Abstract
Inflammatory bowel disease(IBD)is a chronic inflammatory disease characterized by intestinal barrier dysfunction,inflammatory synergistic effects and excessive tissue injury.Gallic acid(GA)is renowned for its remarkable bio-logical activity,encompassing anti-inflammatory and antioxidant properties.However,the underlying mechanisms by which GA protects against intestinal inflammation have not been fully elucidated.The aim of this study is to investigate the effect of GA on the inflammation of a lipopolysaccharide(LPS)-stimulated human colon carcinoma cell line(Caco-2)and on the intestinal barrier dysfunction,and explore the underlying molecular mechanism involved.Our findings demonstrate that 5 µg/mL GA restores the downregulation of the mRNA and protein levels of Claudin-1,Occludin,and ZO-1 and decreases the expressions of inflammatory factors such as IL-6,IL-1β and TNF-αinduced by LPS.In addition,GA exhibits a protective effect by reducing the LPS-enhanced early and late apoptotic ratios,downregulating the mRNA levels of pro-apoptotic factors(Bax,Bad,Caspase-3,Caspase-8,and Caspase-9),and upregulating the mRNA levels of anti-apoptotic factor Bcl-2 in Caco-2 cells.GA also reduces the levels of reactive oxygen species increased by LPS and restores the activity of antioxidant enzymes,namely,superoxide dismutase and catalase,as well as the level of glutathione.More importantly,GA exerts its anti-inflammatory effects by inhibiting the LPS-induced phosphorylation of key signaling molecules in the NF-κB/MAPK pathway,including p65,IκB-α,p38,JNK,and ERK,in Caco-2 cells.Overall,our findings show that GA increases the expres-sions of tight junction proteins,reduces cell apoptosis,relieves oxidative stress and suppresses the activation of the NF-κB/MAPK pathway to reduce LPS-induced intestinal inflammation in Caco-2 cells,indicating that GA has po-tential as a therapeutic agent for intestinal inflammation.
基金项目
浙江省自然科学基金(LY22B070007)
Zhejiang Province Postdoctoral Research Project(ZJ2022090)
国家科技期刊平台
NSTL
万方数据