Anti-inflammatory R-prostaglandins from Caribbean Colombian soft coral Plexaura homomalla

作者：Reina Eduardo; Ramos Freddy A^*; Castellanos Leonardo; Aragon Marcela; Ospina Luis F

来源：Journal of Pharmacy and Pharmacology, 2013, 65(11): 1643-1652.

DOI：10.1111/jphp.12138

• (15R)-prostaglandins
• anti-inflammatory
• elastase
• MPO
• Plexaura homomalla

ObjectivesThis study aims to evaluate the effect of prostaglandins isolated from soft coral Plexaura homomalla, collected in Colombian Caribbean Sea, on in vivo and in vitro inflammation models.
MethodsExtracts from P.homomalla were fractionated and sequentially chromatographed to obtain the prostaglandins: (15R)-PGA(2) (1), (15R)-PGA(2)-Me (2), (15R)-O-Ac-PGA(2) (3), (15R)-O-Ac-PGA(2)-Me (4) and (15R)-PGE(2) (5) in addition to three semi-synthetic prostaglandins obtained by transformations of the natural products. The anti-inflammatory properties of natural and semi-synthetic compounds were determined in vivo using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear oedema model and in vitro leucocyte degranulation, myeloperoxidase (MPO) and elastase enzymatic activities from human polymorphonuclear cells (PMNs). The cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.
Key findingsIn the in vivo assay, (15R)-PGE(2) (1) and (15R)-O-Ac-PGA(2) (3) showed anti-inflammatory activity, as well as in vitro inhibition of elastase release from PMNs. In the PMNs degranulation assay, (15R)-PGE(2) (5), was the most active compound in the inhibition of MPO release. Finally, all the tested prostaglandins showed moderate inhibition for elastase enzyme activity, whereas none of the prostaglandins exhibit significative inhibition on MPO activity.
Conclusion(15R)-PGE(2) (1) and (15R)-O-Ac-PGA(2) (3) present significant inhibition on three important events related to the topical inflammatory response induced by TPA: the oedema formation, the PMNs degranulation, events that modulate MPO and elastase levels at inflammation site, and the inhibition of the enzyme activity.

• 出版日期2013-11