Journal
DRUG DEVELOPMENT RESEARCH
Volume 80, Issue 4, Pages 481-489Publisher
WILEY
DOI: 10.1002/ddr.21521
Keywords
endothelial dysfunction; Ilexgenin A; mitochondrial fission; Nrf2
Categories
Funding
- Government of Jiangsu Province
- Priority Academic Programme Development
- National Natural Science Foundation of China [81573567, BK20181328]
- Natural Science Foundation of Jiangsu Province
Ask authors/readers for more resources
Atherosclerosis (AS) is one of important events involving in the pathological process of coronary artery disease. Many traditional Chinese medicines have been widely used for the treatment of AS. Previous studies have demonstrated that Ilexgenin A (IA) obtained from Ilex hainanensis Merr. could improve AS development. However, its underlying mechanism is still unknown. This study was conducted to explore the possible targets and mechanisms involving in the anti-atheroclerosis effect of IA. The results showed IA significantly promoted NO production, reduced reactive oxygen species (ROS) generation, and inflammatory cytokine production induced by palmitate (PA) in endothelial cells, demonstrating IA could improve endothelial dysfunction. Meanwhile, IA dramatically inhibited dynamin-related protein 1 (Drp1) expression and mitochondrial fission induced by PA whereas proteasome inhibitor epoxomicin attenuated its effect on Drp1 expression, indicating IA decreased Drp1 expression with regulation of proteasome. Furthermore, IA also could increase the expression of proteasome subunit beta type5 (PSMB5) and activate nuclear factor-like 2 (Nrf2). Nrf2 knockdown eliminated the induction effect of IA on PSMB5 expression while abrogated its inhibition on ROS generation and mitochondrial fission stimulated by PA. These results demonstrated that IA could promote PSMB5 expression in an Nrf2-dependent manner, resulting in the suppression of mitochondrial fission, and thus improve endothelial dysfunction. These findings laid a foundation to the future development of IA as an agent to the prevention and treatment of AS.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available