Anti-Candida Activity of Cinnamon Inhibition of Virulence Factors of Clinical Strains of Candida albicans by Essential Oil of Cinnamomum zeylanicum
Essential oil of cinnamon (Cinnamomum zeylanicum) has been used in medicine and food additives. In the present work, we examined the antifungal activity of essential oil extracted from C. zeylanicum bark against oral opportunistic strains of Candida albicans. In addition, we verified the capability of this essential oil to inhibit fungal adhesion to buccal epithelial cells (BECs), germ tube formation, and proteinase activities. Cinnamon oil presented minimum inhibitory concentration (MIC) values that ranged from 31.2 to 125 µg mL-1 against the isolates of the tested C. albicans strains. Cinnamon essential oil could inhibit the adhesion of C. albicans to BECs for all of the isolates tested in present study. The C. albicans strains showed inhibited proteinase production after treatment with cinnamon oil, based on the MIC values determined for each C. albicans strain. Cinnamon oil was also able to inhibit the germ tube formation of all isolates of C. albicans, with the percentage of inhibition ranging from 44.7 to 82.9%. Our results showed that cinnamon oil presented potent antifungal activity and the ability to inhibit virulence factors of oral pathogenic strains of C. albicans.
Adhesion; Cinnamon oil; Germ tube; Proteinase.
Carvalho, P.C.L., de Sa, N.P., Lacerda, I.C.A., Pataro, C., Rosa, L.H., Alves, R.S., Lyon, J.P., Rosa, C.A., Johann, S., 2018. Anti-Candida Activity of Cinnamon Inhibition of Virulence Factors of Clinical Strains of Candida albicans by Essential Oil of Cinnamomum zeylanicum. PSM Microbiol. 3(1): 4-12.
Essential oils are volatile, natural, complex compounds with a strong scent that are produced as secondary metabolites by aromatic plants (Bakkali et al., 2008). The genus Cinnamomum comprises approximately 250 species that are widely distributed in China, India, and Australia (Jayaprakasha et al., 2003). Cinnamomum zeylanicum (cinnamon) bark is used worldwide as a spice. Cinnamon is employed in cooking as a condiment and flavoring material and is largely used in the preparation of certain desserts, chocolate, spicy candies, tea, hot cocoa, and liqueurs (Shan et al., 2005; Sathishkumar et al., 2009). Cinnamon oil from C. zeylanicum bark commonly presents antimicrobial and antifungal properties that have drawn great attention from many researchers (Singh et al., 1995; Hili et al., 1997; Ouattara et al., 1997; Park et al., 2000; Chang et al., 2001; Kim et al., 2004).
Increased fungal resistance to classical drugs, drug toxicity, and the costs involved justify the search for new approaches to developing antifungal drugs. Among those new approaches, essential oils are one of the most promising groups of natural compounds for the prevention and treatment of fungal infection (Silva et al., 2011). Essential oils derived from aromatic plants are well known in traditional medicine as antimicrobial agents and are characterized as food and feed preservatives, as inhibitors of mycotoxin production, and as antimycotic agents (Azzouz and Bullerman, 1982; Knobloch et al., 1989; Guimarães et al., 2010).
Oropharyngeal candidiasis (OPC) is the most common opportunistic infection in immunocompromised patients. Although Candida albicans is a well-known etiological agent of OPC, in addition to being responsible for most yeast infections in humans, several other emerging Candida species, such as C. dubliniensis, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis, have also been associated with this disease (Horn et al., 2009).
Considering increasing pathogen resistance and the toxicity of classical antifungal drugs, investigations of the antimicrobial activities, modes of action, and potential uses of essential oils and their components have garnered new attention in the search for new antimicrobial compounds (Silva et al., 2011). The development of new drugs with improved efficacy and safety or alternative modes of fighting infections are needed. Recent developments in fungal genomics have provided unprecedented opportunities to identify new antifungal drug targets and accomplish subsequent disease control. Targeting virulence and pathogenicity factors should provide alternatives to conventional drug targets and provide new options for the development of potential antifungal therapeutics for the treatment and/or prevention of localized or systemic fungal disease (Gauwerky et al., 2009). According Alksne and Projan (2001), the idea is no longer to try to kill the microorganism acting as a pathogen by any means, but rather to hinder the organism from causing any harm to the host.
In this work, we examined the effects of essential oil extracted from C. zeylanicum against 28 strains of C. albicans isolated from OPC. We also verified the ability of this essential oil to inhibit the germ tube formation, adhesion to buccal epithelial cells (BECs), and proteinase activity of the tested C. albicans isolates.
Alksne, L.E., Projan, S.J., 2001. Bacterial virulence as a target for antimicrobial chemotherapy. Curr. Opin. Biotechnol., 1: 625-636.
Azzouz, M.A., Bullerman, L.B., 1982. Comparative antimycotic effects of selected herbs, spices, plant components and commercial antifungal agents. J. Food Prot. 45: 1298-1301.
Bakkali, F., Averbeck, S., Averbeck, D., Idaomar, M., 2008. Biological effects of essential oils: a review. Food Chem. Toxicol., 46: 446-475.
Brayman, T.G., Wilks, J.W., 2003. Sensitive assay for antifungal activity of glucan synthase inhibitors that uses germ tube formation in Candida albicans as an end point. Antimicrob. Agents Chemother., 47: 3305-3310.
Cassone, A., De Bernardis, F., Mondello, F., Ceddia, T., Agatensi, L., 1987. Evidence for a correlation between proteinase secretion and vulvovaginal candidosis. J. Infect. Dis., 156: 777-783.
Calderone, R.A., Fonzi, W.A., 2001. Virulence factors of Candida albicans. Trends Microbiol., 9: 327-335.
Chang, S.T., Chen, P.F., Chang, S.C., 2001. Antibacterial activity of leaf essential oils and their constituents from Cinnamomum osmophloeum. J. Ethnopharmacol., 77: 123-127.
Clinical and Laboratory Standards Institute (CLSI) (2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeast; Approved Standard- Third edition. CLSI Document M27-S3. Clinical and Laboratory Standard Institute, Waine, PA.
Ellepola, A.N.B., Samaranayake, L.P., 1998a. Adhesion of oral C. albicans to human buccal epithelial cells following limited exposure to antifungal agents. J. Oral Pathol. Med., 27: 325-332.
Ellepola, A.N.B., Samaranayake, L.P., 1998b. Adhesion of oral Candida albicans isolates to denture acrylic following limited exposure to antifungal agents. Arch. Oral Biol., 43: 999-1007.
Enwuru, C.A., Ogunledun, A., Idika, N., Enwuru, N.V., Ogbonna, F., Aniedobe, M., et al., 2008. Fluconazole resistant opportunistic oro-pharyngeal Candida and non Candida yeast-like isolates from HIV infected patients attending ARV clinics in Lagos, Nigeria. Afr. Health Sci., 8: 142-148.
Gabler, I.G., Barbosa, A.C., Vilella, R.R., Lyon, S., Rosa, C.A., 2008. Incidence and Anatomic Localization of Oral Candidiasis in Patients with Aids Hospitalized in a Public Hospital in Belo Horizonte, MG, Brazil. J. Appl. Oral Sci., 16: 247-250.
Gauwerky. K., Borelli, C., Korting, H.C., 2009. Targeting virulence: a new paradigm for antifungals. Drug Discov. Today, 14: 214-222.
Guimarães, L.G., Cardoso, M.G., Zacaroni, L.M., Lima, R.K., Pimentel, F.A., Morais, A.R., 2008. Influência da luz e da temperatura sobre a oxidação do óleo essencial de capim-limão (Cymbopogon citratus (D.C) Stapf). Quím. Nova, 31: 1476-1480.
Guimarães, R., Sousa, M.J., Ferreira, I.C.F.R., 2010. Contribution of essential oils and phenolics to the antioxidant properties of aromatic plants. Ind. Crop. Prod., 32: 152-156.
Hector, R.F., 1993. Compounds active against cell walls of medically important fungi. Clin. Microbiol. Rev.,6: 1-21.
Hili, P., Evans, C.S., Veness, R.G., 1997. Antimicrobial action of essential oils: the effect of dimethylsulphoxide on the activity of cinnamon oil. Lett. Appl. Microbiol., 24: 269-275.
Horn, D.L., Neofytos, D., Anaissie, E.J., Fishman, J.A., Steinbach, W.J., Olyaei, A.J., et al., 2009. Epidemiology and outcomes of candidemia in 2019 patients: data from the Prospective Antifungal Therapy Alliance Registry. Clin. Infect. Dis., 48: 1695-703.
Hube, B., Naglik, J., 2001. Candida albicans proteinases: resolving the mystery of a gene family. Microbiol., 147: 1997-2005.
Jayaprakasha, G.K., Rao, L.J.M., Sakariah, K.K., 2003. Volatile constituents from Cinnamomum zeylanicum fruit stalks and their antioxidant activities. J Agric. Food Chem., 51: 4344-4348.
Johann, S., Silva, D.L., Martins, C.V.B., Zani, C.L., Pizzolatti, M.G., Resende, M.A., 2008. Inhibitory effect of extracts from Brazilian medicinal plants on the adhesion of Candida albicans to buccal epithelial cells. World J. Microb. Biot., 24: 2459-2464.
Johann, S., Soldi, C., Lyon, J.P., Pizzolatti, M.G., Resende, M.A., 2007. Antifungal activity of the amyrin derivatives and in vitro inhibition of Candida albicans adhesion to human epithelial cells. Lett. Appl. Microbiol. 45: 148-153.
Kim, H.O., Park, S.W., Park, H.D., 2004. Inactivation of Escherichia coli O157:H7 by cinnamic aldehyde purified from Cinnamomum cassia shoot. Food Microbiol., 21: 105-110.
Kimura, L.H., Pearsall, N.N. 1978. Adherence of Candida albicans to human buccal epthelial cells. Infect. Imun., 21: 64-68.
Knobloch, K., Pauli, A., Iberl, B., Weigand, H., Weis, N., 1989. Antibacterial and antifungal properties of essential oil components. J. Essent. Oil Res., 1: 119-28.
Lyon, J.P., Resende, M.A., 2006. Correlation between adhesion, enzyme production, and susceptibility to fluconazole in Candida albicans obtained from denture wearers. Oral Surg. Oral Med., 102: 632-638.
Ouattara, B., Simard, R.E., Holley, R.A., Piette, G.J.P., Begin, A., 1997. Antibacterial activity of selected fatty acids and essential oils against six meat spoilage organisms. Int. J. Food Microbiol., 37:155-162.
Park, I.K., Lee, H.S., Lee, S.G., Park, J.D., Ahn, Y.J., 2000. Insecticidal and fumigant activities of Cinnamomum cassia barkderived materials against Mechoris ursulus (Coleoptera: Attelabidae). J. Agric. Food Chem., 48: 2528-2531.
Sathishkumar, M., Sneha, K., Won, S.W., Cho, C.W., Kim, S., Yun, Y.S., 2009. Cinnamon zeylanicum bark extract and powder mediated green synthesis of nano-crystalline silver particles and its bactericidal activity. Colloid Surf. B., 73: 332-338.
Shan, B., Cai, Y.Z., Sun, M., Corke, H.,2005. Antioxidant capacity of 26 spice extracts and characterization of their phenolic constituents. J. Agric. Food Chem., 53: 7749-7759.
Shreaz, S., Bhatia, R., Khan, N., Maurya, I.K., Ahmad, S.I., Muralidhar, S., Manzoor, N., Khan, L.A., 2012. Cinnamic aldehydes affect hydrolytic enzyme secretion and morphogenesis in oral Candida isolates. Microb. Pathogenesis, 52: 251-258.
Silva, F., Ferreira, S., Duarte, A., Mendonça, D.I., Domingues, F.C., 2011. Antifungal activity of Coriandrum sativum essential oil, its mode of action against Candida species and potential synergism with amphotericin B. Phytomedicine,19: 42-47.
Singh, H.B., Srivastava, M., Singh, A.B., Srivastava, A.K., 1995. Cinnamon bark oil, a potent fungitoxicant against fungi causing respiratory tract mycoses. Allergy, 50: 995-999.
Unlu, M., Ergene, E., Unlu, G.V., Zeytinoglu, H.S., Vural, N., 2010. Composition, antimicrobial activity and in vitro cytotoxicity of essential oil from Cinnamomum zeylanicum Blume (Lauraceae). Food Chem. Toxicol., 48: 3274-3280.
Wang, R., Wang, R., Yang, B., 2009. Extraction of essential oils from five cinnamon leaves and identification of their volatile compound compositions. Innov. Food Sci. Emerg. Technol., 10: 289-292.
Author: Priscila Cordeiro de Lima Carvalho, Nívea Pereira de Sá, Inayara Cristina Alves Lacerda, Carla Pataro, Luiz Henrique Rosa, Rodrigo Silva Alves, Juliana Pereira Lyon, Carlos Augusto Rosa, Susana Johann
Published Online: Feb. 16, 2018
Article Type: Research Article