Monteiro Carlos Eduardo da Silva, de Cerqueira Fiorio Bárbara, Silva Francisca Géssica Oliveira, de Fathima Felipe de Souza Maria, Franco Álvaro Xavier, Lima Marcos Aurélio de Sousa, Sales Thiago Meneses Araujo Leite, Mendes Tiago Santos, Havt Alexandre, Barbosa André Luiz Reis, Resende Ângela Castro, de Moura Roberto Soares, de Souza Marcellus Henrique Loiola Ponte, Soares Pedro Marcos Gomes
LEFFAG- Laboratory of Physiopharmacology Study of Gastrointestinal Tract, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
Laboratory of Molecular Toxinology, LTM, Federal University of Ceará, Fortaleza, CE, Brazil.
Nutr Res. 2024 May;125:1-15. doi: 10.1016/j.nutres.2024.01.017. Epub 2024 Feb 3.
Açaí seed extract (ASE) is obtained from Euterpe oleracea Mart. (açaí) plant (Amazon region) has high nutritional and functional value. ASE is rich in polyphenolic compounds, mainly proanthocyanidins. Proanthocyanidins can modulate the immune system and oxidative stress by inhibiting the toll-like receptor-4 (TLR-4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-κB (NF-κB) pathway. A great deal of evidence suggests that inflammatory cytokines and oxidative stress contribute to the pathogenesis of intestinal mucositis, and these events can lead to intestinal dysmotility. We hypothesized that ASE acts as an anti-inflammatory and antioxidant compound in intestinal mucositis induced by 5-fluorouracil (5-FU) through modulation of the TLR-4/MyD88/phosphatidylinositol-3-kinase α/mechanistic target of rapamycin/NF-κBp65 pathway. The animals were divided into linear 5-FU (450 mg/kg) and 5-FU + ASE (10, 30, and 100 mg/kg) groups. The weight loss of the animals was evaluated daily. Samples from duodenum, jejunum, and ileum were obtained for histopathological, biochemical, and functional analyses. ASE reduced weight loss, inflammatory parameters (interleukin-1β; tumor necrosis factor-α; myeloperoxidase activity) and the gene expression of mediators involved in the TLR-2/MyD88/NF-κB pathway. ASE prevented histopathological changes with beneficial effects on gastrointestinal transit delay, gastric emptying, and intestinal absorption/permeability. In conclusion, ASE protects the integrity of the intestinal epithelial barrier by inhibiting the TLR/MyD88/PI3K/mechanistic target of rapamycin/NF-κBp65 pathway.
阿萨伊籽提取物（ASE）取自亚马逊地区的羽叶金虎尾属植物（阿萨伊），具有很高的营养价值和功能价值。ASE富含多酚类化合物，主要是原花青素。原花青素可通过抑制Toll样受体4（TLR-4）/髓样分化初级反应88（MyD88）/核因子κB（NF-κB）途径来调节免疫系统和氧化应激。大量证据表明，炎性细胞因子和氧化应激参与了肠道黏膜炎的发病机制，且这些事件可导致肠道运动障碍。我们推测，ASE通过调节TLR-4/MyD88/磷脂酰肌醇-3激酶α/雷帕霉素作用靶点/NF-κBp65途径，在5-氟尿嘧啶（5-FU）诱导的肠道黏膜炎中发挥抗炎和抗氧化化合物的作用。将动物分为线性5-FU（450 mg/kg）组和5-FU + ASE（10、30和100 mg/kg）组。每天评估动物的体重减轻情况。采集十二指肠、空肠和回肠样本进行组织病理学、生化和功能分析。ASE减轻了体重减轻、炎症参数（白细胞介素-1β；肿瘤坏死因子-α；髓过氧化物酶活性）以及TLR-2/MyD88/NF-κB途径中相关介质的基因表达。ASE预防了组织病理学变化，对胃肠道转运延迟、胃排空以及肠道吸收/通透性具有有益作用。总之，ASE通过抑制TLR/MyD88/PI3K/雷帕霉素作用靶点/NF-κBp65途径保护肠道上皮屏障的完整性。
