Bioactive components and antimicrobial mechanisms of Momordica charantia L. against Cutibacterium acnes

Momordica charantia L. ( M. charantia L. ) is a widely cultivated crop with significant potential for non-food industrial applications. This study aimed to develop a plant-based antibacterial ingredient from its fruit targeting Cutibacterium acnes , a key pathogen in acne vulgaris. Bioassay-guided fractionation via liquid-liquid extraction and column chromatography yielded a bioactive subfraction, EAEMS (Fr 7.4), which showed potent anti- C. acnes activity with a minimum inhibitory concentration (MIC) of 0.25 mg/mL. UPLC-Q/TOF-MS and molecular networking analysis revealed a complex chemical profile rich in triterpenoids, steroids, and glycosides. In vitro and in silico studies on antibacterial mechanisms demonstrated that EAEMS alters bacterial growth kinetics, inhibits biofilm formation, disrupts cell wall and membrane integrity, and interferes with metabolic activity. Cytotoxicity assays confirmed that EAEMS is non-toxic to mammalian cells at 4 × MIC. Among 125 putative compounds, 15 were selected based on drug-likeness and toxicity prediction, with three exhibiting strong binding affinities to key bacterial targets in molecular docking. The absence of cytotoxicity combined with its multi-mechanism anti- C. acnes efficacy positions EAEMS as a promising candidate for developing plant-based anti-acne ingredients, supporting the high-value, non-food utilization of this industrial crop. • EAEMS fraction from Momordica charantia L. fruit exhibits potent anti-C. acnes activity. • Chemical characterization reveals triterpenoids and steroids as main constituents. • Multi-mechanism action disrupts membrane integrity, biofilm formation, and energy metabolism. • Three promising antibacterial candidates identified through in silico screening.