Attenuation of diabetic nephropathy by Chaihuang-Yishen granule through anti-inflammatory mechanism in streptozotocin-induced rat model of diabetics

J Ethnopharmacol. 2014;151(1):556-64. doi: 10.1016/j.jep.2013.11.020. Epub 2013 Nov 22.

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 24h 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: ACEI; ARB; Anti-inflammatory; BMPRII; BUN; CHYS; Chaihuang-Yishen granule; Chinese herbs; Cre; DN; Diabetic nephropathy; EMT; HPLC; IL-1β; IκB; MCP-1; NF-κB; PAN; STZ; TC; TCM; TG; TGF-β1; TNF-α; angiotensin converting enzyme inhibitor; angiotensin receptor blocker; bone morphogenetic protein receptor type II; creatinine; diabetic nephropathy; epithelial-mesenchymal transition; high performance liquid chromatography.; inhibitory proteins of nuclear factor kappaB; interleukin-1beta; monocyte chemotactic peptide-1; nuclear factor kappaB; puromycin aminonucleoside; streptozotocin; total cholesterol; traditional Chinese medicine; transforming growth factor-beta1; triglycerides; tumor necrosis factor-alpha; urea nitrogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Blood Glucose
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Drug Administration Schedule
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / therapeutic use*
  • Fosinopril / therapeutic use
  • Gene Expression Regulation
  • Hypoglycemic Agents / therapeutic use*
  • Kidney / drug effects
  • Kidney / metabolism
  • Male
  • Molecular Structure
  • Rats
  • Rats, Wistar
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Blood Glucose
  • Ccl2 protein, rat
  • Chemokine CCL2
  • Drugs, Chinese Herbal
  • Hypoglycemic Agents
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Fosinopril