Puerarin Suppresses Angiotensin II-Induced Cardiac Hypertrophy by Inhibiting NADPH Oxidase Activation and Oxidative Stress-Triggered AP-1 Signaling Pathways

Authors

  • Chen Gang Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
  • Cao Qiang Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, China.
  • Cui Xiangli Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
  • Pan Shifen Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
  • Shen Chong Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Liu Lihong Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

DOI:

https://doi.org/10.18433/J3N318

Abstract

PURPOSE. To examine the effects of puerarin (Pue) on angiotensin II (AngII)-induced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and oxidative stress-related signaling pathways in the hypertrophic response of cardiomyocytes. METHODS. Primary cardiomyocytes of neonatal C57BL/6J mice were pretreated with Pue (50, 100 μmol/L) and were then stimulated with AngII 1 μmol/L. NADPH oxidase activity and reactive oxygen species (ROS) levels were measured by lucigenin-enhanced chemiluminescence assay and flow cytometry. Western blotting was used to detect the distribution of the oxidase subunits, extracellular signal-regulated kinase (ERK1/2) and c-jun N-terminal kinase (JNK1/2) activation, and an electrophoretic mobility shift assay (EMSA) was performed to analyze the DNA binding activity of activator protein-1 (AP-1). Adult C57BL/6J mice were infused with AngII and were administered with Pue (100, 200 mg·kg-1·d-1) for 15 d. After the treatment, systolic blood pressure (SBP) and left ventricular wall thickness were examined. The ratios of heart weight to body weight (HW/BW) and left ventricular weight to body weight (LVW/BW) were measured, and heart morphometry was assessed. RESULTS. In vitro, Pue dose-dependently blocked the phosphorylation of ERK1/2 and JNK1/2 and eventually abolished AP-1 binding activity through the inhibition of ROS production. Further studies revealed that AngII treatment resulted in increased NADPH oxidase activity, which was suppressed by Pue via the disruption of Rac1 activation and membrane translocation of oxidase subunits. In vivo, Pue attenuated cardiac hypertrophy, as evaluated by decreased HW/BW, LVW/BW, myocyte surface area, and left ventricular wall thickness. CONCLUSIONS. The anti-hypertrophic mechanism of Pue occurred by blocking Rac1-dependent NADPH oxidase activation and downstream redox-sensitive AP-1 signaling pathways.

 

This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Downloads

Download data is not yet available.

Downloads

Published

2015-06-29

How to Cite

Gang, C., Qiang, C., Xiangli, C., Shifen, P., Chong, S., & Lihong, L. (2015). Puerarin Suppresses Angiotensin II-Induced Cardiac Hypertrophy by Inhibiting NADPH Oxidase Activation and Oxidative Stress-Triggered AP-1 Signaling Pathways. Journal of Pharmacy & Pharmaceutical Sciences, 18(2), 235–248. https://doi.org/10.18433/J3N318

Issue

Section

Pharmaceutical Sciences; Review Articles