Abstract
Berberine with and without fluconazole was tested by an agar disk diffusion assay in which clinical isolates of Candida albicans were applied onto yeast extract-peptone-dextrose agar plate. Berberine, which had no intrinsic antifungal activity at the concentration tested, exerted a powerful antifungal activity in combination of fluzonazole. Combinations of berberine and fluconazole were also tested by the checkerboard assay to determine whether they had favorable or unfavorable antifungal interactions. The MIC of fluconazole was 1.9 μg/ml when the drug was tested alone and decreased to 0.48 μg/ml in the presence of berberine concentrations of 1.9 μg/ml. However, berberine at concentrations of >1.9 μg/ml combined with a fluconazole supra-MIC (i.e., >1.9 μg/ml) eliminated the residual turbidity in the incubation wells. This endpoint fitted to the definition of MIC-0 (optically clear wells) and reflected the absence of a trailing effect, which is the result of a residual growth at fluconazole concentrations greater than the MIC.
This is a preview of subscription content, log in via an institution to check access.
References
Birdsall TC (1997) Berberine: therapeutic potential of an alkaloid found in several medicinal plants. Altern Med Rev 2(2):94–103
Clinical and Laboratory Standards Institute (CLSI) (2004) Method for antifungal disk diffusion susceptibility testing of yeasts: NCCLS document M44-A. National Committee for Clinical Laboratory Standards, Wayne, Pa, pp 1–36
Gudlaugsson O, Gillespie S, Lee K, Vande Berg J, Hu J, Messer S, Herwaldt L, Pfaller M, Diekema D (2003) Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis 37:1172–1177
Jennings BR, Ridler PJ (1983) Interaction of chromosomal stains with DNA, an electrofluorescence study. Biophys Struct Mech 10:71–79
Ko W, Yao X, Lau C, Law W, Chen Z, Kwok W, Ho K, Huang Y (2000) Vasorelaxant and antiproliferative effects of berberine. Eur J Pharmacol 399:187–196
Kuo C, Chi C, Liu T (2004) The anti-inflammatory potential of berberine in vitro and in vivo. Cancer Lett 203:127–137
Lewis K (2001) In search of natural substrates and inhibitors of MDR pumps. J Mol Microbiol Biotechnol 3:247--254
Lipsitch M, Bergstrom CT, Levin BR (2000) The epidemiology of antibiotic resistance in hospitals: paradoxes and prescriptions. Proc Natl Acad Sci USA 97:1938–1943
Marchetti O, Moreillon P, Glauser MP, Bille J, Sanglard D (2000) Potent synergism of the combination of fluconazole and cyclosporine in Candida albicans. Antimicrob Agents Chemother 44:2373–2381
Marinova E, Nikolova D, Popova D, Gallacher G, Ivanovska N (2000) Suppression of experimental autoimmune tubulointerstitial nephritis in BALB/c mice by berberine. Immunopharmacology 48:9–16
Mitani N, Murakami K, Yamaura T, Ikeda T, Saiki I (2001) Inhibitory effect of berberine on the mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma. Cancer Lett 165:35–42
Odds F (2003) Synergy, antagonism, and what the checkerboard puts between them. J Antim Chemother 52:1
Park KS, Kang KC, Kim JH, Adams DJ, Johng TN, Paik YK (1999) Differential inhibitory effects of protoberberines on sterol and chitin biosyntheses in Candida albicans. J Antimicrob Chemother 43:667–674
Perea S, Patterson TF (2002) Antifungal resistance in pathogenic fungi. Clin Infect Dis 35:1073–1080
Polak A (1990) Combination therapy in systemic mycosis. J Chemother 2:211–217
Severina II, Muntyan MS, Lewis K, Skulachev VP (2001) Transfer of cationic antibacterial agents beerberine, palmatine and benzalkonium through bimolecular planar phospholipid film and Staphylococcus aureus membrane. IUBMB-Life Sci 52:321–324
Stermitz FR, Lorenz P, Tawara JN, Zenewicz LA, Lewis K (2000a) Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5′-methoxyhydnocarpin, a multidrug pump inhibitor. Proc Natl Acad Sci 97:1433–1437
Stermitz FR, Tawara-Matsuda J, Lorenz P, Mueller P, Zenewicz L, Lewis K (2000b) 5′-Methoxyhydnocarpin-D and pheophorbide A: Berberis species components that potentiate berberine growth inhibition of resistant Staphylococcus aureus. J Nat Prod 63:1146–1149
Stermitz FR, Beeson TD, Mueller PJ, Hsiang JF, Lewis K (2001) Staphylococcus aureus MDR efflux pump inhibitors from a Berberis and a Mahonia (sensu strictu) species. Biochem Syst Ecol 29:793–798
Vollekova A, Kost’alova D, Kettmann V, Toth J (2003) Antifungal activity of Mahonia aquifolium extract and its major protoberberine alkaloids. Phytother Res 17:834–837
White TC, Marr KA, Bowden RA (1998) Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin Microbiol Rev 11(2):382–402
Zhao XZ, Guo X (1989) Antiarrhythmic effect and electrophysiologic study of berberine. Zhong Hua Xin Xue Guan Bing Za Zhi 17:159–161
Acknowledgments
This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Capacitação e Aperfeiçoamento de Pessoal de Nível Superior, (Capes), Fundação Araucária, and Programa de Pós-graduação em Análises Clínicas da Universidade Estadual de Maringá. Part of the experiments were carried out at the Complexo de Central de Apoio a Pesquisa (COMCAP) MCT/FINEP/UEM.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Iwazaki, R.S., Endo, E.H., Ueda-Nakamura, T. et al. In vitro antifungal activity of the berberine and its synergism with fluconazole. Antonie van Leeuwenhoek 97, 201–205 (2010). https://doi.org/10.1007/s10482-009-9394-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10482-009-9394-8