Lipids

, Volume 45, Issue 3, pp 225–236

Lysophosphatidylcholine Containing Docosahexaenoic Acid at the sn-1 Position is Anti-inflammatory

  • Long Shuang Huang
  • Nguyen Dang Hung
  • Dai-Eun Sok
  • Mee Ree Kim
Original Article

DOI: 10.1007/s11745-010-3392-5

Cite this article as:
Huang, L.S., Hung, N.D., Sok, DE. et al. Lipids (2010) 45: 225. doi:10.1007/s11745-010-3392-5
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Abstract

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 PGE2. 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 ED50 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 LTC4, 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.

Keywords

Anti-inflammatoryNitric oxideDHA-lysoPtdCho17-HPDHA- lysoPtdChoDocosahexaenoicLPSZymosan ARAW 264.7 cell

Abbreviations

lysoPtdCho

Lysophosphatidylcholine

LNA

Linoleic acid

ARA

Arachidonic acid

DHA

Docosahexaenoic acid

LNA-lysoPtdCho

1-Linoleoyl-2-lyso-sn-glycerol-3-phosphocholine

ARA-lysoPtdCho

1-Arachidonyl-2-lyso-sn-glycerol-3-phosphocholine

DHA-lysoPtdCho

1-Docosahexaenoyl-2-lyso-sn-glycerol-3-phosphocholine

14-HPDHA-lysoPtdCho

1-14(S)-hydroperoxy-4,7,10,13,15,19-docosahexaenoyl-2-lyso-sn-glycerol-3-phosphocholine

17-HPDHA-lysoPtdCho

1-17(S)-hydroperoxy-4,7,10,13,15,19-docosahexaenoyl-2-lyso-sn-glycerol-3 phosphocholine

LOX

Lipoxygenase

ED50

50% effective dose

IC50

50% inhibitory concentration

PLA2

Phospholipase A2

LTC4

Leukotriene C4

PGE2

Prostaglandin E2

IL-6

Interleukin-6

TNF-α

Tumor necrosis factor alpha

NO

Nitric oxide

Copyright information

© AOCS 2010

Authors and Affiliations

  • Long Shuang Huang
    • 1
  • Nguyen Dang Hung
    • 1
  • Dai-Eun Sok
    • 1
  • Mee Ree Kim
    • 2
  1. 1.College of PharmacyChungnam National UniversityTaejonKorea
  2. 2.Department of Food and NutritionChungnam National UniversityTaejonKorea