Nitric Oxide and Plant-Derived Flavonoids in Antimicrobial and Antibiofilm Strategies

The increasing prevalence of antibiotic resistance and biofilmassociated infections necessitates the development of innovative therapeutic strategies. This review aims to summarize current knowledge on the combined antimicrobial potential of plantderived flavonoids and medical gases, with particular emphasis on their synergistic mechanisms against bacterial pathogens and biofilm-associated infections. A comprehensive review of the available scientific literature was conducted to evaluate the antimicrobial and antibiofilm properties of flavonoids and medical gases. Studies examining their mechanisms of action were analyzed to assess potential synergistic interactions among these agents. Flavonoids demonstrate significant antibacterial and antibiofilm activities through multiple mechanisms, including disruption of bacterial membranes, inhibition of key enzymes, and interference with quorum-sensing pathways. Medical gases such as nitric oxide exhibit antimicrobial activity primarily by inducing oxidative and nitrosative stress, redox imbalance, and modulating bacterial gene expression. When combined, flavonoids and medical gases may produce synergistic antimicrobial effects by simultaneously targeting multiple bacterial survival pathways. Additionally, both agents have been reported to modulate host immune responses, influence cellular redox homeostasis, and alter biofilm architecture. The combination of flavonoids and medical gases represents a promising therapeutic approach for the management of biofilm-related and chronic infections. However, the molecular and cellular mechanisms underlying their synergistic interactions remain insufficiently understood. Future research should address these knowledge gaps and develop translational strategies for the clinical application of flavonoid–gas combinations in antimicrobial therapy.