A review on herbal Nrf2 activators with preclinical evidence in cardiovascular diseases

Phytother Res. 2021 Sep;35(9):5068-5102. doi: 10.1002/ptr.7137. Epub 2021 Apr 24.

Abstract

Cardiovascular diseases (CVDs) are an ever-growing problem and are the most common cause of death worldwide. The uncontrolled production of reactive oxygen species (ROS) and the activation of ROS associated with various cell signaling pathways with oxidative cellular damage are the most common pathological conditions connected with CVDs including endothelial dysfunction, hypercontractility of vascular smooth muscle, cardiac hypertrophy and heart failure. The nuclear factor E2-related factor 2 (Nrf2) is a basic leucine zipper redox transcription factor, together with its negative regulator, kelch-like ECH-associated protein 1 (Keap1), which serves as a key regulator of cellular defense mechanisms to combat oxidative stress and associated diseases. Multiple lines of evidence described here support the cardiac protective property of Nrf2 in various experimental models of cardiac related disease conditions. In this review, we emphasized the molecular mechanisms of Nrf2 and described the detailed outline of current findings on the therapeutic possibilities of the Nrf2 activators specifically from herbal origin in various CVDs. Based on evidence from various preclinical experimental models, we have highlighted the activation of Nrf2 pathway as a budding therapeutic option for the prevention and treatment of CVDs, which needs further investigation and validation in the clinical settings.

Keywords: Nrf2; cardiovascular diseases (CVDs); oxidative stress; preclinical evidences; reactive oxygen species.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases* / drug therapy
  • Humans
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress
  • Plant Preparations / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury

Substances

  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Plant Preparations
  • Reactive Oxygen Species