects via activation of GSK3 beta and inhibition of Wnt3a/beta-catenin signalling pathway.
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