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用于缓解乙醇诱导的急性胃损伤的多功能没食子酸自组装水凝胶

Multifunctional gallic acid self-assembled hydrogel for alleviation of ethanol-induced acute gastric injury.

作者信息

Huang Haibo, Hou Yiyang, Chen Lihang, He Wanying, Wang Xinchuang, Zhang Dan, Hu Jiangning

机构信息

SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.

SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.

出版信息

Int J Pharm. 2023 Oct 15;645:123372. doi: 10.1016/j.ijpharm.2023.123372. Epub 2023 Sep 15.

Abstract

Ethanol-induced acute gastric injury is a prevalent type of digestive tract ulcer, yet conventional treatments strategies frequently encounter several limitations, such as poor bioavailability, degradation of enzymes and adverse side effects. Gallic acid (GA), a natural compound extracted from dogwood, has demonstrated potential protective effects in mitigating acute gastric injury. However, its poor stability and limited bioavailability have restricted applications in vivo. To address these issues, we report a hydrogel constructed only by gallic acid with high bioavailability for alleviation of gastric injury. Molecular dynamic simulation studies revealed that the self-assembly of GA into hydrogel was predominantly attributed to π-π and hydrogen bonds. After assembling, the GA hydrogel exhibits superior anti-oxidative stress, anti-apoptosis and anti-inflammatory properties compared with free GA. As anticipated, in vitro experiments demonstrated that GA hydrogel possessed the remarkable ability to promote the proliferation of GES-1 cells, and alleviates apoptosis and inflammation caused by ethanol. Subsequent in vivo investigation further confirmed that GA hydrogel significantly alleviated ethanol-triggered acute gastric injury. Mechanistically, GA hydrogel treatment enhanced the antioxidant capacity, reduced oxidative stress while simultaneously suppressing the secretion of pro-inflammatory cytokines and reduced the production of pro-apoptotic proteins during the process of gastric injury. Our finding suggest that this multifunctional GA hydrogel is a promising candidate for gastric injury, particularly in cases of ethanol-induced acute gastric injury.

摘要

乙醇诱导的急性胃损伤是一种常见的消化道溃疡类型,但传统治疗策略常常遇到一些局限性,如生物利用度差、酶降解和不良副作用。没食子酸(GA)是从山茱萸中提取的一种天然化合物,已显示出在减轻急性胃损伤方面的潜在保护作用。然而,其稳定性差和生物利用度有限限制了其在体内的应用。为了解决这些问题,我们报道了一种仅由没食子酸构建的具有高生物利用度的水凝胶,用于减轻胃损伤。分子动力学模拟研究表明,GA自组装形成水凝胶主要归因于π-π键和氢键。组装后,GA水凝胶与游离GA相比,具有优异的抗氧化应激、抗凋亡和抗炎特性。正如预期的那样,体外实验表明,GA水凝胶具有促进GES-1细胞增殖的显著能力,并减轻乙醇引起的细胞凋亡和炎症。随后的体内研究进一步证实,GA水凝胶显著减轻了乙醇引发的急性胃损伤。从机制上讲,GA水凝胶治疗增强了抗氧化能力,降低了氧化应激,同时在胃损伤过程中抑制了促炎细胞因子的分泌并减少了促凋亡蛋白的产生。我们的研究结果表明,这种多功能GA水凝胶是治疗胃损伤的有前途的候选药物,特别是在乙醇诱导的急性胃损伤病例中。

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