Biomol Ther.  2017 Mar;25(2):158-164. 10.4062/biomolther.2016.034.

Hypericin, a Naphthodianthrone Derivative, Prevents Methylglyoxal-Induced Human Endothelial Cell Dysfunction

• Do MH
• Kim SY

• KMID: 2375035
• DOI: http://doi.org/10.4062/biomolther.2016.034

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.

Keyword

Advanced glycation end products; Methylglyoxal; HUVECs; Hypericin; Apoptosis

MeSH Terms

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
Glucose
Glycosylation End Products, Advanced
Mitogen-Activated Protein Kinases
Protein Kinase C
Pyruvaldehyde
Reactive Oxygen Species