Adjuvant potential of Satureja hortensis metabolites with antibiotics against Gram-positive and Gram-negative bacterial strains

Alburqan, Marah and Kincses, Annamária and Paizs, Melinda and Barta, Anita and Veres, Katalin and Csámpai, Antal and Yazdani, Morteza and Hohmann, Judit (2025) Adjuvant potential of Satureja hortensis metabolites with antibiotics against Gram-positive and Gram-negative bacterial strains. PHARMACEUTICAL BIOLOGY, 63 (1). pp. 716-729. ISSN 1388-0209

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Abstract

Context: The global rise in bacterial resistance to existing antibiotics has led to increased mortality rates and escalating healthcare costs, underscoring the urgent need for new classes of antibacterial agents that can act synergistically with current antimicrobials. Objective: This study aimed to isolate bioactive compounds from Satureja hortensis L. (Lamiaceae) and evaluate their effects in combination with ciprofloxacin (CIP), ampicillin (AMP), gentamicin (GEN), and tetracycline (TET). Materials and methods: The adjuvant potential of naringenin (N), 5,6-dihydroxy-7,3′,4′- trimethoxyflavone (TMF), cilicione-a (Cil), rosmarinic acid (Rs), rosmarinic acid methyl ester (MRs), and fulgidic acid was evaluated by determining the minimum inhibitory concentrations (MICs) of selected antibiotics in presence of sub-inhibitory concentrations of these compounds. The assays were performed against ten bacterial strains using the twofold broth microdilution method. Test samples were prepared in 96-well microtiter plates, incubated at 37°C for 18 h, and dimethyl sulfoxide was used as the solvent control. Results: N, Rs, and MRs reduced the MIC value of GEN from 0.78µM to 0.097µM against the drug-resistant Escherichia coli AG100 strain. Additionally, the combinations of N and MRs with CIP reduced its MIC from 3.125µM to 0.39µM against Klebsiella pneumoniae. A MIC reduction (from 50µM to 12.5µM) was observed against the methicillin- and oxacillin-resistant Staphylococcus aureus strain when N, Cil, Rs, and MRs were combined with AMP. The MIC changed from 0.125µM to 0.03125µM against Bacillus subtilis when N and TMF were combined with GEN. Discussion and conclusions: These findings highlight the potential of such combinations to enhance antibiotic efficacy, lower the required dosages, and contribute to mitigating the emergence of antimicrobial resistance.

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