Inhibition of Bacterial Efflux Pumps by Crude Extracts and Essential Oil from Myristica fragrans Houtt. (Nutmeg) Seeds against Methicillin-Resistant Staphylococcus aureus

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.

Efflux Pump Mediated Antimicrobial Resistance by Staphylococci in Health-Related Environments: Challenges and the Quest for Inhibition

“…The fractional inhibitory concentration index (FICi) value is often used to describe the interaction between EPIs and antimicrobial compounds [ 249 , 250 ] and can be defined by the following formula: FICi = FIC antimicrobial + FIC inhibitor …”

Therapeutic, and pharmacological prospects of nutmeg seed: A comprehensive review for novel drug potential insights

“… The synergistic effect between ciprofloxacin’s and Crude extract & Essential Oil revealed the most significant viability of MRSA. Oo et al, 2021 Antiviral activity Malabaricones B and C Licarins A, B and C in sillico evaluation of phytochemicals from nutmeg seed against COVID-19 Molecular docking, Testing solvent to extract compounds. Compounds in the M. fragrans hold promise for future medical benefit against COVID19.…”

Phytoconstituents and Ergosterol Biosynthesis-Targeting Antimicrobial Activity of Nutmeg (Myristica fragans Houtt.) against Phytopathogens

“…Concerning other NME constituents, methoxyeugenol (2,6-dimethoxy-4-allylphenol or 4-allyl-2,6-dimethoxy phenol) is a phenylpropene, a methoxyphenol, and a derivative of eugenol. It is present in toxic Japanese star anise [ 37 , 38 ] and nutmeg extract, but not in nutmeg essential oil [ 39 ]. Elemicin (3,4,5-trimethoxyallylbenzene) is also a phenylpropene.…”