Otagiri Shinsuke, Ohnishi Shunsuke, Ohara Masatsugu, Fu Qingjie, Yamamoto Koji, Yamamoto Keiko, Katsurada Takehiko, Sakamoto Naoya
Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Front Pharmacol. 2020 Aug 14;11:1277. doi: 10.3389/fphar.2020.01277. eCollection 2020.
Oleoylethanolamide (OEA) is an endogenous fatty acid ethanolamide known for its anti-inflammatory effects and its influence on gut microbiota composition; however, the effects of OEA in inflammatory bowel disease (IBD) remain unknown. During experiments, OEA downregulated the expression of tumor necrosis factor (TNF)-α and reduced phosphorylation of inhibitor of kappa (Iκ) Bα induced by lipopolysaccharide in human embryonic kidney cells. Moreover, OEA downregulated the expression of interleukin (IL)-8 and IL-1β and inhibited the phosphorylation of IκBα and p65 induced by TNF-α in human enterocytes (Caco-2). The effect of OEA in reducing the expression of IL-8 was blocked by the peroxisome proliferator-activated receptor (PPAR)-α antagonist. During experiments on rats, colitis was induced by the oral administration of 8% dextran sulfate sodium from day 0 through day 5, and OEA (20 mg/kg) was intraperitoneally injected once a day from day 0 for 6 days. OEA administration significantly ameliorated the reduction in body weight, the increase in disease activity index score, and the shortening of colon length. In rectums, OEA administration reduced the infiltration of macrophages and neutrophils and tended to reduce the histological score and the expression of inflammatory cytokines. Administration of OEA produced significant improvement in a colitis model, possibly by inhibiting the nuclear factor kappa B signaling pathway through PPAR-α receptors. OEA could be a potential new treatment for IBD.
油酰乙醇胺（OEA）是一种内源性脂肪酸乙醇胺，以其抗炎作用及其对肠道微生物群组成的影响而闻名；然而，OEA在炎症性肠病（IBD）中的作用仍不清楚。在实验过程中，OEA下调了人胚肾细胞中肿瘤坏死因子（TNF）-α的表达，并减少了脂多糖诱导的κB抑制因子（Iκ）Bα的磷酸化。此外，OEA下调了人肠上皮细胞（Caco-2）中白细胞介素（IL）-8和IL-1β的表达，并抑制了TNF-α诱导的IκBα和p65的磷酸化。过氧化物酶体增殖物激活受体（PPAR）-α拮抗剂阻断了OEA降低IL-8表达的作用。在大鼠实验中，从第0天到第5天通过口服8%的葡聚糖硫酸钠诱导结肠炎，从第0天开始每天腹腔注射一次OEA（20mg/kg），持续6天。给予OEA可显著改善体重减轻、疾病活动指数评分增加和结肠长度缩短的情况。在直肠中，给予OEA减少了巨噬细胞和中性粒细胞的浸润，并倾向于降低组织学评分和炎症细胞因子的表达。给予OEA在结肠炎模型中产生了显著改善，可能是通过PPAR-α受体抑制核因子κB信号通路实现的。OEA可能是一种潜在的IBD新治疗方法。
