Shengqing Jiangzhuo capsule ameliorates diabetic nephropathy by improving Keap1/Nrf2 signaling pathway

J Pharm Pharmacol. 2024 Sep 3;76(9):1149-1159. doi: 10.1093/jpp/rgae095.

Abstract

Background: Diabetic nephropathy (DN) is a major contributor to end-stage renal failure, and lacking effective treatment options. Shengqing Jiangzhuo capsule (SQJZJN), a traditional Chinese medicine prescription with known efficacy in chronic kidney disease, has not been thoroughly investigated for its potential in DN protection.

Methods: Eight-week-old male C57BLKS/J db/db, C57BLKS/J db/m mice, and human glomerular mesangial cell (HMC) cells cultured with high glucose were used as experimental models in this study.

Results: The in vivo investigation showed that SQJZJN can significantly ameliorate renal pathological damage, reduce serum creatinine, and lower urinary microalbumin levels in db/db mice. In vitro, SQJZJN treatment mitigated advanced glycation end products (AGEs) and reactive oxygen species (ROS), leading to a reduction in renal cell apoptosis. Mechanistically, SQJZJN activated the Keap1/Nrf2/ARE pathway by promoting nuclear factor erythroid-derived 2-related factor 2 (Nrf2), γ-glutamylcysteine synthetase heavy subunit (γ-GCS), and Heme oxygenase-1 (HO-1) expressions, while decreasing Kelch-like ECH-associated protein 1 (KEAP1) expressions.

Conclusion: These findings suggest that SQJZJN exerts a protective effect on DN, potentially through the activation of the Keap1/Nrf2/ARE pathway.

Keywords: Shengqing Jiangzhuo capsule; db/db mice; diabetic nephropathy; human glomerular mesangial cells.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Diabetic Nephropathies* / drug therapy
  • Diabetic Nephropathies* / metabolism
  • Disease Models, Animal
  • Drugs, Chinese Herbal* / pharmacology
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Kelch-Like ECH-Associated Protein 1* / metabolism
  • Male
  • Mesangial Cells / drug effects
  • Mesangial Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species* / metabolism
  • Signal Transduction* / drug effects

Substances

  • Drugs, Chinese Herbal
  • Glycation End Products, Advanced
  • Keap1 protein, mouse
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Reactive Oxygen Species