Antifungal and synergistic effects of an ethyl acetate extract of the edible brown seaweed Eisenia bicyclis against Candida species

  • Kim, Ki-Hyun (Busan Regional Korea Food and Drug Administration) ;
  • Eom, Sung-Hwan (Department of Food Science and Technology, Pukyong National University) ;
  • Kim, Hyo-Jung (Department of Food Science and Technology, Pukyong National University) ;
  • Lee, Dae-Sung (Marine Biodiversity Institutes of Korea) ;
  • Nshimiyumukiza, Ossiniel (KOICA-PKNU International Graduate Program of Fisheries Science, Pukyong National University) ;
  • Kim, Dongsoo (Korea Food Research Institute) ;
  • Kim, Young-Mog (Department of Food Science and Technology, Pukyong National University) ;
  • Lee, Myung-Suk (Department of Microbiology, Pukyong National University)
  • Received : 2014.04.02
  • Accepted : 2014.04.20
  • Published : 2014.06.30


With the continuing demand for new solutions in the development of effective and safe candidiasis therapies, we investigated the efficacy of an antifungal agent from the marine brown alga Eisenia bicyclis. The methanolic extract of E. bicyclis evinced potential antifungal activity against Candida species. The ethyl acetate (EtOAc)-soluble extract from E. bicyclis demonstrated the strongest antifungal activity against Candida species among five solvent-soluble extracts. Indeed, the EtOAc-soluble extract showed minimum inhibitory concentrations (MICs) ranging from 4 to 8 mg/mL. Furthermore, the EtOAc-soluble extract considerably reversed high-level fluconazole resistance of Candida species. The MIC values of fluconazole against Candida species decreased substantially (from 64 to $4{\mu}g/mL$) in combination with the MIC of the EtOAc-soluble extract (4 mg/mL). The fractional inhibitory concentration indices of fluconazole ranged from 0.531 to 0.625 in combination with 4, 2, or 1 mg/mL of the EtOAc-soluble extract against Candida isolates, indicating that these combinations exert a marked synergistic effect against Candida isolates. These findings imply that compounds derived from E. bicyclis can be a potential source of natural antifungal agents against Candida species.



  1. Ahn BR, Moon HE, Kim HR, Jung HA and Choi JS. 2012. Neuroprotective effect of edible brown alga Eisenia bicyclis on amyloid beta peptide-induced toxicity in PC12 cells. Arch Pharm Res 35, 1989-1998.
  2. Choi JG, Kang OH, Brice OO, Lee YS, Chae HS, Oh YC, Sohn DH, Park H, Choi HG, Kim SG, Shin DW and Kwon DY. 2010. Antibacterial activity of Ecklonia cava against methicillin-resistant Staphylococcus aureus and Salmonella spp. Foodborne Pathog Dis 7, 435-441.
  3. Clinical and Laboratory Standards Institute (CLSI). 2004. Method for Antifungal Disk Diffusion Susceptibility Testing of Yeasts: Approved Guideline M44-A. CLSI, Wayne, PA, US.
  4. Clinical and Laboratory Standards Institute (CLSI). 2008. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts: Approved Standard. 3rd ed. CLSI document M27-A3. CLSI, Wayne, PA, US.
  5. Eom SH, Kim DH, Lee SH, Yoon NY, Kim JH, Kim TH, Chung YH, Kim SB, Kim YM, Kim HW, Lee MS and Kim YM. 2013. In vitro antibacterial activity and synergistic antibiotic effects of phlorotannins isolated from Eisenia bicyclis against methicillin‐resistant Staphylococcus aureus. Phytother Res 27, 1260-1264.
  6. Ermakova S, Men'shova R, Vishchuk O, Kim SM, Um BH, Isakov V and Zvyagintseva T. 2013. Water-soluble polysaccharides from the brown alga Eisenia bicyclis: Structural characteristics and antitumor activity. Algal Res 2, 51-58.
  7. Isnansetyo A and Kamei Y. 2009. Anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of MC21-B, an antibacterial compound produced by the marine bacterium Pseudoalteromonas phenolica O-$BC30^T$. Int J Antimicrob Agents 34, 131-135.
  8. Jeong ES, Yoon YH and Kim JK. 2009. Contrasting correlation in the inhibition response of ADP-induced platelet aggregation and the anti-coagulant activities of algal fucoidans derived from Eisenia bicyclis and Undaria pinnatifida sporophylls (Mekabu). Fish Aquat Sci 12, 194-202.
  9. Jung HA, Jin SE, Ahn BR, Lee CM and Choi JS. 2013. Anti-inflammatory activity of edible brown alga Eisenia bicyclis and its constituents fucosterol and phlorotannins in LPS-stimulated RAW264.7 macrophages. Food Chem Toxicol 59, 199-206.
  10. Kang KA, Lee KH, Chae S, Zhang R, Jung MS, Ham YM, Baik JS, Lee NH and Hyun JW. 2006. Cytoprotective effect of phloroglucinol on oxidative stress induced cell damage via catalase activation. J Cell Biochem 97, 609-620.
  11. Khaled N, Hiba M and Asma C. 2012. Antioxidant and antifungal activities of Padina pavonica and Sargassum vulgare from the Lebanese Mediterranean Coast. Adv Environ Biol 6, 42-48.
  12. Lilly LB. 2012. Drug-induced liver disease. In: Hepatology: Diagnosis and Clinical Management. Heathcote J, ed. Wiley-Blackwell, Hoboken, NJ, US, pp. 235-243.
  13. Lopes G, Pinto E, Andrade PB and Valentao P. 2013. Antifungal activity of phlorotannins against dermatophytes and yeasts: approaches to the mechanism of action and influence on Candida albicans virulence factor. PloS One 8, 1-10.
  14. Maegawa M. 1990. Ecological studies of Eisenia bicyclis (Kjellma) Setchell and Ecklonia cava Kjellman. Bull Fac Bioresour Mie Univ 4, 73-145.
  15. Nagayama K, Iwamura Y, Shibata T, Hirayama I and Nakamura T. 2002. Bactericidal activity of phlorotannins from the brown alga Ecklonia kurome. J Antimicrob Chemother 50, 889-893.
  16. Okada Y, Ishimaru A, Suzuki R and Okuyama T. 2004. A new phloroglucinol derivative from the brown alga Eisenia bicyclis: potential for the effective treatment of diabetic complications. J Nat Prod 67, 103-105.
  17. Perea S, Gonzalez G, Fothergill AW, Kirkpatrick WR, Rinaldi MG and Patterson TF. 2002. In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp. Antimicrob Agents Chemother 46, 3039-3041.
  18. Pfaller MA. 2012. Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med 125, S3-S13.
  19. Rodloff AC, Koch D and Schaumann R. 2011. Epidemiology and antifungal resistance in invasive candidiasis. Eur J Med Res 16, 187-195.
  20. Sharma M, Manoharlal R, Puri N and Prasad R. 2010. Antifungal curcumin induces reactive oxygen species and triggers an early apoptosis but prevents hyphae development by targeting the global repressor TUP1 in Candida albicans. Biosci Rep 30, 391-404.
  21. Shibata T, Nagayama K, Tanaka R, Yamaguchi K and Nakamura T. 2003. Inhibitory effects of brown algal phlorotannins on secretory phospholipase $A_2s$, lipoxygenases and cyclooxygenases. J Appl Phycol 15, 61-66.
  22. Weig M and Muller FM. 2001. Synergism of voriconazole and terbinafine against Candida albicans isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis. Antimicrob Agents Chemother 45, 966-968.
  23. Xie CF, Qu JB, Wu XZ, Liu N, Ji M and Lou HX. 2010. Antifungal macrocyclic bis (bibenzyls) from the Chinese liverwort Ptagiochasm intermedlum L. Nat Prod Res 24, 515-520.
  24. Yoon NY, Lee SH, Wijesekara I and Kim SK. 2011. In vitro and intracellular antioxidant activities of brown alga Eisenia bicyclis. Fish Aquat Sci 14, 179-185.
  25. Yoon NY, Lee SH, Shim KB, Lim CW, Lee MH, Cho HA and Xie CL. 2013. Quinone reductase induction activity of phlorotannins derived from Eisenia bicyclis in Hepa1c1c7 cells. Fish Aquat Sci 16, 1-5.

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