LC-MS profiling of Terminalia chebula seed reveals mechanistic insights supporting activity against multidrug-resistant diabetic foot ulcer isolate.

Terminalia chebula is a widely used medicinal herb in traditional phytotherapy, valued for its extensive range of therapeutic uses. In this study, the seed extract (TCS) was investigated for its potential against multidrug-resistant (MDR) pathogens associated with diabetic foot ulcer (DFU) infections. The clinical isolate Pseudomonas aeruginosa (DW07) was extremely resistant to standard antibiotics, reaffirming its MDR phenotype. Chemical profiling of TCS with liquid chromatography showed a dense phytochemical profile containing ellagic acid, chebulagic acid, punicalagin, corilagin, and chebulinic acid, which is all attributed to specific anti-pathogenic activities like quorum sensing inhibition, biofilm inhibition, efflux pump obstruction, and disrupting bacterial adhesion. The extract showed dose-dependent antibacterial activity with a minimum inhibitory concentration of 0.70 ppm, and was found to greatly inhibit biofilm formation to the extent of 87.57 %. Transcriptomic analysis also showed wide modulation of bacterial physiology as 54 genes were differentially expressed and significant downregulation of virulence-related proteins such as short-chain dehydrogenase oxidoreductase, histidine kinase, and PtxR. Gene Ontology classification identified functional effects on DNA binding, lipopolysaccharide biosynthesis, and major metabolic pathways. Overall, these findings indicate that the phytochemical variability of T. chebula seeds not only establishes a molecular foundation for its traditional application but also attests to its potential as a plant-based therapeutic approach in the phytomedical management of chronic wound infections due to MDR pathogens.