Synergistic Antifungal Activity of Magnoliae Cortex and Syzyii Flos against Candida albicans

  • YOON, Jeemin (Department of Forest Products and Biotechnology, Kookmin University) ;
  • KIM, Tae-Jong (Department of Forest Products and Biotechnology, Kookmin University)
  • Received : 2021.01.08
  • Accepted : 2021.02.10
  • Published : 2021.03.25


Candida albicans is a dermal fungus of the human body that is known to cause oral candidiasis, vaginal candidiasis, and bloodstream infections in immunocompromised people or in certain environmental conditions. As cases of strains resistant to antifungal agents in C. albicans have been reported, studies using plant materials as safe antifungal agents are being actively conducted. In this study, a total of 17 edible plant extracts showed antifungal activity against C. albicans as a result of evaluating a 280-plant extract library using paper disk diffusion method. Among them, the four extracts with the strongest antifungal activity (Cinnamomi Cortex, Cinnamomi Ramulus, Magnoliae Cortex, and Syzygii Flos) were selected and evaluated for synergistic antifungal activity against C. albicans. The combination of Magnoliae Cortex and Syzygii Flos showed a synergistic activity. The antifungal activity was evaluated based on the concentrations of magnolol and eugenol, the respective components of Magnoliae Cortex and Syzygii Flos. Magnolol and eugenol showed synergistic antifungal activities at the concentration ratio of 1:25 - 1:61. The antifungal activity of these two compounds contributes 28 to 48% to the synergistic antifungal activity of the combination of Magnoliae Cortex and Syzygii Flos extract. In this study, we propose that a combination of Magnoliae Cortex and Syzygii Flos can effectively inhibit the growth of C. albicans and that magnolol and eugenol are the responsible inhibitory compounds.



  1. Adfa, M., Romayasa, A., Kusnanda, A.J., Avidlyandi, A., Yudha, S., Banon, C., Gustian, I. 2020. Chemical components, antitermite and antifungal activities of Cinnamomum parthenoxylon wood vinegar. Journal of the Korean Wood Science and Technology 48(1): 107-116.
  2. Amborabe, B.-E., Fleurat-Lessard, P., Chollet, J.-F., Roblin, G. 2002. Antifungal effects of salicylic acid and other benzoic acid derivatives towards Eutypa lata: structure-activity relationship. Plant Physiology and Biochemistry 40(12): 1051-1060.
  3. Bais, Y., Chaudhari, S.B., Belani, S., Umakar, A.R. 2013. Evaluation of antimicrobial activity of plant leaf Argemone mexicana. International Journal of Pharmacy and Biological Sciences 3(1): 41-45.
  4. Bang, K.-H., Lee, D.-W., Park, H.-M., Rhee, Y.-H. 2000a. Inhibition of fungal cell wall synthesizing enzymes by trans-cinnamaldehyde. Bioscience, Biotechnology, and Biochemistry 64(5): 1061-1063.
  5. Bang, K.H., Kim, Y.K., Min, B.S., Na, M.K., Rhee, Y.H., Lee, J.P., Bae, K.H. 2000b. Antifungal activity of magnolol and honokiol. Archives of Pharmacal Research 23(1): 46-49.
  6. Bhowmik, D., Kumar, K.P.S., Yadav, A., Srivastava, S., Paswan, S., Dutta, A.S. 2012. Recent trends in Indian traditional herbs Syzygium aromaticum and its health benefits. Journal of Pharmacognosy and Phytochemistry 1(1): 13-22.
  7. Blaszczyk, T., Krzyzanowska, J., Lamer-Zarawska, E. 2000. Screening for antimycotic properties of 56 traditional Chinese drugs. Phytotherapy Research 14(3): 210-212.
  8. Bodey, G.P., Luna, M. 1974. Skin lesions associated with disseminated candidiasis. JAMA 229(11): 1466-1468.
  9. Cai, L. 1996. Compounds from Syzygium aromaticum possessing growth inhibitory activity against oral pathogens. Journal of Natural Products 59(10): 987-990.
  10. Cardoso, N.N.R., Alviano, C.S., Blank, A.F., Romanos, M.T.V., Fonseca, B.B., Rozental, S., Rodrigues, I.A., Alviano, D.S. 2016. Synergism effect of the essential oil from Ocimum basilicum var. Maria Bonita and its major components with fluconazole and its influence on ergosterol biosynthesis. Evidence-Based Complementary and Alternative Medicine 2016(Article ID 5647182).
  11. Chami, F., Chami, N., Bennis, S., Trouillas, J., Remmal, A. 2004. Evaluation of carvacrol and eugenol as prophylaxis and treatment of vaginal candidiasis in an immunosuppressed rat model. Journal of Antimicrobial Chemotherapy 54(5): 909-914.
  12. Chen, Y.-H., Lu, M.-H., Guo, D.-S., Zhai, Y.-Y., Miao, D., Yue, J.-Y., Yuan, C.-H., Zhao, M.-M., An, D.-R. 2019. Antifungal effect of magnolol and honokiol from Magnolia officinalis on Alternaria alternata causing tobacco brown spot. Molecules (Basel, Switzerland) 24(11): 2140.
  13. Cheng, S.-S., Liu, J.-Y., Chang, E.-H., Chang, S.-T. 2008. Antifungal activity of cinnamaldehyde and eugenol congeners against wood-rot fungi. Bioresource Technology 99(11): 5145-5149.
  14. Chusri, S., Siriyong, T., Na-Phatthalung, P., Voravuthikunchai, S.P. 2014. Synergistic effects of ethnomedicinal plants of Apocynaceae family and antibiotics against clinical isolates of Acinetobacter baumannii. Asian Pacific Journal of Tropical Medicine 7(6): 456-461.
  15. Darvishi, E., Omidi, M., Bushehri, A.A.S., Golshani, A., Smith, M.L. 2013. The antifungal eugenol perturbs dual aromatic and branched-chain amino acid permeases in the cytoplasmic membrane of yeast. PloS ONE 8(10): e76028-e76028.
  16. de Oliveira Pereira, F., Mendes, J.M., de Oliveira Lima, E. 2013. Investigation on mechanism of antifungal activity of eugenol against Trichophyton rubrum. Medical Mycology 51(5): 507-513.
  17. de Toledo, C.E.M., Britta, E.A., Ceole, L.F., Silva, E.R., de Mello, J.C.P., Dias Filho, B.P., Nakamura, C.V., Ueda-Nakamura, T. 2011. Antimicrobial and cytotoxic activities of medicinal plants of the Brazilian cerrado, using Brazilian cachaca as extractor liquid. Journal of Ethnopharmacology 133(2): 420-425.
  18. Donders, G., Bellen, G., Mendling, W. 2010. Management of recurrent vulvo-vaginal candidosis as a chronic illness. Gynecologic and Obstetric Investigation 70(4): 306-321.
  19. Duarte, M.C.T., Figueira, G.M., Sartoratto, A., Rehder, V.L.G., Delarmelina, C. 2005. Anti-Candida activity of Brazilian medicinal plants. Journal of ethnopharmacology 97(2): 305-311.
  20. Edmond, M.B., Wallace, S.E., McClish, D.K., Pfaller, M.A., Jones, R.N., Wenzel, R.P. 1999. Nosocomial bloodstream infections in United States hospitals: A three-year analysis. Clinical Infectious Diseases 29(2): 239-244.
  21. Epstein, J.B. 1990. Antifungal therapy in oropharyngeal mycotic infections. Oral Surgery, Oral Medicine, Oral Pathology 69(1): 32-41.
  22. Fanos, V., Cataldi, L. 2000. Amphotericin B-induced nephrotoxicity: A review. Journal of Chemotherapy 12(6): 463-470.
  23. Garcia-Cuesta, C., Sarrion-Perez, M.-G., Bagan, J.V. 2014. Current treatment of oral candidiasis: A literature review. Journal of Clinical and Experimental Dentistry 6(5): e576-e582.
  24. Ham, Y., Kim, T.-J. 2018. Plant extracts inhibiting biofilm formation by Streptococcus mutans without antibiotic activity. Journal of the Korean Wood Science and Technology 46(6): 692-702.
  25. He, M., Du, M., Fan, M., Bian, Z. 2007. In vitro activity of eugenol against Candida albicans biofilms. Mycopathologia 163(3): 137-143.
  26. Hedderwick, S., Kauffman, C. 1997. Opportunistic fungal infections: superficial and systemic candidiasis. Geriatrics 52(10): 50-54.
  27. Hidaya, A., Turjaman, M., Faulina, S.A., Ridwan, F., Aryanto, Najmulah, Irawadi, T.T., Iswanto, A.H. 2019. Antioxidant and antifungal activity of endophytic fungi associated with agarwood trees. Journal of the Korean Wood Science and Technology 47(4): 459-471.
  28. Ho, K.-Y., Tsai, C.-C., Chen, C.-P., Huang, J.-S., Lin, C.-C. 2001. Antimicrobial activity of honokiol and magnolol isolated from Magnolia officinalis. Phytotherapy Research 15(2): 139-141.
  29. Hwang, E.-I., Kwon, B.-M., Lee, S.-H., Kim, N.-R., Kang, T.-H., Kim, Y.-T., Park, B.-K., Kim, S.-U. 2002. Obovatols, new chitin synthase 2 inhibitors of Saccharomyces cerevisiae from Magnolia obovata. Journal of Antimicrobial Chemotherapy 49(1): 95-101.
  30. NCCLS. 2002. Reference method for broth dilution antifungal susceptibility testing of yeasts; Approved standard-2nd ed., NCCLS document M27-A2 (ISBN 1-56238-469-4). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA.
  31. Jarvis, W.R., Edwards, J.R., Culver, D.H., Hughes, J.M., Horan, T., Emori, T.G., Banerjee, S., Tolson, J., Henderson, T., Gaynes, R.P., Martone, W.J., National Nosocomial Infections Surveillance System. 1991. Nosocomial infection rates in adult and pediatric intensive care units in the United States. The American Journal of Medicine 91(3): S185-S191.
  32. Kim, K.-S., Kim, H. 2004. Analytical method for the determination of standard compounds in oriental medicine materials listed in the Korean pharmacopoeia (KPVIII). Korean Journal of Crop Science 49(spc1): 117-145.
  33. Kim, S.H., Lee, S.Y., Cho, S.M., Hong, C.Y., Park, M.J., Choi, I.G. 2016. Evaluation on anti-fungal activity and synergy effects of essential oil and their constituents from Abies holophylla. Journal of the Korean Wood Science and Technology 44(1): 113-123.
  34. Kumamoto, C.A., Vinces, M.D. 2005. Alternative Candida albicans lifestyles: growth on surfaces. Annual Review of Microbiology 59(1): 113-133.
  35. Lee, J., Jung, E., Park, J., Jung, K., Lee, S., Hong, S., Park, J., Park, E., Kim, J., Park, S., Park, D. 2005. Anti-inflammatory effects of magnolol and honokiol are mediated through inhibition of the downstream pathway of MEKK-1 in NF-κB activation signaling. Planta Medica 71(04): 338-343.
  36. Lee, K.-G., Shibamoto, T. 2001. Antioxidant property of aroma extract isolated from clove buds [Syzygium aromaticum (L.) Merr. et Perry]. Food Chemistry 74(4): 443-448.
  37. Lee, O.H., Son, J.Y. 2006. Antimicrobial activity of clove extract by extraction solvents. Journal of The Korean Society of Food Science and Nutrition 33(3): 494-499.
  38. Li, Z.-J., Guo, X., Dawuti, G., Aibai, S. 2015. Antifungal activity of ellagic acid in vitro and in vivo. Phytotherapy Research 29(7): 1019-1025.
  39. Liu, H., Schmitz, J.C., Wei, J., Cao, S., Beumer, J.H., Strychor, S., Cheng, L., Liu, M., Wang, C., Wu, N., Zhao, X., Zhang, Y., Liao, J., Chu, E., Lin, X. 2014. Clove extract inhibits tumor growth and promotes cell cycle arrest and apoptosis. Oncology Research 21(5): 247-259.
  40. Ma, J.-N., Ma, C.-M. 2015. Chapter 71-Antifungal inhibitory activities of caffeic and quinic acid derivatives, in: Preedy, V. R., (Ed.), Coffee in Health and Disease Prevention, Academic Press, San Diego 2015, pp. 635-641.
  41. Mukherjee, P.K., Sheehan, D.J., Hitchcock, C.A., Ghannoum, M.A. 2005. Combination treatment of invasive fungal infections. Clinical Microbiology Reviews 18(1): 163-194.
  42. Nweze, E.I., Eze, E.E. 2009. Justification for the use of Ocimum gratissimum L in herbal medicine and its interaction with disc antibiotics. BMC Complementary and Alternative Medicine 9: 37-37.
  43. Pfaller, M.A., Diekema, D.J., Gibbs, D.L., Newell, V.A., Ellis, D., Tullio, V., Rodloff, A., Fu, W., Ling, T.A. 2010. Results from the ARTEMIS DISK global antifungal surveillance study, 1997 to 2007: a 10.5-year analysis of susceptibilities of Candida species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion. Journal of Clinical Microbiology 48(4): 1366-1377.
  44. Pinto, E., Vale-Silva, L., Cavaleiro, C., Salgueiro, L. 2009. Antifungal activity of the clove essential oil from Syzygium aromaticum on Candida, Aspergillus and dermatophyte species. Journal of Medical Microbiology 58(11): 1454-1462.
  45. Rosato, A., Vitali, C., Gallo, D., Balenzano, L., Mallamaci, R. 2008. The inhibition of Candida species by selected essential oils and their synergism with amphotericin B. Phytomedicine 15(8): 635-638.
  46. Sague, C.M.B., Jarvis, W.R., System, N.N.I.S. 1993. Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980-1990. The Journal of Infectious Diseases 167(5): 1247-1251.
  47. Sakaue, Y., Domon, H., Oda, M., Takenaka, S., Kubo, M., Fukuyama, Y., Okiji, T., Terao, Y. 2016. Anti-biofilm and bactericidal effects of magnolia bark-derived magnolol and honokiol on Streptococcus mutans. Microbiology and Immunology 60(1): 10-16.
  48. Seal, T. 2016. Quantitative HPLC analysis of phenolic acids, flavonoids and ascorbic acid in four different solvent extracts of two wild edible leaves, Sonchus arvensis and Oenanthe linearis of North-Eastern region in India. Journal of Applied Pharmaceutical Science 6(02): 157-166.
  49. Shan, B., Cai, Y.Z., Sun, M., Corke, H. 2005. Antioxidant capacity of 26 spice extracts and characterization of their phenolic constituents. Journal of Agricultural and Food Chemistry 53(20): 7749-7759.
  50. Shen, C.-C., Ni, C.-L., Shen, Y.-C., Huang, Y.-L., Kuo, C.-H., Wu, T.-S., Chen, C.-C. 2009. Phenolic constituents from the stem bark of Magnolia officinalis. Journal of Natural Products 72(1): 168-171.
  51. Shen, J.-L., Man, K.-M., Huang, P.-H., Chen, W.-C., Chen, D.-C., Cheng, Y.-W., Liu, P.-L., Chou, M.-C., Chen, Y.-H. 2010. Honokiol and magnolol as multifunctional antioxidative molecules for dermatologic disorders. Molecules (Basel, Switzerland) 15(9): 6452-6465.
  52. Shi, C., Zhang, X., Sun, Y., Yang, M., Song, K., Zheng, Z., Chen, Y., Liu, X., Jia, Z., Dong, R., Cui, L., Xia, X. 2016. Antimicrobial activity of ferulic acid against Cronobacter sakazakii and possible mechanism of action. Foodborne Pathogens and Disease 13(4): 196-204.
  53. Shobana, S., Akhilender Naidu, K. 2000. Antioxidant activity of selected Indian spices. Prostaglandins, Leukotrienes and Essential Fatty Acids 62(2): 107-110.
  54. Silva, I.C.G.d., Santos, H.B.d.P., Cavalcanti, Y.W., Nonaka, C.F.W., Sousa, S.A.d., Castro, R.D.d. 2017. Antifungal activity of eugenol and its association with nystatin on Candida albicans. Brazilian Research in Pediatric Dentrtry and Integrated Clinic 17(1): e3235.
  55. Singh, A.K., Dhamanigi, S.S., Asad, M. 2009. Anti-stress activity of hydro-alcoholic extract of Eugenia caryophyllus buds (clove). Indian journal of pharmacology 41(1): 28-31.
  56. Sobel, J.D. 2007. Vulvovaginal candidosis. The Lancet 369(9577): 1961-1971.
  57. Sugar, A.M., Hitchcock, C.A., Troke, P.F., Picard, M. 1995. Combination therapy of murine invasive candidiasis with fluconazole and amphotericin B. Antimicrobial Agents and Chemotherapy 39(3): 598-601.
  58. Sun, L.-M., Liao, K., Liang, S., Yu, P.-H., Wang, D.-Y. 2015. Synergistic activity of magnolol with azoles and its possible antifungal mechanism against Candida albicans. Journal of Applied Microbiology 118(4): 826-838.
  59. Tampieri, M.P., Galuppi, R., Macchioni, F., Carelle, M.S., Falcioni, L., Cioni, P.L., Morelli, I. 2005. The inhibition of Candida albicans by selected essential oils and their major components. Mycopathologia 159(3): 339-345.
  60. Taveira, G.B., Carvalho, A.O., Rodrigues, R., Trindade, F.G., Da Cunha, M., Gomes, V.M. 2016. Thionin-like peptide from Capsicum annuum fruits: mechanism of action and synergism with fluconazole against Candida species. BMC Microbiology 16(1): 12.
  61. Vaijayanthimala, J., Anandi, C., Udhaya, V., Pugalendi, K.V. 2000. Anticandidal activity of certain South Indian medicinal plants. Phytotherapy Research 14(3): 207-209.<207::AID-PTR564>3.0.CO;2-I
  62. Wagner, H., Ulrich-Merzenich, G. 2009. Synergy research: Approaching a new generation of phytopharmaceuticals. Phytomedicine 16(2): 97-110.
  63. Wan, C., Li, P., Chen, C., Peng, X., Li, M., Chen, M., Wang, J., Chen, J. 2017. Antifungal activity of Ramulus cinnamomi explored by 1H-NMR based metabolomics approach. Molecules (Basel, Switzerland) 22(12): 2237.
  64. Whaley, S.G., Berkow, E.L., Rybak, J.M., Nishimoto, A.T., Barker, K.S., Rogers, P.D. 2017. Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species. Frontiers in Microbiology 7(2173).
  65. Xiang, M.-J., Liu, J.-Y., Ni, P.-H., Wang, S., Shi, C., Wei, B., Ni, Y.-X., Ge, H.-L. 2013. Erg11 mutations associated with azole resistance in clinical isolates of Candida albicans. FEMS Yeast Research 13(4): 386-393.
  66. Zhao, Y., Stensvold, C.R., Perlin, D.S., Arendrup, M.C. 2013. Azole resistance in Aspergillus fumigatus from bronchoalveolar lavage fluid samples of patients with chronic diseases. Journal of Antimicrobial Chemotherapy 68(7): 1497-1504.
  67. Zhou, P., Fu, J., Hua, H., Liu, X. 2017. In vitro inhibitory activities of magnolol against Candida spp. Drug Design, Development and Therapy 11: 2653-2661.