Antagonistic Bioactive Phytochemicals Against Microbial Superbugs: A Systematic Review and Descriptive Quantitative Synthesis of Discovery Pathways, Functional Mechanisms, Translational Applications, and Sustainable Production Strategies
Year: 2026
Type: preprint
Study design: Systematic Review
Abstract: Antimicrobial resistance continues to undermine the effectiveness of existing antibiotics, creating an urgent need for new therapeutic strategies that can either replace or strengthen conventional antimicrobial agents. Plant-derived bioactive secondary metabolites represent one of the richest sources of chemically diverse compounds with antimicrobial potential. Although numerous studies have reported the antibacterial properties of medicinal plants, the available evidence remains fragmented, often focusing on individual plant species without systematically examining which phytochemical classes are responsible for antimicrobial activity, how these compounds exert their effects, their capacity to restore antibiotic susceptibility, or their prospects for practical application. This systematic review aims to provide a comprehensive and critically appraised synthesis of the evidence on bioactive phytochemicals with activity against microbial superbugs. The review follows PRISMA 2020 guidance and systematically searches major bibliographic databases to identify studies investigating plant-derived compounds and extracts with measurable anti-pathogen outcomes. Evidence is organised within an integrated framework that follows the progression from compound discovery through functional mechanisms to translational application, while also considering the role of sustainable extraction and production strategies. The review examines the antimicrobial performance of major phytochemical groups, including flavonoids, phenolic compounds, terpenoids, essential oil constituents and alkaloids, against clinically important bacterial pathogens. Particular attention is given to their mechanisms of action, including membrane disruption, inhibition of efflux pumps, interference with quorum sensing, suppression of biofilm formation, attenuation of virulence, and their ability to act synergistically with existing antibiotics. The review also evaluates evidence relating to extraction approaches, formulation, safety considerations, and the feasibility of translating promising compounds into antimicrobial therapies, food preservation systems, infection control measures, and other practical applications. Where sufficient quantitative data are available, descriptive quantitative synthesis is undertaken to characterise the reported antimicrobial potency of phytochemicals. Because most primary studies report minimum inhibitory concentrations without the variance measures required for conventional meta-analysis, the review summarises the distribution of antimicrobial activity rather than generating pooled effect estimates. Risk of bias and certainty of evidence are evaluated using established appraisal frameworks to provide a balanced interpretation of the available literature. The expected outcome of this review is a structured evidence base that identifies the phytochemical classes with the strongest antimicrobial potential, clarifies the mechanisms most consistently associated with activity against resistant pathogens, highlights opportunities for antibiotic-potentiating combinations, and identifies the principal gaps limiting clinical translation. By integrating mechanistic evidence, quantitative synthesis, sustainability considerations and translational relevance within a single analytical framework, the review is expected to provide researchers, clinicians and drug-development scientists with practical priorities for future experimental research, standardised reporting, sustainable production strategies and the development of phytochemical-based interventions to combat antimicrobial resistance.
Language: English
Subfield: Food Science
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7168166262