Baicalein ameliorates renal interstitial fibrosis by inducing myofibroblast apoptosis in vivo and in vitro

Objective To investigate the anti-fibrotic effects of baicalein and its influence on myofibroblasts in vivo and in vitro. Materials and Methods An in vivo unilateral ureteric obstruction (UUO) mouse model and an in vitro transforming growth factor beta 1 (TGF-beta 1) activated normal rat kidney (NRK)-49F cell model were established. Baicalein treatment was then investigated in these models to assess its anti-fibrotic effects and potential mechanisms of action. Results Baicalein attenuated renal fibrosis by ameliorating kidney injury, reducing deposition of fibronectin and collagen type 1, and inducing apoptosis in myofibroblasts in the UUO mouse model. Baicalein also induced apoptosis of TGF-beta 1-activated myofibroblasts in vitro in a dose-dependent manner. Furthermore, baicalein triggered a cascade of mitochondrion-associated apoptosis by upregulating cleaved-caspase-3, Bcl2-associated X protein (Bax), and cleaved-caspase-9 while downregulating the protein expression of B-cell lymphoma 2 (Bcl-2). Additionally, down-regulation of phosphorylated protein kinase B (pAkt) was found in the baicalein-induced pro-apoptotic components. Conclusions The present findings show that baicalein can ameliorate tubulointerstitial fibrosis by inducing myofibroblast apoptosis through the mitochondrion-associated intrinsic pathway, which may be mediated by the inhibition of the phosphoinositide-3-kinase/Akt (PI3k/Akt) pathway.