The Group IVA cytosolic phospholipase A(2) (GIVA PLA(2)) is a particularly attractive target for drug development because it is the rate-limiting provider of proinflammatory mediators. We previously reported the discovery of novel 2-oxoamides that inhibit GIVA PLA(2) [Kokotos, G.; et al. J. Med. Chem. 2002, 45, 2891-2893]. In the present work, we have further explored this class of inhibitors and found that the 2-oxoamide functionality is more potent when it contains a long 2-oxoacyl residue and a free carboxy group. Long-chain 2-oxoamides based on gamma-aminobutyric acid and gamma-norleucine are potent inhibitors of GIVA PLA(2). Such inhibitors act through a fast and reversible mode of inhibition in vitro, are able to block the production of arachidonic acid and prostaglandin E(2) in cells, and demonstrate potent in vivo anti-inflammatory and analgesic activity.

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Olive leaf extract, rich in oleuropein, formed an inclusion complex with beta-cyclodextrin (beta-CD) upon mixing of the components in aqueous media and subsequent freeze-drying. Inclusion complex formation was confirmed by differential scanning calorimetry (DSC). DSC thermograms indicated that the endothermic peaks of both the olive leaf extract and the physical mixture of olive leaf extract with beta-CD, attributed to the melting of crystals of the extract, were absent in DSC thermogram of inclusion complex. Moreover, DSC studies under oxidative conditions indicated that the complex of olive leaf extract with beta-CD was protected against oxidation, since it remained intact at temperatures where the free olive leaf extract was oxidized. Phase solubility studies afforded A L type diagrams, 1:1 complex stoichiometry, a moderate binding constant ( approximately 300 M (-1)), and an increase of the aqueous solubility by approximately 50%. The formation of the inclusion complex was also confirmed by nuclear magnetic resonance (NMR) studies of beta-CD solutions in the presence of both pure oleuropein and olive leaf extract. The NMR data have established the formation of a 1:1 complex with beta-CD that involves deep insertion of the dihydroxyphenethyl moiety inside the cavity from its secondary side.

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Crude composition, lipid composition, and tocopherols, ascorbic acid, cholesterol, phytosterols, and squalene content together with fatty acids and antiplatelet activities of total, neutral, and polar lipids of avgotaracho (wax-covered, dried, and salted Mugil cephalus roe) were studied and compared with those of similar products. Wax and steryl esters accounted for 63.7% of roe lipids followed by phosphatidylcholine (PC), which comprised 20.3%. Wax esters were rich in saturated fatty alcohols, monounsaturated fatty acids, and long chain omega3 highly unsaturated fatty acids (HUFA). The fatty acid distribution in roe total and neutral lipids was similar to that of wax esters, while in polar lipids, the omega3 HUFA predominated. Avgotaracho provides significant amounts of protein, fat, alpha-tocopherol, ascorbic acid, and PC, certain amounts of squalene and phytosterols, and cholesterol at levels comparable to hens' eggs. Total, polar, and neutral lipids of avgotaracho exhibited a strong inhibition of platelet activating factors and thrombin, with polar lipids being more active. The results obtained indicate that avgotaracho is a food of high nutritive value, rich in protein and lipids with a healthy lipid profile in terms of omega3/omega6 ratio and major fatty acid classes, while the antiplatelet activity of its oil indicates a putative antithrombotic potential.