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


OBJECTIVE
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.


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.
Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Li
L
Wang
Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Ai-Li
AL
Cao
Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Yang-Feng
YF
Chi
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Zheng-Cai
ZC
Ju
Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Pei-Hao
PH
Yin
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: xuemzhang@fudan.edu.cn.
Xue-Mei
XM
Zhang
Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China; Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. Electronic address: pengwen_01@vip.sina.com.
Wen
W
Peng
D000199:Actins; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use*; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use; D005355:Fibrosis / Q000188:drug therapy* / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation
D000199:Actins; D004365:Drugs, Chinese Herbal; D004656:Enalapril; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C498862:Acta2 protein, rat; C552041:yougui
5-HMF (PubChem CID: 237332); Carboxymethyl cellulose (PubChem CID: 6328154); Cinnamic acid (PubChem CID: 444539); Gallic acid (PubChem CID: 370); Kaempferide (PubChem CID: 5281666); Loganin (PubChem CID: 87691); Morroniside (PubChem CID: 11228693); Quercerin (PubChem CID: 5280343); Renal tubulointerstitial fibrosis; Rutin (PubChem CID: 5280805); Smad2/3; Sweroside (PubChem CID: 161036); TGF-β; Unilateral ureteral obstruction; You-gui Pill