Premium
Lysophosphatidylcholine Containing Docosahexaenoic Acid at the sn ‐1 Position is Anti‐inflammatory
Author(s) -
Huang Long Shuang,
Hung Nguyen Dang,
Sok DaiEun,
Kim Mee Ree
Publication year - 2010
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-010-3392-5
Subject(s) - lysophosphatidylcholine , docosahexaenoic acid , zymosan , chemistry , pharmacology , clinical chemistry , arachidonic acid , metabolite , lipidology , oral administration , biochemistry , medicine , endocrinology , fatty acid , phospholipid , in vitro , phosphatidylcholine , polyunsaturated fatty acid , enzyme , membrane
Lysophosphatidylcholine is known to be a lipid mediator in various cellular responses. In this study, we examined the anti‐inflammatory actions of lysophosphatidylcholine containing docosahexaenoic acid esterified at the sn ‐1 position. First, in RAW 264.7 cells, DHA‐lysoPtdCho suppressed the LPS‐induced formation of NO concentration‐dependently. However, ARA‐lysoPtdCho showed a partial suppression, and LNA‐lysoPtdCho had no significant effect. Additionally, DHA‐lysoPtdCho also reduced the level of TNF‐α or IL‐6, but not PGE 2 . In animal experiments, the i.v. administration of ARA‐lysoPtdCho (150 or 500 μg/kg) prevented zymosan A‐induced plasma leakage remarkably with a maximal efficacy (Emax) of 50%, in contrast to no effect with LNA‐lysoPtdCho. Remarkably, DHA‐lysoPtdCho suppressed zymosan A‐induced plasma leakage with an ED 50 value of 46 μg/kg and an Emax value of around 95%. Additionally, mechanistic studies indicated that the anti‐inflammatory action of DHA‐lysoPtdCho was partially related to the reduced formation of LTC 4, TNF‐α, and IL‐6. When the interval time between lysoPtdCho administration and zymosan A challenge was extended up to 2 h, such a suppressive action of DHA‐lysoPtdCho was augmented, suggesting that a DHA‐lysoPtdCho metabolite is important for anti‐inflammatory action. In support of this, 17‐HPDHA‐lysoPtdCho showed a greater anti‐inflammatory action than DHA‐lysoPtdCho. Furthermore, a similar anti‐inflammatory action was also observed with i.p. administration of DHA‐lysoPtdCho or a 17( S )‐hydroperoxy derivative. Additionally, oral administration of DHA‐lysoPtdCho also expressed a significant anti‐inflammatory action. Taken together, it is proposed that DHA‐lysoPtdCho and its metabolites may be anti‐inflammatory lipids in vivo systems.