Oral Administration of 2-Docosahexaenoyl Lysophosphatidylcholine Displayed Anti-Inflammatory Effects on Zymosan A-Induced Peritonitis

Abstract

Lysophosphatidylcholines (lysoPCs) have been known to be bioactive lipid mediators, which take part in various biological and pathological processes. In the present study, we examined the anti-inflammatory actions of 2-docosahexaenoyl lysophosphatidylcholine (2-docosahexaenoyl-lysoPC) in vitro as well as in vivo systems. When RAW 264.7 cells were treated with 2-docoshexaenoyl-lysoPC, a concentration-dependent decrease of LPS-induced formation of nitric oxide (NO), tumor necrosis factor alpha (TNF-α), or IL-6 was observed. Additionally, oral administration of 2-docosahexaenoyl-lysoPC was found to inhibit zymosan A-induced plasma leakage dose-dependently in mice with ED(50) value of 50 μg/kg and E (max) value of about 65%. Moreover, mechanistic study revealed that the anti-inflammatory action of 2-docosahexaenoyl-lysoPC seemed to be related largely to LTC(4) inhibition, but not PGE(2) inhibition. Moreover, 2-(17-hydroperoxydocosahexaneoyl)-lysoPC, intravenously administrated, was more effective than 2-docosahexaenoyl-lysoPC in the inhibition of zymosan A-induced plasma leakage, suggesting that 2-(17-hydroperoxydocosahexaneoyl)-lysoPC, a product from oxygenation of 2-docosahexaenoyl-lysoPC by 15-lipoxygenase (LOX), may be an active metabolite, intimately responsible for anti-inflammatory actions, generated from 2-docosahexaenoyl-lysoPC. In a related study, 2-docosahexaenoyl-lysoPC was found to be more efficient than 1-docosahexaenoyl-lysoPC or docosahexaenoic acid (DHA) as substrate for 15-lipoxygenases such as soybean LOX-1, leukocyte 12/15-LOX, and human 15-LOX-2. Taken altogether, it is suggested that 2-docosahexaenoyl-lysoPC and its oxygenation products may exert anti-inflammatory action after oral administration.

Tulathromycin Exerts Proresolving Effects in Bovine Neutrophils by Inhibiting Phospholipases and Altering Leukotriene B4, Prostaglandin E2, and Lipoxin A4Production

“…In view of its multifaceted roles in airway inflammation, future studies will examine the impact of tulathromycin on PGE 2 production and the consequence of this effect on airway inflam- mation. Using the experimental protocol described here, zymosan was found to significantly increase PGE 2 production 24 h postchallenge, consistent with previous studies using other models in vivo (43)(44)(45) or in vitro (46), an effect that was blocked by tulathromycin. Another immunomodulating antibiotic for cattle and pigs, tilmicosin, also blocks PGE 2 production in LPS-stimulated bovine alveolar macrophages via a decrease in COX-2 expression and/or partial inhibition of secretory phospholipase A 2 activity (47,48).…”

Resolvin E2 Formation and Impact in Inflammation Resolution

“…This relatively simplified biosynthetic route may partially explain the identification of resolvins such as RvE2 in non-human sources, such as marine organisms and fish rich in omega-3 fatty acids (34, 35). Furthermore, SPM introduced via the gastrointestinal tract can be bioactive (36), as it was recently also shown that docosahexaenoic acid in 2-docosahexaenoic acid-lysophosphatidylcholine, a substrate of 15-LOX (both plant and human), produces orally active, anti-inflammatory compounds related to the resolvins (37). …”

Feeding Healthy Beagles Medium-Chain Triglycerides, Fish Oil, and Carnitine Offsets Age-Related Changes in Serum Fatty Acids and Carnitine Metabolites

“…Of major importance, Huang et al [32] showed that the diverse properties of the GPC class of lysophospholipids are highly dependent on the type of FA attached to the GPC. Hung et al [33] suggested that 2-DHA-GPC may be more efficient than 1-DHA-GPC as an anti-inflammatory agent when administered orally to mice. DHA migrates very easily from the sn -2 position of GPC, which could be considered as the physiological form of DHA-GPC, to the sn -1 position, which is much more stable [34].…”