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

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.

Keywords: Apoptosis; Gallic acid; Gastric injury; Inflammation; Oxidative stress; Self-assembly.