Paeonol protects endothelial function in endoplasmic recticulum stress-induced oxidative stress in mice

M. R. Mustafa, W. C. Ker, Y. S. Lau, D. Murugan. University of Malaya, Kuala Lumpur, MALAYSIA.

Introduction: Endothelial dysfunction is a common feature of cardiovascular related diseases. Increase in reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress have been reported to contribute to endothelial dysfunction(1,2). In the present study, we explored the vascular protective effects of chronic treatment with paeonol (2'-hydroxy-4'-methoxyacetophenone), the main active phenolic compound of Moutan Cortex, the root bark of Paeonia suffruticosa Andrew on ER stress-induced endothelial dysfunction in mice.

Method: Male C57/BL6J mice were injected intraperitoneally with tunicamycin (1 mg/kg/week for 2 weeks) to induce ER stress. In addition, mice were co-administered with either paeonol (20 mg/kg/oral gavage), reactive oxygen species (ROS) scavenger; tempol (20 mg/kg/day) or ER stress inhibitor; tauroursodeoxycholic acid (TUDCA, 150 mg/kg/day) for 2 weeks. Blood pressure and body weight were monitored, and the aorta isolated. ROS level was measured by dihydroethidium (DHE) staining and lucigenin-enhanced chemiluminescence assay.

Results: Chronic treatment with tunicamycin increased blood pressure, reduced body weight and attenuated endothelium dependent relaxations (EDRs) of mice aorta. These effects of tunicamycin were ameliorated by co-treatment with either paeonol, TUDCA and tempol. Similarly, co-treatment with all three drugs prevented the tunicamycin induced elevations of ROS level . Conclusion: Taken together, the present results suggest that chronic treatment with paeonol improved EDRs in mice aorta ex vivo by inhibiting ER stress via scavenging of ROS.

References:1. Galan M et al., (2012)Arterioscler Thromb Vasc Biol, 32(7):1652-1661. 2. Galan M et al (2014)Biochimica et biophysica acta, 1843(6):1063-1075.