Exp Mol Med.  2005 Oct;37(5):436-446.

Natural compounds, fraxin and chemicals structurally related to fraxin protect cells from oxidative stress

• Whang WK
• Park HS
• Ham I
• Oh M
• Namkoong H
• Kim HK
• Hwang DW
• Hur SY
• Kim TE
• Park YG
• Kim JR
• Kim JW

Abstract

Coumarins comprise a group of natural phenolic compounds found in a variety of plant sources. In view of the established low toxicity, relative cheapness, presence in the diet and occurrence in various herbal remedies of coumarins, it appears prudent to evaluate their properties and applications further. The purpose of this study is to investigate cellular protective activity of coumarin compound, fraxin extracted from Weigela florida var. glabbra, under oxidative stress, to identify genes expressed differentially by fraxin and to compare antioxidative effect of fraxin with its structurally related chemicals. Of the coumarins, protective effects of fraxin against cytotoxicity induced by H2O2 were examined in human umbilical vein endothelial cells (HUVECs). Fraxin showed free radical scavenging effect at high concentration (0.5 mM) and cell protective effect against H2O2-mediated oxidative stress. Fraxin recovered viability of HUVECs damaged by H2O2- treatment and reduced the lipid peroxidation and the internal reactive oxygen species level elevated by H2O2 treatment. Differential display reverse transcription-PCR revealed that fraxin upregulated antiapoptotic genes (clusterin and apoptosis inhibitor 5) and tumor suppressor gene (ST13). Based on structural similarity comparing with fraxin, seven chemicals, fraxidin methyl ether (29.4% enhancement of viability), prenyletin (26.4%), methoxsalen (20.8 %), diffratic acid (19.9%), rutoside (19.1%), xanthyletin (18.4%), and kuhlmannin (18.2%), enhanced more potent cell viability in the order in comparison with fraxin, which showed only 9.3% enhancement of cell viability. These results suggest that fraxin and fraxin-related chemicals protect HUVECs from oxidative stress.

Keyword

antioxidants; apoptosis; coumarins; fraxin; oxidative stress; plants, medicinal

MeSH Terms

Catalase/metabolism
Cell Survival/drug effects
Cells, Cultured
Coumarins/*chemistry/*pharmacology
Endothelial Cells/drug effects/metabolism
Humans
Hydrogen Peroxide/pharmacology
Lipid Peroxidation/drug effects
Molecular Structure
Oxidative Stress/*drug effects
Reactive Oxygen Species/metabolism
Research Support, Non-U.S. Gov't
Structure-Activity Relationship
Superoxide Dismutase/metabolism
Umbilical Cord/drug effects/metabolism