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

Proceedings of the National Academy of Sciences of the United States of America - Tập 97 Số 4 - Trang 1433-1437 - 2000
Frank R. Stermitz1, Peter Lorenz1, Jeanne N. Tawara1, Lauren A. Zenewicz1, Kim Lewis1
1Department of Chemistry, Colorado State University, Fort Collins, CO 80523; and Biotechnology Center, Tufts University, Medford, MA 02155

Tóm tắt

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 S. 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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Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 97 Số 4

1433-1437

Thông tin tác giả