title: Goldenseal (Hydrastis canadensis L.) extracts synergistically enhance the antibacterial activity of berberine via efflux pump inhibition.
abstract: Goldenseal (Hydrastis canadensis L.) is used to combat inflammation and infection. Its antibacterial activity in vitRO has been attributed to its alkaloids, the most abundant of which is berberine. The goal of these studies was to compare the composition, antibacterial activity, and efflux pump inhibitory activity of ethanolic extracts prepared from roots and aerial portions of H. canadensis. Ethanolic extracts were prepared separately from roots and aerial portions of six H. canadensis plants. Extracts were analyzed for alkaloid concentration using LC-MS and tested for antimicrobial activity against Staphylococcus aureus (NCTC 8325-4) and for inhibition of ethidium bromide efflux. Synergistic antibacterial activity was observed between the aerial extract (FIC 0.375) and to a lesser extent the root extract (FIC 0.750) and berberine. The aerial extract inhibited ethidium bromide efflux from wild-type S. aureus but had no effect on the expulsion of this compound from an isogenic derivative deleted for norA. Our studies indicate that the roots of H. canadensis contain higher levels of alkaloids than the aerial portions, but the aerial portions synergize with berberine more significantly than the roots. Furthermore, extracts from the aerial portions of H. canadensis contain efflux pump inhibitors, while efflux pump inhibitory activity was not observed for the root extract. The three most abundant H. canadensis alkaloids, berberine, hydrastine, and canadine, are not responsible for the efflux pump inhibitory activity of the extracts from H. canadensis aerial portions.
authors.affiliation: Department of Chemistry/Biochemistry, The University of North Carolina Greensboro, Greensboro, NC 27402, USA.
authors.forename: Keivan A
authors.initials: KA
authors.lastname: Ettefagh
authors.forename: Johnna T
authors.initials: JT
authors.lastname: Burns
authors.forename: Hiyas A
authors.initials: HA
authors.lastname: Junio
authors.forename: Glenn W
authors.initials: GW
authors.lastname: Kaatz
authors.forename: Nadja B
authors.initials: NB
authors.lastname: Cech
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D044182:Benzylisoquinolines / Q000302:isolation & purification / Q000494:pharmacology; D001599:Berberine / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology; D004357:Drug Synergism; D004996:Ethidium / Q000493:pharmacokinetics / Q000494:pharmacology; D039321:Hydrastis / Q000737:chemistry*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors*; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D044182:Benzylisoquinolines; D001599:Berberine; D004996:Ethidium; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010936:Plant Extracts; C075040:NorA protein, Staphylococcus; C013024:hydrastine; C004645:canadine