The resolvin D2 and omega-3 polyunsaturated fatty acid as a new possible therapeutic approach for inflammatory bowel diseases.

IF 3.8 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Scientific Reports Pub Date : 2024-11-20 DOI:10.1038/s41598-024-80051-8

Fabio Henrique Mendonça Chaim, Lívia Bitencourt Pascoal, Marina Moreira de Castro, Bruna Biazon Palma, Bruno Lima Rodrigues, João José Fagundes, Marciane Milanski, Luiz Roberto Lopes, Raquel Franco Leal

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Abstract

Inflammatory bowel diseases (IBD) are idiopathic disorders characterized by chronic gastrointestinal inflammation. Given conventional therapies' adverse effects and clinical failures, novel approaches are being investigated. Recent studies have highlighted the role of specialized pro-resolving lipid mediators (SPMs) in the active resolution of chronic inflammation. In this regard, omega-3 fatty acid-derived Resolvin D2 (RvD2) appears to play a protective role in the pathophysiology of IBD. Therefore, we characterized the RvD2 pathway and its receptor expression in the intestinal mucosa of experimental colitis induced by dextran sulfate sodium. We also evaluated the preventive impact of an omega-3-enriched diet and the therapeutic efficacy of RvD2 compared with anti-TNF-α treatment. We found an increase in TNFα and IL22 expression and decreased levels of enzymes involved in RvD2 biosynthesis, such as PLA₂, 15-LOX, 5-LOX, and its receptor GPR18 in experimental colitis. Omega-3 supplementation reduced the Disease Activity Index (DAI), weight loss, colonic shortening, and inflammation. These results and the increased IL-10 transcriptional levels after RvD2 treatment suggest that this mediator attenuated experimental colitis. These results enhance our understanding of the molecular mechanisms involved in the exacerbated inflammatory response present in experimental colitis and suggest that RvD2 and its omega-3 precursor offer a promising therapeutic approach for IBD.

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解析素 D2 和欧米伽-3 多不饱和脂肪酸是治疗炎症性肠病的一种可能的新方法。

炎症性肠病（IBD）是一种以慢性胃肠道炎症为特征的特发性疾病。鉴于传统疗法的不良反应和临床失败，人们正在研究新的方法。最近的研究强调了专门的促进缓解脂质介质（SPMs）在积极缓解慢性炎症中的作用。在这方面，ω-3 脂肪酸衍生的 Resolvin D2（RvD2）似乎在 IBD 的病理生理学中发挥着保护作用。因此，我们研究了右旋糖酐硫酸钠诱导的实验性结肠炎肠粘膜中的 RvD2 通路及其受体表达。我们还评估了富含欧米伽-3饮食的预防作用，以及RvD2与抗TNF-α治疗相比的疗效。我们发现，在实验性结肠炎中，TNFα和IL22的表达增加，参与RvD2生物合成的酶，如PLA2、15-LOX、5-LOX及其受体GPR18的水平降低。补充欧米伽-3能降低疾病活动指数（DAI）、减轻体重、缩短结肠和减少炎症。这些结果以及 RvD2 治疗后 IL-10 转录水平的增加表明，这种介质可减轻实验性结肠炎。这些结果加深了我们对实验性结肠炎炎症反应加剧所涉及的分子机制的了解，并表明 RvD2 及其欧米加-3 前体为 IBD 提供了一种很有前景的治疗方法。

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来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

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