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Xiaokeping mixture inhibits diabetic nephropathy in streptozotocin-induced rats through blocking TGF-β1/Smad7 signaling

Authors Xin C, Xia Z, Jiang C, Lin M, Li G

Received 7 August 2015

Accepted for publication 19 October 2015

Published 30 November 2015 Volume 2015:9 Pages 6269—6274

DOI https://doi.org/10.2147/DDDT.S93964

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Wei Duan


Chuanwei Xin, Zhongni Xia, Cheng Jiang, Mengmeng Lin, Gonghua Li

Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, People’s Republic of China

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.
Conclusion: The data obtained from the present study indicate that XKP may be a therapeutic agent for DN.

Keywords: Xiaokeping mixture, diabetic nephropathy, transforming growth factor-beta, Smad7

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