Synergy in a medicinal plant: Antimicrobial action of berberine potentiated by 5 '-methoxyhydnocarpin, a multidrug pump inhibitor

作者:

StermitzFRLorenzTawaraJNZenewiczLALewis

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摘要:

Multidrug resistance pumps (MDRs) protect microbial cells from both synthetic and natural antimicrobials. Amphipathic cations are preferred substrates of MDRs. Berberine alkaloids, which are cationic antimicrobials produced by a variety of plants, are readily extruded by MDRs, Several Berberis medicinal plants producing berberine were found also to synthesize an inhibitor of the NorA MDR pump of a human pathogen Staphylococcus aureus. The inhibitor was identified as 5'-methoxyhydnocarpin (5'-MHC), previously reported as a minor component of chaulmoogra oil, a traditional therapy for leprosy. 5'-MHC is an amphipathic weak acid and is distinctly different from the cationic substrates of NorA, 5'-MHC had no antimicrobial activity alone but strongly potentiated the action of berberine and other NorA substrates against S, aureus, MDR-dependent efflux of ethidium bromide and berberine from 5, aureus cells was completely inhibited by 5'-MHC. The level of accumulation of berberine in the cells was increased strongly in the presence of 5'-MHC, indicating that this plant compound effectively disabled the bacterial resistance mechanism against the berberine antimicrobial.

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DOI:

10.1073/pnas.030540597

被引量:

1147

年份:

2000

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2011
被引量:104

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