Wen-pi-tang-Hab-Wu-ling-san reduces ureteral obstructive renal fibrosis by the reduction of oxidative stress, inflammation, and TGF-β/Smad2/3 signaling

Kidney fibrosis results in chronic renal disease. The current treatment of chronic renal diseases is limited to angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Recently, we found that Wen-pi-tang-Hab-Wu-ling-san (WHW) extract, which has been used to treat renal diseases in herbal medicine for a long time, plays anti-fibrogenic. Here, we investigated the role of WHW in the kidney fibrosis induced by unilateral ureteral obstruction (UUO) in mice. C57BL/6 male mice were subjected to UUO on day 0 and then administered with either WHW (2, 10, or 50 mg/kg of body weight) or vehicle orally from 1 day after UUO to finish the experiment. WHW-administration significantly mitigated the UUO-induced kidney fibrotic changes including tubular atrophy and dilatation, collagen accumulation, expansion of interstitial space and leukocyte infiltration. WHW prevented the increases of oxidative stress by the prevention of UUO-induced decreases of catalase, copper-zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD), resulting in reduced production of oxidative stress. Furthermore, WHW reduced transforming growth factor-β (TGF-β) expression and phosphorylation of Smad2/3 stimulated by UUO. In conclusion, WHW prevented kidney fibrosis following UUO by the inhibition of inflammation, oxidative stress and TGF-β/Smad2/3 signaling pathway.