关键词: GALNT2 ethanol foxtail millet gastric mucosal injury isoferulic acid

Mesh : Animals Gastric Mucosa / drug effects pathology Ethanol Rats, Wistar Rats Male Setaria Plant Plant Extracts / pharmacology Humans Epithelial Cells / drug effects Molecular Docking Simulation Disease Models, Animal

来  源:   DOI:10.3390/nu16132148   PDF(Pubmed)

Abstract:
Excessive alcohol consumption has led to the prevalence of gastrointestinal ailments. Alleviating gastric disorders attributed to alcohol-induced thinning of the mucus layer has centered on enhancing mucin secretion as a pivotal approach. In this study, foxtail millet bran polyphenol BPIS was divided into two components with MW < 200 D and MW > 200 D by molecular interception technology. Combined with MTT, cell morphology observation, and trypan blue staining, isoferulic acid (IFA) within the MW < 200 D fraction was determined as the effective constituent to mitigate ethanol-induced damage of gastric epithelial cells. Furthermore, a Wistar rat model with similar clinical features to alcohol-induced gastric mucosal injury was established. Then, gastric morphological observation, H&E staining, and assessments of changes in gastric hexosamine content and gastric wall binding mucus levels were carried out, and the results revealed that IFA (10 mg/Kg) significantly ameliorated alcohol-induced gastric mucosal damage. Finally, we applied techniques including Co-IP, molecular docking, and fluorescence spectroscopy and found that IFA inhibited the alcohol-induced downregulation of N-acetylgalactosamintransferase 2 (GALNT2) activity related to mucus synthesis through direct interaction with GALNT2 in gastric epithelial cells, thus promoting mucin synthesis. Our study lays a foundation for whole grain dietary intervention tailored to individuals suffering from alcoholic gastric mucosal injury.
摘要:
过量饮酒导致胃肠道疾病的流行。缓解归因于酒精引起的粘液层变薄的胃病已经集中于增强粘蛋白分泌作为关键方法。在这项研究中,采用分子截留技术将谷草谷糠多酚BPIS分为MW<200D和MW>200D两个组分。结合MTT,细胞形态学观察,和锥虫蓝染色,MW<200D部分内的异阿魏酸(IFA)被确定为减轻乙醇诱导的胃上皮细胞损伤的有效成分。此外,建立了与酒精引起的胃粘膜损伤具有相似临床特征的Wistar大鼠模型。然后,胃形态学观察,H&E染色,并评估胃己糖胺含量和胃壁结合粘液水平的变化,结果表明,IFA(10mg/Kg)显着改善了酒精引起的胃粘膜损伤。最后,我们应用了包括Co-IP在内的技术,分子对接,和荧光光谱,发现IFA通过与胃上皮细胞中的GALNT2直接相互作用,抑制酒精诱导的与粘液合成相关的N-乙酰氨基半乳糖转移酶2(GALNT2)活性下调,从而促进粘蛋白合成。我们的研究为针对酒精性胃粘膜损伤患者的全谷物饮食干预奠定了基础。
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