Danggui Shaoyao San Ameliorates Renal Fibrosis via Regulation of Hypoxia and Autophagy

Abstract EN

Danggui Shaoyao San (DSS), a traditional Chinese medicinal prescription, was widely used to reinforce earth to activate collaterals in ancient times.

Recently, many clinical studies found that DSS had a renoprotection.

In this study, we evaluated the effect of DSS on unilateral ureteral obstruction- (UUO-) induced renal fibrosis in rats and investigated the mechanisms underlying the effect.

Sprague Dawley (SD) rats were randomized to UUO or Sham operation.

After 1 day, the rats that underwent UUO were randomized to treatment for four experimental groups (n=10 each group): Sham, UUO only, UUO+ benazepril (Bena), and UUO+DSS.

After 4 weeks, we demonstrated that DSS significantly suppressed UUO-induced renal hypertrophy by gravimetric.

In addition, DSS obviously prevented UUO-induced disorder in renal structure and renal function by HE and biochemistry test.

We also found that DSS abrogated UUO-induced renal fibrosis by Masson’s staining and collagen volume fraction (CVF) analysis; this is consistent with the western blot analysis that showed DSS abrogated the UUO-induced enhanced TGF-β1 and weakened BMP-7.

Compared with the UUO only group, rats treated with DSS exhibited significant increase in vascular density, followed by decrease in hypoxia and HIF-1α protein level through western blot and immunofluorescence analysis.

Furthermore, we also determined proteins of autophagy and DSS enhanced autophagy to prevent the damage-induced by UUO.

Taken together, our findings demonstrated that DSS had a renoprotection effect in ameliorating renal fibrosis possibly via attenuating tissue hypoxia and regulating autophagy.