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• W2907616977 abstract "Plant-derived medicines have played a major role in the history of man, especially as anti-infective agents. In the wake of the emergence of multidrug-resistant microbial infections, natural products are still a potential source of drug leads since they contain a wide array of structurally diverse compounds. Alongside the classical approach of finding anti-infective agents, this study also sought to investigate the potential of Swazi medicinal plants as efflux inhibitors in bacterial cell systems. This is because bacteria utilise the efflux system to avert the inhibitory action of antibiotics which may lead to multidrug resistance. The development of efflux inhibitors is one of the methods being employed to counter multidrug resistance in bacteria. Seven plant species used as traditional medicines in Swaziland for the treatment of infections were identified and collected with the assistance of traditional healers or local people who had knowledge of medicinal plants. The plants were Breonadia salicina, Ozoroa sphaerocarpa, Dioscorea sylvatica, Dioscorea cotinifolia, Syzygium cordatum, Ehretia rigida and Helichrysum acutatum. After preliminary screening of the plant extracts for antimicrobial activity using various Staphylococcus aureus strains and Escherichia coli; as well as for antibiotic potentiating activity using S. aureus strains over-expressing MDR efflux proteins (SA-1199B (NorA) and XU212 (TetK) pump), a diverse range of phytochemicals were isolated and characterised from the plants using chromatographic and spectroscopic (IR, UV, MS, NMR) techniques. Some cardanols and anacardic acids from Ozoroa sphaerocarpa exhibited antimicrobial activity against a range of microorganisms (MIC 8 – 512 µg/mL) whilst dioscin, from Dioscorea sylvatica, displayed anti-Candida activity (MIC 1 µg/mL). None of the plant extracts, nor the isolated compounds, had antimycobacterial activity against Mycobacterium smegmatis and M. aurum. At a sub-inhibitory concentration, (Z)-3-(heptadec-8-en-1-yl)phenol, from O. sphaerocarpa and ursolic acid, from B. salicina, potentiated the activity of tetracycline and norfloxacin against the S. aureus XU212 and SA-1199B strains, respectively. Their activity resulted in a 512-fold reduction in the minimum inhibitory concentration (MIC) of both antibiotics on the S. aureus strains. Some cinnamic acid derivatives isolated from D. sylvatica and D. cotinifolia also potentiated the activity of tetracycline and norfloxacin. The efflux pump inhibitory activity of the compounds was investigated using the ethidium bromide accumulation assay and a bibenzyl, from D. sylvatica and some diaryl nonadiones and a ω-hydroxy acid ester from D. cotinifolia, resulted in an increase in intracellular ethidium bromide accumulation in the SA-1199B strain, suggesting NorA pump inhibition. Ethidium bromide was not found to be a strong substrate for the TetK pump in the XU212 strain. Apart from moronic acid, isolated from O. sphaerocarpa, which showed some comparable efflux pump inhibition to reserpine, all the compounds which exhibited tetracycline-potentiating activity did not show a corresponding TetK pump inhibition activity. This suggested that some other mechanism of antibiotic potentiation activity was a possibility. Of the isolated compounds, dioscin was the most selective towards fungal cells compared to the human dermal cells; whilst ursolic acid was the least selective, showing toxicity to the human dermal cells at its active concentration. The anacardic acids and moronic acid also showed some degree of selectivity. In conclusion, the results of the study showed the potential of Swazi medicinal plants as a source of antimicrobial drug leads; as well as their potential use in combination therapy for the management of bacterial resistance." @default.
• W2907616977 created "2019-01-11" @default.
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• W2907616977 date "2018-01-28" @default.
• W2907616977 modified "2023-09-24" @default.
• W2907616977 title "Antimicrobial and efflux inhibiting activity of natural products from Swazi medicinal plants" @default.
• W2907616977 hasPublicationYear "2018" @default.
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