Attenuation of diabetic nephropathy by Chaihuang-Yishen granule through anti-inflammatory mechanism in streptozotocin-induced rat model of diabetics |
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Authors: | Haojun Zhang Tingting Zhao Yuewen Gong Xi Dong Weiku Zhang Sifan Sun Hua Wang Yanting Gu Xiaoguang Lu Meihua Yan Ping Li |
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Institution: | 1. Department of Pharmacology, Institute of Clinical Medical Sciences, China–Japan Friendship Hospital, Beijing 100029, China;2. Faculty of Pharmacy, University of Manitoba, Winnipeg, MB, Canada;3. Guang''anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China |
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Abstract: | Ethnopharmacological relevanceTraditional Chinese medical herbs have been used in China for a long time to treat different diseases. Based on traditional Chinese medicine (TCM) principle, Chaihuang-Yishen granule (CHYS) was developed and has been employed clinically to treat chronic kidney disease including diabetic nephropathy (DN). The present study was designed to investigate its mechanism of action in treatment of DN.Materials and methodsDiabetic rats were established by having a right uninephrectomy plus a single intraperitoneal injection of STZ. Rats were divided into four groups of sham, diabetes, diabetes with CHYS and diabetes with fosinopril. CHYS and fosinopril were given to rats by gavage for 20 weeks. Samples from blood, urine and kidney were collected for biochemical, histological, immunohistochemical and molecular analyses.ResultsRats treated with CHYS showed reduced 24 h urinary protein excretion, decreased serum TC and TG levels, but CHYS treatment did not affect blood glucose level. Glomerular mesangial expansion and tubulointerstitial fibrosis in diabetic rats were significantly alleviated by CHYS treatment. Moreover, CHYS administration markedly reduced mRNA levels of NF-κB p65 and TGF-β1, as well as decreased protein levels of NF-κB p65, MCP-1, TNF-α and TGF-β1 in the kidney of diabetic rats.ConclusionsCHYS ameliorates renal injury in diabetic rats through reduction of inflammatory cytokines and their intracellular signaling. |
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Keywords: | DN diabetic nephropathy CHYS Chaihuang-Yishen granule STZ streptozotocin NF-κB nuclear factor kappaB IκB inhibitory proteins of nuclear factor kappaB MCP-1 monocyte chemotactic peptide-1 TNF-α tumor necrosis factor-alpha IL-1β interleukin-1beta TGF-β1 transforming growth factor-beta1 EMT epithelial-mesenchymal transition TCM traditional Chinese medicine ACEI angiotensin converting enzyme inhibitor ARB angiotensin receptor blocker BMPRII bone morphogenetic protein receptor type II PAN puromycin aminonucleoside TC total cholesterol TG triglycerides BUN urea nitrogen Cre creatinine HPLC high performance liquid chromatography |
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