Bioactive coumarin-derivative esculetin decreases hepatic stellate cell activation via induction of cellular senescence via the PI3K-Akt-GSK3β pathway

Activation of hepatic stellate cells (HSC) leads to initiation and progression fibrosis. HSC senescence is inversely correlated with proliferation activation. Therefore, induction may be a strategy treat Coumarin-derivatives like esculetin have been suggested inhibit fibrogenic cells. in this study we aimed investigate the effect on activation . Primary rat were used all experiments. Real-time cell analyzer BrdU incorporation assay determine proliferation. Gene expression senescence-associated genes Cdkn1a (p21), P53, markers Acta2, Col1a1 quiescence Pparg Lrat measured by RT-qPCR. Senescence associated β-Galactosidase (SA-β-Gal) staining was identify senescent HSC. Our results demonstrate that increased decreased Protein P21 Cip1 , accompanied phosphorylation Ser473 Akt Ser9 GSK3β esculetin. The dependent PI3K-Akt signaling. We conclude induces reverses activated phenotype depends PI3K-Akt-GSK3β Esculetin could potential therapeutic drug for treatment fibrosis inducing senescence.