Phytochemicals: New Avenues in Anticandidal Activity

  • Richa RaghuwanshiEmail author


Human fungal infections have significantly increased in recent years particularly in immunocompromised hosts. Candidiasis is one of them. The emergence of new virulence factors and drug resistance in its aetiological agent Candida spp. beckons the need for new drug discoveries, as the present-day drugs are insufficient in combating the disease. Therapeutic alternatives can be the medicinal plants and phytocompounds, which have been in traditional system of medicine for their empirical antifungal properties. They could be reliable alternatives to overcome the disadvantages of antifungal drugs that include undesirable side effects, toxicity, recurrence, drug-drug interactions, and multiple drug resistance. The present article reviews the anticandidal activity of different medicinal plants and phytochemicals under the major classes of secondary metabolites such as phenolics, alkaloids, terpenoids, saponins, flavonoids, proteins, and peptides.


Anticandidal activity Medicinal plants Phytocompounds 


  1. 1.
    Leroy O, Gangneux JP, Montravers P et al (2009) Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005–2006). Crit Care Med 37:1612–1618CrossRefPubMedGoogle Scholar
  2. 2.
    Vincent JL, Rello J, Marshall JE et al (2009) International study of the prevalence and outcomes of infection in intensive care units. JAMA 302:2323–2329CrossRefPubMedGoogle Scholar
  3. 3.
    Pfaller MA, Diekema DJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20:133–163CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Prieto D, Correia I, Pla J et al (2016) Adaptation of Candida albicans to commensalism in the gut. Future Microbiol 11:567–583CrossRefPubMedGoogle Scholar
  5. 5.
    Arendrup MC, Fuursted K, Gahrn-Hansen B et al (2008) Semi-national surveillance of fungaemia in Denmark 2004-2006: increasing incidence of fungaemia and numbers of isolates with reduced azole susceptibility. Clin Microbiol Infect 14:487–494CrossRefPubMedGoogle Scholar
  6. 6.
    Arendrup MC, Fuursted K, Gahrn-Hansen B et al (2005) Semi national surveillance of fungemia in Denmark: notably high rates of fungemia and numbers of isolates with reduced azole susceptibility. J Clin Microbiol 43:4434–4440CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Arendrup MC (2014) Update on antifungal resistance in Aspergillus and Candida. Clin Microbiol Infect 20(6):42–48Google Scholar
  8. 8.
    Borg-von Zepelin M, Meyer I, Thomssen R et al (1999) HIV-Protease inhibitors reduce cell adherence of Candida albicans strains by inhibition of yeast secreted aspartic proteases. J Invest Dermatol 113:747–751CrossRefPubMedGoogle Scholar
  9. 9.
    Kim J, Sudbery P (2011) Candida albicans, a major human fungal pathogen. J Microbiol 49:171–177CrossRefPubMedGoogle Scholar
  10. 10.
    Brunke S, Hube B (2013) Two unlike cousins: Candida albicans and Candida glabrata infection strategies. Cell Microbiol 15:701–708CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ferreira AV, Prado CG, Carvalho RR et al (2013) Candida albicans and non-C. albicans Candida species: comparison of biofilm production and metabolic activity in biofilms, and putative virulence properties of isolates from hospital environments and infections. Mycopathologia 175:265–272CrossRefPubMedGoogle Scholar
  12. 12.
    Mayer FL, Wilson D, Hube B (2013) Candida albicans pathogenicity mechanisms. Virulence 4:119–128CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Sardi JCO, Scorzoni L, Bernardi T et al (2013) Candida species: current epidemiology, pathogenicity, biofilm formation natural antifungal products and new therapeutic options. J Med Microbiol 62:10–24CrossRefPubMedGoogle Scholar
  14. 14.
    Calderone RA, Fonzi WA (2001) Virulence factors of Candida albicans. Trends Microbiol 9:327–355CrossRefPubMedGoogle Scholar
  15. 15.
    Hube B (2004) From commensal to pathogen: stage- and tissue-specific gene expression of Candida albicans. Curr Opin Microbiol 7:336–341CrossRefPubMedGoogle Scholar
  16. 16.
    Gullo FP, Sardi JCO, Santos VAFFM et al (2012) Antifungal activity of maytenin and pristimirin. J Evid Based Complement Altern Med 2012:1–6CrossRefGoogle Scholar
  17. 17.
    Henriques M, Azeredo J, Oliveira R (2006) Candida albicans and Candida dubliniensis: comparison of biofilm formation in terms of biomass and activity. Br J Biomed Sci 63:5–11CrossRefPubMedGoogle Scholar
  18. 18.
    Kamba AS, Hassan LG (2010) Phytochemical screening and antimicrobial activities of Euphorbia balsamifera leaves, stems and roots against some pathogenic microorganisms. Af J Pharm Pharmacol 4:645–652Google Scholar
  19. 19.
    Toure A, Bahi C, Ouattara K et al (2011) Phytochemical screening and in vitro antifungal activities of extracts of leaves of Morinda morindoides (Morinda, Rubiaceae). J Med Plants Res 5:6780–6786Google Scholar
  20. 20.
    Chojnacka EBML, Staniszewska M (2015) Tetrazole activity against Candida albicans. The role of KEX2 mutations in the sensitivity to (±)-1-[5-(2-chlorophenyl)-2H-tetrazol- 2-yl] propan-2-yl acetate. Bioorg Med Chem Lett 25:2657–2663CrossRefGoogle Scholar
  21. 21.
    Pfaller MA, Diekema DJ, Sheehan DJ (2006) Interpretive breakpoints for fluconazole and Candida revisited: a blueprint for the future of antifungal susceptibility testing. Clin Microbiol Rev 19:435–447CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Grant SM, Clissold SP (1990) Fluconazole: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial and systemic mycoses. Drugs 39:877–916CrossRefPubMedGoogle Scholar
  23. 23.
    Sanguinetti M, Posteraro B, Lass-Florl C (2015) Antifungal drug resistance among Candida species: Mechanisms and clinical impact. Mycoses 5:2–13CrossRefGoogle Scholar
  24. 24.
    White TC, Holleman S, Dy F et al (2002) Resistance mechanisms in clinical isolates of Candida albicans. Antimicrob Agents Chemother 46:1704–1713CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Shokri H (2014) Genotypic variation and antifungal susceptibly of Candida zeylanoides clinical isolates. J Mycol Med 24:179–184CrossRefPubMedGoogle Scholar
  26. 26.
    Grasela TH, Goodwin SD, Walawander MK (1990) Prospective surveillance of intravenous amphotericin B use patterns. Pharmacotherapy 10:341–348PubMedGoogle Scholar
  27. 27.
    Fanos V, Cataldi L (2000) Amphotericin B-induced nephrotoxicity: a review. J Chemother 12:463–470CrossRefPubMedGoogle Scholar
  28. 28.
    Agarwal S, Thakur K, Kanga A et al (2008) Catheter-related candidemia caused by Candida lipolytica in a child with tubercular meningitis. Ind J Pathol Microbiol 51:298–300CrossRefGoogle Scholar
  29. 29.
    Lupan L, Bandula R, Vasilescu M et al (1996) Spectroscopic study on nystatin conformation modification generated by its interaction with the solvent. J Anal Chem 355:409–411Google Scholar
  30. 30.
    Koehn FE, Carter GT (2005) The evolving role of natural products in drug discovery. Nat Rev Drug Discov 4:206–220CrossRefPubMedGoogle Scholar
  31. 31.
    Meng JC, Hu YF, Chen JH et al (2001) Antifungal highly oxygenated guaianolides and other constituents from Ajania fruticulosa. Phytochemistry 58:1141–1145CrossRefPubMedGoogle Scholar
  32. 32.
    Lavault M, Landreau A, Larcher G et al (2005) Antileishmanial and antifungal activities of xanthanolides isolated from Xanthium macrocarpum. Fitoterapia 76:363–366CrossRefPubMedGoogle Scholar
  33. 33.
    Sabanero M, Quijano L, Rios T et al (1995) Encelin: a fungal growth inhibitor. Planta Med 61:185–186CrossRefPubMedGoogle Scholar
  34. 34.
    Starks CM, Williams RB, Goering MG et al (2010) Antibacterial clerodane diterpenes from Goldenrod (Solidago virgaurea). Phytochemistry 71:104–109CrossRefPubMedGoogle Scholar
  35. 35.
    Renault S, De Lucca AJ, Boue S et al (2003) CAY-I, a novel antifungal compound from cayenne pepper. Med Mycol 41:75–82CrossRefPubMedGoogle Scholar
  36. 36.
    Du Z, Zhu N, Ze-Ren-Wang-Mu N et al (2003) Two new antifungal saponins from the Tibetan herbal medicine Clematis tangutica. Planta Med 69:547–551CrossRefPubMedGoogle Scholar
  37. 37.
    Plaza A, Cinco M, Tubaro A et al (2003) New triterpene glycosides from the stems of Anomospermum grandifolium. J Nat Prod 66:1606–1610CrossRefPubMedGoogle Scholar
  38. 38.
    Sauton M, Mitaine AC, Miyamoto T et al (2004) A new steroidal saponin from Dioscorea cayenensis. Chem Pharm Bull 52:1353–1355CrossRefGoogle Scholar
  39. 39.
    Pistelli L, Bertoli A, Lepori E et al (2002) Antimicrobial and antifungal activity of crude extracts and isolated saponins from Astragalus verrucosus. Fitoterapia 73:336–339CrossRefPubMedGoogle Scholar
  40. 40.
    Mandal P, Sinha SP, Mandal NC (2005) Antimicrobial activity of saponins from Acacia auriculiformis. Fitoterapia 76:462–465CrossRefPubMedGoogle Scholar
  41. 41.
    Mel’nichenko EG, Kirsanova MA, Grishkovets VI et al (2003) Antimicrobial activity of saponins from Hedera taurica Carr. Mikrobiol Z 65:8–12PubMedGoogle Scholar
  42. 42.
    Zamilpa A, Tortoriello J, Navarro V et al (2002) Five new steroidal saponins from Solanum chrysotrichum leaves and their antimycotic activity. J Nat Prod 65:1815–1819CrossRefPubMedGoogle Scholar
  43. 43.
    Bedir E, Khan IA, Walker LA (2002) Biologically active steroidal glycosides from Tribulus terrestris. Pharmazie 57:491–493PubMedGoogle Scholar
  44. 44.
    Zhang JD, Xu Z, Cao YB et al (2006) Antifungal activities and action mechanisms of compounds from Tribulus terrestris L. J Ethnopharmacol 103:76–84CrossRefPubMedGoogle Scholar
  45. 45.
    Zhang JD, Cao YB, Xu Z et al (2005) In vitro and in vivo antifungal activities of the eight steroid saponins from Tribulus terrestris L. with potent activity against fluconazole-resistant fungal pathogens. Biol Pharm Bull 28:2211–2215CrossRefPubMedGoogle Scholar
  46. 46.
    Kumar M, Sarma P, Dkhar MS et al (2017) Assessment of chemically characterised Gaultheria fragrantissima Wall. essential oil and its major component as safe plant based preservative for millets against fungal, aflatoxin contamination and lipid peroxidation during storage. J Food Sci Technol 55:111–119CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Lee DG, Park Y, Kim MR et al (2004) Anti-fungal effects of phenolic amides isolated from the root bark of Lycium chinense. Biotechnol Lett 26:1125–1130CrossRefPubMedGoogle Scholar
  48. 48.
    Naldoni FJ, Claudino AL, Cruz JW Jr et al (2009) Antimicrobial activity of benzophenones and extracts from the fruits of Garcinia brasiliensis. J Med Food 12:403–407CrossRefPubMedGoogle Scholar
  49. 49.
    De Leo M, Braca A, De Tomasi N et al (2004) Phenolic compounds from Baseonema acuminatum leaves: isolation and antimicrobial activity. Planta Med 70:841–846CrossRefPubMedGoogle Scholar
  50. 50.
    Andrae-Marobela K, Ghislain FW, Okatch H et al (2013) Polyphenols: a diverse class of multi-target anti-HIV-1 agents. Curr Drug Metab 14:392–413CrossRefPubMedGoogle Scholar
  51. 51.
    Cowan MM (1999) Plant products as antimicrobial agents. Clin Microbiol Rev 12:564–582CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Yigit D, Yigit N, Mavi A (2009) Antioxidant and antimicrobial activities of bitter and sweet apricot (Prunus armeniaca L.) kernels. Braz J Med Biol Res 42:346–352CrossRefPubMedGoogle Scholar
  53. 53.
    Alcerito T, Barbo FE, Negri G et al (2002) Foliar epicuticular wax of Arrabidaea brachypoda: flavonoids and antifungal activity. Biochem Syst Ecol 30:677–683CrossRefGoogle Scholar
  54. 54.
    Sohn HY, Son KH, Kwon CS et al (2004) Antimicrobial and cytotoxic activity of 18 prenylated flavonoids isolated from medicinal plants: Morus alba L., Morus mongolica Schneider, Broussnetia papyrifera (L.) Vent, Sophora flavescens Ait and Echinosophora koreensis Nakai. Phytomedicine 11:666–672CrossRefPubMedGoogle Scholar
  55. 55.
    Ragasa CY, Co AL, Rideout JA (2005) Antifungal metabolites from Blumea balsamifera. Nat Prod Res 19:231–237CrossRefPubMedGoogle Scholar
  56. 56.
    Rao MS, Duddeck H, Dembinski R (2002) Isolation and structural elucidation of 3,4′,5,7-tetraacetyl quercetin from Adina cordifolia (Karam ki Gaach). Fitoterapia 73:353–355CrossRefPubMedGoogle Scholar
  57. 57.
    Lalla RV, Patton LL, Dongari-Bagtzoglou A (2013) Oral candidiasis: pathogenesis, clinical presentation, diagnosis and treatment strategies. J Calif Dental Assoc 41:263–268Google Scholar
  58. 58.
    Serpa R, Franca EJ, Furlaneto-Maia L et al (2012) In vitro antifungal activity of the flavonoid baicalein against Candida species. J Med Microbiol 61:1704–1708CrossRefPubMedGoogle Scholar
  59. 59.
    Herrera CL, Alvear M, Barrientos L et al (2010) The antifungal effect of six commercial extracts of Chilean propolis on Candida spp. Ciencia E Invest Agraria 37:75–84CrossRefGoogle Scholar
  60. 60.
    Yousefbeyk F, Gohari AR, Hashemighahderijani Z et al (2014) Bioactive terpenoids and flavonoids from Daucus littoralis Smith subsp. hyrcanicus Rech. f, an endemic species of Iran. DARU J Pharmaceu Sci 22:12CrossRefGoogle Scholar
  61. 61.
    Wachter GA, Hoffmann JJ, Furbacher T et al (1999) Antibacterial and antifungal flavanones from Eysenhardtia texana. Phytochemistry 52:1469–1471CrossRefPubMedGoogle Scholar
  62. 62.
    Agnihotri VJK, ElSohly HN, Khan SI et al (2008) Constituents of Nelumbo nucifera leaves and their antimalarial and antifungal activity. Phytochem Lett 1:89–93CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Aguero MB, Svetaz L, Baroni V et al (2014) Urban propolis from San Juan province (Argentina): Ethnopharmacological uses and antifungal activity against Candida and dermatophytes. Ind Crops Prod 57:166–173CrossRefGoogle Scholar
  64. 64.
    Liu W, Li LP, Zhang JD et al (2014) Synergistic antifungal effect of glabridin and fluconazole. PLoS one 9:pe103442CrossRefGoogle Scholar
  65. 65.
    Greathouse GA, Walkins GH (1938) Berberine as a factor in the resistance of Mahonia trifoliate and M. swaseya to Phymatotrichum root-rot. Am J Bot 25:743–748CrossRefGoogle Scholar
  66. 66.
    Freile M, Giannini M, Sortino M et al (2006) Antifungal activity of aqueous extracts and of Berberine isolated from Berberis heterophylla. Acta Farm Bona 25:83–88Google Scholar
  67. 67.
    Dabur R, Chhillar AK, Yadav V et al (2005) In vitro antifungal activity of 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate, a dihydro–pyrrole derivative. J Med Microbiol 54:549–552CrossRefPubMedGoogle Scholar
  68. 68.
    Slobodníková L, Kost’álová D, Labudová D et al (2004) Antimicrobial activity of Mahonia aquifolium crude extract and its major isolated alkaloids. Phytother Res 18:674–676CrossRefPubMedGoogle Scholar
  69. 69.
    Bonvicini F, Antognoni F, Iannello C et al (2014) Relevant and selective activity of Pancratium illyricum L. against Candida albicans clinical isolates: a combined effect on yeast growth and virulence. BMC Complement Altern Med 14:409CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Klausmeyer P, Chmurny GN, McCloud TG et al (2004) A novel antimicrobial indolizinium alkaloid from Aniba panurensis. J Nat Prod 67:1732–1735CrossRefPubMedGoogle Scholar
  71. 71.
    Park Y, Choi BH, Kwak JS et al (2005) Kunitz-type serine protease inhibitor from potato (Solanum tuberosum L. cv. Jopung). J Agric Food Chem 53:6491–6496CrossRefPubMedGoogle Scholar
  72. 72.
    Giordani R, Regli P, Kaloustian J et al (2004) Antifungal effect of various essential oils against Candida albicans. Potentiation of antifungal action of amphotericin B by essential oil from Thymus vulgaris. Phytother Res 18:990–995CrossRefPubMedGoogle Scholar
  73. 73.
    Nakamura CV, Ishida K, Faccin LC et al (2004) In vitro activity of essential oil from Ocimum gratissimum L. against four Candida species. Res Microbiol 155:579–586CrossRefPubMedGoogle Scholar
  74. 74.
    Salgueiro LR, Piato E, Goncalves MJ et al (2004) Active antifungal substances from natural resources. Planta Med 70:572–575CrossRefPubMedGoogle Scholar
  75. 75.
    Cavaleiro C, Pinto E, Goncalves MJ et al (2006) Antifungal activity of Juniperus essential oils against dermatophyte, Aspergillus and Candida strains. J Appl Microbiol 100:1333–1338CrossRefPubMedGoogle Scholar
  76. 76.
    Hamza OJM, Beukel CJPB, Matee MIN et al (2006) Antifungal activity of some Tanzanian plants used traditionally for the treatment of fungal infections. J Ethnopharmacol 108:124–132CrossRefPubMedGoogle Scholar
  77. 77.
    Braga FG, Bouzada MLM, Fabri RL et al (2007) Antileishmanial and antifungal activity of plants used in traditional medicine in Brazil. J Ethnopharmacol 111:396–402CrossRefPubMedGoogle Scholar
  78. 78.
    Krisch J, Ordogh L, Galgoczy L et al (2009) Anticandidal effect of berry juices and extracts from Ribes species. Cent Eur J Biol 4:86–89Google Scholar
  79. 79.
    Bernardes I, Felipe Rodrigues MP, Bacelli GK et al (2012) Aloe vera extract reduces both growth and germ tube formation by Candida albicans. Mycoses 55:257–261CrossRefPubMedGoogle Scholar
  80. 80.
    Al Bagieh NH, Idowu A, Salako NO (1994) Effect of aqueous extract of miswak on the in vitro growth of Candida albicans. Microbios 80:107–113Google Scholar
  81. 81.
    Aqil F, Zahin M, Ahmad I (2010) Antifungal activity of medicinal plant extracts and phytocompounds: a review. In: Ahmad I et al (eds) Combating fungal infections. Springer, Berlin/Heidelberg, pp 449–484CrossRefGoogle Scholar
  82. 82.
    Sharanappa R, Vidyasagar GM (2013) Anti-candida activity of medicinal plants: a review. Inter J Pharm Pharm Sci 5:9–16Google Scholar
  83. 83.
    Rathod T, Padalia H, Chanda S (2015) The potential of plant extracts against multidrug resistant Candida species – a review. In: Mendez-Vilas A (ed) The battle against microbial pathogens: basic science, technological advances and educational programs, pp 246–256Google Scholar
  84. 84.
    Seleem D, Pardi V, Murata RM (2017) Review of flavonoids: a diverse group of natural compounds with anti- Candida albicans activity in vitro. Arch Oral Biol 76:76–83CrossRefPubMedGoogle Scholar
  85. 85.
    Katoch M, Salgotra A, Singh G (2014) Endophytic fungi found in association with Bacopa monnieri as potential producers of industrial enzymes and antimicrobial bioactive compounds. Braz Arch Biol Technol 57:714–722CrossRefGoogle Scholar
  86. 86.
    Sharma D, Roy V, Saraf A (2017) An update on phytochemicals analysis and medicinal prospects of Indian herb Withania somnifera. Ambient Sci 4:1–6CrossRefGoogle Scholar
  87. 87.
    Williamson EM (2001) Synergy and other interactions in phytomedicines. Phytomedicine 8:401–409CrossRefPubMedGoogle Scholar
  88. 88.
    Rakholiya K, Chanda S (2012) In vitro interaction of certain antimicrobial agent in combination with plant extracts against some pathogenic bacterial strains. Asian Pac J Trop Biomed 2:S1466–S1470CrossRefGoogle Scholar
  89. 89.
    Nahrstedt A, Butterweck V (2010) Lessons learned from herbal medicinal products: the example of St. John’s wort. J Nat Prod 73:1015–1021CrossRefPubMedGoogle Scholar
  90. 90.
    Wagner H, Merzenich GU (2009) Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine 16:97–110CrossRefPubMedGoogle Scholar
  91. 91.
    Chanda S, Rakholiya K, Dholakia K et al (2013) Antimicrobial, antioxidant and synergistic properties of two nutraceutical plants: Terminalia catappa L. and Colocasia esculenta L. Turk J Biol 37:81–91Google Scholar
  92. 92.
    Avijgan M, Mahboubi M, Nasab MM et al (2014) Synergistic activity between Echinophora platyloba DC ethanolic extract and azole drugs against clinical isolates of Candida albicans from women suffering chronic recurrent vaginitis. J de Mycol Med 24:112–116CrossRefGoogle Scholar
  93. 93.
    Santos KKA, Matias EFF, Sobral-Souza CE et al (2013) Trypanocide, cytotoxic, and anti-candida activities of natural products: Hyptis martiusii Benth. Eur J Integr Med 5:427–431CrossRefGoogle Scholar
  94. 94.
    Castano VT, Royero JC, Londono BZ et al (2011) Anti-Candida albicans activity, cytotoxicity and interaction with antifungal drugs of essential oils and extracts from aromatic and medicinal plants. Asocia Colom De Infectol 15:160–167Google Scholar
  95. 95.
    Wagner H (2006) Multitarget therapy–the future of treatment for more than just functional dyspepsia. Phytomedicine 13:122–129CrossRefPubMedGoogle Scholar
  96. 96.
    Pankey G, Ashcraft D, Patel N (2005) In vitro synergy of daptomycin plus rifampin against Enterococcus faecium resistant to both linezolid and vancomycin. Antimicrob Agents Chemother 49:5166–5168CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Botany, Mahila MahavidyalayaBanaras Hindu UniversityVaranasiIndia

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