Linoleoyl Ethanolamide is a fatty acid ethanolamide with Ki values of 10 and 25μM for cannabinoid receptors (CB1 and CB2), respectively. Linoleoyl Ethanolamide competitively inhibits anandamide hydrolysis and exhibits anti-allergic and anti-inflammatory effects[1-2]. Linoleoyl Ethanolamide has also been identified as a multifunctional compound associated with various physiological processes and disease development, including appetite regulation, depression, and cancer progression[3-4].
In vitro, Linoleoyl Ethanolamide (10–100μM) pretreated RAW264.7 macrophages for 30 minutes, followed by lipopolysaccharide (LPS, 100ng/mL) stimulation for 24 hours, significantly suppressed LPS-induced pro-inflammatory cytokine (TNF-α, IL-1β, IL-6) mRNA expression and TNF-α protein secretion. Linoleoyl Ethanolamide also inhibited LPS-induced Toll-like receptor 4 (TLR4) signaling pathway activation and nuclear factor κB (NF-κB) p65 nuclear translocation, while reducing cyclooxygenase-2 (Cox-2) mRNA expression and prostaglandin E2 (PGE2) release[5]. At 48μM, Linoleoyl Ethanolamide inhibited DNP-HSA-mediated degranulation in RBL-2H3 cells by decreasing β-hexosaminidase release, demonstrating anti-allergic activity [6].
In vivo, Linoleoyl Ethanolamide (10mg/kg) was administered intraperitoneally (i.p.) to male Sprague-Dawley (SD) rats with high-fat diet (HFD)-induced obesity for 14 consecutive days after 12 weeks of HFD feeding. LEA significantly reduced HFD-induced weight gain, lowered plasma triglycerides, total cholesterol, and inflammatory markers (IL-6 and TNF-α), and improved liver function (reduced AST and ALT activity)[7]. Linoleoyl Ethanolamide (10mg/kg and 20mg/kg, i.p.) was administered 6.5 hours before ischemia to male SD rats subjected to middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion (I/R) injury. Linoleoyl Ethanolamide significantly reduced cortical infarct volume and markedly improved neurological deficit scores caused by MCAO[8].
References:
[1] Lin S, Khanolkar AD, Fan P, et al. Novel analogues of arachidonylethanolamide (anandamide): affinities for the CB1 and CB2 cannabinoid receptors and metabolic stability. J Med Chem. 1998 Dec 31;41(27):5353-61.
[2] Wang X, Chen Y, Jin Q, et al. Synthesis of linoleoyl ethanolamide. J Oleo Sci. 2013;62(6):427-33.
[3] Tian XY, Xing JW, Zheng QQ, et al. 919 Syrup Alleviates Postpartum Depression by Modulating the Structure and Metabolism of Gut Microbes and Affecting the Function of the Hippocampal GABA/Glutamate System. Front Cell Infect Microbiol. 2021 Aug 20;11:694443.
[4] Vered S, Beiser AS, Sulimani L, et al. The association of circulating endocannabinoids with neuroimaging and blood biomarkers of neuro-injury. Alzheimers Res Ther. 2023 Sep 12;15(1):154.
[5] Ishida T, Nishiumi S, Tanahashi T, et al. Linoleoyl ethanolamide reduces lipopolysaccharide-induced inflammation in macrophages and ameliorates 2,4-dinitrofluorobenzene-induced contact dermatitis in mice. Eur J Pharmacol. 2013 Jan 15;699(1-3):6-13.
[6] Kim IH, Kanayama Y, Nishiwaki H, et al. Structure-Activity Relationships of Fish Oil Derivatives with Antiallergic Activity in Vitro and in Vivo. J Med Chem. 2019 Nov 14;62(21):9576-9592.
[7] Tovar R, de Ceglia M, Ubaldi M, et al. Hypaphorine exerts anti-inflammatory effects in sepsis induced acute lung injury via modulating DUSP1/p38/JNK pathway. Kaohsiung J Med Sci. 2021 Oct;37(10):883-893.
[8] Garg P, Duncan RS, Kaja S, et al. Lauroylethanolamide and linoleoylethanolamide improve functional outcome in a rodent model for stroke. Neurosci Lett. 2011 Apr 4;492(3):134-8.
Linoleoyl Ethanolamide是一种脂肪酸乙醇酰胺，与大麻素受体（CB1和CB2受体）的Ki值分别为10和25μM，可竞争性抑制anandamide水解，并表现出抗过敏和抗炎作用[1-2]。Linoleoyl Ethanolamide 也被指出是机体多机能和疾病发展相关的化合物，包括食欲、抑郁症以及癌症发展等[3-4]。
在体外，Linoleoyl Ethanolamide（10–100μM）预处理RAW264.7巨噬细胞30分钟后，再用脂多糖（LPS，100ng/mL）刺激24小时，显著抑制了LPS诱导的促炎因子（TNF-α、IL-1β、IL-6）mRNA表达和TNF-α蛋白分泌，同时抑制了LPS诱导的Toll样受体4（TLR4）信号通路激活及核因子κB（NF-κB）p65核转位，还降低了环氧合酶-2（Cox-2）mRNA表达和前列腺素E2（PGE2）释放[5]。Linoleoyl Ethanolamide（48μM）通过减少β-己糖胺酶释放抑制RBL-2H3细胞的DNP-HSA介导脱颗粒，显示抗过敏活性[6]。
在体内，Linoleoyl Ethanolamide（10mg/kg）通过腹腔注射给药，用于治疗高脂饮食（HFD）诱导的肥胖雄性Sprague-Dawley（SD）大鼠模型，给药时间为HFD喂养12周后连续14天。Linoleoyl Ethanolamide能显著减少HFD诱导的体重增加，降低血浆甘油三酯、总胆固醇及炎症标志物（IL-6和TNF-α）水平，并改善肝功能（降低AST和ALT活性）[7]。Linoleoyl Ethanolamide（10mg/kg和20mg/kg）通过腹腔注射给药，用于预处理雄性Sprague-Dawley（SD）大鼠的中脑动脉闭塞（MCAO）脑缺血/再灌注（I/R）损伤模型，给药时间为缺血前6小时30分钟。Linoleoyl Ethanolamide能显著减少皮质梗死体积，并显著改善由MCAO引起的神经功能缺损评分[8]。