Apigenin alleviates STZ-induced diabetic cardiomyopathy

Mol Cell Biochem. 2017 Apr;428(1-2):9-21. doi: 10.1007/s11010-016-2913-9. Epub 2017 Feb 7.

Abstract

Apigenin is an important component of fruits and vegetables in human daily diets. Several cellular and animal models have been performed to demonstrate its anti-oxidant and anti-inflammatory bioactivities. However, the cardioprotective effects of apigenin in diabetic cardiomyopathy (DCM) remain unclear. In this study, we intended to explore the roles of apigenin in cardiac remodeling of DCM. Male C57BL/6 J mice were treated with streptozotocin (STZ, 50 mg/kg) for 5 consecutive days to induce DCM. The echocardiography and catheter-based measurements of hemodynamic parameters were performed to evaluate the cardiac function. Paraffin slices of harvested hearts were prepared for histological pathological analysis and TUNEL assay. Oxidative assay kits were used to detect Glutathione Peroxidase (GPx), Lipid Peroxidation Malondialdehyde (MDA), and Superoxide Dismutase (SOD). Western blot and real-time PCR were used for accessing the expressions of protein and mRNA. Diabetes mellitus exacerbated the cardiac dysfunction, fibrosis, and overaccumulation of 4-hydroxynonenal accompanying with down-regulation of Bcl2, GPx, and SOD, up-regulation of MDA, cleaved caspase3, and pro-apoptotic protein Bax, and contribution to the translocation of NF-κB. All these pathological changes could be effectively blunted by treatment of apigenin in vivo. Finally, H9c2 treated with high glucose or apigenin was used for further investigation of these effects in vitro; what is more, we also compared the effects between apigenin and Resveratrol in in vitro experiments. Our experiments have demonstrated that apigenin may be a potential drug for diabetic patients suffering from DCM.

Keywords: Apigenin; Apoptosis; Diabetic cardiomyopathy; Inflammation; Oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / pharmacology
  • Apigenin / administration & dosage*
  • Apigenin / pharmacology
  • Cardiotonic Agents / administration & dosage*
  • Cardiotonic Agents / pharmacology
  • Cell Line
  • Diabetic Cardiomyopathies / chemically induced
  • Diabetic Cardiomyopathies / drug therapy*
  • Gene Expression Regulation / drug effects
  • Humans
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Rats
  • Resveratrol
  • Stilbenes / administration & dosage
  • Stilbenes / pharmacology
  • Streptozocin / adverse effects*

Substances

  • Antioxidants
  • Cardiotonic Agents
  • Stilbenes
  • Streptozocin
  • Apigenin
  • Resveratrol