Plant-Derived Phytochemicals and Polyherbal Formulations in AntimicrobialResistance: Mechanistic Evidence, Evidence Hierarchy, and TranslationalConstraints

The increasing global burden of antimicrobial resistance (AMR) has stimulated renewed interest in plant-derived phytochemicals and polyherbal formulations as potential adjuncts to conventional antimicrobial therapy. This article presents a narrative review, supported by a structured literature search, that synthesizes mechanistic and translational evidence on plant-based strategies targeting resistant bacterial pathogens. Literature was identified through searches of major scientific databases, including PubMed, Scopus, and Web of Science, with emphasis on studies published over the past two decades. Evidence is critically organised according to experimental level, distinguishing in vitro findings, in vivo observations, and available clinical data. Plant-derived compounds, including alkaloids, flavonoids, terpenoids, phenolics, and saponins, exhibit diverse antimicrobial and antibiofilm activities. Reported mechanisms include membrane disruption, inhibition of quorum sensing and biofilm formation, interference with nucleic acid and protein synthesis, modulation of efflux pumps, and attenuation of resistance-associated pathways. While reproducible antibacterial activity is frequently observed under laboratory conditions, animal studies remain limited, and robust clinical trials are scarce. Polyherbal formulations derived from traditional medical systems propose multi-target synergistic effects; however, pharmacodynamic validation and dose standardization remain insufficient. Key translational challenges include variability in extract composition, incomplete pharmacokinetic and pharmacodynamic characterization, limited bioavailability, potential toxicity, and clinically relevant herb–drug interactions. Many antimicrobial effects reported in vitro occur at concentrations that have not yet been demonstrated to be achievable or safe in humans. Emerging approaches such as nano-enabled delivery systems and omics-guided phytochemical characterisation may improve therapeutic precision but require rigorous validation. Overall, plant-derived products are best positioned as adjunctive resistance-modifying strategies rather than replacements for conventional antibiotics, pending standardised development and high-quality clinical evaluation.