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Inflammation

, Volume 34, Issue 3, pp 147–160 | Cite as

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

  • Nguyen Dang Hung
  • Mee Ree Kim
  • Dai-Eun SokEmail author
Article

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.

KEY WORDS

anti-inflammatory 2-docosahexaenoyl-lysoPC zymosan A nitric oxide LTC4 PGE2 RAW 264.7 cell 

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

Notes

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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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.College of PharmacyChungnam National UniversityYuseong-KuRepublic of Korea
  2. 2.Department of Food and NutritionChungnam National UniversityYuseong-KuRepublic of Korea

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