Biomol Ther (Seoul)  
Hypericin, a Naphthodianthrone Derivative, Prevents Methylglyoxal-Induced Human Endothelial Cell Dysfunction
Moon Ho Do1 and Sun Yeou Kim1,2,3,*
1College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea
2Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936, Republic of Korea
3Gachon Medical Research Institute, Gil Medical Center, Incheon 21565, Republic of Korea
E-mail: sunnykim@gachon.ac.kr
Tel: +82-32-899-6411, Fax: +82-32-899-8962
Received: February 18, 2016; Revised: April 19, 2016; Accepted: April 22, 2016; Published online: June 13, 2016.
© The Korean Society of Applied Pharmacology. All rights reserved.

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.
Keywords: Advanced glycation end products, Methylglyoxal, HUVECs, Hypericin, Apoptosis


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