Browse > Article
http://dx.doi.org/10.17480/psk.2015.59.6.259

Synergistic Antifungal Activity against Disseminated Candidiasis by Combination Therapy of Crataegi Fructus Extract and Fluconazole  

Han, Yongmoon (Department of ImmunoMicrobiology, College of Pharmacy, Dongduk Women's University)
Publication Information
YAKHAK HOEJI / v.59, no.6, 2015 , pp. 259-265 More about this Journal
Abstract
In recent, there are increasing reports about pharmacological activities of Crataegi Fructus which has been used for many centuries as medicinal and food sources in East Asia. However, its antifungal efficacy needs to be investigated. Thus, in the current study, we determined synergistic antifungal activity of the Crataegi Fructus extract (CFE) when combined with fluconazole (FLC) against disseminated candidiasis due to Candida albicans. This fungus is one of the most problematic fungal pathogens. Data resulting from a microdilution susceptibility test showed that CFE had a dose-dependent antifungal activity. When the extract was combined with FLC, the activity was synergistic. For example, the antifungal activity by the combination of CFE at $20{\mu}g/ml$ plus FLC at $0.1{\mu}g/ml$ was 4 times more effective than antifungal activity by FLC alone at the same concentration (P<0.05). In the murine model of disseminated candidiasis, the combination therapy potentiated resistance of mice, resulting in 80% of C. albicans-infected animals surviving the entire period of 40 days observation, whereas mice given CFE alone or FLC alone all died with 17 and 23 days, respectively, although they survived longer than the untreated control animals (P<0.05). The CFE's antifungal activity seemed to be related to the blockage of hyphal production of C. albicans yeast cells. In summary, CFE has a synergistic antifungal activity, which can be produced by combining CFE with FLC. Thus, our data strongly indicate that CFE may be a potential candidate as an antifungal agent for combination therapy.
Keywords
Crataegi Fructus extract; Candida albicans; fluconazole; combination therapy; disseminated candidiasis; synergistic antifungal activity;
Citations & Related Records
Times Cited By KSCI : 6  (Citation Analysis)
연도 인용수 순위
1 Lee, K. K., Maccallum, D. M., Jacobsen, M. D., Walker, L. A., Odds, F. C., Gow, N. A. and Munro, C. A. : Elevated cell wall chitin in Candida albicans confers echinocandin resistance in vivo. Antimicrob. Agents Chemother. 56, 208 (2012).   DOI
2 Angiolella, L., Stringaro, A. R., De Bernardis, F., Posteraro, B., Bonito, M., Toccacieli, L., Torosantucci, A., Colone, M., Sanguinetti, M., Cassone, A. and Palamara, A. T. : Increase of virulence and its phenotypic traits in drug-resistant strains of Candida albicans. Antimicrob. Agents Chemother. 52, 927 (2008).   DOI
3 Schaberg, D. R., Culver, D. H. and Gaynes, R. P. : Major trends in the microbial etiology of nosocomial infection. Am. J. Med. 16, 72S (1991).
4 Edwards, J. E. : Invasive Candida infections: evolution of a fungal pathogen. N. Engl. J. Med. 324, 1060 (1991).   DOI
5 Gow, N. A., Brown, A. J. and Odds, F. C. : Fungal morphogenesis and host invasion. Curr. Opin. Microbiol. 5, 366 (2002).   DOI
6 Sobel, J. D. : Epidemiology and pathogenesis of recurrent vulvovaginal candidiasis. Am. J. Obstet. Gynecol. 152, 924 (1985).   DOI
7 Sobel, J. D. : Pathogenesis and epidemiology of vulvovaginal candidiasis. Ann. N. Y. Acad. Sci. 544, 547 (1988).   DOI
8 Odds, F. C., Brown, A. J. and Gow, N. A. : Antifungal agents: mechanisms of action. Trends Microbiol. 11, 272 (2003).   DOI
9 Bae, M. H. and Kim, H. H. : Mechanism of Crataegi Fructus extract induced endothelium-dependent vasorelaxation in rabbit carotid artery. Kor. J. Herbology 18, 169 (2003).
10 Lee, J. H., Lee, J. Y., Park, J. H., Jung, H. S., Kim, J. S., Kang, S. S., Kim, Y. S. and Han, Y. : Immunoregulatory activity by daucosterol, a ${\beta}$-sitosterol glycoside, induces protective Th1 immune response against disseminated candidiasis in mice. Vaccine 25, 3834 (2007).   DOI
11 Han, Y. and Lee, J. H. : Berberine synergy with amphotericin B against disseminated candidiasis in mice. Biol. Pharm. Bull. 28, 541 (2005).   DOI
12 Han, Y. : Synergic anticandidal effect of epigallocatechin-Ogallate combined with amphotericin B in a murine model of disseminated candidiasis and its anticandidal mechanism. Biol. Pharm. Bull. 30, 1693 (2007).   DOI
13 Yin, F., Li, L., Chen, Y., Lu, T., Li, W., Cai, B. and Yin, W. : Quality control of processed Crataegi Fructus and its medicinal parts by ultra high performance liquid chromatography with electrospray ionization tandem mass spectrometry. J. Sep. Sci. 38, 2630 (2015).   DOI
14 Lee, J. H., Park, J. H., Kim, Y. S. and Han, Y. : Chlorogenic acid, a polyphenolic compound, treats mice with septic arthritis caused by Candida albicans. Int. Immunopharmacol. 8, 1681 (2008).   DOI
15 Islam, S., Singer, M. and Kulhanjian J. A. : Toxic epidermal necrolysis in a neonate receiving fluconazole. J. Perinatol. 34, 792 (2014).   DOI
16 Egunsola, O., Adefurin, A., Fakis, A., Jacqz-Aigrain, E., Choonara, I. and Sammons, H. : Safety of fluconazole in paediatrics: a systematic review. Eur. J. Clin. Pharmacol. 69, 1211 (2013).   DOI
17 Hong, S. S., Hwang, J. S., Lee, S. A., Han, X. H., Ro, J. S. and Lee, K. S. : Inhibitors of monoamine oxidase activity from the fruits of Crataegus pinnatifida Bunge. Kor. J. Pharmacogn. 33, 285 (2002).
18 Bodey, G. P. : The emergence of fungi as major hospital pathogens. J. Hosp. Infect. 11, 411 (1988).   DOI
19 Arturo, C. : Antibodies and fungi: an evolving paradigm with opportunities for the development of new antifungal therapies and vaccines. Rev. Iberoam. Micol. 14, 2 (1997).
20 Baselski, V. S., Robison, M. K., Pifer, L. W. and Woods, D. R. : Rapid detection of Pneumocystis carinii in bronchoalveolar lavage samples by using cellufluor staining. J. Clin. Microbiol. 28, 393 (1990).
21 An, B. J., Kang, B. Y. and Lee, J. T. : Development of cosmetic material from Korean Crataegi Fructus extract. Kor. J. Herbology 17, 39 (2002).
22 Lin, H. H., Charles, A. L., Hsieh, C. W., Lee, Y. C. and Ciou, J. Y. : Antioxidant effects of 14 Chinese traditional medicinal herbs against human low-density lipoprotein oxidation. J. Tradit. Complement Med. 5, 51 (2014).
23 Kao, E. S., Wang, C. J., Lin, W. L., Yin, Y. F., Wang, C. P. and Tseng. T. H. : Anti-inflammatory potential of flavonoid contents from dried fruit of Crataegus pinnatifida in vitro and in vivo. J. Agric. Food. Chem. 53, 430 (2005).   DOI
24 Seo, B. I. : Preventive effects of water extracts from on Crataegi Fructus on hyperlipiderma and liver damage induced by alcohol. Kor. J. Herbology 20, 35 (2005).
25 Ahn, K. S., Hahm, M. S., Park, E. J., Lee, H. K. and Kim, I. H. : Corosolic acid isolated from the fruit of Crataegus pinnatifida var. psilosa is a protein kinase C inhibitor as well as a cytotoxic agent. Planta Med. 64, 468 (1998).   DOI
26 Chan, A. S., Yip, E. C., Yung, L. Y., Pang, H., Luk, S. C., Pang, S. F. and Wong, Y. H. : Immuno-regulatory effects of CKBM on the activities of mitogen-activated protein kinases and the release of cytokines in THP-1 monocytic cells. Biol. Pharm. Bull. 28, 1645 (2005).   DOI
27 Ryu, H. Y., Kim, Y. K., Kwun, I. S., Kwan, C. S., Jin, I. N. and Sohn, H. Y. : Thrombin inhibition activity of fructus extract of Crataegus pinnatifida Bunge. J. Life Sci. 17, 535 (2007).   DOI
28 Qin, R,. Xiao, K., Li, B., Jiang, W., Peng, W., Zheng, J. and Zhou, H. : The combination of catechin and epicatechin callate from Fructus Crataegi potentiates beta-lactam antibiotics against methicillin-resistant staphylococcus aureus (MRSA) in vitro and in vivo. Int. J. Mol. Sci. 14, 1802 (2013)   DOI
29 Choi, O. K., Kim, Y., Cho, G. S. and Sung, C. K. : Screening for antimicrobial activity from korean plants. Kor. J. Food. Nutr. 15, 301 (2002).
30 Ryu, H. Y., Park, S. J., Lee, B. H. and Sohn, H. Y. : Antimicrobial activity of fruit of Crataegus pinnatifida Bunge against multidrug resistant pathogenic Pseudomonas aeruginosa and Candida sp. Kor. J. Micobiol. Biotechnol. 38, 77 (2010).
31 Yu, Y. E., Park, E. Y., Jung, D. H., Byun, S. H. and Kim, S. C. : Antibacterial activity of oriental medicinal herb extracts against skin pathogens. J. Life Sci. 20, 1143 (2010).   DOI
32 Kim, J., Park, Y. J., Park, K. D., Jung, B., Choi, M. Y. and Han, Y. : Antimicrobial activities of Crataegi Frucutus methanol extract. Dongduk Yakhak Res. 14, 33 (2010).
33 Park, S. W., Yook, C. S. and Lew, H. K. : Chemical components from the fruits of Crataegus pinnatifida var. psilosa. Kor. J. Pharmacogn. 25, 328 (1994).
34 Han, Y. and Cutler, J. E. : Antibody response that protects against disseminated candidiasis. Infect. Immun. 63, 2714 (1995).
35 Han, Y., Morrison, R. P. and Cutler, J. E. : A vaccine and monoclonal antibodies that enhance mouse resistance to Candida albicans vaginal infection. Infect. Immun. 66, 5771 (1998).