Skip to Content
Merck
  • Astragaloside IV inhibits renal tubulointerstitial fibrosis by blocking TGF-β/Smad signaling pathway in vivo and in vitro.

Astragaloside IV inhibits renal tubulointerstitial fibrosis by blocking TGF-β/Smad signaling pathway in vivo and in vitro.

Experimental biology and medicine (Maywood, N.J.) (2014-06-01)
Li Wang, Yang-Feng Chi, Ze-Ting Yuan, Wen-Chao Zhou, Pei-Hao Yin, Xue-Mei Zhang, Wen Peng, Hui Cai
ABSTRACT

Astragaloside IV (AS-IV) is a major active ingredient from Radix astragali, which has been considered as a renoprotective agent; however, its molecular mechanisms are unclear. Thus, we designed to investigate the renoprotective effects and mechanisms of AS-IV in rat model of renal fibrosis induced by unilateral ureteral obstruction (UUO) in vivo and TGF-β1-stimulated rat renal fibroblasts (NRK-49F) in vitro. Sprague-Dawley rats were randomly divided into six groups: sham operation, UUO, UUO/AS-IV (3.3, 10, 33 mg·kg(-1)·d(-1)), and UUO/enalapril (4 mg·kg(-1)·d(-1)). Renal function, tubulointerstitial damage index score, extracellular matrix (ECM) deposition, and the expressions of TGF-β1, connective tissue growth factor (CTGF), α-SMA, fibronectin, collagen I, III, Smad2/3, phosphorylated-Smad2/3, and Smad7 were measured. In addition, the expressions of CTGF, α-SMA, fibronectin, collagen I, III, Smad2/3, phosphorylated-Smad2/3, and Smad7 were measured in TGF-β1-stiumlated NRK-49F cell line. AS-IV significantly decreased UUO-induced renal fibrosis and functional impairment, which are associated with inhibition of TGF-β1, CTGF, α-SMA, and collagen matrix expression, and a decrease in serum creatinine and urea nitrogen. The renoprotective effects of AS-IV on fibrosis were associated with up-regulation of Smad7, thereby blocking up-regulations of TGF-β1, CTGF, and α-SMA, and activation of phosphorylated-Smad2/3. These effects were further conformed in NRK-49F cell line stimulated by TGF-β1. Moreover, knockdown of Smad7 gene in NRK-49F cells was able to prevent AS-IV-induced inhibition to Smad2/3 signaling activation, expression of CTGF, α-SMA, and ECM proteins in response to TGF-β1. Renal tubulointerstitial fibrosis was attenuated by treatment with AS-IV, which was closely related to induction of Smad7, thereby inhibiting TGF-β/Smad signaling.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, ≥99.0% (KT)
Millipore
Astragaloside IV, >98.0%
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ≥98.0% (KT)
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Creatinine, anhydrous, ≥98%
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, BioUltra, ≥99% (titration)
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
Supelco
Dimethyl sulfoxide, for inorganic trace analysis, ≥99.99995% (metals basis)
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt solution, BioUltra, for molecular biology, pH 8.0, ~0.5 M in H2O
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., ACS reagent, ≥99.9% (GC)
Sigma-Aldrich
Dimethyl sulfoxide, ReagentPlus®, ≥99.5%
Supelco
Dimethyl sulfoxide, analytical standard
Sigma-Aldrich
Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
USP
Dimethyl sulfoxide, United States Pharmacopeia (USP) Reference Standard
Dimethyl sulfoxide, European Pharmacopoeia (EP) Reference Standard
Supelco
Creatinine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., dried, ≤0.02% water
Sigma-Aldrich
Dimethyl sulfoxide, suitable for HPLC, ≥99.7%
Astragaloside IV, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Dimethyl sulfoxide, ACS reagent, ≥99.9%