Polyherbal Formulation Ameliorates Diabetic Cardiomyopathy Through Attenuation of Cardiac Inflammation and Oxidative Stress Via NF-κB/Nrf-2/HO-1 Pathway in Diabetic Rats

J Cardiovasc Pharmacol. 2022 Jan 1;79(1):e75-e86. doi: 10.1097/FJC.0000000000001167.

Abstract

The present study was intended to evaluate the effect of polyherbal formulation (PHF) made with 3 nutraceuticals, such as Piper nigrum, Terminalia paniculata, and Bauhinia purpurea on inflammation and oxidative stress in diabetic cardiomyopathy (DCM), which is induced by streptozotocin and nicotinamide administration in rats. We supplemented DCM rats with PHF (250 and 500 mg/kg/BW) for 45 days and evaluated their effects on oxidative stress markers, proinflammatory cytokines, and messenger RNA expressions of the nuclear factor erythroid 2-related factor-2 (Nrf-2) and its linked genes [heme oxygenase-1 (HO-1), superoxide dismutase, catalase] along with inflammatory genes [tumour necrosis factor α and nuclear factor kappa B (NF-κB)]. Our study demonstrated that PHF successfully attenuated inflammation and oxidative stress via messenger RNA upregulation of Nrf-2, HO-1, superoxide dismutase, and catalase and concomitantly with downregulation of tumour necrosis factor α and NF-κB. Conversely, PHF also protected hyperglycemia-mediated cardiac damage, which was confirmed with histopathological and scanning electron microscopy analysis. In conclusion, our results suggested that PHF successfully ameliorated hyperglycemia-mediated inflammation and oxidative stress via regulation of NF-κB/Nrf-2/HO-1 pathway. Therefore, these results recommend that PHF may be a prospective therapeutic agent for DCM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Blood Glucose / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diabetic Cardiomyopathies / enzymology
  • Diabetic Cardiomyopathies / pathology
  • Diabetic Cardiomyopathies / prevention & control*
  • Disease Models, Animal
  • Gene Expression Regulation
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Hypoglycemic Agents / pharmacology*
  • Inflammation Mediators / metabolism*
  • Male
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / enzymology
  • Myocytes, Cardiac / ultrastructure
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Oxidative Stress / drug effects*
  • Plant Preparations / pharmacology*
  • Rats
  • Rats, Wistar
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Blood Glucose
  • Cytokines
  • Hypoglycemic Agents
  • Inflammation Mediators
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, rat
  • Plant Preparations
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat