Pueraria tuberosa extract inhibits iNOS and IL-6 through suppression of PKC-α and NF-kB pathway in diabetes-induced nephropathy

J Pharm Pharmacol. 2018 Aug;70(8):1102-1112. doi: 10.1111/jphp.12931. Epub 2018 May 16.

Abstract

Objectives: Inflammation plays an important role in the pathogenesis of diabetic nephropathy (DN). The aim of this study was to explore the anti-inflammatory role of PTY-2r (extracted from Pueraria tuberosa), on streptozotocin (STZ)-induced DN rats.

Methods: Diabetes was induced by intraperitoneal injection of STZ (55mg/kg) in rats. After 60 days, the rats were randomly divided into three groups (n = 6/each group), namely DN control group 2, DN rats treated with PTY-2r at dose of 100 mg/100 g, group 3 and 50 mg/100 g, group 4, p.o for 20 days. The normal rats were chosen as a normal control (NC) group 1.

Key findings: In DN rats, the expression of iNOS and inflammatory cytokines (IL-6 and TNF-α) was significantly increased. Raised expression of PKC-α was also found. As NF-kB is the main transcription factor for the inflammatory response-mediated progression of DN, variation in NF-kB expression and its activated phosphorylated derivative (pNF-kB) were also evaluated and increase in expression was obtained in the kidney of DN rats. PTY-2r treatment significantly reversed these changes in dose-dependent manner.

Conclusions: This study suggested that the nephroprotective effect of PTY-2r is possibly due to downregulation of PKC-α and NF-kB pathway and normalizing the expression of inflammatory cytokines and iNOS in the kidney of DN rats.

Keywords: drugs from natural sources; miscellaneous; other.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / therapeutic use*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / immunology
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / immunology
  • Interleukin-6 / antagonists & inhibitors*
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Plant Extracts / isolation & purification
  • Plant Extracts / therapeutic use*
  • Protein Kinase C-alpha / metabolism*
  • Pueraria / chemistry*
  • Rats, Inbred Strains
  • Signal Transduction / drug effects
  • Streptozocin

Substances

  • Anti-Inflammatory Agents
  • Il6 protein, rat
  • Interleukin-6
  • NF-kappa B
  • Plant Extracts
  • Streptozocin
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Protein Kinase C-alpha