Peroxynitrite scavenging and cytoprotective activity of 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether from the marine alga Symphyocladia latiuscula.
Peroxynitrite (ONOO(-)), formed from the reaction of superoxide (O(2)*(-)) and nitric oxide (*NO), is a cytotoxic species that can oxidize several cellular components such as proteins, lipids, and DNA. It has been implicated in diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, and atherosclerosis. Due to the lack of endogenous enzymes responsible for ONOO(-) inactivation, developing a specific ONOO(-) scavenger is of considerable importance. The aim of this study was to evaluate the ability of marine natural products to scavenge ONOO(-) and to protect cells against ONOO(-). Methanolic extracts of 17 marine alga were tested for their ONOO(-) scavenging activity. Among them, Symphyocladia latiuscula showed the potent scavenging activity. CH(2)CH(2) fraction was partitioned with CH(2)CH(2) following n-hexanal extraction from the methanol extract of S. latiuscula. It was highly effective for ONOO(-) scavenging activity. Further analysis of the active fractionated extract identified 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (TDB) as a potent ONOO(-) scavenger. The data demonstrated that TDB led to decreased ONOO(-)-mediated nitration of tyrosine through electron donation. TDB showed significant inhibition on nitration of bovine serum albumin and low-density lipoprotein by ONOO(-) in a dose-dependent manner. It also provided cytoprotection from cell damage induced by ONOO(-). TDB can be developed as an effective peroxynitrite scavenger for the prevention of the involved diseases.
Chung
H Y
HY
Department of Pharmacy, Pusan National University, Pusan 609-735, Korea. hyjung@hyowon.pusan.ac.kr
Choi
H R
HR
Park
H J
HJ
Choi
J S
JS
Choi
W C
WC
D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects; D016877:Oxidants / Q000378:metabolism* / Q000633:toxicity; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000378:metabolism* / Q000633:toxicity; D000461:Rhodophyta / Q000378:metabolism*
C439224:2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether; D004987:Ethers; D016166:Free Radical Scavengers; D016877:Oxidants; D030421:Peroxynitrous Acid