You-gui Pill ameliorates renal tubulointerstitial fibrosis via inhibition of TGF-β/Smad signaling pathway

Li Wang, Ai Li Cao, Yang Feng Chi, Zheng Cai Ju, Pei Hao Yin, Xue Mei Zhang, Wen Peng

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19 Scopus citations

Abstract

Ethnopharmacological relevance You-gui Pill (YGP), a traditional Chinese medicinal prescription, was widely used to warm and recuperate "kidney-yang" clinically for hundreds of years in China. Recent studies found that YGP had a potential benefit for renoprotection. Aim of the study The present study aimed to elucidate the in vivo and in vitro efficacy of YGP on renal tubulointerstitial fibrosis, and the molecular mechanism is also investigated. Materials and methods Rat renal tubulointerstitial fibrosis model was elicited by unilateral ureteral obstruction (UUO). Sprague-Dawley rats underwent UUO and were studied after 14 days. Animals were randomly subjected to six groups: sham, UUO, UUO/YGP (0.14, 0.42, 1.26 g/kg/d), and UUO/enalapril (10 mg/kg/d). HE, Masson and ELISA were used for evaluate renal injury and function. Immunohistochemical analysis and western blot were used to detect the expressions of α-SMA, fibronectin, collagen matrix and Smads. In vitro studies were investigated in TGF-β1-stiumlated NRK-49F cell line. Results Oral administration of YGP significantly decreased UUO-induced inflammatory cell infiltration, tubular atrophy and interstitial fibrosis, and there was no significant difference between YGP at 1.26 g/kg and enalapril at 10 mg/kg treatment (P>0.05). Meanwhile, serum creatinine and blood urea nitrogen levels were reduced dramatically (P<0.01). In coincide with the decreased of TGF-β1, α-SMA, fibronectin and collagen matrix expressions were also declined with YGP treatment in both UUO kidneys and TGF-β1-stimulated NRK-49F cell line. Additionally, nuclear translocation of p-Smad2/3 was markedly down-regulated by YGP (P<0.001), with a relative mild up-regulated expression of Smad7 (P<0.05). Conclusions Our findings demonstrate that YGP had a renoprotective effect in ameliorating renal tubulointerstitial fibrosis, and this activity possibly via suppression of the TGF-β and its downstream regulatory signaling pathway, including Smad2/3.

Original languageEnglish
Pages (from-to)229-238
Number of pages10
JournalJournal of Ethnopharmacology
Volume169
DOIs
StatePublished - 25 Apr 2015
Externally publishedYes

Keywords

  • 3D HPLC three-dimensional high performance liquid chromatography
  • ANOVA one-way analysis of variances
  • BUN blood urea nitrogen
  • CMC carboxymethyl cellulose
  • ECM extracellular matrix
  • FBS fetal bovine serum
  • GAPDH glyceraldehyde-3-phosphate dehydrogenase
  • HRP horseradish peroxidase
  • LDH lactate dehydrogenase
  • MMP-2 matrix metalloproteinase 2.
  • SDS-PAGE SDS polyacrylamide gel electrophoresis
  • TCM Traditional Chinese Medicine
  • TIF tubulointerstitial fibrosis
  • UUO unilateral ureteral obstruction
  • YGP You-gui Pill
  • α-SMA α-smooth muscle actin

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