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

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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 ED50 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 LTC4 inhibition, but not PGE2 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.

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Abbreviations

DHA:

docosahexaenoic acid

17-HDoHA:

17-hydroxydocoxahexaenoic acid

1-linoleoyl-lysoPC:

1-linoleoyl-lysophosphatidylcholine

1-arachidonoyl-lysoPC:

1-arachidonoyl-lysophosphatidylcholine

1-docosahexaenoyl-lysoPC:

1-docosahexaenoyl-lysophosphatidylcholine

2-docosahexaenoyl-lysoPC:

2-docosahexaenoyl-lysophosphatidylcholine

LOX:

lipoxygenase

ED50 :

50% effective dose

PLA2 :

phospholipase A2

LTC4 :

leukotriene C4

PGE2 :

prostaglandin E2

IL-6:

Interleukin-6

TNF-α:

tumor necrosis factor alpha

NO:

nitric oxide

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Acknowledgement

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF 2009-0069242).

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Authors and Affiliations

  1. College of Pharmacy, Chungnam National University, Yuseong-Ku, Taejon, 305-764, Republic of Korea

    Nguyen Dang Hung & Dai-Eun Sok

  2. Department of Food and Nutrition, Chungnam National University, Yuseong-Ku, Taejon, 305-764, Republic of Korea

    Mee Ree Kim

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  1. Nguyen Dang Hung
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Hung, N.D., Kim, M.R. & Sok, DE. Oral Administration of 2-Docosahexaenoyl Lysophosphatidylcholine Displayed Anti-Inflammatory Effects on Zymosan A-Induced Peritonitis. Inflammation 34, 147–160 (2011). https://doi.org/10.1007/s10753-010-9218-z

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