Abstract

Uçucu yağların standart antifungal maddeler ile kombinasyonları, sentetik ilaçların olumsuz etkilerini azaltabilir ve kandidiyaz dahil olmak üzere çeşitli patolojilere karşı alternatif bir yaklaşım olarak kullanılabilir. Bu çalışmanın amacı, Farmakope kalitesindeki Lavanta (Lavandula angustifolia Miller) uçucu yağlarının ketokonazol ile kombinasyonlarının patojen Candida albicans ATCC 10231, C. krusei NRRL Y-7179 ve C. glabrata ATCC 66032 suşlarına karşı antikandidal  etkinliğini belirlemektir. İncelenen uçucu yağların kimyasal  içerikleri hem gaz kromatografisi/alev iyonlaşma dedektörü (GK / AİD) hem de gaz kromatografisi/kütle spektrometresi (GK/KS) yöntemleriyle belirlenmiştir. Esansiyel yağların antikandidal aktiviteleri, mikrodilüsyon metodu ile in vitro olarak incelenmiştir. Lavanta uçucu yağları ve ketokonazol kombinasyon çalışmaları dama tahtası yöntemi kullanılarak test edilmiştir.  Lavanta uçucu yağları ile ketokonazol kombinasyon çalışması sonuçları, test edilen tüm Candida suşlarına karşı “aditif” ve “indiferent” etkili olduğu görülmüştür. Sonuç olarak, lavanta uçucu yağlarının ketokonazol kombinasyonu ile gözlemlenen etkiler, patojenik Candida suşlarına karşı kullanımda etkili olabilir.

Project Number

Project: 1301S005

EVALUATION OF ANTICANDIDAL EFFECTS OF ESSENTIAL OILS OF COMMERCIAL LAVENDER (Lavandula angustifolia Miller) IN COMBINATION WITH KETOCONAZOLE AGAINTS SOME Candida Berkhout STRAINS

Abstract

Application of combination studies with essential oils and standard antifungal drugs may reduce adverse effects of synthetic drugs and serve as alternative approach against various pathologies including candidiasis. The aim of the present study was to determine the interaction of two commercial lavender (Lavandula angustifolia Miller) essential oils in combination with ketoconazole against clinical and standard strains of the human pathogens Candida albicans ATCC 10231, C. krusei NRRL Y-7179 and C. glabrata ATCC 66032. The chemical compositions of the investigated essential oils were confirmed both by gas chromatography/flame ionization detector (GC/FID) and gas chromatography/mass spectrometry (GC/MS) methods. Anticandidal activities of the essential oils were screened in vitro by the microdilution method. The resulting interaction of combining lavender essential oils and ketoconazole was tested using the checkerboard method. The results showed that the interaction between essential oils and ketoconazole revealed additive and indifferent effects against the tested strains. In conclusion, the effects observed by the combination of lavender essential oils and ketoconazole may be encouraging to be used against pathogenic Candida strains.

Keywords

• Lavender (Lavandula angustifolia),Candida albicans,Candida glabrata,Ketoconazole,Candida krusei

Supporting Institution

Anadolu University Scientific Research

Project Number

Project: 1301S005

Thanks

The authors would like to thank Anadolu University Scientific Research Project: 1301S005 for the financial support.

References

1. 1. Amber, K., Aijaz, A., Immaculata, X., Luqman, K.A. & Nikhat, M. 2010. Anticandidal effect of Ocimum sanctum essential oil and its synergy with fluconazole and ketoconazole. Phytomedicine, 17(12): 921-925.
2. 2. Akortha, E.E., Nwaugo, V.O., & Chikwe, N.O. 2009. Antifungal resistance among Candida species from patients with genitourinary tract infection isolated in Benin City, Edo state, Nigeria. African Journal of Microbiology Research, 3(11): 694-699.
3. 3. Bassole I.H.N. & Juliani, H.R. 2012. Essential oils in combination and their antimicrobial properties. Molecules, 17(4): 3989-4006.
4. 4. Burt, S. 2004. Essential oils: their antibacterial properties and potential applications in foods-a review. International Journal of Food Microbiology, 94(3), 223-253.
5. 5. Casalinuovo, I.A., Di Francesco, P. & Garaci, E. 2004. Fluconazole resistance in Candida albicans: a review of mechanisms. European Review for Medical and Pharmacological Sciences, 8: 69-78.
6. 6. Cassella, S., Cassella, J.P. & Smith, I. 2002. Synergistic antifungal activity of tea tree (Melaleuca alternifolia) and lavender (Lavandula angustifolia) essential oils against dermatophyte infection. International Journal of Aromatherapy, 12(1): 2-15.
7. 7. Cavanagh, H.M.A. & Wilkinson, J.M. 2002. Biological activities of lavender essential oil. Phytotherapy Research, 16(4): 301-308.
8. 8. Chen, Y., Zeng, H., Tian, J., Ban, X., Ma, B. & Wang, Y. 2013. Antifungal mechanism of essential oil from Anethum graveolens seeds against Candida albicans. Journal of medical microbiology, 62(8): 1175-1183.

9. 9. Clinical and Laboratory Standards Institute (CLSI). 2002. Reference Method for broth dilution antifungal susceptibility testing of yeast approved standard, M27-A2. 940 West Valley Road, Wayne, Pennsylvania, USA: Clinical and Laboratory Standards Institute.
10. 10. Cleff, M.B., Meinerz, A.R., Xavier, M., Schuch, L.F., Meireles, M.C.A., Rodrigues, M.R.A. & Mello, J.R.B.D. 2010. In vitro activity of Origanum vulgare essential oil against Candida species. Brazilian Journal of Microbiology, 41(1): 116-123.
11. 11. Cottarel, G. & Wierzbowski, J. 2007. Combination drugs, an emerging option for antibacterial therapy. Trends in Biotechnology, 25(12): 547-555.
12. 12. Cox, S.D., Mann, C.M., Markham, J.L., Bell, H.C., Gustafson, J.E., Warmington, J.R. & Wyllie, S.G. 2000. The mode of antimicrobial action of the essential oil of Melaleuca alternifolia (tea tree oil). Journal of Applied Microbiology, 88(1): 170-175.
13. 13. Danh, L.T., Triet, N.D.A., Zhao, J., Mammucari, R. & Foster, N. 2013. Comparison of chemical composition, antioxidant and antimicrobial activity of lavender (Lavandula angustifolia L.) essential oils extracted by supercritical CO2, hexane and hydrodistillation. Food and Bioprocess Technology, 6(12): 3481-3489.
14. 14. Dauria, F.D., Tecca, M., Strippoli, V., Salvatore, G., Battinelli, L. & Mazzanti, G. 2005. Antifungal activity of Lavandula angustifolia essential oil against Candida albicans yeast and mycelial form. Medical Mycology, 43(5): 391-396.
15. 15. De Rapper, S., Kamatou, G., Viljoen, A. & van Vuuren, S. 2013. The in vitro antimicrobial activity of Lavandula angustifolia essential oil in combination with other aroma-therapeutic oils. Evidence-Based Complementary and Alternative Medicine, 2013: 852049.
16. 16. De Rapper, S., Viljoen, A. & van Vuuren, S. 2016. The in vitro antimicrobial effects of Lavandula angustifolia essential oil in combination with conventional antimicrobial agents. Evidence-Based Complementary and Alternative Medicine, 2016: 2752739.
17. 17. ESO 2000, 1998. The Complete database of essential oils. The Netherlands: Boelens Aroma Chemical Information Service.
18. 18. Fismer, K. L., & Pilkington, K. 2012. Lavender and sleep: A systematic review of the evidence. European Journal of Integrative Medicine, 4(4), 436-447.
19. 19. Göger, G., Demirci, B., Ilgın, S. & Demirci, F. 2018. Antimicrobial and toxicity profiles evaluation of the chamomile (Matricaria recutita L.) essential oil combination with standard antimicrobial agents. Industrial Crops and Products, 120: 279-285.
20. 20. Hasanbeigi, A., Shahmir, P. & Amraie, M. 2015. Study of antifungal resistance of Candida types against some of common antifungal drugs. International Journal of Pharmaceutical Sciences Research, 6(2): 241.
21. 21. Hosseinzadeh, S., Jafarikukhdan, A., Hosseini, A., & Armand, R. 2015. The application of medicinal plants in traditional and modern medicine: a review of Thymus vulgaris. International Journal of Clinical Medicine, 6(09), 635.
22. 22. Joulain D. & Koenig, W.A. 1998. The Atlas of spectra data of sesquiterpene hydrocarbons. Hamburg: EB-Verlag.
23. 23. Jamil, B., Bokhari, M.T.M., Saeed, A., Bokhari, M.Z.M., Hussain, Z., Khalid, T. & Abbasi, S. A. 2017. Candidiasis: Prevalence and resistance profiling in a tertiary care hospital of Pakistan. JPMA. The Journal of the Pakistan Medical Association, 67(5): 688.
24. 24. Jianu, C., Pop, G., Gruia, A.T. & Horhat, F.G. 2013. Chemical composition and antimicrobial activity of essential oils of lavender (Lavandula angustifolia) and lavandin (Lavandula x intermedia) grown in Western Romania. International Journal of Agriculture and Biology, 15(4): 772-776.
25. 25. Kırımer, N., Mokhtarzadeh, S., Demirci, B., Goger, F., Khawar, K.M., & Demirci, F. 2017. Phytochemical profiling of volatile components of Lavandula angustifolia Miller propagated under in vitro conditions. Industrial Crops and Products, 96: 120-125.
26. 26. Koenig, W.A., Joulain, D. & Hochmuth, D.H. 2001. Terpenoids and related constituents of essential oils. Library of MassFinder 2.1. Hamburg.
27. 27. Khan, A., Ahmad, A., Akhtar, F., Yousuf, S., Xess, I., Khan, L.A., & Manzoor, N. 2010. Ocimum sanctum essential oil and its active principles exert their antifungal activity by disrupting ergosterol biosynthesis and membrane integrity. Research in Microbiology, 161(10): 816-823.
28. 28. Lodhia, M.H., Bhatt, K.R. & Thaker, V.S. 2009. Antibacterial activity of essential oils from palmarosa, evening primrose, lavender and tuberose. Indian Journal of Pharmaceutical Sciences, 71(2): 134.
29. 29. Magill, S.S., Shields C., Sears, C.L., Choti, M. & Merz, W.G. 2006. Triazole cross-resistance among Candida spp.: Case report, occurrence among bloodstream isolates, and implications for antifungal therapy. Journal of Clinical Microbiology, 44: 529-535.
30. 30. Metzger, S. & Hofmann, H. 1997. Fluconazole-resistant Candida species from HIV infected patients with recurrent Candida stomatitis: cross resistance to itraconazole and ketoconazole. Mycoses, 40: 56-63.
31. 31. McLafferty, F.W. & Stauffer, D.B. 1989. The Wiley/NBS Registry of Mass Spectral Data. J. Wiley and Sons, New York.
32. 32. Pinto, E., Pina-Vaz, C., Salgueiro, L., Gonçalves, M. J., Costa-de-Oliveira, S., Cavaleiro, C. & Martinez-de-Oliveira, J. 2006. Antifungal activity of the essential oil of Thymus pulegioides on Candida, Aspergillus and dermatophyte species. Journal of Medical Microbiology, 55(10): 1367-1373.
33. 33. 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.
34. 34. Pfaller, M.A., Diekema, D.J., Gibbs, D.L., Newell, V.A., Nagy, E. & Dobiasova, S. 2008. Global Antifungal Surveillance Group. 2008. Candida krusei, a multidrug-resistant opportunistic fungal pathogen: geographic and temporal trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005. Journal of Clinical Microbiology, 46(2): 515-521.
35. 35. Pozzatti, P., Loreto, E.S., Lopes, P.G.M., Athayde, M.L., Santurio, J.M. & Alves, S.H. 2010. Comparison of the susceptibilities of clinical isolates of Candida albicans and Candida dubliniensis to essential oils. Mycoses, 53(1): 12-15.
36. 36. Samber, N., Khan, A., Varma, A., & Manzoor, N. 2015. Synergistic anti-candidal activity and mode of action of Mentha piperita essential oil and its major components. Pharmaceutical Biology, 53(10): 1496-1504.
37. 37. Sanglard, D. & Odds, F. C. 2002. Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences. The Lancet Infectious Diseases, 2(2): 73-85.
38. 38. Sardi, J.C.O., Scorzoni, L., Bernardi, T., Fusco-Almeida, A.M. & Mendes Giannini, M.J.S. 2013. Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options. Journal of Medical Microbiology, 62: 10-24.
39. 39. Shin, S. & Kang, C.A. 2003. Antifungal activity of the essential oil of Agastache rugosa Kuntze and its synergism with ketoconazole. Letters in Applied Microbiology, 36: 111-115.
40. 40. Shin, S. 2003. Anti-Aspergillus activities of plant essential oils and their combination effects with ketoconazole or amphotericin B. Archieves of Pharmacal Research, 26: 389-393.
41. 41. Shellie, R., Mondello, L., Marriott, P. & Dugo, G. 2002. Characterisation of lavender essential oils by using gas chromatography–mass spectrometry with correlation of linear retention indices and comparison with comprehensive two-dimensional gas chromatography. Journal of Chromatography A, 970(1-2): 225-234.
42. 42. Sokovic, M., Glamoclija, J., Marin, P.D., Brkic, D. & Van Griensven, L.J. 2010. Antibacterial effects of the essential oils of commonly consumed medicinal herbs using an in vitro model. Molecules, 15(11): 7532-7546.
43. 43. Stringaro, A., Vavala, E., Colone, M., Pepi, F., Mignogna, G., Garzoli, S. & Angiolella, L. 2014. Effects of Mentha suaveolens essential oil alone or in combination with other drugs in Candida albicans. Evidence-Based Complementary and Alternative Medicine, Volume 2014, Article ID 125904, 9 pp.
44. 44. Stanojevic, D., Comic, L., Stefanovic, O. & Solujic-Sukdolak, S. 2010. In vitro synergistic antibacterial activity of Salvia officinalis L. and some preservatives. Archives of Biological Sciences Belgrade, 62(1): 175-83.
45. 45. Vuuren, S.V. & Viljoen, A.M. 2007. Antimicrobial activity of limonene enantiomers and 1, 8‐cineole alone and in combination. Flavour and Fragrance Journal, 22(6): 540-544.
46. 46. Van Vuuren, S.F., Suliman, S. & Viljoen, A.M. 2009. The antimicrobial activity of four commercial essential oils in combination with conventional antimicrobials. Letters in Applied Microbiology, 48(4): 440-446.
47. 47. Yap, P.S.X., Krishnan, T., Yiap, B.C., Hu, C.P., Chan, K.G. & Lim, S.H.E. 2014. Membrane disruption and anti‐quorum sensing effects of synergistic interaction between Lavandula angustifolia (lavender oil) in combination with antibiotic against plasmid‐conferred multi‐drug‐resistant Escherichia coli. Journal of Applied Microbiology, 116(5): 1119-1128.
48. 48. Zomorodian, K., Rahimi, M.J., Pakshir, K., Motamedi, M., Ghiasi, M.R. & Rezashah, H. 2011. Determination of antifungal susceptibility patterns among the clinical isolates of Candida species. Journal of Global Infectious Diseases, 3(4): 357.