Abstract
Blood flukes of the genus Schistosoma are the causative agents of human schistosomiasis, a debilitating disease that afflicts over 200 million people worldwide. Praziquantel is the drug of choice but concerns over praziquantel resistance have renewed interest in the search for alternative drug therapies. Carvacrol, a naturally occurring monoterpene phenol and food additive, has been shown high medicinal importance, including antimicrobials activities. The aim of this study was to evaluate in vitro effect of carvacryl acetate, a derivative of carvacrol, on Schistosoma mansoni adult worms. We demonstrated that carvacryl acetate at 6.25 μg/mL has antischistosomal activity, affecting parasite motility and viability. Additionally, confocal laser scanning microscopy pictures revealed morphological alterations on the tegumental surface of worms, where some tubercles appeared to be swollen with numerous small blebs emerging from the tegument around the tubercles. Furthermore, experiments performed using carvacryl acetate at sub-lethal concentrations (ranging from 1.562 to 6.25 μg/mL) showed an inhibitory effect on the daily egg output of paired adult worms. Thus, carvacryl acetate is toxic at high doses, while at sub-lethal doses, it significantly interferes with the reproductive fitness of S. mansoni adult worms. Due to its safety and wide use in the industry, carvacryl acetate is a promising natural product-derived compound and it may represent a step forward in the search for novel anthelmintic agents, at a time when there is an urgent need for novel drugs.
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Ahmad A, Khan A, Akhtar F, Yousuf S, Xess I, Khan LA, Manzoor N (2011) Fungicidal activity of thymol and carvacrol by disrupting ergosterol biosynthesis and membrane integrity against Candida. Eur J Clin Microbiol Infect Dis 30:41–50. doi:10.1007/s10096-010-1050-8
Allegretti SM, Oliveira CNF, Oliveira RN, Frezza TF, Rehder VLG (2012) The use of Brazilian medicinal plants to combat Schistosoma mansoni. In: Rokni MB (ed) Schistosomiasis. InTech, Rijeka, pp 27–70. doi:10.5772/27399
Anthony JP, Fyfe L, Smith H (2005) Plant active components—a resource for antiparasitic agents? Trends Parasitol 21:462–468. doi:10.1016/j.pt.2005.08.004
Anthony KP, Deolu-Sobogun SA, Saleh MA (2012) Comprehensive assessment of antioxidant activity of essential oils. J Food Sci 77:C839–C843. doi:10.1111/j.1750-3841.2012.02795.x
Araujo N, Kohn A, Oliveira AA, Katz N (2002) Schistosoma mansoni: the action of lovastatin on the murine model. Rev Soc Bras Med Trop 35:35–38. doi:10.1590/S0037-86822002000100007
Baser KH (2008) Biological and pharmacological activities of carvacrol and carvacrol bearing essential oils. Curr Pharm Des 14:3106–3119. doi:10.2174/13106
Botros S, Bennett J (2007) Praziquantel resistance. Expert Opin Drug Discov 2(Suppl 1):535–540. doi:10.1517/17460441.2.S1.S35
Caffrey CR (2007) Chemotherapy of schistosomiasis: present and future. Curr Opin Chem Biol 11:433–439. doi:10.1016/j.cbpa.2007.05.031
Caixeta SC, Magalhães LG, de Melo NI, Wakabayashi KA, Aguiar Gde P, Aguiar Dde P, Mantovani AL, Alves JM, Oliveira PF, Tavares DC, Groppo M, Rodrigues V, Cunha WR, Veneziani RC, da Silva Filho AA, Crotti AE (2011) Chemical composition and in vitro schistosomicidal activity of the essential oil of Plectranthus neochilus grown in Southeast Brazil. Chem Biodivers 8:2149–2157. doi:10.1002/cbdv.201100167
Cetin H, Yanikoglu A (2006) A study of the larvicidal activity of Origanum (Labiatae) species from southwest Turkey. J Vector Ecol 31:118–122
Coskun S, Girisgin O, Kürkcüoglu M, Malyer H, Girisgin AO, Kirimer N, Baser KH (2008) Acaricidal efficacy of Origanumonites L. essential oil against Rhipicephalus turanicus (Ixodidae). Parasitol Res 103:259–261. doi:10.1007/s00436-008-0956-x
de Melo NI, Magalhaes LG, de Carvalho CE, Wakabayashi KA, de P Aguiar G, Ramos RC, Mantovani AL, Turatti IC, Rodrigues V, Groppo M, Cunha WR, Veneziani RC, Crotti AE (2011) Schistosomicidal activity of the essential oil of Ageratum conyzoides L. (Asteraceae) against adult Schistosoma mansoni worms. Molecules 16:762–773. doi:10.3390/molecules16010762
de Moraes J, Nascimento C, Miura LM, Leite JR, Nakano E, Kawano T (2011) Evaluation of the in vitro activity of dermaseptin 01, a cationic antimicrobial peptide, against Schistosoma mansoni. Chem Biodivers 8:548–558. doi:10.1002/cbdv.201000163
de Moraes J, Nascimento C, Yamaguchi LF, Kato MJ, Nakano E (2012) Schistosoma mansoni: in vitro schistosomicidal activity and tegumental alterations induced by piplartine on schistosomula. Exp Parasitol 132:222–227. doi:10.1016/j.exppara.2012.07.004
de Oliveira RN, Rehder VL, Santos Oliveira AS, Júnior IM, de Carvalho JE, de Ruiz AL, de Lourdes Sierpe Jeraldo V, Linhares AX, Allegretti SM (2012) Schistosoma mansoni: in vitro schistosomicidal activity of essential oil of Baccharis trimera (less) DC. Exp Parasitol 132:135–143. doi:10.1016/j.exppara.2012.06.005
Eissa MM, El-Azzouni MZ, Amer EI, Baddour NM (2011) Miltefosine, a promising novel agent for Schistosomiasis mansoni. Int J Parasitol 41:235–242. doi:10.1186/1756-3305-4-73
Escobar P, Milena Leal S, Herrera LV, Martinez JR, Stashenko E (2010) Chemical composition and antiprotozoal activities of Colombian Lippia spp essential oils and their major components. Mem Inst Oswaldo Cruz 105:184–190
Ferreira JF, Peaden P, Keiser J (2011) In vitro trematocidal effects of crude alcoholic extracts of Artemisia annua, A. absinthium, Asimina triloba, and Fumaria officinalis: trematocidal plant alcoholic extracts. Parasitol Res 109:1585–1592. doi:10.1007/s00436-011-2418-0
Gryseels B, Polman K, Clerinx J, Kestens L (2006) Human schistosomiasis. Lancet 368:1106–1118. doi:10.1016/S0140-6736(06)69440-3
Irie Y, Basch PF, Beach N (1983) Reproductive ultrastructure of adult Schistosoma mansoni grown in vitro. J Parasitol 69:559–566
Jiraungkoorskul W, Sahaphong S, Sobhon P, Riengrojpitak S, Kangwanrangsan N (2005) Effects of praziquantel and artesunate on the tegument of adult Schistosoma mekongi harboured in mice. Parasitol Int 54:177–183. doi:10.1016/j.parint.2005.04.001
Jiraungkoorskul W, Sahaphong S, Sobhon P, Riengrojpitak S, Kangwanrangsan N (2006) Schistosoma mekongi: the in vitro effect of praziquantel and artesunate on the adult fluke. Exp Parasitol 113:16–23. doi:10.1016/j.exppara.2005.12.001
Kayser O, Kiderlen AF, Croft SL (2003) Natural products as antiparasitic drugs. Parasitol Res 90(Suppl 2):S55–S62. doi:10.1007/s00436-002-0768-3
Koné WM, Vargas M, Keiser J (2012) Anthelmintic activity of medicinal plants used in Côte d’Ivoire for treating parasitic diseases. Parasitol Res 110:2351–2362. doi:10.1007/s00436-011-2771-z
Lai WL, Chuang HS, Lee MH, Wei CL, Lin CF, Tsai YC (2012) Inhibition of herpes simplex virus type 1 by thymol-related monoterpenoids. Planta Med. doi:10.1055/s-0032-1315208
Machado M, Sousa Mdo C, Salgueiro L, Cavaleiro C (2010) Effects of essential oils on the growth of Giardia lamblia trophozoites. Nat Prod Commun 5:137–141
Magalhães LG, Machado CB, Morais ER, Moreira EB, Soares CS, da Silva SH, Da Silva Filho AA, Rodrigues V (2009) In vitro schistosomicidal activity of curcumin against Schistosoma mansoni adult worms. Parasitol Res 104:1197–1201. doi:10.1007/s00436-008-1311-y
Magalhães LG, Kapadia GJ, da Silva Tonuci LR, Caixeta SC, Parreira NA, Rodrigues V, Da Silva Filho AA (2010) In vitro schistosomicidal effects of some phloroglucinol derivatives from Dryopteris species against Schistosoma mansoni adult worms. Parasitol Res 106:395–401. doi:10.1007/s00436-009-1674-8
Magalhães LG, de Souza JM, Wakabayashi KA, Laurentiz Rda S, Vinhólis AH, Rezende KC, Simaro GV, Bastos JK, Rodrigues V, Esperandim VR, Ferreira DS, Crotti AE, Cunha WR, e Silva ML (2012) In vitro efficacy of the essential oil of Piper cubeba L. (Piperaceae) against Schistosoma mansoni. Parasitol Res 110:1747–1754. doi:10.1007/s00436-011-2695-7
Manneck T, Haggenmüller Y, Keiser J (2010) Morphological effects and tegumental alterations induced by mefloquine on schistosomula and adult flukes of Schistosoma mansoni. Parasitology 137:85–98. doi:10.1017/S0031182009990965
Miranda MA, Magalhães LG, Tiossi RF, Kuehn CC, Oliveira LG, Rodrigues V, McChesney JD, Bastos JK (2012) Evaluation of the schistosomicidal activity of the steroidal alkaloids from Solanum lycocarpum fruits. Parasitol Res 111:257–262. doi:10.1007/s00436-012-2827-8
Mitsui Y, Miura M, Aoki Y (2009) In vitro effects of artesunate on the survival of worm pairs and egg production of Schistosoma mansoni. J Helminthol 83:7–11. doi:10.1017/S0022149X08070235
Moraes J (2012) Antischistosomal natural compounds: present challenges for new drug screens. In: Rodriguez-Morales AJ (ed) Current topics in tropical medicine. Intech, Rijeka, pp 333–358. doi:10.5772/27740
Moraes J, Silva MP, Ohlweiler FP, Kawano T (2009) Schistosoma mansoni and other larval trematodes in Biomphalaria tenagophila (Planorbidae) from Guarulhos, São Paulo State, Brazil. Rev Inst Med Trop São Paulo 51:77–82. doi:10.1590/S0036-46652009000200004
Moraes J, Nascimento C, Lopes PO, Nakano E, Yamaguchi LF, Kato MJ, Kawano T (2011) Schistosoma mansoni: in vitro schistosomicidal activity of piplartine. Exp Parasitol 127:357–364. doi:10.1016/j.exppara.2010.08.021
Mostafa OM, Eid RA, Adly MA (2011) Antischistosomal activity of ginger (Zingiber officinale) against Schistosoma mansoni harbored in C57 mice. Parasitol Res 109:395–403. doi:10.1007/s00436-011-2267-x
Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335. doi:10.1021/np200906s
Pearce EJ, MacDonald AS (2002) The immunobiology of schistosomiasis. Nat Rev Immunol 2:499–511. doi:10.1038/nri843
Pica-Mattoccia L, Cioli D (2004) Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment. Int J Parasitol 34:527–533. doi:10.1016/j.ijpara.2003.12.003
Prieto-Garcia JM, Iacopini P, Cioni P, Chericoni S (2007) In vitro activity of the essential oils of Origanum vulgare, Satureja montana and their main constituents in peroxynitrite-induced oxidative processes. Food Chem 104:889–895. doi:10.1016/j.foodchem.2006.10.064
Sanderson L, Bartlett A, Whitfield PJ (2002) In vitro and in vivo studies on the bioactivity of a ginger (Zingiber officinale) extract towards adult schistosomes and their egg production. J Helminthol 76:241–247. doi:10.1079/JOH2002116
Smithers SR, Terry RJ (1965) The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of adults worms. Parasitology 55:695–700
Soković M, Glamočlija J, Marin PD, Brkić D, van Griensven LJ (2010) Antibacterial effects of the essential oils of commonly consumed medicinal herbs using an in vitro model. Molecules 15:7532–7546. doi:10.3390/molecules15117532
Staudt U, Schmahl G, Blaschke G, Mehlhorn H (1992) Light and scanning electron microscopy studies on the effects of the enantiomers of praziquantel and its main metabolite on Schistosoma mansoni in vitro. Parasitol Res 78:392–397. doi:10.1007/BF00931694
Steinauer ML (2009) The sex lives of parasites: investigating the mating system and mechanisms of sexual selection of the human pathogen Schistosoma mansoni. Int J Parasitol 39:1157–1163. doi:10.1016/j.ijpara.2009.02.019
Steinmann P, Keiser J, Bos R, Tanner M, Utzinger J (2006) Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people atrisk. Lancet Infect Dis 6:411–425. doi:10.1016/S1473-3099(06)70521-7
Tang X, Chen S, Wang L (2011) Purification and identification of carvacrol from the root of Stellera chamaejasme and research on its insecticidal activity. Nat Prod Res 25:320–325. doi:10.1080/14786419.2010.532796
Utzinger J, Keiser J (2004) Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control. Expert Opin Pharmacother 5:263–285. doi:10.1517/14656566.5.2.263
Van der Werf MJ, de Vlas SJ, Brooker S, Looman CW, Nagelkerke NJ, Habbema JD, Engels D (2003) Quantification of clinical morbidity associated with schistosome infection in sub Saharan Africa. Acta Trop 86:125–139. doi:10.1016/S0001-706X(03)00029-9
Veras LM, Guimarães MA, Campelo YD, Vieira MM, Nascimento C, Lima D, Vasconcelos L, Nakano E, Kuckelhaus S, Batista MC, Leite JR, Moraes J (2012) Activity of epiisopiloturine against Schistosoma mansoni. Curr Med Chem 19:2051–2058. doi:10.2174/092986712800167347
Vogel AI, Tatchell AR, Furnis BS, Hannaford AJ, Smith PWG (1996) Vogel’s text book of practical organic chemistry, 5th edn. Prentice-Hall, Englewood Cliffs
Yu H, Zhang ZL, Chen J, Pei A, Hua F, Qian X, He J, Liu CF, Xu X (2012) Carvacrol, a food-additive, provides neuroprotection on focal cerebral ischemia/reperfusion injury in mice. PLoS One 7:e33584. doi:10.1371/journal.pone.0033584
Acknowledgements
We thank Mr. Alexsander S. Souza (Parasitology Laboratory, Butantan Institute, São Paulo, SP, Brazil) for expert help with the confocal microscopy studies. This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Brazil Grant numbers: 06/56216-8 and 00/11624-5).
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Moraes, J., Carvalho, A.A.L., Nakano, E. et al. Anthelmintic activity of carvacryl acetate against Schistosoma mansoni . Parasitol Res 112, 603–610 (2013). https://doi.org/10.1007/s00436-012-3172-7
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DOI: https://doi.org/10.1007/s00436-012-3172-7