The spread of multidrug-resistant bacteria around the world is rising, and new antibiotics are urgently needed to address the drug resistance crisis. Natural products have become a focal point in the research and development of antibacterial drugs, owing to their structural diversity and biological activity. Kaempferol, in particular, exhibits a range of biological properties, including antioxidant, antibacterial, and antitumor activities, and holds potential for application across various domains. This review aims to provide a comprehensive overview of the extraction, biosynthesis, and antibacterial activity of kaempferol, as well as to elucidate its antibacterial mechanisms. In addition, we also reviewed the synergistic combination of kaempferol with antibiotics, such as the combination of kaempferol with colistin or penicillin, which significantly improved their therapeutic effect. Finally, the preparation of kaempferol nanoparticles and their applications in antibacterial treatments were discussed.

Background: The rapid emergence of antibiotic resistance in E. coli has outpaced the development of new drugs, creating an urgent demand for novel therapeutic strategies. Methods: We screened ten antibiotics in combination with isochlorogenic acid C (ICAC) against multidrug-resistant (MDR) E. coli. Synergistic effects of antibiotics and ICAC were evaluated by measuring the leakage of alkaline phosphatase (AKP), potassium ions (K⁺), as well as changes in total protein, and ATP levels. The integrity of bacterial membrane and cell wall was visualized by SEM and CLSM. The underlying mechanisms were elucidated via proteomic analysis and molecular docking. Finally, the protective effect of ICAC in vivo was evaluated using an intraperitoneal infection model in SPF female BALB/c mice. Results: ICAC exerted a specific synergistic effect with ciprofloxacin, significantly enhancing its efficacy. The combination disrupted bacterial membrane and cell wall integrity, increased permeability, and inhibited ATP synthesis. Mechanistically, ICAC may target OmpF and inhibit fatty acid biosynthesis. This interference reduced β-oxidation and the influx of acetyl-CoA into the TCA cycle, thereby impairing bacterial energy metabolism and destabilizing the membrane. In vivo validation using a mouse peritonitis model confirmed that the combination treatment effectively alleviated systemic E. coli infection. Conclusion: ICAC may potentiate the antibacterial activity of ciprofloxacin through targeting of OmpF, which disrupts bacterial membrane integrity and energy metabolism, providing a promising candidate strategy for combating infections caused by the tested antibiotic-resistant E. coli.