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.

PubMed
Abstract

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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