Terminalia chebula Retz. As a resistance-modifying botanical drug against priority pathogens: a systematic review

The global rise of antimicrobial resistance (AMR) among priority bacterial pathogens represents a critical threat to public health, necessitating the development of alternative therapeutic strategies. Terminalia chebula Retz. (Terminalia chebula), a traditionally used medicinal plant rich in hydrolysable tannins, flavonoids, and polyphenolic metabolites, has emerged as a promising candidate due to its broad-spectrum antimicrobial and pharmacological properties.

This systematic review critically evaluates the in-vitro antimicrobial activity and resistance-modifying potential of T. chebula fruit extracts against ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species and Escherichia coli as a representative of the Enterobacteriaceae (now Enterobacterales) family. A comprehensive literature search was conducted across PubMed, Scopus, ScienceDirect, and Google Scholar databases in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251024476). Based on predefined criteria, 24 studies were included for qualitative analysis.

The findings demonstrate that T. chebula extracts exhibit in vitro antimicrobial activity, with ethanolic and methanolic extracts showing enhanced higher efficacy, particularly against multidrug-resistant strains of S. aureus, and P. aeruginosa, and E. coli. Notably, few studies reported synergistic interactions between phytochemicals and conventional antibiotics, suggesting antibiotic resistance-modifying roles. Mechanistic insights suggest that metabolites such as chebulagic acid, chebulinic acid, and gallic acid contribute to antimicrobial activity by disrupting the bacterial cell membranes, inhibiting biofilm formation, and interfering with resistance pathways. However, substantial variations in extraction methods and experimental designs limit cross-study comparability, highlighting the need for standardized protocols.

Overall, the evidence supports the potential of T. chebula act as a resistance-modifying and an antibiotic adjuvant. Future studies should prioritize bioassay-guided isolation, mechanistic validation, and preclinical evaluation to facilitate translational application in combating AMR.