Abstract

Myristicafragrans Houtt. (Nutmeg) is a widely known folk medicine across several parts of Asia, particularly used in antimicrobial treatment. Bacterial resistance involves the expression of efflux pump systems (chromosomal norA and mepA) in methicillin-resistant Staphylococcus aureus (MRSA). Crude extract (CE) and essential oil (EO) obtained from nutmeg were applied as efflux pump inhibitors (EPIs), thereby enhancing the antimicrobial activity of the drugs they were used in. The major substances in CE and EO, which function as EPIs, in a descending order of % peak area include elemicin, myristicin, methoxyeugenol, myristicin, and asarone. Here, we investigated whether the low amount of CE and EO used as EPIs was sufficient to sensitize MRSA killing using the antibiotic ciprofloxacin, which acts as an efflux system. Interestingly, synergy between ciprofloxacin and CE or EO revealed the most significant viability of MRSA, depending on norA and mepA, the latter being responsible for EPI function of EO. Therefore, CE and EO obtained from nutmeg can act as EPIs in combination with substances that act as efflux systems, thereby ensuring that the MRSA strain is susceptible to antibiotic treatment.

Highlights

  • Myristica fragrans Houtt. is a well-known traditional medicine that is used in several countries, especially those in Asia [1]

  • TPC: total phenolic content, TFC: total flavonoid content; a Gallic acid equivalents (GAE)/100 g of dry weight was measured at 620 nm; b Quercetin equivalent (QE)/100 g of dry weight was measured at 450 nm

  • The results found that the CIP/crude extract (CE) combination against MRSA351, 352, and 353 showed a significantly increased bacterial growth inhibition by 81.6% ± 9.4, 69.5% ± 6.8, and 67.5% ± 2.8 of inhibition, respectively, (Figure 4A) compared with CE treatment group, while there were no difference in MRSA354 and 355

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Summary

Introduction

Myristica fragrans Houtt. (nutmeg) is a well-known traditional medicine that is used in several countries, especially those in Asia [1]. The pharmacological importance of nutmeg seed extract (essential oil) as an antimicrobial agent against Gram positive and Gram negative bacteria, and fungi is widely reported and is of great interest [6,7], those of the main constituents of nutmeg including sabinene, 4-terpineol, myristicin, elemicin, tetradecanoic acid, α-pinene, β-pinene, β-phellandrene, methoxyeugenol, and γ-terpine, β-myrcene and their function as potential antimicrobial agents [6,7,8,9]. EOs have been widely reported as disinfectant, with its major and minor components playing a role, as the antimicrobial chemical class control the EO’s mechanism against pathogens. They affect single or multiple targets within the pathogens. The identification of the mode of action depends on the composition of the EOs [10]

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