A comprehensive review on Kaempferol as a therapeutic flavonoid against ESKAPE and multiple drug-resistant bacteria: Recent advances and challenges

The emergence of multidrug-resistant (MDR) bacteria, particularly the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), is considered a major threat to global public health. Kaempferol, a naturally occurring flavonoid found in many plants, has been demonstrated to hold great promise as a therapeutic agent with strong antimicrobial properties against these resistant pathogens. In this review, the current state of research on kaempferol's antimicrobial activities is examined, with particular emphasis placed on its mechanisms of action against ESKAPE bacteria and other MDR organisms. It has been reported in the literature that kaempferol exerts antimicrobial effects through multiple pathways, including disruption of bacterial cell membranes, interference with DNA replication, inhibition of essential enzymes, alteration of efflux pump systems, and disruption of biofilm formation. Significant synergistic effects have also been observed when kaempferol is combined with traditional antibiotics, potentially restoring their effectiveness against resistant strains. Favourable safety profiles, low toxicity at therapeutic concentrations, and good bioavailability have been noted in comparison with other flavonoids. However, challenges remain in relation to comprehensive clinical validation, delivery system optimization, and the standardization of extraction methods. This review highlights the most recent evidence suggesting the potential of kaempferol as an alternative or adjunctive therapy in the fight against antibiotic resistance, while also identifying critical areas that require further research for successful clinical translation.