Theaflavins, theaflavin-3,3′-digallate, and its nanoparticles attenuate chronic alcohol-induced gastric injury and hepatic fibrosis by activating the AMPK/mTOR/Beclin1/LC3 autophagy pathway and modulating intestinal microbiota in ICR mice

IF 3.8 2区农林科学 Q2 FOOD SCIENCE & TECHNOLOGY

Journal of Functional Foods Pub Date : 2025-07-16 DOI:10.1016/j.jff.2025.106957

Ying Wang , Dan Zhang , Jiahong Chen , Ziyu Kong , Ling Wu , Zenghui Liu , Qingqing Zhai , Yan Xu

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Abstract

This study investigated the protective effects of theaflavins (TFs), theaflavin-3,3′-digallate (TFDG), and TFDG nanoparticles (TFDGN) against chronic alcohol-induced gastric and hepatic injuries in mice. Using an eight-week alcohol administration model, this study demonstrated that TFs, TFDG, and TFDGN significantly reduced mortality, liver index, and serum biomarkers of hepatic injury, while increasing glutathione levels. Histopathology confirmed the attenuation of hepatic inflammation, fibrosis, and gastric mucosal damage. Mechanistically, these compounds activated gastric cell autophagy via the downregulation of p-mTOR and the upregulation of p-AMPK, Beclin1, and LC3-II. Additionally, they modulated gut microbiota by enriching probiotics (Lactobacillus, Akkermansia and Oscillibacter) while reducing pathogens (Allobaculum, Faecalibaculum and Enterococcus). Among the tested compounds, TFDGN exhibited superior efficacy. These findings demonstrate that TFs, TFDG, and TFDGN provide protection against alcohol-induced damage by regulating autophagy, reducing fibrosis, and restoring gut microbiota balance, highlighting their potential as natural therapeutics for alcohol-related gastric and hepatic disorders.

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茶黄素、茶黄素-3,3 ' -二二酸酯及其纳米颗粒通过激活AMPK/mTOR/Beclin1/LC3自噬途径和调节肠道微生物群，减轻慢性酒精诱导的胃损伤和肝纤维化

本研究探讨了茶黄素（TFs）、茶黄素-3,3 ' -二二酸酯（TFDG）和TFDG纳米颗粒（TFDGN）对小鼠慢性酒精性胃和肝损伤的保护作用。通过8周的酒精给药模型，本研究证明tffs、TFDG和TFDGN显著降低死亡率、肝脏指数和肝损伤的血清生物标志物，同时增加谷胱甘肽水平。组织病理学证实肝脏炎症、纤维化减弱，胃粘膜损伤。在机制上，这些化合物通过下调p-mTOR和上调p-AMPK、Beclin1和LC3-II来激活胃细胞自噬。此外，它们通过丰富益生菌（乳酸杆菌，Akkermansia和Oscillibacter）来调节肠道微生物群，同时减少病原体（Allobaculum， Faecalibaculum和Enterococcus）。在所测试的化合物中，TFDGN表现出较好的疗效。这些研究结果表明，tffs、TFDG和TFDGN通过调节自噬、减少纤维化和恢复肠道微生物群平衡来防止酒精诱导的损伤，突出了它们作为酒精相关胃和肝脏疾病的天然疗法的潜力。

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来源期刊

Journal of Functional Foods FOOD SCIENCE & TECHNOLOGY-

CiteScore

9.60

自引率

1.80%

发文量

428

审稿时长

76 days

期刊介绍： Journal of Functional Foods continues with the same aims and scope, editorial team, submission system and rigorous peer review. We give authors the possibility to publish their top-quality papers in a well-established leading journal in the food and nutrition fields. The Journal will keep its rigorous criteria to screen high impact research addressing relevant scientific topics and performed by sound methodologies. The Journal of Functional Foods aims to bring together the results of fundamental and applied research into healthy foods and biologically active food ingredients. The Journal is centered in the specific area at the boundaries among food technology, nutrition and health welcoming papers having a good interdisciplinary approach. The Journal will cover the fields of plant bioactives; dietary fibre, probiotics; functional lipids; bioactive peptides; vitamins, minerals and botanicals and other dietary supplements. Nutritional and technological aspects related to the development of functional foods and beverages are of core interest to the journal. Experimental works dealing with food digestion, bioavailability of food bioactives and on the mechanisms by which foods and their components are able to modulate physiological parameters connected with disease prevention are of particular interest as well as those dealing with personalized nutrition and nutritional needs in pathological subjects.