College of Pharmacy, Chungnam National University, Yuseong-Ku, Taejon, 305-764, Republic of Korea.
Inflammation. 2011 Jun;34(3):147-60. doi: 10.1007/s10753-010-9218-z.
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.
溶血磷脂酰胆碱（lysoPCs）是生物活性脂质介质，参与多种生物和病理过程。在本研究中，我们在体外和体内系统中研究了 2-二十二碳六烯酰基溶血磷脂酰胆碱（2-docosahexaenoyl-lysoPC）的抗炎作用。当 RAW 264.7 细胞用 2-二十二碳六烯酰基溶血磷脂酰胆碱处理时，观察到 LPS 诱导的一氧化氮（NO）、肿瘤坏死因子-α（TNF-α）或 IL-6 的形成呈浓度依赖性降低。此外，发现口服 2-二十二碳六烯酰基溶血磷脂酰胆碱可剂量依赖性地抑制酵母聚糖 A 诱导的血浆渗漏，其 ED50 值为 50μg/kg，E(max)值约为 65%。此外，机制研究表明，2-二十二碳六烯酰基溶血磷脂酰胆碱的抗炎作用似乎主要与 LTC4 抑制有关，而与 PGE2 抑制无关。此外，静脉内给予 2-(17-过氧二十二碳六烷酰基)-溶血磷脂酰胆碱比 2-二十二碳六烯酰基溶血磷脂酰胆碱更有效地抑制酵母聚糖 A 诱导的血浆渗漏，表明 2-(17-过氧二十二碳六烷酰基)-溶血磷脂酰胆碱是一种活性代谢物，由 15-脂氧合酶（LOX）对 2-二十二碳六烯酰基溶血磷脂酰胆碱的氧化生成，可能与其抗炎作用密切相关。在相关研究中，2-二十二碳六烯酰基溶血磷脂酰胆碱作为底物比 1-二十二碳六烯酰基溶血磷脂酰胆碱或二十二碳六烯酸（DHA）更有效地被大豆 LOX-1、白细胞 12/15-LOX 和人 15-LOX-2 等 15-脂氧合酶利用。总的来说，这表明口服后，2-二十二碳六烯酰基溶血磷脂酰胆碱及其氧化产物可能发挥抗炎作用。
