Wen-pi-tang-Hab-Wu-ling-san attenuates kidney fibrosis induced by ischemia/ reperfusion in mice

Renal fibrosis is highly implicated as a cause of chronic renal failure, for which suitable therapeutics have not yet been developed. Recently, it was reported that Wen-pi-tang-Hab-Wu-ling-san (WHW) extract attenuates epithelial cells undergoing mesenchymal transition in cultured Madin-Darby canine kidney cells. This study investigated whether WHW extract prevents renal fibrosis induced by ischemia/reperfusion (I/R) in mice. Ischemia/reperfusion resulted in kidney fibrosis at 14 days after the procedure. When WHW was administered orally to mice beginning from 2 days after the onset of ischemia until killing, the fibrosis was significantly reduced. WHW administration significantly prevented a post-ischemic decrease of copper-zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) activities, leading to decreased lipid peroxidation and hydrogen peroxide production. In addition, WHW administration attenuated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2 (JNK1/2) and attenuated the activation of nuclear factor-kappa B (NF-κB) in the kidneys subjected to ischemia. In conclusion, WHW extract attenuated the renal fibrosis and the attenuation was associated with a reduction of oxidative stress and an inhibition of ERK1/2, JNK1/2, p38 and NF-κB activation. WHW extract may be an attractive agent to attenuate the progression of fibrosis.