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A polyphenol-rich açaí seed extract protects against 5-fluorouracil-induced intestinal mucositis in mice through the TLR-4/MyD88/PI3K/mTOR/NF-κBp65 signaling pathway.
Nutrition Research ( IF 4.5 ) Pub Date : 2024-02-03 , DOI: 10.1016/j.nutres.2024.01.017
Carlos Eduardo da Silva Monteiro , Bárbara de Cerqueira Fiorio , Francisca Géssica Oliveira Silva , Maria de Fathima Felipe de Souza , Álvaro Xavier Franco , Marcos Aurélio de Sousa Lima , Thiago Meneses Araujo Leite Sales , Tiago Santos Mendes , Alexandre Havt , André Luiz Reis Barbosa , Ângela Castro Resende , Roberto Soares de Moura , Marcellus Henrique Loiola Ponte de Souza , Pedro Marcos Gomes Soares

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. Several evidences suggest 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 through 5-FU-mediated modulation of the TLR-4/MyD88/phosphatidylinositol-3-kinase α (PI3Kα)/mechanistic target of rapamycin (mTOR)/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 (IL-1β; TNF-α; MPO 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/mTOR/NF-κBp65 pathway.

中文翻译:

富含多酚的巴西莓籽提取物通过 TLR-4/MyD88/PI3K/mTOR/NF-κBp65 信号通路预防 5-氟尿嘧啶诱导的小鼠肠粘膜炎。

巴西莓种子提取物 (ASE) 购自 Euterpe oleracea Mart。(巴西莓)植物(亚马逊地区)具有很高的营养和功能价值。ASE富含多酚化合物,主要是原花青素。原花青素可以通过抑制 Toll 样受体 4 (TLR-4)/骨髓分化初级反应 88 (MyD88)/核因子-κB (NF-κB) 通路来调节免疫系统和氧化应激。多项证据表明,炎症细胞因子和氧化应激有助于肠粘膜炎的发病机制,这些事件可导致肠道动力障碍。我们假设 ASE 通过 5-FU 介导的 TLR-4/MyD88/磷脂酰肌醇-3-激酶 α (PI3Kα)/雷帕霉素 (mTOR)/NF 机制靶标的调节,在肠粘膜炎中发挥抗炎和抗氧化化合物的作用-κBp65途径。将动物分为线性 5-FU [450 mg/kg] 和 5-FU + ASE [10、30 和 100 mg/kg] 组。每天评估动物的体重减轻。从十二指肠、空肠和回肠获取样本用于组织病理学、生化和功能分析。ASE 可减少体重减轻、炎症参数(IL-1β、TNF-α、MPO 活性)以及参与 TLR-2/MyD88/NF-κB 途径的介质的基因表达。ASE 可预防组织病理学变化,对胃肠道传输延迟、胃排空和肠道吸收/渗透性产生有益影响。总之,ASE通过抑制TLR/MyD88/PI3K/mTOR/NF-κBp65通路来保护肠上皮屏障的完整性。
更新日期:2024-02-03
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