Isorhamnetin exerts antifibrosis effects by attenuating PDGF-BB--induced HSC-T6 cells activation via suppressing PI3K-AKT Signaling Pathway, a new remedy for liver fibrosis

Abstract

Abstract Background Liver inflammation and fibrosis are the results of chronic liver injuries, which activated myofibroblasts in the liver to produce more proteins in the extracellular matrix. The origin of myofibroblasts is quiescent hepatic stellate cells. Isorhamnetin as a natural flavonoid widely distributed in fruits and vegetables has anti-inflammatory activity and avoids cell proliferation and migration. Objectives We studied the effect of Isorhamnetin as an antifibrotic following stimulation by PDGF- BB in the HSC-T6 cells, as well as related mechanisms in vitro. Methods First of all, we used PDGF- BB to activate the HSC-T6 cells. After that, we used Isorhamnetin to treat activated cells for 24h. Finally, we compared the mRNA expression amount of collagen1 (COLA1), Alpha Smooth Muscle Actin (α-SMA), and level of phosphorylated AKT protein with our control group. Results The obtained data revealed the expression of the COLA1, α-SMA genes, as well as the amount of phosphorylate-AKT protein in the cells treated with PDGF-BB, significantly rose in comparison with our control. In addition, 75 and 100 µM concentrations of Isorhamnetin markedly declined the COLA1, α-SMA expression, and the phosphorylated AKT protein in the HSC-T6 cells. Conclusions Isorhamnetin significantly decreased HSC-T6 activation by preventing the PI3K-AKT cell signaling and reducing the expression of COLA1, α-SMA within liver fibrosis in vitro, so Isorhamnetin can prohibit liver fibrosis progression. In terms of these data, Isorhamnetin use can be recommended as a helpful therapeutic factor to treat liver fibrosis.