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)-N-.), is a cytotoxic species that can oxidize several c ellular components such as proteins, lipids, and DNA. It has been implicate d in diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, an d atherosclerosis. Due to the lack of endogenous enzymes responsible for ON OO- inactivation, developing a specific ONOO- scavenger is of considerable importance. The aim of this study was to evaluate the ability of marine nat ural products to scavenge ONOO- and to protect cells against ONOO-. Methano lic extracts of 17 marine alga were tested for their ONOO- scavenging activ ity. Among them, Symphyocladia latiuscula showed the potent scavenging acti vity. CH2CH2 fraction was partitioned with CH2CH2 following n-hexanal extra ction from the methanol extract of S. latiuscula. It was highly effective f or ONOO- scavenging activity. Further analysis of the active fractionated e xtract identified 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (TDB) as a potent ONOO- scavenger. The data demonstrated that TDB led to decreased O NOO--mediated nitration of tyrosine through electron donation. TDB showed s ignificant inhibition on nitration of bovine serum albumin and low-density lipoprotein by ONOO- in a dose-dependent manner. It also provided cytoprote ction from cell damage induced by ONOO-. TDB can be developed as an effecti ve peroxynitrite scavenger for the prevention of the involved diseases.