Icariin attenuates renal fibrosis in chronic kidney disease by inhibiting interleukin-1β/transforming growth factor-β-mediated activation of renal fibroblasts

Icariin (ICA) is a bioactive flavonoid extracted from Epimedium brevicornum Maxim and exhibits a variety of pharmacological activities including antiinflammatory and antioxidant effects. Recently, icariin has shown renoprotective role by inhibiting pathological matrix. However, the underlying mechanisms of the efficacy remain unknown. This study aimed to determine the effects of icariin on renal fibrosis and explore its molecular mechanisms. Chronic kidney disease (CKD) was induced in rats with 5/6 ablation and infarction (A/I) operation. Four weeks later, rats were treated with vehicle or 20 mg/kg (low dose) or 40 mg/kg (high dose) of icariin by daily gavage. Furthermore, to further elucidate the effect mechanisms of icariin, in vitro, NRK-49F cells stimulated by 8 ng/ml IL-1 beta were treated with icariin in the presence or absence of SB431542 or the neutralizing antibody of transforming growth factor-beta (TGF-beta) for 24 h. We showed that icariin treatment for 8 weeks dose-dependently improved 5/6 (A/I)-induced kidney injury and fibrosis, and blocked the release of inflammatory cytokine IL-1 beta. In vitro, icariin inhibited IL-1 beta/TGF-beta-mediated activation of renal fibroblasts. In summary, anti-fibrotic effects of icariin were interconnected with the inhibition of renal fibroblast activation caused by IL-1 beta/TGF-beta signaling.

Automated summary

Research findings show that icariin can alleviate kidney injury and fibrosis, while inhibiting the release of inflammatory cytokine IL-1 beta. The study suggests that the anti-fibrotic effects of icariin are associated with the inhibition of renal fibroblast activation caused by IL-1 beta/TGF-beta signaling pathway.