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Attenuation of diabetic nephropathy by Chaihuang-Yishen granule through anti-inflammatory mechanism in streptozotocin-induced rat model of diabetics
Authors:Haojun Zhang  Tingting Zhao  Yuewen Gong  Xi Dong  Weiku Zhang  Sifan Sun  Hua Wang  Yanting Gu  Xiaoguang Lu  Meihua Yan  Ping Li
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
Abstract:

Ethnopharmacological relevance

Traditional 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 methods

Diabetic 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.

Results

Rats 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.

Conclusions

CHYS ameliorates renal injury in diabetic rats through reduction of inflammatory cytokines and their intracellular signaling.
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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