Chemical composition, antiparasitic and cytotoxic activities of aqueous extracts of Ziziphus joazeiro Mart
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摘要
Objective: To compare the in vitro antiparasitic activity of aqueous extracts from Ziziphus joazeiro leaves and stem bark against Trypanosoma cruzi, Leishmania braziliensis, and Leishmania infantum, as well as to evaluate its cytotoxicity in mammalian cells, in addition to identifying the chemical composition of the extracts. Methods: Ziziphus joazeiro leaf and stem bark aqueous extracts were prepared by cold extraction maceration and subjected to ultra-efficient liquid chromatography coupled to a quadrupole/time of flight system. The susceptibility assays used Trypanosoma cruzi CLB5 strains and promastigote forms of Leishmania braziliensis and Leishmania infantum for antiparasitic activity of the extracts. Moreover, mammalian fibroblasts NCTC clone 929 were used for cytotoxicity analysis. Results: Terpenoid compounds, flavonoids and phenolic acid were identified in extracts. The stem bark aqueous extracts presented more significant results in terms of antiparasitic activity compared with the leaf aqueous extracts, especially against Leishmania braziliensis and Leishmania infantum promastigote forms with an IC50 < 500 μg/mL. The cytotoxicity evaluation showed moderate toxicity of the stem bark aqueous extracts, which is relevant information for the rational use of this plant part since it is widely used by the population. Conclusions: These preliminary results may contribute to the formulation of new therapeutic agents against this group of neglected diseases, so further investigations are required to delineate the mechanisms of action mainly of the aqueous extract of stem bark of Ziziphus joazeiro.
Objective: To compare the in vitro antiparasitic activity of aqueous extracts from Ziziphus joazeiro leaves and stem bark against Trypanosoma cruzi, Leishmania braziliensis, and Leishmania infantum, as well as to evaluate its cytotoxicity in mammalian cells, in addition to identifying the chemical composition of the extracts. Methods: Ziziphus joazeiro leaf and stem bark aqueous extracts were prepared by cold extraction maceration and subjected to ultra-efficient liquid chromatography coupled to a quadrupole/time of flight system. The susceptibility assays used Trypanosoma cruzi CLB5 strains and promastigote forms of Leishmania braziliensis and Leishmania infantum for antiparasitic activity of the extracts. Moreover, mammalian fibroblasts NCTC clone 929 were used for cytotoxicity analysis. Results: Terpenoid compounds, flavonoids and phenolic acid were identified in extracts. The stem bark aqueous extracts presented more significant results in terms of antiparasitic activity compared with the leaf aqueous extracts, especially against Leishmania braziliensis and Leishmania infantum promastigote forms with an IC50 < 500 μg/mL. The cytotoxicity evaluation showed moderate toxicity of the stem bark aqueous extracts, which is relevant information for the rational use of this plant part since it is widely used by the population. Conclusions: These preliminary results may contribute to the formulation of new therapeutic agents against this group of neglected diseases, so further investigations are required to delineate the mechanisms of action mainly of the aqueous extract of stem bark of Ziziphus joazeiro.
Objective: To compare the in vitro antiparasitic activity of aqueous extracts from Ziziphus joazeiro leaves and stem bark against Trypanosoma cruzi, Leishmania braziliensis, and Leishmania infantum, as well as to evaluate its cytotoxicity in mammalian cells, in addition to identifying the chemical composition of the extracts. Methods: Ziziphus joazeiro leaf and stem bark aqueous extracts were prepared by cold extraction maceration and subjected to ultra-efficient liquid chromatography coupled to a quadrupole/time of flight system. The susceptibility assays used Trypanosoma cruzi CLB5 strains and promastigote forms of Leishmania braziliensis and Leishmania infantum for antiparasitic activity of the extracts. Moreover, mammalian fibroblasts NCTC clone 929 were used for cytotoxicity analysis. Results: Terpenoid compounds, flavonoids and phenolic acid were identified in extracts. The stem bark aqueous extracts presented more significant results in terms of antiparasitic activity compared with the leaf aqueous extracts, especially against Leishmania braziliensis and Leishmania infantum promastigote forms with an IC50 < 500 μg/mL. The cytotoxicity evaluation showed moderate toxicity of the stem bark aqueous extracts, which is relevant information for the rational use of this plant part since it is widely used by the population. Conclusions: These preliminary results may contribute to the formulation of new therapeutic agents against this group of neglected diseases, so further investigations are required to delineate the mechanisms of action mainly of the aqueous extract of stem bark of Ziziphus joazeiro.
引文
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[8]Mennai I,Hanfer M,Esseid C,Benayache S,Ameddah S,Menad A,et al.Chemical composition,in vitro antiparasitic,antimicrobial and antioxidant activities of Frankenia thymifolia Desf.Nat Prod Res 2019;24:1-6.Doi:10.1080/14786419.2018.1561685.
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[12]Santos CS,Gomes AMT,Souza FS,Marques SC,Lobo MP,Oliveira DC.Representa??es sociais de profissionais de saúde sobre doen?as negligenciadas.Esc Anna Nery 2017;21(1):1-9.Doi:10.5935/1414-8145.20170016.
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[14]Silva EL,Nicoletti MA.Controle e tratamento das doen?as negligenciadas:vis?o da situa??o atual.Rev Saúde 2013;7(3):65-81.
[15]Freitas AVL,Coelho MFB,Pereira YB,Freitas Neto EC,Azevedo RAB.Diversidade e usos de plantas medicinais nos quintais da comunidade de S?o Jo?o da Várzea em Mossoró,RN.Rev Bras Pl Med 2015;17(4):845-856.Doi:10.1590/1983-084X/14_080.
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[18]Matos FJA.Farmácias vivas.4 ed.Fortaleza,CE:Editora UFC;2002,p.36-40.
[19]Le Senne A,Muelas-Serrano S,Fernandez-Portillo C,Escario Já,Gómez-Barrio A.Biological characterization of a beta-galactosidase expressing clone of Trypanosoma cruzi CL strain.Mem Inst Oswaldo Cruz2002;97:1101-1105.
[20]Vega C,Rolón M,Martínez-Fernández AR,Escario JA,Gómez-Barrio A.A new pharmacological screening assay with Trypanosoma cruzi epimastigotes expressing beta-galactosidase.Parasitol Res 2005;95:296-298.
[21]Mikus J,Steverding D.A simple colorimetric method to screen drug cytotoxicity against Leishmania using dye Alamar Blue?.Parasitol Int2000;48:265-259.
[22]Rolón M,Seco E,Vega C,Nogal JJ,Escario JA,Gómez-Barrio A,et al.Selective activity of polyene macrolides produced by genetically modified Streptomyces on Trypanosoma cruzi.Int J Antimicrob Agents2006;28:104-109.
[23]Kaleem WA,Muhammad N,Khan H,Rauf A.Pharmacological and phytochemical studies of genus Zizyphus.Int J Sci Res 2014;21(8):1243-1263.Doi:10.5829/idosi.mejsr.2014.21.08.21099.
[24]Pu Y,Ding T,Zhang N,Jiang P,Liu D.Identification of bitter compounds from dried fruit of Ziziphus jujuba cv.Junzao.Int J Food Prop 2017;20:1-34.Doi:10.1080/10942912.2017.1288133.
[25]Brito SMO,Coutinho HDM,Talvani A,Coronel C,Barbosa AGR,Veja C,et al.Analysis of bioactivities and chemical composition of Ziziphus joazeiro Mart.using HPLC-DAD.Food Chem 2015;1(186):185-191.Doi:10.1016/j.foodchem.2014.10.031.
[26]Gomes DC,Lima HG,Vaza AV,Santos NS,Santos FO,DiasêR,et al.In vitro anthelmintic activity of the Zizyphus joazeiro bark against gastrointestinal nematodes of goats and its cytotoxicity on Vero cells.Vet Parasitol 2016;15(226):10-16.Doi:10.1016/j.vetpar.2016.06.004.
[27]Faria RX,Souza ALA,Lima B,Tietbohl LAC,Fernandes CP,Amaral RR,et al.Plants of Brazilian restingas with tripanocide activity against Trypanosoma cruzi strains.J Bioenerg Biomembr 2017;49(6):473-483.Doi:10.1007/s10863-017-9733-9.
[28]Kim AD,Kang KA,Zhang R,Lim CM,Kim HS,Kim DH,et al.Ginseng saponin metabolite induces apoptosis in MCF-7 breast cancer cells through the modulation of AMP-activated protein kinase.Environ Toxicol Pharmacol 2010;30(2):134-140.Doi:10.1016/j.etap.2010.04.008.
[29]Li N,Wu CF,Xu XY,Liu ZY,Li X,Zhao YQ.Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum.Eur J Med Chem 2012;50:173-178.Doi:10.1016/j.ejmech.2012.01.052.
[30]Hu Q,Chen YY,Jiao QY,Khan A,Li F,Han DF,et al.Triterpenoid saponins from the pulp of Sapindus mukorossi and their antifungal activities Qingwen.Phytochemistry 2018;147:1-8.Doi:10.1016/j.phytochem.2017.12.004.
[31]Qu L,Wang J,Ruan J,Yao X,Huang P,Wang Y,et al.Spirostane-type saponins obtained from Yucca schidigera.Molecules 2018;23(1):2-12.Doi:10.3390/molecules23010167.
[32]Wina E,Muetzel S,Becker K.The impact of saponins or saponincontaining plant materials on ruminant production-A review.J Agric Food Chem 2005;53(21):8093-8105.Doi:10.1021/jf048053d.
[33]Moses T,Pollier J,Almagro L,Buyst D,Montagu MV,Pedre?o MA,et al.Combinatorial biosynthesis of sapogenins and saponins in Saccharomyces cerevisiae using a C-16毩hydroxylase from Bupleurum falcatum.Proc Natl Acad Sci U S A 2014;111(4):1634-1639.Doi:10.1371/journal.pone.0165954.
[34]Podolak I,Galanty A,Sobolewska D.Saponins as cytotoxic agents:Areview.Phytochem Rev 2010;9(3):425-474.Doi:10.1007/s11101-010-9183-z.
[2]Vasconcelos RS,Kovaleski DF,Tesser Junior ZC.Doen?as negligenciadas:Revis?o da literatura sobre as interven??es propostas.Saúde Transforma??o Soc 2016;6(2):114-131.
[3]Reis ACMS,Borges DPL,D’ávila VCGF,Barbosa MS,Ternes YMF,Santiago SB,et al.O cenário de políticas públicas do brasil diante do quadro das doen?as negligenciadas.Saúde Ciência em A??o 2016;2(2):99-107.
[4]Morais-Braga MFB,Souza TM,Santos KKA,Andrade JC,Guedes GMM,Tintino SR,et al.Citotocixidade e atividade antiparasitária de Lygodium venustum SW.Acta Toxicol Argent 2013;21(1):50-56.
[5]DNDi.Diseases and projects.[Online]Available from:https://www.dndial.org/doencas/doenca-chagas/[Accessed on 22 Jan 2017].
[6]World Health Organization.Información general:Enfermedad de Chagas.[Online]Available from:http://www.paho.org/hq/index.php?option=com_content&view=article&id=5856&Itemid=41506&lang=es226[Accessed on 15 Dec 2017].
[7]Gontijo B,Carvalho MLR.Leishmaniose tegumentar americana.Rev Soc Bras Med Trop 2003;36(1):71-80.Doi:10.1590/S0037-86822003000100011.
[8]Mennai I,Hanfer M,Esseid C,Benayache S,Ameddah S,Menad A,et al.Chemical composition,in vitro antiparasitic,antimicrobial and antioxidant activities of Frankenia thymifolia Desf.Nat Prod Res 2019;24:1-6.Doi:10.1080/14786419.2018.1561685.
[9]Chappuis F,Sundar S,Hailu A,Ghalib H,Rijal S,Peeling RW,et al.Visceral leishmaniasis:What are the needs for diagnosis,treatment and control?Nat Rev Microbiol 2007;5(11):873-882.Doi:10.1038/nrmicro1748.
[10]World Health Organization.Clinical forms of the leishmaniases.[Online]Available from:http://www.who.int/leishmaniasis/disease/en/[Accessed on 23 Jan 2018].
[11]Organiza??o Panamericana da Saúde-OPAS/OMS.Leishmanioses:Informe Epidemiológico das Américas.Informe Leishmanioses No7.[Online]Available from:http://iris.paho.org/xmlui/bitstream/handle/123456789/34857/Leish Report6_por.pdf?sequence=5[Accessed on 22 Jan 2018].
[12]Santos CS,Gomes AMT,Souza FS,Marques SC,Lobo MP,Oliveira DC.Representa??es sociais de profissionais de saúde sobre doen?as negligenciadas.Esc Anna Nery 2017;21(1):1-9.Doi:10.5935/1414-8145.20170016.
[13]Gontijo CMF,Melo MN.Leishmaniose Visceral no Brasil:quadro atual,desafios e perspectivas.Rev Bras Epidemiol 2004;7(3):338-349.Doi:10.1590/S1415-790X2004000300011.
[14]Silva EL,Nicoletti MA.Controle e tratamento das doen?as negligenciadas:vis?o da situa??o atual.Rev Saúde 2013;7(3):65-81.
[15]Freitas AVL,Coelho MFB,Pereira YB,Freitas Neto EC,Azevedo RAB.Diversidade e usos de plantas medicinais nos quintais da comunidade de S?o Jo?o da Várzea em Mossoró,RN.Rev Bras Pl Med 2015;17(4):845-856.Doi:10.1590/1983-084X/14_080.
[16]Almeida CFCBR,Silva TCL,Amorim ELC,Maia MBS,Albuquerque UP.Life strategy and chemical composition as predictors of the selection of medicinal plants from the Caatinga(Northeast Brazil).J Arid Environ2005;62:127-142.
[17]Nisar M,Adzu B,Inamullah K,Bashir A,Ihsan A,Gilani AH.Antinociceptive and antipyretic activities of the Zizyphus oxyphylla Edgew.Leaves.Phytother Res 2007;21(7):693-695.Doi:10.1002/ptr.2139.
[18]Matos FJA.Farmácias vivas.4 ed.Fortaleza,CE:Editora UFC;2002,p.36-40.
[19]Le Senne A,Muelas-Serrano S,Fernandez-Portillo C,Escario Já,Gómez-Barrio A.Biological characterization of a beta-galactosidase expressing clone of Trypanosoma cruzi CL strain.Mem Inst Oswaldo Cruz2002;97:1101-1105.
[20]Vega C,Rolón M,Martínez-Fernández AR,Escario JA,Gómez-Barrio A.A new pharmacological screening assay with Trypanosoma cruzi epimastigotes expressing beta-galactosidase.Parasitol Res 2005;95:296-298.
[21]Mikus J,Steverding D.A simple colorimetric method to screen drug cytotoxicity against Leishmania using dye Alamar Blue?.Parasitol Int2000;48:265-259.
[22]Rolón M,Seco E,Vega C,Nogal JJ,Escario JA,Gómez-Barrio A,et al.Selective activity of polyene macrolides produced by genetically modified Streptomyces on Trypanosoma cruzi.Int J Antimicrob Agents2006;28:104-109.
[23]Kaleem WA,Muhammad N,Khan H,Rauf A.Pharmacological and phytochemical studies of genus Zizyphus.Int J Sci Res 2014;21(8):1243-1263.Doi:10.5829/idosi.mejsr.2014.21.08.21099.
[24]Pu Y,Ding T,Zhang N,Jiang P,Liu D.Identification of bitter compounds from dried fruit of Ziziphus jujuba cv.Junzao.Int J Food Prop 2017;20:1-34.Doi:10.1080/10942912.2017.1288133.
[25]Brito SMO,Coutinho HDM,Talvani A,Coronel C,Barbosa AGR,Veja C,et al.Analysis of bioactivities and chemical composition of Ziziphus joazeiro Mart.using HPLC-DAD.Food Chem 2015;1(186):185-191.Doi:10.1016/j.foodchem.2014.10.031.
[26]Gomes DC,Lima HG,Vaza AV,Santos NS,Santos FO,DiasêR,et al.In vitro anthelmintic activity of the Zizyphus joazeiro bark against gastrointestinal nematodes of goats and its cytotoxicity on Vero cells.Vet Parasitol 2016;15(226):10-16.Doi:10.1016/j.vetpar.2016.06.004.
[27]Faria RX,Souza ALA,Lima B,Tietbohl LAC,Fernandes CP,Amaral RR,et al.Plants of Brazilian restingas with tripanocide activity against Trypanosoma cruzi strains.J Bioenerg Biomembr 2017;49(6):473-483.Doi:10.1007/s10863-017-9733-9.
[28]Kim AD,Kang KA,Zhang R,Lim CM,Kim HS,Kim DH,et al.Ginseng saponin metabolite induces apoptosis in MCF-7 breast cancer cells through the modulation of AMP-activated protein kinase.Environ Toxicol Pharmacol 2010;30(2):134-140.Doi:10.1016/j.etap.2010.04.008.
[29]Li N,Wu CF,Xu XY,Liu ZY,Li X,Zhao YQ.Triterpenes possessing an unprecedented skeleton isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum.Eur J Med Chem 2012;50:173-178.Doi:10.1016/j.ejmech.2012.01.052.
[30]Hu Q,Chen YY,Jiao QY,Khan A,Li F,Han DF,et al.Triterpenoid saponins from the pulp of Sapindus mukorossi and their antifungal activities Qingwen.Phytochemistry 2018;147:1-8.Doi:10.1016/j.phytochem.2017.12.004.
[31]Qu L,Wang J,Ruan J,Yao X,Huang P,Wang Y,et al.Spirostane-type saponins obtained from Yucca schidigera.Molecules 2018;23(1):2-12.Doi:10.3390/molecules23010167.
[32]Wina E,Muetzel S,Becker K.The impact of saponins or saponincontaining plant materials on ruminant production-A review.J Agric Food Chem 2005;53(21):8093-8105.Doi:10.1021/jf048053d.
[33]Moses T,Pollier J,Almagro L,Buyst D,Montagu MV,Pedre?o MA,et al.Combinatorial biosynthesis of sapogenins and saponins in Saccharomyces cerevisiae using a C-16毩hydroxylase from Bupleurum falcatum.Proc Natl Acad Sci U S A 2014;111(4):1634-1639.Doi:10.1371/journal.pone.0165954.
[34]Podolak I,Galanty A,Sobolewska D.Saponins as cytotoxic agents:Areview.Phytochem Rev 2010;9(3):425-474.Doi:10.1007/s11101-010-9183-z.