Apoptotic and antihepatofibrotic effect of honokiol via activation of GSK3β and suppression of Wnt/β-catenin pathway in hepatic stellate cells.

Abstract

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 (α-SMA), transforming growth factor beta 1 (TGF-β1), phospho-Smad3, phospho-AKT, cyclin D1, c-Myc, Wnt3a, β-catenin, and activated phosphorylation of glycogen synthase kinase 3 beta (GSK3β) in HSCs. Conversely, GSK3β inhibitor SB216763 reversed the effect of honokiol on PARP, α-SMA, phospho-GSK3β, β-catenin and sub G1 population in LX-2 cells. Overall, honokiol exerts apoptotic and antifibrotic effects via activation of GSK3β and inhibition of Wnt3a/β-catenin signalling pathway.

• Authors: Il Ho Lee, Eunji Im, Hyo-Jung Lee, Deok Yong Sim, Jae Hee Lee, Ji Hoon Jung, Ji Eon Park, Bum Sang Shim, Sung-Hoon Kim
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 35 Issue 1 Pg. 452-462 (Jan 2021) ISSN: 1099-1573 [Electronic] England
• PMID: 32776713 (Publication Type: Journal Article)
• Copyright: © 2020 John Wiley & Sons Ltd.

Chemical References

• Actins
• Biphenyl Compounds
• CCND1 protein, human
• CTNNB1 protein, human
• Lignans
• SMAD3 protein, human
• Smad3 Protein
• TGFB1 protein, human
• Transforming Growth Factor beta1
• beta Catenin
• honokiol
• Cyclin D1
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• CASP3 protein, human
• Caspase 3

Topics

• Actins (metabolism)
• Biphenyl Compounds (pharmacology)
• Caspase 3 (metabolism)
• Cell Line
• Cyclin D1
• Glycogen Synthase Kinase 3 beta (metabolism)
• Hep G2 Cells
• Hepatic Stellate Cells (drug effects)
• Humans
• Lignans (pharmacology)
• Liver Cirrhosis
• Phosphorylation
• Smad3 Protein (metabolism)
• Transforming Growth Factor beta1 (metabolism)
• Wnt Signaling Pathway (drug effects)
• beta Catenin (metabolism)