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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Research Article

Antitumoral and Anticholinesterasic Activities of the Seven Species from Rubiaceae

Author(s): Carla R.F. Volobuff, Pedro C.O. Junior, Sidney M. dos Santos, Zefa V. Pereira, Diego C. Ferreira, Claudia A.L. Cardoso, Ana L.T.G. Ruiz, Mary A. Foglio, João E. de Carvalho and Anelise S.N. Formagio*

Volume 20, Issue 4, 2019

Page: [302 - 308] Pages: 7

DOI: 10.2174/1389201020666190211154550

Price: $65

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Abstract

Background: The genus Psychotria and Palicourea are reported as a source of alkaloids and iridoids, which exhibit biological activities. This study aimed to evaluate antiproliferative and anticholinesterase activities and quantification of the alkaloids of seven species among the genus found in Mato Grosso do Sul region in Brazil.

Methods: Concentrations of alkaloids were measured spectrophotometrically. The extracts were submitted to antiproliferative activity against ten cell lines. The anticholinesterase activity of the extracts was developed using brain structures of male Wistar rats: cerebral cortex, hippocampus, hypothalamus and striatum by the Ellman method.

Results: Alkaloids from Psychotria and Palicourea species were quantified which showed values of 47.6 to 21.9 µg/g. Regarding the antiproliferative potential, Palicourea crocea demonstrated selectivity against the 786-0 cell line (GI50: 22.87 µg/mL). Psychotria leiocarpa inhibited cell growth against OVCAR-3 (GI50: 3.28 µg/mL), K-562 (GI50: 5.26 µg/mL), HaCaT (GI50: 27.20 µg/mL), PC-3 (GI50: 34.92 µg/mL), MCF-7 (GI50: 35.80 µg/mL) and P. capillacea showed activity against OVCAR-3 (GI50: 2.33 µg/ml) and U251 (GI50: 16.66 µg/ml). The effect of acetylcholinesterase inhibition was more effective in the hippocampus, demonstrating inhibition for Paliourea crocea, Psychotria deflexa, P. brachybotrya and P. leiocarpa of 70%, 57%, 50% and 40%, respectively, followed by P. poeppigiana and P. capillacea, inhibiting 21%, compared to the control.

Conclusion: Herein, the present work showed for the first time, anticholinesterasic and antiproliferative activities of extracts of Palicourea and Psychotria seem to be mainly associated with the levels of alkaloids in the leaves of these species.

Keywords: Alkaloids, anticholinesterasic, antiproliferative, Psychotria, Palicourea, biological activity.

Graphical Abstract
[1]
Liwszyc, G.E.; Vourib, I.; Rasanenb, J.; Issakainen, J. Daime - a ritual herbal potion. J. Ethnopharmacol., 1992, 36, 91-92.
[2]
McKenna, D.J.; Towers, G.H.; Abbott, F. Monoamine oxidase inhibitors in South American hallucinogenic plants: Trypatamine and β-carboline constituents of Ayahusca. J. Ethnopharmacol., 1984, 10, 195-223.
[3]
Ribeiro, M.A.S.; Gomes, C.M.B.; Formagio, A.S.N.; Pereira, Z.V.; Melo, U.Z.; Basso, E.A.; Sarragiotto, M.H. Structural characterization of dimeric índole alkaloids from Psychotria brachybotrya by NMR spectroscopy and theoretical calculations. Tetrahedron Lett., 2016, 57, 1331-1334.
[4]
Cragg, G.M.; Newman, D.J.; Yang, S.S. Natural product extracts of plants and marine origin having antileukemia potential The NCI experience. J. Nat. Prod., 2006, 69, 488-498.
[5]
Lopes, S.; von Poser, G.L.; Kerber, V.A.; Farias, F.M.; Konrath, E.L.; Moreno, P.; Sobral, M.E.; Zuanazzi, J.A.S.; Henriques, A.T. Taxonomic significance of alkaloids and iridoid glucosides in the tribe Psychotrieae (Rubiaceae). Biochem. Syst. Ecol., 2004, 32, 1187-1195.
[6]
Souza, D.C.; Souza, M.C. Levantamento florístico das tribos Psychotrieae, Coussareeae e Morindeae (Rubiaceae) na região de Porto Rico, alto rio Paraná. Acta Scientiarum, 1998, 20, 207-212.
[7]
Pereira, Z.V.; Kinoshita, L.S. Rubiaceae Juss. do Parque Estadual das Várzeas do Rio Ivinhema, MS, Brasil. Hoehnea. Fap UNIFESP (SciELO), 2013, 40(2), 205-251.
[8]
Barbosa, M.R.V. Check-list das Rubiaceae do estado Mato Grosso do Sul, Brasil. Iheringia Ser. Bot., 2018, 73, 335-341.
[9]
Düsman, L.T.; Jorge, T.C.M.; Souza, M.C. Monoterpene Indole Alkaloids from Palicourea crocea. J. Nat. Prod., 2004, 67, 1886-1888.
[10]
Narine, L.L.; Maxwell, A.R. Monoterpenoid indole alkaloids from Palicourea crocea. Phytochem. Lett., 2009, 2, 34-36.
[11]
Berger, A.; Kostyan, M.K.; Klose, S.I. Loganin and secologanin derived tryptamine-iridoid alkaloids from Palicourea crocea and Palicourea padifolia (Rubiaceae). Phytochemistry, 2015, 116, 162-169.
[12]
Berger, A.; Preinfalf, A.; Robien, W.; Brecker, L.; Valant-Vetschera, K.; Schinnerl, J. New reports on flavonoids, benzoic- and chlorogenic acids as rare features in the Psychotria alliance (Rubiaceae). Biochem. Syst. Ecol., 2016, 66, 145-153.
[13]
Ribeiro, M.A.S.; Gomes, C.M.B.; Formagio, A.S.N.; Pereira, Z.V.; Melo, U.Z.; Basso, E.A.; Sarragiotto, M.H. Structural characterization of dimeric índole alkaloids from Psychotria brachybotrya by NMR spectroscopy and theoretical calculations. Tetrahedron Lett., 2016, 57, 1331-1334.
[14]
Araújo, R.C.P.; Neves, F.A.R.; Formagio, A.S.N.; Kassuya, C.A.L.; Stefanello, M.E.A.; Souza, V.V.; Pavan, F.R.; Croda, J. Evaluation of the anti-Mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic. BMC Complement. Altern. Med., 2014, 14, 209.
[15]
Lopes, S.O.; Moreno, P.R.H.; Henriques, A.T. Growth characteristics and chemical analysis of Psychotria carthagenensis cell suspension cultures. Enzyme Microb. Technol., 2000, 26, 259-264.
[16]
Formagio, A.S.N.; Volobuff, C.R.F.; Santiago, M.; Cardoso, C.A.L.; Vieira, M.C.; Pereira, Z.V. Evaluation of antioxidant activity, total flavonoids, tannins and phenolic compounds in Psychotria leaf extracts. Antioxidants, 2014, 3, 745-757.
[17]
Bertelli, P.R.; Biegelmeyer, R.; Rico, E.P.; Klein-Junior, L.C.; Toson, N.S.B.; Minetto, L.; Bordignon, S.A.L.; Gasper, A.L.; Moura, S.; de Oliveira, D.L.; Henriques, A.T. Toxicological profile and acetylcholinesterase inhibitory potential of Palicourea deflexa, a source of β-carboline alkaloids. Comp. Biochem. Physiol., 2017, 201, 44-50.
[18]
Matsuura, H.N.; Fett-Neto, A.G. The major indole alkaloid N, β-D-glucopyranosyl vincosamide from leaves of Psychotria leiocarpa Cham. & Schltdl. is not an antifeedant but shows broad antioxidant activity. Nat. Prod. Res., 2013, 27, 402-411.
[19]
Moraes, T.M.S.; de Araújo, M.H.; Bernardes, N.R.; de Oliveira, D.B.; Lasunskaia, E.B.; Muzitano, M.F.; Da Cunha, M. Antimycobacterial activity and alkaloid prospection of Psychotria species (Rubiaceae) from the Brazilian Atlantic Rainforest. Planta Med., 2011, 77, 964-970.
[20]
Elisabetsky, E.; Amador, T.A.; Leal, M.B.; Nunes, D.S.; Carvalho, A.C.T.; Verotta, L. Merging ethnopharmacology with chemotaxonomy: an approach to unveil bioactive natural products. The case of Psychotria alkaloids as potential analgesics. Ciênc. Cult. J. Braz. Assoc. Adv. Sci., 1997, 49, 378-385.
[21]
Villasmil, J.; Abad, M.J.; Arsenak, M.; Fernández, A.; Ruiz, M.C.; Williams, B.; Michelangeli, F.; Herrera, F.; Taylor, P. Citotoxic and antitumor activities of Venezuelan plant extracts in vitro and in vivo. Pharmacologyonline, 2006, 3, 808-816.
[22]
Caballero-George, C.; Vanderheyden, P.M.L.; Solis, P.N.; Pieters, L.; Shahat, A.A.; Gupta, M.P.; Vauquelin, G.; Vlietinck, A.J. Biological screening of selected medicinal Panamanian plants by radioligand-binding techniques. Phytomedicine, 2001, 8, 59-70.
[23]
Oliveira, M.A.C.; Albuquerque, M.M.; Xavier, H.S.; Strattmann, R.R.; Grangeiro Júnior, S.; Queiroz, A.T. Development and validation of a method for the quantification of total alkaloids as berberine in an herbal medicine containing Berberis vulgaris L. Rev. Bras. Farmacogn., 2006, 16, 357-364.
[24]
Monks, A.; Scudiero, D.; Skehan, P.; Shoemaker, R.; Paull, K.; Vistica, D.; Hose, C.; Langley, J.; Cronise, P.; Vaigro-Wolff, A.; Gray-Goodrich, M.; Campbell, H.; Mayo, J.; Boyd, M. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J. Natl. Cancer Inst., 1991, 83, 757-766.
[25]
Ellman, G.L.; Courtney, K.D.; Andres, V.; Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 1961, 7, 88-95.
[26]
Bradford, M.M. A rapid and sensitive method for quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 1976, 72, 248-254.
[27]
Faria, E.O.; Kato, L.; de Oliveira, C.M.A.; Carvalho, B.G.; Silva, C.C.; Sales, L.S.; Schuquel, I.T.A.; Silveira-Lacerda, E.P.; Delprete, P.G. Quaternary β-carboline alkaloids from Psychotria prunifolia (Kunth) Steyerm. Phytochem. Lett., 2010, 3, 133-136.
[28]
Dos Santos, C.P.; Soldi, T.C.; Torres, A.R.; Anders, A.M.; Simões-Pires, C.; Marcourt, L.; Gottfried, C.; Henriques, A.T. Monoamine oxidase inhibition by monoterpene indole alkaloids and fractions obtained from Psychotria suterella and Psychotria laciniata. J. Enzyme Inhib. Med. Chem., 2012, 28, 611-618.
[29]
Farias, F.M.; Konrath, E.L.; Zuanazzi, J.A.S.; Henriques, A.T. Strictosamide from Psychotria nuda (Cham. et Schltdl) Wawra (Rubiaceae). Biochem. Syst. Ecol., 2008, 36, 919-920.
[30]
Kerber, V.A.; Gregianini, T.S.; Paranhos, J.T.; Schwambach, J.; Farias, F.; Fett, J.P.; Fett-neto, A.G.; Zuanazzi, J.A.S.; Quirion, J.C.; Elizabetsky, E.; Henriques, A.T. Brachycerine, a novel monoterpene indole alkaloid from Psychotria brachyceras. J. Nat. Prod., 2001, 64, 677-679.
[31]
Farias, F.M.; Passos, C.S.; Arbo, M.D.; Zuanazzi, J.A.S.; Steffen, V.M.; Henriques, A.T. Monoamine levels in rat striatum after acute intraperitoneal injection of strictosidinic acid isolated from Psychotria myriantha Mull. Arg. (Rubiaceae). Phytomedicine, 2010, 17, 289-291.
[32]
Do Nascimento, C.A.; Lião, L.M.; Kato, L.; da Silva, C.C.; Tanaka, C.M.A.; Schuquel, I.T.A.; de Oliveira, C.M.A. A tetrahydro β-carboline trisaccharide from Palicourea coriacea (Cham.) K. Schum. Carbohydr. Res., 2008, 343, 1104-1107.
[33]
Marques de Oliveira, A.; Lyra Lemos, R.P.; Conserva, L.M. β-Carboline alkaloids from Psychotria barbiflora DC. (Rubiaceae). Biochem. Syst. Ecol., 2013, 50, 339-341.
[34]
Calixto, N.O.; Pinto, M.E.F.; Ramalho, S.D.; Burger, M.C.M.; Bobey, A.F.; Young, M.C.M.; Bolzani, V.S.; Pinto, A.C. The genus Psychotria: phytochemistry, chemotaxonomy, ethnopharmacology and biological properties. J. Braz. Chem. Soc., 2016, 1355-1378.
[35]
Sévenet, T.; Pusset, J. Alkaloids from the medicinal plants of new caledonia. Alkaloids: Chem. Pharmacol., 1996, 48, 1-73.
[36]
Both, F.L.; Kerber, V.A.; Henriques, A.T.; Elisabetsky, E. 2002. Analgesic properties of umbellatine from Psychotria umbellata. Pharm. Biol., 2002, 40, 336-341.
[37]
Both, F.L.; Meneghini, L.; Kerber, V.A.; Henriques, A.T.; Elisabetsky, E. Psychopharmacological profile of the alkaloid psychollatine as a 5HT2A/C serotonin modulator. J. Nat. Prod., 2005, 68, 374-380.
[38]
Both, F.L.; Meneghini, L.; Kerber, V.A.; Henriques, A.T.; Elisabetsky, L. Role of glutamate and dopamine receptors in the psychopharmacological profile of the indole alkaloid psychollatine. J. Nat. Prod., 2006, 69, 342-345.
[39]
Farias, F.M.; Passos, C.S.; Arbo, M.D.; Barros, D.M.; Gottfried, C.; Steffen, V.M.; Henriques, A.T. Strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae), decreases serotonin levels in rat hippocampus. Fitoterapia, 2012, 86, 1138-1143.
[40]
Simões-Pires, C.A.; Farias, F.M.; Marston, A.; Queiroz, E.F.; Chaves, C.G.; Henriques, A.T.; Hostettmann, K. Indole monoterpenes with antichemotactic activity from Psychotria myriantha: chemotaxonomic significance. Nat. Prod. Commun., 2006, 1, 1101-1106.
[41]
Cordell, G.A. Introduction to alkaloids; Wiley-Interscience: New York, 1981.
[42]
Liu, Y.; Wang, J.S.; Wang, X.B.; Kong, L.Y. Two novel dimeric indole alkaloids from the leaves and twigs of Psychotria henryi. Fitoterapia, 2013, 86, 178-182.
[43]
Adjibadé, Y.; Kuballa, B.; Cabalion, P.; Jung, M.L.; Beck, J.P.; Anton, R. Cytotoxicity on human leukemic and rat hepatoma cell lines of alkaloids extracts of Psychotria forsteriana. Planta Med., 1989, 55, 567-568.
[44]
Adjibadé, Y. Saad. H.; Kuballa, B.; Beck, J.P.; Sévenet, T.; Cabalion, P.; Anton, R. In vitro cytotoxicity of polyindolenine alkaloids on rat hepatoma cell lines. Structure activity relationships. J. Ethnopharmacol., 1990, 29, 127-136.
[45]
Gerlach, S.L.; Rathinakumar, R.; Chakravarty, G.; Göransson, U.; Wimley, W.C.; Darwin, S.P.; Mondal, D. Anticancer and chemosensitizing abilities of cycloviolacin O2 from Viola odorata and psyle cyclotides from Psychotria leptothyrsa. Biopolymers, (Pept. Sci.), 2010, 94, 618-625.
[46]
Benzi, G.; Morreti, A. Is there a rationale for the use of acetylcholinesterase inhibitors in the therapy of Alzheimer’s disease? Eur. J. Pharmacol., 1998, 346, 1-13.
[47]
Inouye, K.; Oliveira, G.H. Avaliação crítica do tratamento farmacológico atual para Doença de Alzheimer. Infarma, 2004, 15, 11-12.
[48]
Standaert, D.G.; Young, A.B. In: Goodman & Gilman. As bases farmacológicas da terapêutica, 10a. Ed.; Brunton, L.L.; Lazo, J.S.; Parker, K.L., eds.; Mc Graw Hill 2006, cap. 20.
[49]
Scott, L.J.; Goa, K.L. Galanthamine: A review of its use in Alzheimer’s disease. Drugs, 2000, 60, 1095-1122.
[50]
Orhan, I.E.; Orha, G.; Gurkas, E. An overview on natural cholinesterase inhibitors - a multi-targeted drug class - and their mass production. Mini Rev. Med. Chem., 2011, 11, 836-842.
[51]
Barbosa-Filho, J.M.; Medeiros, K.C.P.; Diniz, M.F.F.M.; Batista, L.M.; Athayde-Filho, P.F.; Silva, M.S.; da-Cunha, E.V.L.; Almeida, J.R.G.S.; Quintans-Júnior, L.J. Natural products inhibitors of the enzyme acetylcholinesterase. Rev. Bras. Farmacogn., 2006, 16, 258-285.
[52]
Xiao, S.; Lin, W.; Wang, C.; Yang, M. Synthesis and biological evaluation of DNA targeting flexible side-chain substituted beta-carboline derivatives. Bioorg. Med. Chem. Lett., 2001, 11, 437-441.
[53]
Deveau, A.M.; Labroli, M.A.; Dieckhaus, C.M.; Barthen, M.T.; Smith, K.S.; Macdonald, T.L. The synthesis of amino-acid functionalized beta-carbolines as topoisomerase II inhibitors. Bioorg. Med. Chem. Lett., 2001, 11, 1251-1255.

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