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Nerolidol, the main constituent of Piper aduncum essential oil, has anti-Leishmania braziliensis activity

Published online by Cambridge University Press:  09 May 2017

LIGIA FERNANDA CEOLE ,
MARIA DAS GRAÇAS CARDOSO  and
MAURILIO JOSÉ SOARES
LIGIA FERNANDA CEOLE
Affiliation:
Laboratory of Cell Biology, Carlos Chagas Institute/Fiocruz-PR, Rua Prof. Algacyr Munhoz Mader 3775 Bloco C, Cidade Industrial, 81350-010 Curitiba-PR, Brazil
MARIA DAS GRAÇAS CARDOSO
Affiliation:
Department of Chemistry, Federal University of Lavras, Av. Doutor Sylvio Menicucci 1001, Kennedy, 37200-000 Lavras-MG, Brazil
MAURILIO JOSÉ SOARES*
Affiliation:
Laboratory of Cell Biology, Carlos Chagas Institute/Fiocruz-PR, Rua Prof. Algacyr Munhoz Mader 3775 Bloco C, Cidade Industrial, 81350-010 Curitiba-PR, Brazil
*
*Corresponding author: Laboratório de Biologia Celular, Instituto Carlos Chagas/Fiocruz-PR, Rua Prof. Algacyr Munhoz Mader 3775, Cidade Industrial 81350-010 Curitiba, PR, Brazil. E-mail: [email protected]
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Summary

Leishmania (Viannia) braziliensis is a protozoan that causes mucocutaneous leishmaniasis, which is an infectious disease that affects more than 12 million people worldwide. The available treatment is limited, has side-effects or is inefficient. In a search for alternative compounds of natural origin, we tested the microbicidal activity of Piper aduncum essential oil (PaEO) on this parasite. Our data showed that PaEO had an inhibitory effect on the growth of L. braziliensis promastigotes with an IC50/24 h=77·9 µg mL−1. The main constituent (nerolidol: 25·22%) presented a similar inhibitory effect (IC50/24 h = 74·3 µg mL−1). Ultrastructural observation of nerolidol-treated parasites by scanning and transmission electron microscopies revealed cell shrinkage and morphological alterations in the mitochondrion, nuclear chromatin and flagellar pocket. Flow cytometry analysis showed a reduction in the cell size, loss of mitochondrial membrane potential, phosphatidylserine exposure and DNA degradation, which when associated with the morphological changes indicated that nerolidol induced incidental cell death in the L. braziliensis promastigotes. The results presented here indicate that nerolidol derivatives are promising compounds for further evaluation against Leishmania parasites.

Keywords

cell deathessential oilLeishmania braziliensisnerolidolPiper aduncum
Type
Research Article
Information
Parasitology , Volume 144 , Issue 9 , August 2017 , pp. 1179 - 1190
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Copyright
Copyright © Cambridge University Press 2017 

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References

REFERENCES

Ali, B., Al-Wabel, N. A., Shams, S., Ahamad, A., Khan, S. A. and Anwar, F. (2015). Essential oils used in aromatherapy: a systemic review. Asian Pacific Journal of Tropical Biomedicine 5, 601–611.CrossRefGoogle Scholar
Anthony, J. P., Fyfe, L. and Smith, H. (2005). Plant active components - a resource for antiparasitic agents? Trends in Parasitology 21, 462–468.CrossRefGoogle ScholarPubMed
Araújo, M. J., Câmara, C. A., Born, F. S., Moraes, M. M. and Badji, C. A. (2012). Acaricidal activity and repellency of essential oil from Piper aduncum and its components against Tetranychus urticae . Experimental & Applied Acarology 57, 139–155.CrossRefGoogle ScholarPubMed
Arevalo, J., Ramirez, L., Adaui, V., Zimic, M., Tulliano, G., Miranda-Verástegui, C., Lazo, M., Loayza-Muro, R., De Doncker, S., Maurer, A., Chappuis, F., Dujardin, J. C., Llanos-Cuentas, A. and Llanos-Cuentas, A. (2007). Influence of Leishmania (Viannia) species on the response to antimonial treatment in patients with American tegumentary leishmaniasis. Journal of Infectious Diseases 195, 1846–1851.CrossRefGoogle ScholarPubMed
Arroyo-Acevedo, J., Chávez-Asmat, R. J., Anampa-Guzmán, A., Donaires, R. and Ráez-Gonzáles, J. (2015). Protective effect of Piper aduncum capsule on DMBA-induced breast cancer in rats. Breast Cancer: Basic and Clinical Research 9, 41–48.Google ScholarPubMed
Arruda, D. C., D'Alexandri, F. L., Katzin, A. M. and Uliana, S. R. (2005). Antileishmanial activity of the terpene nerolidol. Antimicrobial Agents and Chemotherapy 49, 1679–1687.CrossRefGoogle ScholarPubMed
Awasthi, B. P., Kathuria, M., Pant, G., Kumari, N. and Mitra, K. (2016). Plumbagin, a plant-derived naphthoquinone metabolite induces mitochondria mediated apoptosis-like cell death in Leishmania donovani: an ultrastructural and physiological study. Apoptosis 21, 941–953.CrossRefGoogle ScholarPubMed
Basano, S. A. and Camargo, L. M. A. (2004). Leishmaniose tegumentar americana: histórico, epidemiologia e perspectivas de controle. Revista Brasileira de Epidemiologia 7, 328–337.CrossRefGoogle Scholar
Bernuci, K. Z., Iwanaga, C. C., Fernandez-Andrade, C. M. M., Lorenzetti, F. B., Torres-Santos, E. C., Faiões, V. S., Gonçalves, J. E., Amaral, W., Deschamps, C., Scodro, R. B. L., Cardoso, R. F., Baldin, V. P. and Cortez, D. A. G. (2016). Evaluation of chemical composition and antileishmanial and antituberculosis activities of essential oils of Piper species. Molecules 21, 1698.CrossRefGoogle ScholarPubMed
Brajtburg, J. and Bolard, J. (1996). Carrier effects on biological activity of amphotericin B. Clinical Microbiology Reviews 9, 512–531.CrossRefGoogle ScholarPubMed
Brasil. Ministério da Saúde (2009). Guia de Vigilância Epidemiológica, 7th Edn. Ministério da Saúde, Brasília DF, Brazil, 816 p.Google Scholar
Camargos, H. S., Moreira, R. A., Mendanha, S. A., Fernandes, K. S., Dorta, M. L. and Alonso, A. (2014). Terpenes increase the lipid dynamics in the Leishmania plasma membrane at concentrations similar to their IC50 values. PLoS ONE 9, e104429.CrossRefGoogle ScholarPubMed
Capello, T. M., Martins, E. G., Farias, C. F., Figueiredo, C. R., Matsuo, A. L., Passero, L. F., Oliveira-Silva, D., Sartorelli, P. and Lago, J. H. (2015). Chemical composition and in vitro cytotoxic and antileishmanial activities of extract and essential oil from leaves of Piper cernuum . Natural Product Communications 10, 285–288.CrossRefGoogle ScholarPubMed
Carmo, D. F. M., Amaral, A. C., Machado, G. M., Leon, L. L. and Silva, J. R. (2012). Chemical and biological analyses of the essential oils and main constituents of Piper species. Molecules 17, 1819–1829.CrossRefGoogle Scholar
Chouhan, G., Islamuddin, M., Want, M. Y., Ozbak, H. A., Hemeg, H. A., Sahal, D. and Afrin, F. (2015). Leishmanicidal activity of Piper nigrum bioactive fractions is interceded via apoptosis in vitro and substantiated by Th1 immunostimulatory potential in vivo . Frontiers in Microbiology 6, 1368.CrossRefGoogle ScholarPubMed
Cook, S. (2016). The Forest of the Lacandon Maya: An Ethnobotanical Guide. Springer, New York, USA.CrossRefGoogle Scholar
Corpas-López, V., Merino-Espinosa, G., Díaz-Sáez, V., Morillas-Márquez, F., Navarro-Moll, M. C. and Martín-Sánchez, J. (2016). The sesquiterpene (-)-α-bisabolol is active against the causative agents of Old World cutaneous leishmaniasis through the induction of mitochondrial-dependent apoptosis. Apoptosis 21, 1071–1081.CrossRefGoogle ScholarPubMed
de Moraes, J. (2015). Natural products with antischistosomal activity. Future Medicinal Chemistry 7, 801–820.CrossRefGoogle ScholarPubMed
Donega, M. A., Mello, S. C., Moraes, R. M., Jain, S. K., Tekwani, B. L. and Cantrell, C. L. (2014). Pharmacological activities of cilantro's aliphatic aldehydes against Leishmania donovani . Planta Medica 80, 1706–1711.Google ScholarPubMed
Dutta, A., Ghoshal, A., Mandal, D., Mondal, N. B., Banerjee, S., Sahu, N. P. and Mandal, C. (2007). Racemoside A, an anti-leishmanial, water-soluble, natural steroidal saponin, induces programmed cell death in Leishmania donovani . Journal of Medical Microbiology 56, 1196–1204.CrossRefGoogle ScholarPubMed
El-Kattan, A. F., Asbill, C. S., Kim, N. and Michniak, B. B. (2001). The effects of terpene enhancers on the percutaneous permeation of drugs with different lipophilicities. International Journal of Pharmaceutics 215, 229–240.CrossRefGoogle ScholarPubMed
Escobar, P., Milena Leal, S., Herrera, L. V., Martinez, J. R. and Stashenko, E. (2010). Chemical composition and antiprotozoal activities of Colombian Lippia spp essential oils and their major components. Memórias do Instituto Oswaldo Cruz 105, 184–190.CrossRefGoogle ScholarPubMed
Esperandim, V. R., Ferreira, D. S., Rezende, K. C. S., Magalhães, L. G., Souza, J. M., Pauletti, P. M., Januário, A. H., Laurentz, R. S., Bastos, J. K., Símaro, G. V., Cunha, W. R. and Andrade e Silva, M. L. (2013). In vitro antiparasitic activity and chemical composition of the essential oil obtained from the fruits of Piper cubeba . Planta Medica 79, 1653–1655.Google ScholarPubMed
Fumarola, L., Spinelli, R. and Brandonisio, O. (2004). In vitro assays for evaluation of drug activity against Leishmania spp. Research in Microbiology 155, 224–230.CrossRefGoogle ScholarPubMed
Gaínza, Y. A., Fantatto, R. R., Chaves, F. C. M., Bizzo, H. R., Esteves, S. N. and Chagas, A. C. S. (2016). Piper aduncum against Haemonchus contortus isolates: cross resistance and the research of natural bioactive compounds. Brazilian Journal of Veterinary Parasitology 25, 383–393.Google ScholarPubMed
Gannavaram, S. and Debrabant, A. (2012). Programmed cell death in Leishmania: biochemical evidence and role in parasite infectivity. Frontiers in Cellular and Infection Microbiology 2, 1–9.CrossRefGoogle ScholarPubMed
Garcia, F. P., Lazarin-Bidóia, D., Ueda-Nakamura, T., Silva, S. O. and Nakamura, C. V. (2013). Eupomatenoid-5 isolated from leaves of Piper regnellii induces apoptosis in Leishmania amazonensis . Evidence-Based Complementary and Alternative Medicine 2013, 940531.CrossRefGoogle ScholarPubMed
Guru, P. Y., Agrawal, A. K., Singha, U. K., Singhal, A. and Gupta, C. M. (1989). Drug targeting in Leishmania donovani infections using tuftsin-bearing liposomes as drug vehicles. FEBS Letters 245, 204–208.CrossRefGoogle ScholarPubMed
Gutiérrez, Y., Montes, R., Scull, R., Sánchez, A., Cos, P., Monzote, L. and Setzer, W. N. (2016). Chemodiversity associated with cytotoxicity and antimicrobial activity of Piper aduncum var. ossanum . Chemistry & Biodiversersity 13, 1715–1719.CrossRefGoogle ScholarPubMed
Houël, E., Gonzalez, G., Bessière, J. M., Odonne, G., Eparvier, V., Deharo, E. and Stien, D. (2015). Therapeutic switching: from antidermatophytic essential oils to new leishmanicidal products. Memórias do Instituto Oswaldo Cruz 110, 106–113.CrossRefGoogle ScholarPubMed
Islamuddin, M., Sahal, D. and Afrin, F. (2014). Apoptosis-like death in Leishmania donovani promastigotes induced by eugenol-rich oil of Syzygium aromaticum . Journal of Medical Microbiology 63, 74–85.CrossRefGoogle ScholarPubMed
Inacio, J. D., Canto-Cavalheiro, M. M., Menna-Barreto, R. F. and Almeida-Amaral, E. E. (2012). Mitochondrial damage contribute to epigallocatechin-3-gallate induced death in Leishmania amazonensis . Experimental Parasitology 132, 151–155.CrossRefGoogle ScholarPubMed
Izumi, E., Ueda-Nakamura, T., Veiga, V. F., Pinto, A. C. and Nakamura, C. V. (2012). Terpenes from Copaifera demonstrated in vitro antiparasitic and synergic activity. Journal of Medicinal Chemistry 55, 2994–3001.CrossRefGoogle ScholarPubMed
Jimenez, V., Paredes, R., Sosa, M. A. and Galanti, N. (2008). Natural programmed cell death in T. cruzi epimastigotes maintained in axenic cultures. Journal of Cellular Biochemistry 105, 688–698.CrossRefGoogle Scholar
Jiménez-Ruiz, A., Alzate, J. F., Macleod, E. T., Lüder, C. G., Fasel, N. and Hurd, H. (2010). Apoptotic markers in protozoan parasites. Parasites & Vectors 3, 104.CrossRefGoogle ScholarPubMed
Jones, T. C., Johnson, W. D., Barretto, A. C., Lago, E., Badaro, R., Cerf, B., Reed, S. G., Netto, E. M., Tada, M. S., Franca, T. F., Wiese, K., Golightly, L., Fikrig, E., Costa, J. M. L., Cuba, C. C. and Marsden, P. D. (1987). Epidemiology of American cutaneous leishmaniasis due to Leishmania braziliensis braziliensis . The Journal of Infectious Diseases 156, 73–83.CrossRefGoogle ScholarPubMed
Kayser, O., Kiderlen, A. F. and Croft, S. L. (2003). Natural products as antiparasitic drugs. Parasitology Research 90(Suppl. 2), S55–S62.CrossRefGoogle ScholarPubMed
Kessler, R. L., Gradia, D. F., Rampazzo, R. C. P., Lourenço, É., Fidêncio, N. J., Manhaes, L., Probst, C. M., Ávila, A. R. and Fragoso, S. P. (2013). Stage-regulated GFP expression in Trypanosoma cruzi: applications from host–parasite interactions to drug screening. PLOS ONE 8, e67441.CrossRefGoogle ScholarPubMed
Khademvatan, S., Gharavi, M. J. and Saki, J. (2011). Miltefosine induces metacaspase and PARP genes expression in Leishmania infantum . The Brazilian Journal of Infectious Diseases 15, 442–448.CrossRefGoogle ScholarPubMed
Lakshmi, V., Pandey, K., Kapil, A., Singh, N., Samant, M. and Dube, A. (2007). In vitro and in vivo leishmanicidal activity of Dysoxylum binectariferum and its fractions against Leishmania donovani . Phytomedicine 14, 36–42.CrossRefGoogle ScholarPubMed
Lapczynski, A., Bhatia, S. P., Letizia, C. S. and Api, A. M. (2008). Fragrance material review on nerolidol (isomer unspecified). Food and Chemical Toxicology 46(Suppl.), S247–S250.CrossRefGoogle ScholarPubMed
Lazarin-Bidóia, D., Desoti, V. C., Martins, S. C., Ribeiro, F. M., Ud Din, Z., Rodrigues-Filho, E., Ueda-Nakamura, T., Nakamura, C. V. and Silva, S. O. (2016). Dibenzylideneacetones are potent trypanocidal compounds that affect the Trypanosoma cruzi redox system. Antimicrobial Agents and Chemotherapy 60, 890–903.CrossRefGoogle ScholarPubMed
Lee, N., Bertholet, S., Debrabant, A., Muller, J., Duncan, R. and Nakhasi, H. L. (2002). Programmed cell death in the unicellular protozoan parasite Leishmania . Cell Death and Differentiation 9, 53–64.CrossRefGoogle ScholarPubMed
Lindoso, J. A., Cunha, M. A., Queiroz, I. T. and Moreira, C. H. (2016). Leishmaniasis-HIV coinfection: current challenges. HIV/AIDS: Research and Palliative Care 8, 147–156.Google ScholarPubMed
Majdalawieh, A. F. and Carr, R. I. (2010). In vitro investigation of the potential immunomodulatory and anti-cancer activities of black pepper (Piper nigrum) and cardamom (Elettaria cardamomum). Journal of Medicinal Food 13, 371–381.CrossRefGoogle ScholarPubMed
Mamood, S. N., Hidayatulfathi, O., Budin, S. B., Rohi, G. A. and Zulfakar, M. H. (2017). The formulation of the essential oil of Piper aduncum Linnaeus (Piperales: Piperaceae) increases its efficacy as an insect repellent. Bulletin of Entomological Research 107, 49–57.CrossRefGoogle ScholarPubMed
Marinho, F. A., Gonçalves, K. C. S., Oliveira, S. S., Oliveira, A. C. S. C., Bellio, M., d'Avila-Levy, C. M., Santos, A. L. S. and Branquinha, M. H. (2011). Miltefosine induces programmed cell death in Leishmania amazonensis promastigotes. Memórias do Instituto Oswaldo Cruz 106, 507–509.CrossRefGoogle ScholarPubMed
Marques, A. M., Barreto, A. L., Batista, E. M., Curvelo, J. A., Velozo, L. S., Moreira, D. L., Guimarães, E. F., Soares, R. M. and Kaplan, M. A. (2010). Chemistry and biological activity of essential oils from Piper claussenianum (Piperaceae). Natural Product Communications 5, 1837–1840.CrossRefGoogle ScholarPubMed
Marques, A. M., Paiva, R. A., Fonseca, L. M., Capella, M. A. M., Guimarães, E. F. and Kaplan, M. A. C. (2013). Preliminary anticancer potency evaluation and phytochemical investigation of methanol extract of Piper claussenianum (Miq.) C. DC. Journal of Applied Pharmaceutical Science 3, 13–18.Google Scholar
Masic, A., Hernandez, A. M. V., Hazra, S., Glaser, J., Holzgrabe, U., Hazra, B. and Schurigt, U. (2015). Cinnamic acid bornyl ester derivatives from Valeriana wallichii exhibit antileishmanial in vivo activity in Leishmania major-infected BALB/c mice. PLoS ONE 10, e0142386.CrossRefGoogle ScholarPubMed
Mendes, E. A., Desoti, V. C., Silva, S. O., Ueda-Nakamura, T., Dias Filho, B. P., Yamada-Ogatta, S. F., Sarragiotto, M. H. and Nakamura, C. V. (2016). C5 induces different cell death pathways in promastigotes of Leishmania amazonensis . Chemico-Biological Interactions 256, 16–24.CrossRefGoogle ScholarPubMed
Misni, N., Othman, H. and Sulaiman, S. (2011). The effect of Piper aduncum Linn. (Family: Piperaceae) essential oil as aerosol spray against Aedes aegypti (L.) and Aedes albopictus Skuse. Tropical Biomedicine 28, 249–258.Google ScholarPubMed
Misra, P., Kumar, A., Khare, P., Gupta, S., Kumar, N. and Dube, A. (2009). Pro-apoptotic effect of the landrace Bangla Mahoba of Piper betle on Leishmania donovani may be due to the high content of eugenol. Journal of Medical Microbiology 58, 1058–1066.CrossRefGoogle Scholar
Monzote, L., García, M., Montalvo, A. M., Scull, R. and Miranda, M. (2010). Chemistry, cytotoxicity and antileishmanial activity of the essential oil from Piper auritum . Memórias do Instituto Oswaldo Cruz 105, 168–173.CrossRefGoogle ScholarPubMed
Ndjonka, D., Rapado, L. N., Silber, A. M., Liebau, E. and Wrenger, C. (2013). Natural products as a source for treating neglected parasitic diseases. International Journal of Molecular Sciences 14, 3395–3439.CrossRefGoogle ScholarPubMed
Okunade, A. H., Charles, D., Clark, A. M. and Lentz, D. (1997). Antimicrobial properties of the constituents of Piper aduncum . Phytotherapy Research 11, 142–144.3.0.CO;2-Y>CrossRefGoogle Scholar
Organização Pan-Americana da Saúde / Organização Mundial da Saúde (2015). Informe Epidemiológico das Américas. Informe Leishmanioses No. 3. Organização Pan-Americana da Saúde/Organização Mundial da Saúde, Washington, DC, USA.Google Scholar
Organización Panamericana de la Salud (2013). Leishmaniasis en las Américas: recomendaciones para el tratamiento. Organización Panamericana de la Salud, Washington, DC, USA.Google Scholar
Petit, P. X. (1992). Flow cytometric analysis of rhodamine 123 fluorescence during modulation of the membrane potential in plant mitochondria. Plant Physiology 98, 279–286.CrossRefGoogle ScholarPubMed
Proto, W. R., Coombs, G. H. and Mottram, J. C. (2013). Cell death in parasitic protozoa: regulated or incidental? Nature Reviews Microbiology 11, 58–66.CrossRefGoogle ScholarPubMed
Rodrigues, J. H., Ueda-Nakamura, T., Corrêa, A. G., Sangi, D. P. and Nakamura, C. V. (2014). A quinoxaline derivative as a potent chemotherapeutic agent, alone or in combination with benznidazole, against Trypanosoma cruzi . PLoS ONE 9, e85706.CrossRefGoogle ScholarPubMed
Shadab, M., Jha, B., Asad, M., Deepthi, M., Kamran, M. and Ali, N. (2017). Apoptosis-like cell death in Leishmania donovani treated with KalsomeTM 10, a new liposomal amphotericin B. PLoS ONE 12, e0171306.CrossRefGoogle Scholar
Srivastava, S., Shankar, P., Mishra, J. and Singh, S. (2016). Possibilities and challenges for developing a successful vaccine for leishmaniasis. Parasites & Vector 9, 277.CrossRefGoogle ScholarPubMed
Sunila, E. S. and Kuttan, G. (2004). Immunomodulatory and antitumor activity of Piper longum Linn. and piperine. Journal of Ethnopharmacology 90, 339–346.CrossRefGoogle ScholarPubMed
Thao, N. P., Luyen, B. T., Widowati, W., Fauziah, N., Maesaroh, M., Herlina, T., Manzoor, Z., Ali, I., Koh, Y. S. and Kim, Y. H. (2016). Anti-inflammatory flavonoid C-glycosides from Piper aduncum leaves. Planta Medica 82, 1475–1481.Google ScholarPubMed
Ullah, N., Nadhman, A., Siddiq, S., Mehwish, S., Islam, A., Jafri, L. and Hamayun, M. (2016). Plants as antileishmanial agents: current scenario. Phytotherapy Research 30, 1905–1925.CrossRefGoogle ScholarPubMed
Villamizar, L. H., Cardoso, M. G., Andrade, J., Teixeira, M. L. and Soares, M. J. (2017). Linalool, a Piper aduncum essential oil component, has selective activity against Trypanosoma cruzi trypomastigote forms at 4 °C. Memórias do Instituto Oswaldo Cruz 112, 131–139.CrossRefGoogle Scholar
Welburn, S. C., Macleod, E., Figarella, K. and Duzensko, M. (2006). Programmed cell death in African trypanosomes. Parasitology 132, S7–S18.CrossRefGoogle ScholarPubMed
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