Atividade antineoplásica e tripanocida de Hovenia dulcis Thunb. cultivada in vivo e in vitro

Castro, Tatiana Carvalho de; Pelliccione, Victor Leonardo Bastos; Figueiredo, Maria Raquel; Soares, Renata Oliveira de Araújo; Bozza, Marcelo T.; Viana, Vera Regina Campos; Albarello, Norma; Figueiredo, Solange Faria Lua

doi:10.1590/S0102-695X2002000300047

Resumos

Muitas são as substâncias do metabolismo vegetal que têm despertado grande interesse, principalmente no setor de fármacos. No presente estudo, foram avaliadas as atividades antineoplásica e tripanocida de extratos vegetais de Hovenia dulcis (Rhamnaceae) cultivada sob condições in vivo e in vitro. Extratos metanólicos das folhas de material jovem desenvolvido in vivo e in vitro, exibiram altas porcentagens na inibição do crescimento de todas as linhagens de células tumorais testadas, enquanto extratos etanólicos do pseudofruto mostraram seletividade com elevado percentual de inibição do crescimento celular nas linhagens SP2/0 e BW. Quanto à atividade tripanocida, os extratos aquoso do pseudofruto e metanólico das folhas das plantas germinadas in vivo, apresentaram percentual de inibição em 48 h, de 95% e 100%, respectivamente.

Plants produce a wide range of secondary metabolites, many of which are pharmaceutically important. In this paper were evaluated anti-cancer and trypanocidal activities from Hovenia dulcis (Rhamnaceae) in vivo and in vitro propagated plants. Methanolic extracts of young leaves from in vivo and in vitro material were remarkably active for all tumor cells lines tested, while ethanolic extracts of pseudofruit showed high degree of selectivity against to SP2/0 and BW cells in culture. Mortality of 95 and 100% (48 h) on Trypanosoma cruzi were observed on the aqueous extract of pseudofruit and methanolic extracts of leaves from seedlings.

Atividade antineoplásica e tripanocida de Hovenia dulcis Thunb. cultivada in vivo e in vitro

Tatiana Carvalho de Castro^I,^* * labplan@uerj.br ; Victor Leonardo Bastos Pelliccione^I; Maria Raquel Figueiredo^II; Renata Oliveira de Araújo Soares^III; Marcelo T. Bozza^III; Vera Regina Campos Viana; Norma Albarello^I; Solange Faria Lua Figueiredo^I

^ILaboratório de Biotecnologia de Plantas (LABPLAN), DBAV IBRAG, Universidade do Estado do Rio de Janeiro

^IILaboratório de Química de Produtos Naturais, FIOCRUZ, Far-Manguinhos

^IIILaboratório de Farmacologia Aplicada I, FIOCRUZ, Far-Manguinhos, Rio de Janeiro, RJ, Brasil

RESUMO

Muitas são as substâncias do metabolismo vegetal que têm despertado grande interesse, principalmente no setor de fármacos. No presente estudo, foram avaliadas as atividades antineoplásica e tripanocida de extratos vegetais de Hovenia dulcis (Rhamnaceae) cultivada sob condições in vivo e in vitro. Extratos metanólicos das folhas de material jovem desenvolvido in vivo e in vitro, exibiram altas porcentagens na inibição do crescimento de todas as linhagens de células tumorais testadas, enquanto extratos etanólicos do pseudofruto mostraram seletividade com elevado percentual de inibição do crescimento celular nas linhagens SP2/0 e BW. Quanto à atividade tripanocida, os extratos aquoso do pseudofruto e metanólico das folhas das plantas germinadas in vivo, apresentaram percentual de inibição em 48 h, de 95% e 100%, respectivamente.

ABSTRACT

Plants produce a wide range of secondary metabolites, many of which are pharmaceutically important. In this paper were evaluated anti-cancer and trypanocidal activities from Hovenia dulcis (Rhamnaceae) in vivo and in vitro propagated plants. Methanolic extracts of young leaves from in vivo and in vitro material were remarkably active for all tumor cells lines tested, while ethanolic extracts of pseudofruit showed high degree of selectivity against to SP2/0 and BW cells in culture. Mortality of 95 and 100% (48 h) on Trypanosoma cruzi were observed on the aqueous extract of pseudofruit and methanolic extracts of leaves from seedlings.

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1 Baísa AM, Quiroz A, Ruíz, JA, Maldonado-Mendonza I, Loyola-Vargas VM. Growth patterns and alkaloid accumulation in hairy root and untransformed root cultures of Datura stramonium Plant Cell Tissue and Organ Culture. 1998; 54:123-130
2 Bastos NR. A Família Rhamnaceae R. Br. no Rio Grande do Sul. Gêneros: Colubrina Rich. ex Brongn., Gouania Jacq. e Hovenia Thunb. Pesquisa Botânica. 1990; 41:99-121
3 Boechat N, Carvalho AS, Fernandez-Ferreira E, Soare ROA, Souza AS, Gibaldi D, Bozza MT, Pinto AC. Novel Nitoimidazoles With Trypanocidal And Cell Growth Inhibition Activites. Cytobios. 2001; 105:83-90
4 Bongaerts RJM. The chorismate branching point in Catharanthus roseus Aspects of anthranilate synthase regulation in relation to indole alkaloid biosynthesis. Thesis (Ph.D.) Universiteit Leiden. 1998
5 Corrêa MP. Dicionário das Plantas úteis do Brasil. Imprensa Nacional. 1984; 1-5
6 Hussain RA, Lin Y, Poveda LJ, Bordas E, Chung BS, Pezzuto JM, Soejarto DD, Kinghorn D. Plant-derived sweetening agentes: saccharide and polyol constituents of some sweettasting plants. Journal Ethnopharmacology. 1990; 28(1):103- 115
7 Kennedy LM, Saul LR, Sefecka R, Stevens DA. Hodulcin: selective sweetness-reducing principle from Hovenia dulcis leaves. Chemical Senses. 1988; 13:529-543
8 Kimura Y, Kobayashi Y, Takeda Y, Ogihara Y. Three new saponins from the leaves of Hovenia dulcis Journal Chemical Society Perkin Trans. I. 1981; 1981:1923-1927
9 Kobayashi Y, Takeda T, Ogihara Y, Litaka Y. Novel dammarane triterpenoid glycosides from the leaves of Hovenia dulcis XRay crystal structure of hovenolactone monohydrate. Journal Chemical Society Perkin Trans. I. 1982; 2795-2799
10 Lisková D, Ordóńez JR, Lux A, López AP. Tissue culture of Karwinskia humbolditiana - a plant producing toxins with antitumoural effects. Plant Cell Tissue Organ Culture. 1994; 36:339-343
11 Malaquias FS, Carvalho TM, Oliveira EF, Pelliccione VLB, Gianfaldoni MG, Figueiredo MR, Henriques MGMO, Rosas EC, Viana VRC, Albarello N, Figueiredo SFL. Atividade antiinflamatória de Cleome spinosa e Hovenia dulcis cultivadas in situ e in vitro In: RESUMOs da XXII Reunião Anual sobre Evolução, Sistemática e Ecologia Micromoleculares. Rio de Janeiro, UFF. 2000; P-09
12 Martínez FJ, Durón RR, Torres NW, Pińeyro-López A. Experimental evidence for toxic damage induced by a dimeric anthracenone: diast T-514 (peroxisomicine A2). Toxicology Letters. 1997; 90:152-162
13 Murashige T, Skoog F. A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiologia Plantarum. 1962; 15:473-497
14 Popoca J, Aguilar A, Alonso D, Villarrea ML. Cytotoxic activity of selected plants used as antitumorals in Mexican traditional medicine. Journal Ethnopharmacology. 1998; 59:173-177
15 Rosas LV, Campos FR, Nascimento SKR, Januário AH, Pereira PS, França SC, Cordeiro MSC, Toldo MPA, Albuquerque S. Avaliação da atividade tripanomicida de extratos de Ampelozizyphus amazonicus Ducke (Rhamnaceae). In: RESUMOs da IV Jornada Paulista de Plantas Medicinais. Ribeirão Preto, UNAERP. 1999; pag.88
16 Suttisri R, Lee I, Kinghorn AD. Plant-derived triterpenoid sweetness inhibitors. Journal Ethnopharmacology 1995; 47(1):9-26
17 Waksman N, Benevides-Cortez G, Rivas-Galindo V. Biologicallly active anthracenones from roots of Karwinskia parvifolia Phytochemistry. 1999; 50:1041-1046
18 Yoshikawa K, Tumura S, Yamada K, Arihara S. Antisweet natural products: VII. Hodulosides I, II, III e IV, and V from the leaves of Hovenia dulcis Thunb. Chemical Phamarceutical Bulletim. 1992; 40(9):2287-2291
19 Yoshikawa K, Nagai Y, Yoshida M, Arihara S. Antisweet natural products. VIII. Structures of hodulosides VI-X from Hovenia dulcis Thunb. var. tomentella Makino. Chemical Pharmaceutical Bulletim. 1993; 41(10):1722-1725
20 Yoshikawa M, Ueda T, Muraoka O, Aoyama H, Matsuda H, Shimoda H, Yamahara J, Murakami N. Absolute stereostructures of hovenidulciosides A1 and A2, bioactive novel triterpene glycosides from hoveniae semen seu fructus, the seeds and fruit of Hovenia dulcis Thunb. Chemical Pharmaceutical Bulletim. 1995; 43(3):532-534
21 Yoshikawa M, Murakami T, Ueda T, Matsuda H, Yamahara J, Murakami N. Bioactive saponins and glycosides. IV. Four methyl-migrated 16,17-seco-dammarane triterpene glycosides from chinese natural medicine, hoveniae semen seu fructus, the seeds and fruit of Hovenia dulcis Thunb.: Absolute stereostructures and inhibitory activity on histamine release of hovenidulciosides A1, A2, B1, and B2. Chemical Pharmaceutical Bulletim. 1996; 44(9):1736-1743
22 Yoshikawa M, Murakami T, Ueda T, Yoshizumi S, Ninomiya K, Murakami N, Matsuda H, Saito M, Fujii W, Tanaka T, Yamahara J. Bioactive constituents of Chinese natural medicines. III. Absolute stereostructures of new dihydroflavonols, hovenitins I, II and III, isolated from hoveniae semen seu fructus, the seed and fruit of Hovenia dulcis Thunb. (Rhamnaceae): inhibitory effect on alcohol-induced muscular relaxation and hepaprotective activity. Yakugaku Zasshi. 1997; 117(2):108-118
23 Yoshimatsu K, Kazuya A, Shimomura K. Clonal propagation of Cephaelis ipecacuanha (II): Characteristics of regenerated plants field-cultivated in two districts. Journal Plant Physiology. 1994; 144:22-25

*

labplan@uerj.br

Datas de Publicação

Publicação nesta coleção
05 Out 2009
Data do Fascículo
2002

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

[1] 1 Baísa AM, Quiroz A, Ruíz, JA, Maldonado-Mendonza I, Loyola-Vargas VM. Growth patterns and alkaloid accumulation in hairy root and untransformed root cultures of Datura stramonium Plant Cell Tissue and Organ Culture. 1998; 54:123-130

[2] 2 Bastos NR. A Família Rhamnaceae R. Br. no Rio Grande do Sul. Gêneros: Colubrina Rich. ex Brongn., Gouania Jacq. e Hovenia Thunb. Pesquisa Botânica. 1990; 41:99-121

[3] 3 Boechat N, Carvalho AS, Fernandez-Ferreira E, Soare ROA, Souza AS, Gibaldi D, Bozza MT, Pinto AC. Novel Nitoimidazoles With Trypanocidal And Cell Growth Inhibition Activites. Cytobios. 2001; 105:83-90

[4] 4 Bongaerts RJM. The chorismate branching point in Catharanthus roseus Aspects of anthranilate synthase regulation in relation to indole alkaloid biosynthesis. Thesis (Ph.D.) Universiteit Leiden. 1998

[5] 5 Corrêa MP. Dicionário das Plantas úteis do Brasil. Imprensa Nacional. 1984; 1-5

[6] 6 Hussain RA, Lin Y, Poveda LJ, Bordas E, Chung BS, Pezzuto JM, Soejarto DD, Kinghorn D. Plant-derived sweetening agentes: saccharide and polyol constituents of some sweettasting plants. Journal Ethnopharmacology. 1990; 28(1):103- 115

[7] 7 Kennedy LM, Saul LR, Sefecka R, Stevens DA. Hodulcin: selective sweetness-reducing principle from Hovenia dulcis leaves. Chemical Senses. 1988; 13:529-543

[8] 8 Kimura Y, Kobayashi Y, Takeda Y, Ogihara Y. Three new saponins from the leaves of Hovenia dulcis Journal Chemical Society Perkin Trans. I. 1981; 1981:1923-1927

[9] 9 Kobayashi Y, Takeda T, Ogihara Y, Litaka Y. Novel dammarane triterpenoid glycosides from the leaves of Hovenia dulcis XRay crystal structure of hovenolactone monohydrate. Journal Chemical Society Perkin Trans. I. 1982; 2795-2799

[10] 10 Lisková D, Ordóńez JR, Lux A, López AP. Tissue culture of Karwinskia humbolditiana - a plant producing toxins with antitumoural effects. Plant Cell Tissue Organ Culture. 1994; 36:339-343

[11] 11 Malaquias FS, Carvalho TM, Oliveira EF, Pelliccione VLB, Gianfaldoni MG, Figueiredo MR, Henriques MGMO, Rosas EC, Viana VRC, Albarello N, Figueiredo SFL. Atividade antiinflamatória de Cleome spinosa e Hovenia dulcis cultivadas in situ e in vitro In: RESUMOs da XXII Reunião Anual sobre Evolução, Sistemática e Ecologia Micromoleculares. Rio de Janeiro, UFF. 2000; P-09

[12] 12 Martínez FJ, Durón RR, Torres NW, Pińeyro-López A. Experimental evidence for toxic damage induced by a dimeric anthracenone: diast T-514 (peroxisomicine A2). Toxicology Letters. 1997; 90:152-162

[13] 13 Murashige T, Skoog F. A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiologia Plantarum. 1962; 15:473-497

[14] 14 Popoca J, Aguilar A, Alonso D, Villarrea ML. Cytotoxic activity of selected plants used as antitumorals in Mexican traditional medicine. Journal Ethnopharmacology. 1998; 59:173-177

[15] 15 Rosas LV, Campos FR, Nascimento SKR, Januário AH, Pereira PS, França SC, Cordeiro MSC, Toldo MPA, Albuquerque S. Avaliação da atividade tripanomicida de extratos de Ampelozizyphus amazonicus Ducke (Rhamnaceae). In: RESUMOs da IV Jornada Paulista de Plantas Medicinais. Ribeirão Preto, UNAERP. 1999; pag.88

[16] 16 Suttisri R, Lee I, Kinghorn AD. Plant-derived triterpenoid sweetness inhibitors. Journal Ethnopharmacology 1995; 47(1):9-26

[17] 17 Waksman N, Benevides-Cortez G, Rivas-Galindo V. Biologicallly active anthracenones from roots of Karwinskia parvifolia Phytochemistry. 1999; 50:1041-1046

[18] 18 Yoshikawa K, Tumura S, Yamada K, Arihara S. Antisweet natural products: VII. Hodulosides I, II, III e IV, and V from the leaves of Hovenia dulcis Thunb. Chemical Phamarceutical Bulletim. 1992; 40(9):2287-2291

[19] 19 Yoshikawa K, Nagai Y, Yoshida M, Arihara S. Antisweet natural products. VIII. Structures of hodulosides VI-X from Hovenia dulcis Thunb. var. tomentella Makino. Chemical Pharmaceutical Bulletim. 1993; 41(10):1722-1725

[20] 20 Yoshikawa M, Ueda T, Muraoka O, Aoyama H, Matsuda H, Shimoda H, Yamahara J, Murakami N. Absolute stereostructures of hovenidulciosides A1 and A2, bioactive novel triterpene glycosides from hoveniae semen seu fructus, the seeds and fruit of Hovenia dulcis Thunb. Chemical Pharmaceutical Bulletim. 1995; 43(3):532-534

[21] 21 Yoshikawa M, Murakami T, Ueda T, Matsuda H, Yamahara J, Murakami N. Bioactive saponins and glycosides. IV. Four methyl-migrated 16,17-seco-dammarane triterpene glycosides from chinese natural medicine, hoveniae semen seu fructus, the seeds and fruit of Hovenia dulcis Thunb.: Absolute stereostructures and inhibitory activity on histamine release of hovenidulciosides A1, A2, B1, and B2. Chemical Pharmaceutical Bulletim. 1996; 44(9):1736-1743

[22] 22 Yoshikawa M, Murakami T, Ueda T, Yoshizumi S, Ninomiya K, Murakami N, Matsuda H, Saito M, Fujii W, Tanaka T, Yamahara J. Bioactive constituents of Chinese natural medicines. III. Absolute stereostructures of new dihydroflavonols, hovenitins I, II and III, isolated from hoveniae semen seu fructus, the seed and fruit of Hovenia dulcis Thunb. (Rhamnaceae): inhibitory effect on alcohol-induced muscular relaxation and hepaprotective activity. Yakugaku Zasshi. 1997; 117(2):108-118

[23] 23 Yoshimatsu K, Kazuya A, Shimomura K. Clonal propagation of Cephaelis ipecacuanha (II): Characteristics of regenerated plants field-cultivated in two districts. Journal Plant Physiology. 1994; 144:22-25