Synergistic Antimicrobial Efficacy of Essential Oil Combinations Against Foodborne Pathogens: A Network Pharmacology Approach

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Arunagirinathan N, Sivasankari S, Sorabh Lakhanpal, Ibrokhim Sapaev, Komal Patel, Raman Verma, D. Karthikeyan

Abstract

Foodborne pathogens remain a significant public health concern and a challenge for the global food industry, leading to widespread illness, deaths, and substantial economic costs. Rising antimicrobial resistance and increasing consumer preference for natural preservatives have driven research into plant-based essential oils (EOs) as viable, sustainable alternatives to synthetic antimicrobials. Evidence shows that combining essential oils can produce synergistic effects, improving their ability to suppress harmful microbes at lower doses while reducing negative impacts on food flavor and aroma. This review explores the combined antimicrobial effectiveness of essential oil mixtures against key foodborne pathogens such as Escherichia coli, Salmonella enterica, Listeria monocytogenes, Staphylococcus aureus, and Bacillus cereus. Special attention is given to network pharmacology—an emerging systems biology method—that helps uncover the complex interactions among multiple components, targets, and biological pathways involved in the antimicrobial action of EO combinations. The analysis covers major bioactive compounds in common essential oils, their molecular targets, and their roles in disrupting microbial membranes, inducing oxidative stress, inhibiting biofilm formation, interfering with quorum sensing, and altering metabolic functions.
It also summarizes recent progress in protein–protein interaction networks, Gene Ontology enrichment, KEGG pathway analysis, and compound–target mapping to better understand how synergy enhances antimicrobial activity. Additionally, the review highlights practical applications of synergistic EO formulations in food preservation techniques like active packaging, nanoencapsulation, and edible coatings, while addressing existing hurdles such as variability in composition, standardization, safety evaluation, and regulatory compliance. Looking ahead, the integration of artificial intelligence, multi-omics approaches, molecular docking, and network pharmacology is discussed as a promising path toward designing more effective, science-based natural antimicrobial solutions. Overall, this work offers a structured approach to developing advanced, synergistic essential oil strategies that improve food safety, prolong shelf life, and help counteract antimicrobial resistance in contemporary food systems.

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