Download PDF
Planta Med 2012; 78(14): 1556-1561
DOI: 10.1055/s-0032-1315042
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Quorum Quenching and Antimicrobial Activity of Goldenseal (Hydrastis canadensis) against Methicillin-Resistant Staphylococcus aureus (MRSA)

Nadja B. Cech
1   Department of Chemistry/Biochemistry, The University of North Carolina Greensboro, Greensboro, NC, USA
,
Hiyas A. Junio
1   Department of Chemistry/Biochemistry, The University of North Carolina Greensboro, Greensboro, NC, USA
,
Laynez W. Ackermann
2   Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA
,
Jeffrey S. Kavanaugh
2   Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA
,
Alexander R. Horswill
2   Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA
› Author Affiliations
Further Information

Publication History

received 25 April 2012
revised 17 June 2012

accepted 18 June 2012

Publication Date:
18 July 2012 (online)

    Permissions and Reprints

Abstract

The popular herbal remedy goldenseal (Hydrastis canadensis L.) is traditionally used to treat skin infections. With this study, we show activity of H. canadensis extracts in vitro against methicillin-resistant Staphylococcus aureus (MRSA). An extract from H. canadensis leaves demonstrated more potent antimicrobial activity than the alkaloid berberine alone (MICs of 75 µg/mL and 150 µg/mL, respectively). LC-MS detected alkaloids and efflux-pump inhibitory flavonoids in the extract, and the latter may explain the enhanced efficacy of the extract compared to berberine alone. We also show evidence of anti-virulence activity as a second mechanism by which H. canadensis acts against S. aureus. The H. canadensis leaf extract (but not the isolated alkaloids berberine, hydrastine, and canadine) demonstrated quorum quenching activity against several clinically relevant MRSA isolates (USA300 strains). Our data suggest that this occurs by attenuation of signal transduction through the AgrCA two-component system. Consistent with this observation, the extract inhibited toxin production by MRSA and prevented damage by MRSA to keratinocyte cells in vitro. Collectively, our results show that H. canadensis leaf extracts possess a mixture of constituents that act against MRSA via several different mechanisms. These findings lend support for the traditional application of crude H. canadensis extracts in the prevention of infection.

Key words

Hydrastis canadensis - Ranunculaceae - quorum quenching - berberine - methicillin-resistant Staphylococcus aureus - anti-virulence

Supporting Information

 

  • References

  • 1 Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 2007; 298: 1763-1771
    CrossrefPubMedGoogle Scholar
  • 2 Roberts RR, Hota B, Ahmad I, Scott D, Foster SD, Abbasi F, Schabowski S, Kampe LM, Ciavarella GG, Supino M, Naples J, Cordell R, Levy SB, Weinstein RA. Hospital and societal costs of antimicrobial-resistant infections in a chicago teaching hospital: implications for antibiotic stewardship. CID 2009; 49: 1175-1184
    CrossrefPubMedGoogle Scholar
  • 3 Waldor MK. Disarming pathogens – a new approach for antibiotic development. New Engl J Med 2006; 354: 296-297
    CrossrefPubMedGoogle Scholar
  • 4 Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal LK, Carey RB, Talan DA. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med 2006; 355: 666-674
    CrossrefPubMedGoogle Scholar
  • 5 Thoendel M, Kavanaugh JS, Flack CE, Horswill AR. Peptide signaling in the Staphylococci. Chem Rev 2011; 111: 117-151
    CrossrefPubMedGoogle Scholar
  • 6 Antunes LCM, Ferreira RBR, Buckner MMC, Finlay BB. Quorum sensing in bacterial virulence. Microbiology 2010; 156: 2271-2282
    CrossrefPubMedGoogle Scholar
  • 7 Mayville P, Ji G, Beavis R, Yang H, Goger M, Novick RP, Muir TW. Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence. Proc Natl Acad Sci USA 1999; 96: 1218-1223
    CrossrefPubMedGoogle Scholar
  • 8 Park J, Jagasia R, Kaufmann GF, Mathison JC, Ruiz DI, Moss JA, Meijler MM, Ulevitch RJ, Janda KD. Infection control by antibody disruption of bacterial quorum sensing signaling. Chem Biol 2007; 14: 1119-1127
    CrossrefPubMedGoogle Scholar
  • 9 Blumenthal M. Herb market levels after five years of boom. Herbalgram 1999; 47: 64-65
    PubMedGoogle Scholar
  • 10 Scazzocchio F, Cometa MF, Tomassini L, Palmery M. Antibacterial activity of Hydrastis canadensis extract and its major isolated alkaloids. Planta Med 2001; 67: 561-564
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Jung HA, Beavers R, Parekh H, Coulburn J, Wu CD. Goldenseal (Hydrastis canadensis) leaves possess antimicrobial activity against oral pathogens. J Dent Res 2006; 85: 475
    PubMedGoogle Scholar
  • 12 Mahady GB, Pendland SL, Stoia A, Chadwick L. In vitro suceptibility of Helicobacter pylori to isoquinoline alkaloids from Sanguinaria canadensis and Hydrastis canadensis . Phytother Res 2003; 17: 217-221
    CrossrefPubMedGoogle Scholar
  • 13 Villinski JR, Dumas ER, Chai HB, Pezzuto JM, Angerhofer CK, Gafner S. Antibacterial activity and alkaloid content of Berberis thunbergii, Berberis vulgaris and Hydrastis canadensis . Pharm Biol 2003; 41: 551-557
    CrossrefPubMedGoogle Scholar
  • 14 Yu HH, Kim KJ, Cha JD, Kim HK, Lee YE, Choi NY, You YO. Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus . J Med Food 2005; 8: 454-461
    CrossrefPubMedGoogle Scholar
  • 15 Stermitz FR, Lorenz P, Tawara JN, Zenewicz LA, Lewis K. Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5′-methoxyhydnocarpin, a multidrug pump inhibitor. Proc Nat Acad Sci USA 2000; 97: 1433-1437
    CrossrefPubMedGoogle Scholar
  • 16 Stermitz FR, Tawara-Matsuda J, Lorenz P, Mueller P, Zenewicz LA, Lewis K. 5′Methoxyhydnocarpin-D and phenophorbide A: Berberis species components that potentiate berberine growth inhibition of resistant Staphylococcus aureus . J Nat Prod 2000; 63: 1146-1149
    CrossrefPubMedGoogle Scholar
  • 17 Ettefagh KA, Burns JT, Junio HA, Kaatz GW, Cech NB. Goldenseal (Hydrastis canadensis L.) extracts synergistically enhance the antibacterial activity of berberine via efflux pump inhibition. Planta Med 2010; 77: 835-840
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Upton R. Goldenseal root Hydrastis canadensis: standards of analysis, quality control, and therapeutics. Santa Cruz: American Herbal Pharmacopoeia; 2001
    Google Scholar
  • 19 Moore M. Herb formulas for clinic and home. Albuquerque, NM: Southwest School of Botanical Medicine; 1995
    Google Scholar
  • 20 Seybold U, Kourbatova EV, Johnson JG, Halvosa SJ, Wang YF, King MD, Ray SM, Blumberg HM. Emergence of community-associated methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of health care-associated blood stream infections. Clin Infect Dis 2006; 42: 647-656
    CrossrefPubMedGoogle Scholar
  • 21 Highlander SK, Hultén KG, Qin X, Jiang H, Yerrapragada S, Mason EO, Shang Y, Williams TM, Fortunov RM, Liu Y, Igboeli O, Petrosino J, Tirumalai M, Uzman A, Fox GE, Cardenas AM, Muzny DM, Hemphill L, Ding Y, Dugan S, Blyth PR, Buhay CJ, Dinh HH, Hawes AC, Holder M, Kovar CL, Lee SL, Liu W, Nazareth LV, Wang Q, Zhou J, Kaplan SL, Weinstock GM. Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus . BMC Microbiol 2007; 7: 99
    CrossrefPubMedGoogle Scholar
  • 22 Lauderdale KJ, Boles BR, Cheung AL, Horswill AR. Interconnections between sigma B, agr, and proteolytic activity in Staphylococcus aureus biofilm maturation. Infect Immun 2009; 77: 1623-1635
    CrossrefPubMedGoogle Scholar
  • 23 Boles BR, Thoendel M, Roth AJ, Horswill AR. Identification of genes involved in polysaccharide-independent Staphylococcus aureus biofilm formation. PloS ONE 2010; 5: e10146
    CrossrefPubMedGoogle Scholar
  • 24 Malone CL, Boles BR, Horswill AR. Biosynthesis of Staphylococcus aureus autoinducing peptides by using the synechocystis DnaB mini-intein. Appl Environ Microbiol 2007; 73: 6036
    CrossrefPubMedGoogle Scholar
  • 25 Kirchdoerfer RN, Garner AL, Flack CE, Mee JM, Horswill AR, Janda KD, Kaufmann GF, Wilson IA. Structural basis for ligand recognition and discrimination of a quorum quenching antibody. J Biol Chem 2011; 286: 17351-17358
    CrossrefPubMedGoogle Scholar
  • 26 Kennedy AD, Wardenburg JB, Gardner DJ, Long D, Whitney AR, Braughton KR, Schneewind O, DeLeo FR. Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. J Infect Dis 2010; 202: 1050-1058
    CrossrefPubMedGoogle Scholar
  • 27 Thoendel M, Horswill AR. Identification of Staphylococcus aureus AgrD residues required for autoinducing peptide biosynthesis. J Biol Chem 2009; 284: 21828-21838
    CrossrefPubMedGoogle Scholar
  • 28 Pang YY, Schwartz J, Thoendel M, Ackermann LW, Horswill AR, Nauseef WM. agr-Dependent interactions of Staphylococcus aureus USA300 with human polymorphonuclear neutrophils. J Innate Immun 2010; 2: 546-559
    CrossrefPubMedGoogle Scholar
  • 29 Kiedrowski MR, Kavanaugh JS, Malone CL, Mootz JM, Voyich JM, Smeltzer MS, Bayles KW, Horswill AR. Nuclease modulates biofilm formation in community-associated methicillin-resistant Staphylococcus aureus . PLoS ONE 2011; 6: e26714
    CrossrefPubMedGoogle Scholar
  • 30 Junio HA, Sy-Cordero AA, Ettefagh KA, Burns JT, Micko KT, Graf TN, Richter SJ, Cannon RE, Oberlies NH, Cech NB. Synergy directed fractionation of botanical medicines: a case study with Goldenseal (Hydrastis canadensis). J Nat Prod 2011; 74: 1621-1629
    CrossrefPubMedGoogle Scholar
  • 31 Cech RA. Making plant medicine. Williams: Horizon Herbs; 2000: 276
    Google Scholar
  • 32 Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 3rd. edition. Villanova, PA: National Committee for Clinical Laboratory Standards; 1993
    Google Scholar
  • 33 Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol 1988; 106: 761-771
    CrossrefPubMedGoogle Scholar
  • 34 Amin AH, Subbaiah TV, Abbasi KM. Berberine sulfate: antimicrobial activity, bioassay, and mode of action. Can J Microbiol 1969; 15: 1067-1076
    CrossrefPubMedGoogle Scholar
  • 35 Yu HH, Kim KJ, Cha JD, Kim HK, Lee YE, Choi NY, You YO. Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus . J Med Food 2005; 8: 454-461
    CrossrefPubMedGoogle Scholar
  • 36 Coulburn J, Chin YW, Parekh H, Yildiz S, Beaver R, Kinghorn AD, Wu CD. Oral antimicrobial compounds from Hydrastis canadensis L. (Goldenseal) leaves. J Dent Res 2007; 86: 2156
    PubMedGoogle Scholar
  • 37 McGraw JB, Sanders SM, Van der Voort M. Distribution and abundance of Hydrastis canadensis L. (Ranunculaceae) and Panax quinquefolius L. (Araliaceae) in the central Appalachian region. J Torrey Bot Soc 2003; 130: 62-69
    CrossrefPubMedGoogle Scholar
  • 38 Holtfreter S, Grumann D, Schmudde M, Nguyen HTT, Eichler P, Strommenger B, Kopron K, Kolata J, Giedrys-Kalemba S, Steinmetz I, Witte W, Bröker BM. Clonal distribution of superantigen genes in clinical Staphylococcus aureus isolates. J Clin Microbiol 2007; 45: 2669-2680
    CrossrefPubMedGoogle Scholar