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Isorhamnetin Exerts Antifibrotic Effects by Attenuating Platelet-Derived Growth Factor-BB-induced HSC-T6 Cells
Mojtaba Rashidi1, Emad Matour1, Hasti Beheshti Nasab1
1Cellular and Molecular Research Center, Medical Basic Science Research Institute, Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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 and 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.
Conclusion:
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.
Insights
Isorhamnetin effectively reduces liver fibrosis markers in activated hepatic stellate cells. This study shows isorhamnetin as a potential therapeutic agent for liver fibrosis by inhibiting key fibrotic pathways.
Area of Science:
- Hepatology and Molecular Biology
- Pharmacology
Background:
- Liver fibrosis is a global health concern with no definitive cure.
- Understanding molecular pathways is crucial for developing effective treatments.
- Platelet-derived growth factor (PDGF)-BB is implicated in liver fibrosis progression.
Purpose of the Study:
- To investigate the antifibrotic effects of isorhamnetin on PDGF-BB-activated hepatic stellate cells (HSC)-T6.
- To evaluate the impact of isorhamnetin on collagen type 1 (COLA1) and alpha-smooth muscle actin (α-SMA) expression.
- To assess the role of isorhamnetin in modulating signaling pathways, specifically phosphorylated AKT.
Main Methods:
- HSC-T6 cells were activated using PDGF-BB.
- Activated cells were treated with varying concentrations of isorhamnetin for 24 hours.
- mRNA expression of COLA1 and α-SMA, and levels of phosphorylated AKT were quantified and compared to controls.
Main Results:
- PDGF-BB significantly increased COLA1, α-SMA expression, and phosphorylated AKT levels.
- Isorhamnetin treatment, particularly at 75 and 100 µM, markedly reduced COLA1 and α-SMA expression.
- Isorhamnetin also decreased the levels of phosphorylated AKT in activated HSC-T6 cells.
Conclusions:
- Isorhamnetin demonstrates significant antifibrotic activity in vitro.
- It effectively reduces hepatic stellate cell activation and key fibrotic markers.
- Isorhamnetin shows potential as a therapeutic agent for treating liver fibrosis.
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