BACKGROUND: The family Apiaceae (genus Centella) includes approximately 50 species, many of which are used in traditional medicine to treat various inflammatory diseases. Traditionally, Centella asiatica has been widely used as a medicinal herb in Ayurvedic medicine. The efficacy of C. asiatica in treating intestinal inflammation remains poorly explored. RESULTS: This study investigated the effects of a hot-water extract of C. asiatica (CA-HE) on inflammation-induced intestinal epithelial cell lines and animal models. CA-HE effectively alleviated IL-1beta-induced inflammatory factors and tight junction (TJ) proteins. In a dextran sulfate sodium (DSS)-induced mouse model of colitis, oral administration of CA-HE induced no toxicological effects and significantly alleviated major clinical symptoms of colitis. Examination of colon specimens revealed that oral administration of CA-HE significantly prevented DSS-induced inflammatory and TJ-associated factors in mice. Histopathological examination of hematoxylin and eosin- and periodic acid-Schiff/Alcian blue-stained colon sections showed that CA-HE alleviated crypt destruction, submucosal edema, inflammatory infiltration and mucin secretion compared to the DSS group. Oral administration of CA-HE increased the total levels of short-chain fatty acids in the cecum and feces. Finally, UHPLC-MS analysis predicted that CA-HE comprises five phenolic compounds (neochlorogenic acid, cryptochlorogenic acid, 1,5-dicaffeoylquinic acid (DCQA), 3,5-DCQA and 4,5-DCQA) and one flavonoid (miquelianin) as key bioactive components. CONCLUSION: Our results suggest that CA-HE could be an alternative candidate to prevent and treat intestinal inflammation. Furthermore, our findings provide foundational data for the use of CA-HE as a bioactive component. (c) 2025 Society of Chemical Industry.