Trivedi Purvi, Myers Tanya, Ray Bithika, Allain Matthew, Zhou Juan, Kelly Melanie, Lehmann Christian
Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Department of Anesthesia, Pain Management, and Perioperative Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Biomedicines. 2024 May 2;12(5):1000. doi: 10.3390/biomedicines12051000.
Inflammatory bowel disease (IBD) is a group of chronic disorders characterized by pain, ulceration, and the inflammation of the gastrointestinal tract (GIT) and categorized into two major subtypes: ulcerative colitis (UC) and Crohn's disease. The inflammation in UC is typically restricted to the mucosal surface, beginning in the rectum and extending through the entire colon. UC patients typically show increased levels of pro-inflammatory cytokines, leading to intestinal epithelial apoptosis and mucosal inflammation, which impair barrier integrity. Chronic inflammation is associated with the rapid recruitment and inappropriate retention of leukocytes at the site of inflammation, further amplifying the inflammation. While UC can be managed using a number of treatments, these drugs are expensive and cause unwanted side effects. Therefore, a safe and effective treatment for UC patients is needed. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide and an analog of the endocannabinoid anandamine. PEA administration has been found to normalize intestinal GIT motility and reduce injury in rodents and humans. In the current study, we examined the efficacy of PEA encapsulated in phytosomes following oral administration in experimental ulcerative colitis. Here, we showed that PEA at a human-equivalent dose of 123 mg/kg (OD or BID) attenuated DSS-induced experimental colitis as represented by the reduction in clinical signs of colitis, reduction in gross mucosal injury, and suppression of leukocyte recruitment at inflamed venules. These findings add to the growing body of data demonstrating the beneficial effects of PEA to control the acute phase of intestinal inflammation occurring during UC.
炎症性肠病（IBD）是一组以疼痛、溃疡和胃肠道（GIT）炎症为特征的慢性疾病，分为两个主要亚型：溃疡性结肠炎（UC）和克罗恩病。UC中的炎症通常局限于黏膜表面，始于直肠并延伸至整个结肠。UC患者通常表现出促炎细胞因子水平升高，导致肠上皮细胞凋亡和黏膜炎症，从而损害屏障完整性。慢性炎症与白细胞在炎症部位的快速募集和不适当滞留有关，进一步加剧了炎症。虽然UC可以通过多种治疗方法进行管理，但这些药物昂贵且会引起不良副作用。因此，需要一种对UC患者安全有效的治疗方法。棕榈酰乙醇胺（PEA）是一种内源性脂肪酸酰胺，是内源性大麻素花生四烯乙醇胺的类似物。已发现给予PEA可使肠道GIT运动正常化，并减少啮齿动物和人类的损伤。在本研究中，我们研究了口服给药后包裹在磷脂体中的PEA在实验性溃疡性结肠炎中的疗效。在此，我们表明，以123 mg/kg（每日一次或每日两次）的等效人剂量的PEA减轻了DSS诱导的实验性结肠炎，表现为结肠炎临床症状的减轻、大体黏膜损伤的减少以及炎症小静脉处白细胞募集的抑制。这些发现进一步证明了PEA在控制UC期间发生的肠道炎症急性期方面的有益作用，相关数据不断增加。
