Cardioprotective and anti-apoptotic effects of Potentilla reptans L. root via Nrf2 pathway in an isolated rat heart ischemia/reperfusion model

Life Sci. 2018 Dec 15:215:216-226. doi: 10.1016/j.lfs.2018.11.021. Epub 2018 Nov 10.

Abstract

Background: Previous studies have shown that proanthocyanidins have cardioprotective effects which are mediated via the release of nitric oxide (NO) ultimately resulting in increasing the antioxidant activity. We have investigated to show whether 1) the total extract and ethyl acetate fraction (Et) of Potentilla reptans root have an ischemic preconditioning (IPC) effect, 2) P. reptans has antioxidant and cardioprotective effects mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and scavenging of reactive oxygen species (ROS), 3) NO, caspase-3 and Bcl-2/Bax are involved in the IPC effect of P. reptans.

Methods: Male Wistar rats were divided into 10 groups. The isolated hearts were subjected to 30 min of ischemia and 100 min of reperfusion. The P. reptans was applied before the main ischemia. The infarct size was estimated by triphenyl-tetrazolium chloride staining. The hemodynamic parameters and ventricular arrhythmias were calculated during the reperfusion. Antioxidant markers and immunohistochemistry assays were determined at the end of the protocol.

Results: The Et significantly decreased the infarct size, arrhythmia scores, ventricular fibrillation incidence, and enhanced the hemodynamic parameters in a concentration-dependent manner against the ischemia/reperfusion group. SOD and CAT activity were increased and MDA level was decreased in response to the Et. Meanwhile, Et attenuated the suppression of Nrf2 expression and reduced the apoptotic indexes. The cardioprotective effect of P. reptans was abrogated by L-NAME.

Conclusions: P. reptans demonstrated that the cardioprotective preconditioning effects via NO release, Nrf2 pathway, and antioxidant activity lead to a decrease in the apoptotic index.

Keywords: Anti-apoptotic; Antioxidant; Ischemia/reperfusion; Ischemic preconditioning; Potentilla reptans root.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Arrhythmias, Cardiac / physiopathology
  • Arrhythmias, Cardiac / prevention & control
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / isolation & purification
  • Cardiotonic Agents / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Ischemic Preconditioning, Myocardial
  • Male
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / prevention & control
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / physiopathology
  • NF-E2-Related Factor 2 / metabolism
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Plant Roots
  • Potentilla / chemistry*
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism

Substances

  • Cardiotonic Agents
  • NF-E2-Related Factor 2
  • Plant Extracts
  • Reactive Oxygen Species
  • NG-Nitroarginine Methyl Ester