Baicalin inhibits PDGF-BB-induced hepatic stellate cell proliferation, apoptosis, invasion, migration and activation via the miR-3595/ACSL4 axis

Hepatic fibrosis is a physiological response to liver injury that includes a range of cell types. The pathogenesis of hepatic fibrosis currently focuses on hepatic stellate cell (HSC) activation into muscle fiber cells and fibroblasts. Baicalin is a flavone glycoside. It is the glucuronide of baicalein, which is extracted from the dried roots of Scutellaria baicalensis Georgi. Previous work focused on the anti-viral, -inflammatory and -tumor properties of baicalin. However, the potential anti-fibrotic effects and mechanisms of baicalin are not known. The present study demonstrated that baicalin influenced the activation, proliferation, apoptosis, invasion and migration of platelet-derived growth factor-BB-induced activated HSC-T6 cells in a dose-dependent manner. To investigate the anti-fibrotic effect of baicalin, a one-color micro (mi)RNA array and reverse transcription-quantitative polymerase chain reaction analyses were used. Results demonstrated that baicalin increased the expression of the miRNA, miR-3595. In addition, the inhibition of miR-3595 substantially reversed the anti-fibrotic effect of baicalin. The present data also suggested that miR-3595 negatively regulates the long-chain-fatty-acid-CoA ligase 4 (ACSL4). Furthermore, ACSL4 acted in a baicalin-dependent manner to exhibit anti-fibrotic effects. Taken together, it was concluded that baicalin induces miR-3595 expression that modulates the expression levels of ACSL4. To the best of our knowledge, the present study is the first to demonstrate that baicalin induces overexpression of human miR-3595, and subsequently decreases the expression of ACSL4, resulting in an anti-fibrotic effect.