Oral administration of 2-docosahexaenoyl lysophosphatidylcholine displayed anti-inflammatory effects on zymosan A-induced peritonitis.
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.
Hung
Nguyen Dang
ND
College of Pharmacy, Chungnam National University, Yuseong-Ku, Taejon, 305-764, Republic of Korea. hung_hanoi_vietnam@yahoo.com
Kim
Mee Ree
MR
Sok
Dai-Eun
DE
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D017997:Leukotriene C4 / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000096:biosynthesis; D010084:Oxidation-Reduction; D010538:Peritonitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D013379:Substrate Specificity; D015054:Zymosan / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008244:Lysophosphatidylcholines; C090324:docosahexaenoyl lysophosphatidylcholine; D004281:Docosahexaenoic Acids; D017997:Leukotriene C4; D009569:Nitric Oxide; D015054:Zymosan; D001093:Arachidonate 15-Lipoxygenase; D015232:Dinoprostone