Oxymatrine inhibits renal fibrosis of obstructive nephropathy by downregulating the TGF-ß1-Smad3 pathway.

This study investigated whether oxymatrine (OMT) treatment can ameliorate renal interstitial fibrosis in unilateral ureteral obstruction (UUO) mice model. Moreover, the potential mechanisms of such treatment were analyzed. Twenty-four C57/BL6 mice were randomly divided into three groups, namely sham group, vehicle plus unilateral ureteral obstruction (UUO)-treated group, and 100 mg/kg/d OMT plus UUO-treated group. All mice were euthanized seven days after surgery, and their kidneys were harvested. Renal injury, fibrosis, expression of proinflammatory cytokines, and the transforming growth factor-ß1/Smads (TGF-ß/Smads) and nuclear factor-kappa B (NF-κB)-signaling pathways were assessed. The results showed OMT significantly prevented kidney injury and fibrosis, as evidenced by decreased expression of collagen-1 and fibronectin. Furthermore, OMT administration inhibited the release of inflammatory factors including tumor necrosis factor-α, (TNF-α) interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), as well as phosphorylated NF-κB p65. In addition, OMT blocked the activation of myofibroblasts by inhibiting the TGF-ß/Smad3-signaling pathway. The findings indicate that OMT-attenuated renal fibrosis and inflammation, and this renoprotective effect may be ascribed to the inactivation of the TGF-ß/Smad3 and NF-κB p65 pathways.

Hesperetin alleviates renal interstitial fibrosis by inhibiting tubular epithelial-mesenchymal transition in vivo and in vitro.

Hesperetin (HES) is a flavonoid that has been reported to exert protective effects against cardiac remodeling, lung fibrosis and hepatic fibrosis. However, reports on the effects and potential mechanisms of HES in renal fibrosis are limited. In the present study, a unilateral ureteric obstruction (UUO) mouse model and a transforming growth factor (TGF)-ß1-activated normal rat kidney (NRK)-52E cell model were established. HES was subsequently administered to these models to evaluate its anti-fibrotic effects and potential underlying mechanisms of action. The results demonstrated that HES reduced obstruction-induced renal injury and deposition of the extracellular matrix components collagen-I and fibronectin in UUO mouse kidneys (P<0.05). Furthermore, HES treatment significantly suppressed EMT, as evidenced by decreased expression of α-smooth muscle actin and E-cadherin, (P<0.05). Additionally, HES inhibited the hedgehog signaling pathway in UUO mice and TGF-ß1-treated NRK-52E cells. The present findings indicate that HES treatment may inhibit EMT and renal fibrosis in vivo and in vitro by antagonizing the hedgehog signaling pathway.