Kaempferol Prevents Against Ang II-induced Cardiac Remodeling Through Attenuating Ang II-induced Inflammation and Oxidative Stress

J Cardiovasc Pharmacol. 2019 Oct;74(4):326-335. doi: 10.1097/FJC.0000000000000713.

Abstract

Heart failure characterized by cardiac remodeling is a global problem. Angiotensin II (Ang II) induces cardiac inflammation and oxidative stress, which also is implicated in the pathophysiology of adverse collagen accumulation-induced remodeling. Kaempferol (KPF), a kind of flavonoid compounds, is capable of anti-inflammatory and antioxidant activities. However, the target of KPF still remains blurred. In this study, we investigated the effect of KPF on Ang II-induced collagen accumulation and explored the underlying mechanisms. Our results suggested that KPF prevented Ang II-induced cardiac fibrosis and dysfunction, in mice challenged with subcutaneous injection of Ang II. In culture cells, KPF significantly reduced Ang II-induced collagen accumulation. Furthermore, KPF remarkably decreased inflammation and oxidative stress in Ang II-stimulated cardiac fibroblasts by modulating NF-κB/mitogen-activated protein kinase and AMPK/Nrf2 pathways.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Angiotensin II*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Cells, Cultured
  • Collagen / metabolism
  • Disease Models, Animal
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibrosis
  • Heart Failure / chemically induced
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Inflammation Mediators / metabolism*
  • Kaempferols / pharmacology*
  • Male
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects*
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Ventricular Function, Left / drug effects*
  • Ventricular Remodeling / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Inflammation Mediators
  • Kaempferols
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, rat
  • Angiotensin II
  • kaempferol
  • Collagen
  • Mitogen-Activated Protein Kinases
  • AMP-Activated Protein Kinases