Exploring the antimicrobial mechanisms of flavonoids with phenolic hydroxyl groups: Implications for novel wound dressings

Antibiotic is widely employed in the management of wound infections, yet its overuse has exacerbated the rise of antimicrobial resistance. Plant extracts, particularly flavonoids, have gained attention for their antibacterial and wound-healing properties, but their diverse chemical structures have created a gap in understanding their antimicrobial mechanisms, limiting their clinical application. Inspired by the lotus leaf, this study analyzed the extract and identified phenolic hydroxyl-containing flavonoids as the main components. Further mechanistic studies showed the presence of hydroxyl groups can promote iron ion reduction, thereby facilitating the generation of reactive oxygen species (ROS). More importantly, ortho-hydroxyl groups were shown to effectively interact with peptidoglycan through the formation of hydrogen bonds, causing cell wall instability and accelerating bacteria death, distinguishing it from previous studies in which flavonoids acted only on bacterial membrane. To explore its therapeutic potential, we developed an antibacterial and exudate-controlling dressing by incorporating lotus leaf extract flavonoids and wax into gauze, which significantly accelerated wound healing. • The antibacterial mechanism of flavonoids was revealed. • Ortho-hydroxyl groups were shown to effectively interact with peptidoglycan through the formation of hydrogen bonds, causing cell wall instability and accelerating bacteria death. • A bionic dressing with antibacterial and diversion functions was developed, which can reduce wound inflammation and significantly promote wound epithelization and collagen deposition. • The work in elucidating the antimicrobial mechanisms of flavonoids provides valuable insights for the development of new drugs and wound care therapies.