Isorhamnetin Exerts Antifibrotic Effects by Attenuating Platelet-Derived Growth Factor-BB-induced HSC-T6 Cells Activation via Suppressing PI3K-AKT Signaling Pathway

Authors
Mojtaba Rashidi
Emad Matour
Hasti Beheshtinasab
Maryam Cheraghzadeh
Elham Shakerian
Cellular and Molecular Research Center, Medical Basic Science Research Institute, Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
10.61186/ibj.3948
Abstract
Background: Currently, liver fibrosis is growing worldwide; unfortunately, there is no definite cure for this disease. Hence, understanding the molecular pathways involved in the development of liver fibrosis can help to find a proper treatment. In this study, we aimed to evaluate the effects of isorhamnetin as an antifibrotic agent on platelet-derived growth factor (PDGF)-BB-activated hepatic stellate cells (HSC)-T6 cells in a concentration-dependent manner. We have also attempted to assess signaling pathways that may affect liver fibrosis.

Methods: PDGF-BB was used to activate the HSC-T6 rat hepatic stellate cell line. The activated cells were treated with Isorhamnetin for 24 h. Finally, we compared the mRNA expression level of COLA1 α-SMA and also the level of phosphorylated AKT protein with the control group.

Results: The obtained data revealed a significant increase in the expression level of the COLA1 and α-SMA genes (p > 0.05), as well as phosphorylated AKT protein, in the cells treated with PDGF-BB. In addition, 75 and 100 µM concentrations of Isorhamnetin markedly declined the COLA1 and α-SMA expression and also the phosphorylated AKT protein level in the HSC-T6 cells.

Conclusions: Our findings suggest that Isorhamnetin decreases HSC-T6 activation, the expression of COLA1 and α-SMA, in vitro, which could act as an antifibrotic element to reduce and treat liver fibrosis disease.
Keywords
Hepatitis
Liver injuries
PI3K-AKT