Astragaloside Ameliorates Kidney Fibrosis by Inhibiting the Sonic Hedgehog Signaling Pathway

Background: Sonic hedgehog (SHH) signaling plays a critical role in promoting renal fibrosis.Astragalosid (As-IV) is the main integrete of the traditional Chinese medicine(TCM) Astragalus membranaceus(Huangqi) .Our preliminary researches indicated that intervention with some TCM formulas containing Huangqi led to a significant amelioration of renal interstitial fibrosis.This study aims to explore the mechanism by which As-IV mitigates renal interstitial fibrosis in mice model of unilateral ureteral obstruction(UUO) through the modulation of the SHH signaling pathway. Methods: Thirty male mice were randomly assigned into five groups: a control group, a UUO model group, and three As-IV treatment groups with low, medium, and high doses. Except for the control group, the other four groups underwent ligation of a single ureter to establish an animal model of renal interstitial fibrosis. The As-IV groups was administered As-IV via daily gavage for 14 days. Then Scr and BUN were measured in all groups. Renal tissue morphology was observed using HE staining, and Masson's trichrome staining was employed to assess the deposition of extracellular matrix(ECM) in the renal tissue. The expression of SHH and its downstream signaling molecules Gli1 and Snail was detected using Western blot analysis. Results: Compared with the control group, the UUO model group exhibited elevated levels of Scr and BUN, increased expression of ECM, and heightened levels of SHH. The protein expression of Gli1 and Snail were markedly upregulated (P < 0.05). In contrast to the UUO model group, As-IV groups significantly reduced Scr and BUN levels, diminished ECM deposition, and downregulated the levels of SHH as well as the protein expression levels of Gli1 and Snail(figure 1). Conclusion: As-IV has been shown to improve renal function and inhibit renal interstitial fibrosis in mice model of UUO, with its effects potentially being associated with the blockade of the SHH signaling pathway. Funding: Government Support – Non-U.S.