Hypericin, a Naphthodianthrone Derivative, Prevents Methylglyoxal-Induced Human Endothelial Cell Dysfunction.
10.4062/biomolther.2016.034
- Author:
Moon Ho DO
1
;
Sun Yeou KIM
Author Information
1. College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea. sunnykim@gachon.ac.kr
- Publication Type:Original Article
- Keywords:
Advanced glycation end products;
Methylglyoxal;
HUVECs;
Hypericin;
Apoptosis
- MeSH:
Apoptosis;
Atherosclerosis;
Cell Death;
Endothelial Cells*;
Glucose;
Glycosylation End Products, Advanced;
Human Umbilical Vein Endothelial Cells;
Humans*;
Hypericum;
Mitogen-Activated Protein Kinases;
Neuralgia;
Protein Kinase C;
Pyruvaldehyde;
Reactive Oxygen Species
- From:Biomolecules & Therapeutics
2017;25(2):158-164
- CountryRepublic of Korea
- Language:English
-
Abstract:
Methylglyoxal (MGO) is a highly reactive metabolite of glucose which is known to cause damage and induce apoptosis in endothelial cells. Endothelial cell damage is implicated in the progression of diabetes-associated complications and atherosclerosis. Hypericin, a naphthodianthrone isolated from Hypericum perforatum L. (St. John’s Wort), is a potent and selective inhibitor of protein kinase C and is reported to reduce neuropathic pain. In this work, we investigated the protective effect of hypericin on MGO-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Hypericin showed significant anti-apoptotic activity in MGO-treated HUVECs. Pretreatment with hypericin significantly inhibited MGO-induced changes in cell morphology, cell death, and production of intracellular reactive oxygen species. Hypericin prevented MGO-induced apoptosis in HUVECs by increasing Bcl-2 expression and decreasing Bax expression. MGO was found to activate mitogen-activated protein kinases (MAPKs). Pretreatment with hypericin strongly inhibited the activation of MAPKs, including P38, JNK, and ERK1/2. Interestingly, hypericin also inhibited the formation of AGEs. These findings suggest that hypericin may be an effective regulator of MGO-induced apoptosis. In conclusion, hypericin downregulated the formation of AGEs and ameliorated MGO-induced dysfunction in human endothelial cells.
