Artículos de revistas
Phytol, A Diterpene Alcohol From Chlorophyll, As A Drug Against Neglected Tropical Disease Schistosomiasis Mansoni
Registro en:
Plos Neglected Tropical Diseases. , v. 8, n. 1, p. 51 - , 2014.
19352727
10.1371/journal.pntd.0002617
2-s2.0-84893806199
Autor
de Moraes J.
de Oliveira R.N.
Costa J.P.
Junior A.L.G.
de Sousa D.P.
Freitas R.M.
Allegretti S.M.
Pinto P.L.S.
Institución
Resumen
Background:Schistosomiasis is a major endemic disease that affects hundreds of millions worldwide. Since the treatment and control of this parasitic disease rely on a single drug, praziquantel, it is imperative that new effective drugs are developed. Here, we report that phytol, a diterpene alcohol from chlorophyll widely used as a food additive and in medicinal fields, possesses promising antischistosomal properties in vitro and in a mouse model of schistosomiasis mansoni.Methods and findings:In vitro, phytol reduced the motor activity of worms, caused their death and confocal laser scanning microscopy analysis showed extensive tegumental alterations in a concentration-dependent manner (50 to 100 μg/mL). Additionally, phytol at sublethal doses (25 μg/mL) reduced the number of Schistosoma mansoni eggs. In vivo, a single dose of phytol (40 mg/kg) administered orally to mice infected with adult S. mansoni resulted in total and female worm burden reductions of 51.2% and 70.3%, respectively. Moreover, phytol reduced the number of eggs in faeces (76.6%) and the frequency of immature eggs (oogram pattern) was significantly reduced. The oogram also showed increases in the proportion of dead eggs. Confocal microcopy studies revealed tegumental damage in adult S. mansoni recovered from mice, especially in female worms.Conclusions:The significant reduction in parasite burden by this chlorophyll molecule validates phytol as a promising drug and offers the potential of a new direction for chemotherapy of human schistosomiasis. Phytol is a common food additive and nonmutagenic, with satisfactory safety. Thus, phytol has potential as a safe and cost-effective addition to antischistosomal therapy. © 2014 de Moraes et al. 8 1 51
Steinmann, P., Keiser, J., Bos, R., Tanner, M., Utzinger, J., Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk (2006) Lancet Infect Dis, 6, pp. 411-425. , 10.1016/S1473-3099(06)70521-7 Gray, D.J., McManus, D.P., Li, Y., Williams, G.M., Bergquist, R., Schistosomiasis elimination: lessons from the past guide the future (2010) Lancet Infect Dis, 10, pp. 733-736. , doi: 10.1016/S1473-3099(10)70099-2 Gryseels, B., Polman, K., Clerinx, J., Kestens, L., Human schistosomiasis (2006) Lancet, 368, pp. 1106-1118. , doi: 10.1016/S0140-6736(06)69440-3 Utzinger, J., Keiser, J., Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control (2004) Expert Opin Pharmacother, 5, pp. 263-285. , doi: 10.1517/14656566.5.2.263 Botros, S., Bennett, J., Praziquantel resistance (2007) Expert Opin Drug Discov, 2 (SUPPL. 1), pp. 535-540. , doi: 10.1517/17460441.2.S1.S35 Caffrey, C.R., Chemotherapy of schistosomiasis: present and future (2007) Curr Opin Chem Biol, 11, pp. 433-439. , doi: 10.1016/j.cbpa.2007.05.031 Kayser, O., Kiderlen, A.F., Croft, S.L., Natural products as antiparasitic drugs (2003) Parasitol Res, 90 (SUPPL. 2), pp. 55-62. , doi: 10.1007/s00436-002-0768-3 Newman, D.J., Cragg, G.M., Natural products as sources of new drugs over the 30 years from 1981 to 2010 (2012) J Nat Prod, 75, pp. 311-335. , doi: 10.1021/np200906s Vetter, W., Schröder, M., Lehnert, K., Differentiation of refined and virgin edible oils by means of the trans- and cis-phytol isomer distribution (2012) J Agric Food Chem, 60, pp. 6103-6107. , doi: 10.1021/jf301373k McGinty, D., Letizia, C.S., Api, A.M., Fragrance material review on phytol (2010) Food Chem Toxicol, 48 (SUPPL.), pp. 59-63. , doi: 10.1016/j.fct.2009.11.012 Santos, C.C.M.P., Salvadori, M.S., Mota, V.G., Costa, L.M., Almeida, A.A.C.O., Antinociceptive and antioxidant activities of phytol in vivo and in vitro models (2013) Neurosci J, , doi: 10.1155/2013/949452, Article ID 949452. doi Ryu, K.R., Choi, J.Y., Chung, S., Kim, D.H., Anti-scratching behavioral effect of the essential oil and phytol isolated from Artemisia princeps Pamp. in mice (2011) Planta Med, 77, pp. 22-26. , doi: 10.1055/s-0030-1250119 Lim, S.Y., Meyer, M., Kjonaas, R.A., Ghosh, S.K., Phytol-based novel adjuvants in vaccine formulation: 1. assessment of safety and efficacy during stimulation of humoral and cell-mediated immune responses (2006) J Immune Based Ther Vaccines, 4, p. 6. , doi: 10.1186/1476-8518-4-6 Chowdhury, R.R., Ghosh, S.K., Phytol-derived novel isoprenoid immunostimulants (2012) Front Immunol, 3, p. 49. , doi: 10.3389/fimmu.2012.00049 Rajab, M.S., Cantrell, C.L., Franzblau, S.G., Fischer, N.H., Antimycobacterial activity of (E)-phytol and derivatives: a preliminary structure-activity study (1998) Planta Med, 64, pp. 2-4. , doi: 10.1055/s-2006-957354 Saikia, D., Parihar, S., Chanda, D., Ojha, S., Kumar, J.K., Antitubercular potential of some semisynthetic analogues of phytol (2010) Bioorg Med Chem Lett, 20, pp. 508-512. , doi: 10.1016/j.bmcl.2009.11.107 Inoue, Y., Hada, T., Shiraishi, A., Hirose, K., Hamashima, H., Biphasic effects of geranylgeraniol, teprenone, and phytol on the growth of Staphylococcus aureus (2005) Antimicrob Agents Chemother, 49, pp. 1770-1774. , doi: 10.1128/AAC.49.5.1770-1774.2005 Allegretti, S.M., Oliveira, C.N.F., Oliveira, R.N., Frezza, T.F., Rehder, V.L.G., The use of Brazilian medicinal plants to combat Schistosoma mansoni (2012) Schistosomiasis. Rijeka: InTech, pp. 27-70. , In: Rokni MB, editor. doi: 10.5772/27399 Moraes, J., Antischistosomal natural compounds: Present challenges for new drug screens (2012) Current topics in tropical medicine, pp. 333-358. , In: Rodriguez-Morales AJ, editor. Rijeka: InTech. doi: 10.5772/27740 Olivier, L., Stirewalt, M.A., An efficient method for exposure of mice to cercarie of Schistosoma mansoni (1952) Int J Parasitol, 38, pp. 19-23 Smithers, S.R., Terry, R.J., The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of adults worms (1965) Parasitology, 55, pp. 695-700 Moraes, J., Nascimento, C., Lopes, P.O., Nakano, E., Yamaguchi, L.F., Schistosoma mansoni: In vitro schistosomicidal activity of piplartine (2011) Exp Parasitol, 127, pp. 357-364. , doi: 10.1016/j.exppara.2010.08.021 de Moraes, J., Carvalho, A.A., Nakano, E., de Almeida, A.A., Marques, T.H., Anthelmintic activity of carvacryl acetate against Schistosoma mansoni (2013) Parasitol Res, 112, pp. 603-610. , doi: 10.1007/s00436-012-3172-7 de Moraes, J., Keiser, J., Ingram, K., Nascimento, C., Yamaguchi, L.F., In vitro synergistic interaction between amide piplartine and antimicrobial peptide dermaseptin against Schistosoma mansoni schistosomula and adult worms (2013) Curr Med Chem, 20, pp. 301-309. , doi: 10.2174/0929867311320020010 Veras, L.M., Guimarães, M.A., Campelo, Y.D., Vieira, M.M., Nascimento, C., Activity of epiisopiloturine against Schistosoma mansoni (2012) Curr Med Chem, 19, pp. 2051-2058. , doi: 10.2174/092986712800167347 de Moraes, J., Nascimento, C., Miura, L.M., Leite, J.R., Nakano, E., Evaluation of the in vitro activity of dermaseptin 01, a cationic antimicrobial peptide, against Schistosoma mansoni (2011) Chem Biodivers, 8, pp. 548-558. , doi: 10.1002/cbdv.201000163 Hotez, P.J., Molyneux, D.H., Fenwick, A., Kumaresan, J., Sachs, S.E., Control of neglected tropical diseases (2007) N Engl J Med, 357, pp. 1018-1027. , doi: 10.1056/NEJMra064142 Pellegrino, J., Oliveira, C.A., Faria, J., Cunha, A.S., New approach to the screening of drugs in experimental schistosomiasis mansoni in mice (1962) Am J Trop Med Hyg, 11, pp. 201-215 Katz, N., Chaves, A., Pellegrino, J.P., A simple device for quantitative stool thick-smear technique in schistosomiasis mansoni (1972) Rev Inst Med Trop Sao Paulo, 14, pp. 397-400 de Moraes, J., Nascimento, C., Yamaguchi, L.F., Kato, M.J., Nakano, E., Schistosoma mansoni: In vitro schistosomicidal activity and tegumental alterations induced by piplartine on schistosomula (2012) Exp Parasitol, 132, pp. 222-227. , doi: 10.1016/j.exppara.2012.07.004 Moraes, J., Silva, M.P., Ohlweiler, F.P., Kawano, T., Schistosoma mansoni and other larval trematodes in Biomphalaria tenagophila (Planorbidae) from Guarulhos, São Paulo State, Brazil (2009) Rev Inst Med Trop São Paulo, 51, pp. 77-82. , doi: 10.1590/S0036-46652009000200004 Mize, C.E., Avigan, J., Baxter, J.H., Fales, H.M., Steinberg, D., Metabolism of phytol-U-14C and phytanic acid-U-14C in the rat (1966) J Lipid Res, 7, pp. 692-697 Mitsui, Y., Miura, M., Aoki, Y., In vitro effects of artesunate on the survival of worm pairs and egg production of Schistosoma mansoni (2009) J Helminthol, 83, pp. 7-11. , doi: 10.1017/S0022149X08070235 Keiser, J., Chollet, J., Xiao, S.H., Mei, J.Y., Jiao, P.Y., Mefloquine - an aminoalcohol with promising antischistosomal properties in mice (2009) PLoS Negl Trop Dis, 3, pp. e350. , doi: 10.1371/journal.pntd.0000350 Botros, S., William, S., Hammam, O., Zídek, Z., Holý, A., Activity of 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine against Schistosomiasis mansoni in mice (2003) Antimicrob Agents Chemother, 47, pp. 3853-3858. , doi: 10.1128/AAC.47.12.3853-3858.2003 Abdulla, M.H., Lim, K.C., Sajid, M., McKerrow, J.H., Caffrey, C.R., Schistosomiasis mansoni: novel chemotherapy using a cysteine protease inhibitor (2007) PLoS Med, 4, pp. e14. , doi: 10.1371/journal.pmed.0040014 Sayed, A.A., Simeonov, A., Thomas, C.J., Inglese, J., Austin, C.P., Identification of oxadiazoles as new drug leads for the control of schistosomiasis (2008) Nat Med, 14, pp. 407-412. , doi: 10.1038/nm1737 Manneck, T., Haggenmüller, Y., Keiser, J., Morphological effects and tegumental alterations induced by mefloquine on schistosomula and adult flukes of Schistosoma mansoni (2010) Parasitology, 137, pp. 85-98. , doi: 10.1017/S0031182009990965 Eissa, M.M., El-Azzouni, M.Z., Amer, E.I., Baddour, N.M., Miltefosine, a promising novel agent for schistosomiasis mansoni (2011) Int J Parasitol, 41, pp. 235-242. , doi: 10.1186/1756-3305-4-73 Mostafa, O.M., Eid, R.A., Adly, M.A., Antischistosomal activity of ginger (Zingiber officinale) against Schistosoma mansoni harbored in C57 mice (2011) Parasitol Res, 109, pp. 395-403. , doi: 10.1007/s00436-011-2267-x Bertão, H.G., da Silva, R.A., Padilha, R.J., de Azevedo Albuquerque, M.C., Ultrastructural analysis of miltefosine-induced surface membrane damage in adult Schistosoma mansoni BH strain worms (2012) Parasitol Res, 110, pp. 2465-2473. , doi: 10.1007/s00436-011-2786-5 de Oliveira, R.N., Rehder, V.L., Santos Oliveira, A.S., Júnior, ÍM., de Carvalho, J.E., Schistosoma mansoni: in vitro schistosomicidal activity of essential oil of Baccharis trimera (less) DC (2012) Exp Parasitol, 132, pp. 135-143. , doi: 10.1016/j.exppara.2012.06.005 Moraes, J., Almeida, A.A., Brito, M.R., Marques, T.H., Lima, T.C., Anthelmintic activity of the natural compound (+)-limonene epoxide against Schistosoma mansoni (2013) Planta Med, 79, pp. 253-258. , doi: 10.1055/s-0032-1328173 Jiraungkoorskul, W., Sahaphong, S., Sobhon, P., Riengrojpitak, S., Kangwanrangsan, N., Effects of praziquantel and artesunate on the tegument of adult Schistosoma mekongi harboured in mice (2005) Parasitol Int, 54, pp. 177-183. , doi: 10.1016/j.parint.2005.04.001 Jiraungkoorskul, W., Sahaphong, S., Sobhon, P., Riengrojpitak, S., Kangwanrangsan, N., Schistosoma mekongi: the in vitro effect of praziquantel and artesunate on the adult fluke (2006) Exp Parasitol, 113, pp. 16-23. , doi: 10.1016/j.exppara.2005.12.001 Shuhua, X., Binggui, S., Chollet, J., Tanner, M., Tegumental changes in adult Schistosoma mansoni harboured in mice treated with praziquantel enantiomers (2000) Acta Trop, 76, pp. 107-117. , doi: 10.1016/S0001-706X(00)00076-0 Brindley, P.J., Sher, A., The chemotherapeutic effect of praziquantel against Schistosoma mansoni is dependent on host antibody response (1987) J Immunol, 139, pp. 215-220 Doenhoff, M.J., Sabah, A.A., Fletcher, C., Webbe, G., Bain, J., Evidence for an immune-dependent action of praziquantel on Schistosoma mansoni in mice (1987) Trans R Soc Trop Med Hyg, 81, pp. 947-951. , doi: 10.1016/0035-9203(87)90360-9 Pica-Mattoccia, L., Cioli, D., Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment (2004) Int J Parasitol, 34, pp. 527-533. , doi: 10.1016/j.ijpara.2003.12.003 Van Nassauw, L., Toovey, S., Van Op den Bosch, J., Timmermans, J.P., Vercruysse, J., Schistosomicidal activity of the antimalarial drug, mefloquine, in Schistosoma mansoni-infected mice (2008) Travel Med Infect Dis, 6, pp. 253-258. , doi: 10.1016/j.tmaid.2008.06.006 Abdul-Ghani, R., Loutfy, N., Sheta, M., Hassan, A., Artemether shows promising female schistosomicidal and ovicidal effects on the Egyptian strain of Schistosoma mansoni after maturity of infection (2011) Parasitol Res, 108, pp. 1199-1205. , doi: 10.1007/s00436-010-2163-9 Sanderson, L., Bartlett, A., Whitfield, P.J., In vitro and in vivo studies on the bioactivity of a ginger (Zingiber officinale) extract towards adult schistosomes and their egg production (2002) J Helminthol, 76, pp. 241-247. , doi: 10.1079/JOH2002116 Vandewaa, E.A., Mills, G., Chen, G.Z., Foster, L.A., Bennett, J.L., Physiological role of HMG-CoA reductase in regulating egg production by Schistosoma mansoni (1989) Am J Physiol, 257, pp. R618-R625 Chen, G.Z., Foster, L., Bennett, J.L., Antischistosomal action of mevinolin: evidence that 3-hydroxy-methylglutaryl-coenzyme a reductase activity in Schistosoma mansoni is vital for parasite survival (1990) Naunyn Schmiedebergs Arch Pharmacol, 342, pp. 477-482 Holmdahl, R., Hultqvist, M., Olofsson, P., (2011) Phytol as a cholesterol lowering agent, , http://www.google.com/patents/US20110015278?hl=pt-BR&cl=en, US 20110015278 A1. Available. Accessed 18 July 2013