title: Monogalactosyldiacylglycerols, potent nitric oxide inhibitors from the marine microalga Tetraselmis chui.
abstract: Methanolic extracts of some marine and freshwater microalgae were tested for their nitric oxide (NO) inhibitory activity on lipopolysaccharide-induced NO production in RAW264.7 macrophage cells. Among the tested extracts, Tetraselmis chui extract showed the strongest NO inhibitory activity, thus selected for further study. NO inhibitory activity guided isolation led to identification of two monogalactosyldiacylglycerols (MGDGs) (2S)-1-O-(6Z,9Z,12Z,15Z-octadecatetranoyl)-2-O-(4Z,7Z,10Z,13Z-hexadecatetranoyl)-3-O-β-D-galactopyranosylglycerol (1) and (2S)-1-O-(9Z,12Z,15Z-octadecatrinoyl)-2-O-(4Z,7Z,10Z,13Z-hexadecatetranoyl)-3-O-β-D-galactopyranosylglycerol (2) from the MeOH extract of T. chui. The stereo-chemistry of 1 was elucidated by classical degradation method. MGDGs 1 and 2 showed strong NO inhibitory activity compared to N(G)-methyl-L-arginine acetate salt, a well known NO inhibitor used as a positive control. Isolated MGDGs suppressed NO production through down-regulation of inducible NO synthase protein. A structure activity relationship study suggested that the polyunsaturated fatty acids of the MGDGs are responsible for NO inhibition. Moreover, increasing unsaturation on the fatty acid side chains enhanced the NO inhibitory potency of the MGDGs.
authors.affiliation: Aquatic and Crop Resource Development, National Research Council Canada, 1411 Oxford Street, Halifax, Nova Scotia B3H 3Z1, Canada. arjun.banskota@nrc-cnrc.gc.ca
authors.forename: Arjun H
authors.initials: AH
authors.lastname: Banskota
authors.forename: Pamela
authors.initials: P
authors.lastname: Gallant
authors.forename: Roumiana
authors.initials: R
authors.lastname: Stefanova
authors.forename: Ronald
authors.initials: R
authors.lastname: Melanson
authors.forename: Stephen J B
authors.initials: SJ
authors.lastname: O'Leary
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D002460:Cell Line / Q000187:drug effects; D000460:Chlorophyta / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000737:chemistry; D038983:Galactolipids / Q000737:chemistry* / Q000494:pharmacology*; D005697:Galactosides / Q000737:chemistry / Q000494:pharmacology; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D058086:Microalgae / Q000737:chemistry; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D019323:omega-N-Methylarginine
chemical_list: D001120:Arginine; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D038983:Galactolipids; D005697:Galactosides; D005990:Glycerol; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C586166:(2S)-1-O-(6Z,9Z,12Z,15Z-octadecatetranoyl)-2-O-(4Z,7Z,10Z,13Z-hexadecatetranoyl)-3-O-beta-D-galactopyranosylglycerol; C092506:N(G)-monomethylarginine acetate; D019323:omega-N-Methylarginine; C009909:monogalactosyldiacylglycerol