PMID- 25087615 OWN - NLM STAT- MEDLINE DCOM- 20151029 LR - 20140916 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 155 IP - 3 DP - 2014 Sep 29 TI - Ureic clearance granule, alleviates renal dysfunction and tubulointerstitial fibrosis by promoting extracellular matrix degradation in renal failure rats, compared with enalapril. PG - 1541-52 LID - S0378-8741(14)00567-4 [pii] LID - 10.1016/j.jep.2014.07.048 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal compound prescription has a unique therapeutic action on chronic kidney disease (CKD) in China. In clinics, Uremic Clearance Granules (UCG), a compounded Chinese patent medicine, has been frequently used to treat chronic renal failure (CRF) patients for nearly 30 years, however, the deep therapeutic mechanisms involved in vivo remain a challenge. This study aims to demonstrate the effects and mechanisms of UCG on renal dysfunction and tubulointerstitial fibrosis by regulating extracellular matrix (ECM) degradation and transforming growth factor (TGF)-beta1/Smad signaling activity in vivo, compared with enalapril. MATERIALS AND METHODS: Twenty-six rats were randomly divided into 4 groups, a sham-operated group (Sham group), a vehicle-intervened group (Vehicle group), a UCG-treated group (UCG group) (5g/kg/day) and an enalapril-treated group (Enalapril group) (20mg/kg/day). The rats with renal failure were induced by adenine (150 mg/kg/day) and unilateral ureteral obstruction (UUO), and killed on day 35 after the administration. Proteinuria, urinary N-acetyl-beta-D-glucosaminidase (UNAG), blood biochemical parameters, renal morphological changes, collagen type IV (CIV), matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of metalloproteinase (TIMP)-1, as well as the key molecular protein expressions in TGF-beta1/Smad signaling pathway were observed, respectively. RESULTS: Adenine administration and UUO induced severe renal damages, as indicated by renal dysfunction, proteinuria and the marked histopathological injuries in the tubules and interstitium, which were associated with MMP-2/TIMP-1 imbalance and TGF-beta1/Smad signaling activity, as shown by up-regulation of the protein expressions of TGF-beta1, TGF-beta receptor type I (RI), TGF-beta receptor type II (RII), Smad2/3, phosphorylated-Smad2/3 (p-Smad2/3) and Smad4, as well as down-regulation of the protein expression of Smad7 in the kidney. UCG treatment, however, significantly not only attenuated renal dysfunction and tubulointerstitial fibrosis, but also improved the protein expressions of MMP-2, TIMP-1, TGF-beta1, TGF-beta RI, p-Smad2/3, Smad4 and Smad7 in the kidney. Besides, the effects of UCG were stronger than those of enalapril partly. CONCLUSION: UCG similar to enalapril, is renoprotective via ameliorating renal dysfunction and tubulointerstitial fibrosis in the renal failure model. The potential mechanisms by which UCG exerts its therapeutical effects in vivo are through promoting ECM degradation and regulating MMP-2/TIMP-1 balance or signaling molecular activity in TGF-beta1/Smad pathway in the kidney. These findings suggest that UCG treatment is undoubtedly useful in preventing the progression of CRF. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Huang, Yan-Ru AU - Huang YR AD - Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjng, China. FAU - Wei, Qing-Xue AU - Wei QX AD - Changshu Hospital of Traditional Chinese Medicine, Changshu, China. FAU - Wan, Yi-Gang AU - Wan YG AD - Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, China. Electronic address: wyg68918@sina.com. FAU - Sun, Wei AU - Sun W AD - Department of Nephrology, Jiangsu Provincial Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing 210029, Nanjing, China. Electronic address: wyg68918@hotmail.com. FAU - Mao, Zhi-Min AU - Mao ZM AD - Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjng, China. FAU - Chen, Hao-Li AU - Chen HL AD - Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjng, China. FAU - Meng, Xian-Jie AU - Meng XJ AD - Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjng, China. FAU - Shi, Xi-Miao AU - Shi XM AD - Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjng, China. FAU - Tu, Yue AU - Tu Y AD - Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjng, China. FAU - Zhu, Quan AU - Zhu Q AD - Guangzhou Consun Drug Research Ltd., Guangzhou, China. LA - eng PT - Journal Article DEP - 20140801 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Drugs, Chinese Herbal) RN - 0 (Protective Agents) RN - 0 (Smad Proteins) RN - 0 (Transforming Growth Factor beta1) RN - 0 (niaoduqing keli) RN - 69PN84IO1A (Enalapril) RN - EC 3.2.1.52 (Acetylglucosaminidase) SB - IM MH - Acetylglucosaminidase/urine MH - Animals MH - Disease Models, Animal MH - Drugs, Chinese Herbal/pharmacology/*therapeutic use MH - Enalapril/pharmacology/therapeutic use MH - Extracellular Matrix/drug effects MH - Fibrosis MH - Kidney/drug effects/metabolism/pathology MH - Male MH - Protective Agents/pharmacology/*therapeutic use MH - Rats, Sprague-Dawley MH - Renal Insufficiency/*drug therapy/metabolism/pathology/urine MH - Smad Proteins/metabolism MH - Transforming Growth Factor beta1/metabolism OTO - NOTNLM OT - Extracellular matrix degradation OT - Matrix metalloproteinases OT - Renal dysfunction OT - TGF-beta1/Smad signaling OT - Tubulointerstitial fibrosis OT - Uremic Clearance Granules EDAT- 2014/08/05 06:00 MHDA- 2015/10/30 06:00 CRDT- 2014/08/05 06:00 PHST- 2014/03/01 00:00 [received] PHST- 2014/07/13 00:00 [revised] PHST- 2014/07/24 00:00 [accepted] PHST- 2014/08/05 06:00 [entrez] PHST- 2014/08/05 06:00 [pubmed] PHST- 2015/10/30 06:00 [medline] AID - S0378-8741(14)00567-4 [pii] AID - 10.1016/j.jep.2014.07.048 [doi] PST - ppublish SO - J Ethnopharmacol. 2014 Sep 29;155(3):1541-52. doi: 10.1016/j.jep.2014.07.048. Epub 2014 Aug 1.