Effect of Guanxin Danshen Formula on diabetic kidney disease in db/db mice through regulation of Nrf2 pathway

ZHANG Bin1,2,3 ZHANG Xue-lian1,2,3 ZHANG Chen-yang1,2,3 SUN Gui-bo1,2,3 SUN Xiao-bo1,2,3

(1.Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China 100193)
(2.Key Laboratory of New Drug Discovery based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China 100193)
(3.Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing, China 100193)

【Abstract】Diabetic kidney disease (DKD) has become a primary cause of end-stage kidney disease, without any effective treatment available. In this study, we assessed the protective effect of Guanxin Danshen Formula (GXDSF) on diabetic nephropathy in db/db mice. The db/m and db/db mice were randomly divided into four groups: a control group, a model group, a metformin group, and a GXDSF group. After 8 weeks’ treatment with GXDSF, metformin or normal saline, the mice were sacrificed, and the blood and kidney tissues were collected for further analysis. Compared with the model group, the TG, TCH and LDL levels significantly decreased in the GXDSF group. The results from HE and PAS staining showed that db/db mice exhibited abnormal kidney tissues with increased glomerular volume, basement membrane thickening and mesangial cell proliferation, which could be significantly alleviated by GXDSF treatment. GXDSF treatment also reduced serum creatinine and BUN. Meanwhile, GXDSF treatment markedly elevated the GSH-PX levels, while reduced the LDH and MDA levels in the kidney tissues. Western blot assay showed that GXDSF evidently up-regulated the protein levels of ERα and p-Akt, and subsequently promoted the HO-1 expression mediated by Nrf2. These data collectively indicated that GXDSF protected db/db mice against DN by regulating the ERα and Nrf2-mediated HO-1 expression.

【Keywords】 Guanxin Danshen Formula ; diabetic kidney disease (DKD); oxidative stress; diabetes mellitus; estrogen receptor;

【DOI】

【Funds】 Funding Project of Key Laboratory of Chinese Academy of Medical Sciences (2018PT35030) National Key Research and Development Project (2018YFC1707408) National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2018ZX0971101-009) National Natural Science Foundation of China (81891012)

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This Article

ISSN:1001-5302

CN:11-2272/R

Vol 45, No. 11, Pages 2595-2600

June 2020

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Abstract

  • 1 Materials
  • 2 Methods
  • 3 Results
  • 4 Discussion
  • References