Terminalia chebula Retz. aqueous extract inhibits the Helicobacter pylori-induced inflammatory response by regulating the inflammasome signaling and ER-stress pathway

ETHNOPHARMACOLOGICAL RELEVANCETerminalia chebula Retz., known as the King of Traditional Tibetan Medicine, is widely used for treating various ailments, particularly stomach disorders. It exhibited inhibitory activity against helicobacter pylori.AIM OF THE STUDYThe exact mechanism by which T. chebula combats H. pylori infection remains unclear. Therefore, this study aimed to investigate its mechanism of action and the key pathways and targets involved.MATERIAL AND METHODSMinimum inhibitory concentration (MIC) assay, scanning electron microscope, and inhibiting kinetics curves were conducted. The mRNA expressions were measured by RNA-seq analysis and RT-QPCR. ELISA and Western blot were used to detect the changes in proteins. The main compounds were analyzed by High-performance Liquid Chromatography. The interaction between the compound and target was predicted by Molecular Docking.RESULTSThe study revealed that T. chebula disrupted the structure of H. pylori bacteria and inhibited Cag A protein expression. Additionally, T. chebula can reduce the expression of flaA, flaB, babA, alpA, alpB, ureE, and ureF genes. Furthermore, T. chebula demonstrated its effectiveness in inhibiting the H. pylori-induced inflammatory response by regulating the inflammasome signaling and ER-stress pathway. Moreover, the study discovered that chebulagic acid has anti-HP activity and inhibits the expression of Cag A protein.CONCLUSIONST. chebula acts as a natural remedy for combating H. pylori infection. Its ability to disrupt the bacterial structure, inhibit key proteins, regulate inflammatory pathways, and the presence of chebulagic acid contribute to its anti-H. pylori activity.