Euphorbia hirta L. as a potential resistance-modifying agent against ESKAPE pathogens: a systematic review

Background The growing issue of antimicrobial resistance (AMR) in bacteria, particularly among the ESKAPE pathogens, has prompted the need to explore additional treatment options. Euphorbia hirta L. ( E. hirta ) is a botanical drug plant with antimicrobial activities attributed to its biologically active metabolites, namely flavonoids, terpenoids, and phenolic acids. Methods This systematic review followed PRISMA guidelines to assess the antimicrobial effects of E. hirta against critical bacterial pathogens. A systematic search and collection of data from 27 peer‐ reviewed articles on the antimicrobial potential of E. hirta against different bacteria were conducted. Extraction solvents such as ethanol, methanol, petroleum ether, ethyl acetate, chloroform, and water were considered in this systematic review. The antimicrobial potential of E. hirta was assessed using methods such as MIC, MBC, and diffusion assays (disk and well diffusion). Results Petroleum ether extract of E. coli, S. aureus , and P. aeruginosa showed the lowest MICs (0.4, 0.125, and 0.4 mg/mL, respectively), while ethanol extracts exhibited potent activity against S. aureus (14.53 mg/mL), K. pneumoniae (19.73 mg/mL), P. aeruginosa (20.06 mg/ mL), and E. faecalis (29 mg/mL). Chloroform extracts showed a relatively constant moderate level of activity against most of the organisms tested. It ranged from 1.45 mg/mL for E. coli and P. aeruginosa . In general, non-polar solvents such as petroleum ether and chloroform provided better results than their polar counterparts, like methanol (up to 100 mg/mL). Conclusion The reported in vitro interactions between E. hirta fractions and conventional antibiotics, such as the observed reduction in MICs for cefepime and ciprofloxacin, suggest a potential resistance‐modifying effect. However, these findings remain preliminary and unsubstantiated for clinical translation. Future research should prioritize bioassay‐guided isolation, mechanistic studies and the development of standardized formulations for its integration into clinical practice for addressing antimicrobial resistance. Systematic Review website, identifier CRD420251025371.