title: Xiaokeping mixture inhibits diabetic nephropathy in streptozotocin-induced rats through blocking TGF-β1/Smad7 signaling.
abstract: BACKGROUND
  Diabetic nephropathy (DN) is a major cause of chronic kidney failure and characterized by excessive deposition of extracellular matrix. Evidence have shown that transforming growth factor-β1 (TGF-β1) is a key mediator in the development of DN. However, treatment of DN by blocking the TGF-β1/Smad7 pathway remains limited. Xiaokeping mixture (XKP), a traditional Chinese herbal compound, has been used for treatment in patients with DN for many years.
  
  
  METHODS
  In the present study, TGF-β1/Smad7 pathway analysis was used to evaluate the therapeutic effect of XKP on DN rats induced by streptozotocin and to address the underlying molecular mechanism. Male rats were divided into four groups: normal control, untreated control group (fed with high fat), irbesartan-treated DN, and XKP-treated DN, respectively. Levels of serum creatinine, blood urea nitrogen, urine protein of 24 hours, and triacylglycerol were detected. Pathological changes of renal tissues were observed by hematoxylin-eosin staining. Immunohistochemical and Western blot analysis were used to detect the expressions of TGF-β1 and Smad7.
  
  
  RESULTS
  The results demonstrated that XKP can effectively reduce the levels of glucose, serum creatinine, blood urea nitrogen, urine protein of 24 hours, and triacylglycerol. Further studies indicated that inhibition of DN in XKP-treated DN rats was associated with inhibition of TGF-β1/Smad7 signaling as demonstrated by downregulation of TGF-β1 but upregulation of Smad7.
  
  
  CONCLUSIONS
  The data obtained from the present study indicate that XKP may be a therapeutic agent for DN.
authors.affiliation: Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, People's Republic of China.
authors.forename: Chuanwei
authors.initials: C
authors.lastname: Xin
authors.affiliation: Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, People's Republic of China.
authors.forename: Zhongni
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, People's Republic of China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, People's Republic of China.
authors.forename: Gonghua
authors.initials: G
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051906:Smad7 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013311:Streptozocin; D013329:Structure-Activity Relationship; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D053773:Transforming Growth Factor beta1; D013311:Streptozocin
keywords: Smad7; Xiaokeping mixture; diabetic nephropathy; transforming growth factor-beta