{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T19:59:47Z","timestamp":1777665587655,"version":"3.51.4"},"reference-count":32,"publisher":"Proceedings of the National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,2,15]]},"abstract":"<jats:p>\n            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\n            <jats:italic>Berberis<\/jats:italic>\n            medicinal plants producing berberine were found also to synthesize an inhibitor of the NorA MDR pump of a human pathogen\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            . The inhibitor was identified as 5\u2032-methoxyhydnocarpin (5\u2032-MHC), previously reported as a minor component of chaulmoogra oil, a traditional therapy for leprosy. 5\u2032-MHC is an amphipathic weak acid and is distinctly different from the cationic substrates of NorA. 5\u2032-MHC had no antimicrobial activity alone but strongly potentiated the action of berberine and other NorA substrates against\n            <jats:italic>S. aureus<\/jats:italic>\n            . MDR-dependent efflux of ethidium bromide and berberine from\n            <jats:italic>S. aureus<\/jats:italic>\n            cells was completely inhibited by 5\u2032-MHC. The level of accumulation of berberine in the cells was increased strongly in the presence of 5\u2032-MHC, indicating that this plant compound effectively disabled the bacterial resistance mechanism against the berberine antimicrobial.\n          <\/jats:p>","DOI":"10.1073\/pnas.030540597","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:37:36Z","timestamp":1027694256000},"page":"1433-1437","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":578,"title":["Synergy in a medicinal plant: Antimicrobial action of berberine potentiated by 5\u2032-methoxyhydnocarpin, a multidrug pump inhibitor"],"prefix":"10.1073","volume":"97","author":[{"given":"Frank R.","family":"Stermitz","sequence":"first","affiliation":[{"name":"Department of Chemistry, Colorado State University, Fort Collins, CO 80523; and Biotechnology Center, Tufts University, Medford, MA 02155"}]},{"given":"Peter","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Colorado State University, Fort Collins, CO 80523; and Biotechnology Center, Tufts University, Medford, MA 02155"}]},{"given":"Jeanne N.","family":"Tawara","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Colorado State University, Fort Collins, CO 80523; and Biotechnology Center, Tufts University, Medford, MA 02155"}]},{"given":"Lauren A.","family":"Zenewicz","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Colorado State University, Fort Collins, CO 80523; and Biotechnology Center, Tufts University, Medford, MA 02155"}]},{"given":"Kim","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Colorado State University, Fort Collins, CO 80523; and Biotechnology Center, Tufts University, Medford, MA 02155"}]}],"member":"341","published-online":{"date-parts":[[2000,2,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/scientificamerican0398-46"},{"key":"e_1_3_3_2_2","first-page":"15","volume-title":"Transport of Molecules Across Microbial Membranes","author":"Lewis K","year":"1999","unstructured":"K Lewis Transport of Molecules Across Microbial Membranes, eds J K Broome-Smith, S Baumberg, C J Stirling, F B Ward (Cambridge Univ. 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