Synergistic Multi-Herb Approaches for Reversing Microbial Biofilms in Chronic Infections

Chronic infections are largely sustained by microbial biofilms, complex, multicellular matrices that confer antimicrobial tolerance and immune evasion. Conventional antibiotic regimens fail to eradicate these resilient structures due to limited penetration, metabolic dormancy, and efflux-mediated resistance. In recent years, phytochemicals have emerged as promising anti-biofilm agents through diverse mechanisms, including quorum-sensing inhibition, extracellular polymeric substance (EPS) disruption, and persister-cell eradication. Compounds such as curcumin, berberine, allicin, cinnamaldehyde, and catechins act at sub-inhibitory concentrations to suppress virulence and enhance antibiotic susceptibility. Multi-herb or polyherbal combinations further potentiate efficacy via synergistic interactions, simultaneously targeting quorum sensing, adhesion, and EPS synthesis while minimising resistance risks. Delivery innovations such as herbal nanoparticles, nanofibers, and mucoadhesive gels improve bioavailability, sustained release, and site-specific action against chronic wounds, oral, and urinary tract biofilms. This review synthesises current evidence on synergistic multi-herb strategies and highlights their mechanistic roles in disrupting biofilm integrity, downregulating virulence gene expression, and reactivating persister metabolism. Despite significant in vitro advances, translational challenges persist due to limited standardisation, dose optimisation, and clinical validation. Integrating polyherbal therapeutics with advanced delivery systems represents a novel, multi-targeted approach for combating chronic infections, reducing antibiotic reliance, and supporting host immune resilience. Future research should focus on systematic synergy modelling, pharmacokinetic profiling, and in vivo evaluation to establish safe, effective phytotherapeutic interventions for biofilm-associated diseases.