Novel Aeruginosin-865 from Nostoc sp as a Potent Anti-inflammatory Agent

Aeruginosin-865 (Aer-865), isolated from terrestrial cyanobacterium Nostoc sp. Lukeova 30/93, is the first aeruginosin-type peptide containing both a fatty acid and a carbohydrate moiety, and is the first aeruginosin to be found in the genus Nostoc. Mass spectrometry, chemical and spectroscopic analysis as well as one- and two-dimensional NMR and chiral HPLC analysis of Marfey derivatives were applied to determine the peptidic sequence: D-Hpla, D-Leu, 5-OH-Choi, Agma, with hexanoic and mannopyranosyl uronic acid moieties linked to Choi. We used an AlphaLISA assay to measure the levels of proinflammatory mediators IL-8 and ICAM-1 in hTNF--stimulated HLMVECs. Aer-865 showed significant reduction of both: with EC50 values of (3.5 +/- 1.5) gmL(-1) ((4.0 +/- 1.7) M) and (50.0 +/- 13.4) gmL(-1) ((57.8 +/- 15.5) M), respectively. Confocal laser scanning microscopy revealed that the anti-inflammatory effect of Aer-865 was directly associated with inhibition of NF-B translocation to the nucleus. Moreover, Aer-865 did not show any cytotoxic effect.