Resistance modulatory and efflux pump inhibitory activities of Kaempferia galanga rhizomes

Antibiotic resistance represents an increasing problem for public health [1]. Bacteria rapidly adapt to environmental conditions and so the application of large amounts of antibiotics (in human and livestock farming) and non-compliance further pushes the development of resistant strains. The presence of efflux pumps on the cell membrane is one way how bacteria can become resistant. These pumps are capable of effluxing toxic compounds from the cytoplasm. Therefore, a possible starting point to reverse these developments is the exploration of efflux pump inhibitors [2].

Plants from the family of Zingiberaceae proved to be a good source for efflux pump inhibitory compounds [3]. In this study the rhizomes of Kaempferia galanga L. were studied for the presence of such components. Three rhizome extracts were manufactured and tested against Mycobacterium smegmatis mc² 155. Especially the hexane extract revealed promising resistance modulatory activities bearing a modulation factor (MF) of 64 with ethidium bromide (EtBr) and an even higher MF of ≥256 when tested with rifampicin. Due to these promising values this extract was bioassay-guided fractionated in order to reveal the most active fractions. GC-MS analysis revealed the presence of ethyl-p-methoxycinnamate in fractions with the highest MF of 32. For this reason an accumulation assay using EtBr as substrate was performed showing superior accumulation behaviour of ethyl-p-methoxycinnamate compared to verapamil and a concentration dependent EtBr accumulation.

Acknowledgements: University of Graz is gratefully acknowledged for providing a PhD scholarship (“Forschungsstipendium für Doktorandinnen”) to Sandra Prasch.

Keywords: Efflux pump inhibitor, Kaempferia galanga, Mycobacterium smegmatis mc² 155.

References:

[1] World Health Organisation. Antimicrobial resistance global report on surveillance 2014. Geneva: WHO, 2014

[2] Fernández L, Hancock REW. Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin Microbiol Rev 2012; 25: 661 – 681

[3] Groeblacher B, Maier V, Kunert O, Bucar F. Putative mycobacterial efflux inhibitors from the seeds of Aframomum melegueta. J Nat Prod 2012; 75: 1393 – 1399