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  • Title: You-gui Pill ameliorates renal tubulointerstitial fibrosis via inhibition of TGF-β/Smad signaling pathway.
    Author: Wang L, Cao AL, Chi YF, Ju ZC, Yin PH, Zhang XM, Peng W.
    Journal: J Ethnopharmacol; 2015 Jul 01; 169():229-38. PubMed ID: 25922264.
    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, 1.26g/kg/d), and UUO/enalapril (10mg/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 1.26g/kg and enalapril at 10mg/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.
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