Acetylcholinesterase inhibitory potential and lack of toxicity of Psychotria carthagenensis infusions

Authors

DOI:

https://doi.org/10.33448/rsd-v10i4.14059

Keywords:

Ayahuasca; AChE; Histopathology; Alkaloids; Biochemical markers; Hematology.

Abstract

We aimed to evaluate the phytochemical composition of the aqueous extract of leaves of Psychotria carthagenensis, and its possible toxicological effects at 200 µg/Kg on Rattus norvegicus. The aqueous extract was used for preliminary phytochemical analyses using standard procedures. After, male albino Wistar rats (N= 6/group) received by gavage for 15 consecutive days, infusions with fresh (FL) and dry leaf (DL) at 200 µg/kg; controls received filtered water (negative) or clonazepam solution at 0.5 mg/kg (positive). Hematological analyses, determination of serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, uric acid, total plasma protein (TPP), quantification of serum cholinesterase (AChE), and histological analyses of kidneys and liver were carried out. By the phytochemical analysis of the aqueous leaf extract, it was possible to detect the total phenols, flavonoids, tannins and alkaloids, the latter having been recorded for the species for the first time in this study. ALT and AST levels indicated an increase in these plasma enzymes, but histological analysis of kidneys and liver showed only slight changes. Inhibition of AChE levels was related mainly to alkaloids. The infusion showed the pharmacological potential of the plant as an alternative in the treatment of neurodegenerative diseases.

References

Acharezzi, B., Tangerino, G. C., Sperandio, L. G., Mestriner, A. C. D., & Malfará, W. R. (2015). Avaliação hepática em ratos wistar expostos ao chá de ayahuasca. Saúde e Pesquisa, Maringá (PR), 8(3), 225-232. doi: 10.177651/1983-1870.2015v8n3p423-430

Almersjö, O., Bengmark, S., Engevik, L., Hafström, L. O., Loughridge, B. P., & Nilsson, L. A. (1968). Serum enzyme changes after hepatic dearterialization in man. Annals of Surgery, 167(1), 9-17. doi: 10.1097/00000658-196801000-00002

Amenta, F., & Tayebati, S. K. (2008). Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction. Current Medicinal Chemistry, 15, 488-498. doi: 10.2174/092986708783503203

Aronson, J. K. (2014). 76 - plant poisons and traditional medicines. In J. Farrar, P. J. Hotez, T. Junghanss, G. Kang, D. Lalloo & N. J. White (Eds.), Manson's tropical infectious diseases. (Twenty-third Edition ed., pp. 1128-1150.e1126). London: W.B. Saunders.

Azwanida, N. N. (2015). A review on the extraction methods use in medicinal plants, principle, strength and limitation. Medicinal & Aromatic Plants, 4(3), 1000196. doi: 10.4172/2167-0412.1000196

Bertucci, A., Haretche, F., Olivaro, C., & Vázquez, A. (2008). Prospección química del bosque de galería del río uruguay. Revista Brasileira de Farmacognosia, 18(1), 21-25. doi: 10.1590/S0102-695X2008000100006

Blumberg, N., Cholette, J. M., Pietropaoli, A. P., Phipps, R., Spinelli, S. L., Eaton, M. P., Refaai, M. A. (2018). 0.9% NaCl (normal saline) - Perhaps not so normal after all? Transfusion and Apheresis Science, 57(1), 127-131. doi: 10.1016/j.transci.2018.02.021

Brecher, G. , & Cronkite, E.P. (1950). Morphology and enumeration of human blood platelets. Journal of Applied Physiology, 3(6), 365-377. doi: 10.1152/jappl.1950.3.6.365

Brecher, G., Schneiderman, M. , & Cronkite, E.P. (1953). The reproducibility and constancy of the platelet count. American Journal of Clinical Pathology, 23(1), 15-26. doi: 10.1093/ajcp/23.1.15

Broadhurst, R. B., & Jones, W. T. (1978). Analysis of condensed tannins using acidified vanillin. Journal of the Science of Food and Agriculture, 29(9), 788-794. doi: 10.1002/jsfa.2740290908

Bruce, R., Todd, J. K., & Ledune, L. (1958). Serum transaminase: Its clinical use in diagnosis and prognosis. British Medical Journal, 2(5105), 1125-1128. doi: 10.1136/bmj.2.5105.1125

Buckholtz, N. S., & Boggan, W. O. (1977). Monoamine oxidase inhibition in brain and liver produced by β-carbolines: Structure-activity relationships and substrate specificity. Biochemistry and Pharmacology, 26(21), 1991-1996. doi: 10.1016/0006-2952(77)90007-7

Calixto, N. O., Pinto, M. E. F., Ramalho, S. D., Burger, Marcela C. M., Bobey, A. F., Young, M. C. M. . Pinto, A. C. (2016). The genus Psychotria: Phytochemistry, chemotaxonomy, ethnopharmacology and biological properties. Journal of the Brazilian Chemical Society, 27(8), 1355-1378. doi: 10.5935/0103-5053.20160149

Colović, M. B., Krstić, D. Z., Lazarević-Pašti, T. D., Bondžić, A. M., & Vasić, V. M. (2013). Acetylcholinesterase inhibitors: Pharmacology and toxicology. Current of Neuropharmacology, 11(3), 315-335. doi: 10.2174/1570159X11311030006

Guia brasileiro de boas práticas para eutanásia em animais: Conceitos e procedimentos recomendados. (2013).

Corrêa, L. R., Soares, G. L. G., & Fett-Neto, A. G. (2008). Allelopathic potential of Psychotria leiocarpa, a dominant understorey species of subtropical forests. South African Journal of Botany, 74(4), 583-590. doi: 10.1016/j.sajb.2008.02.006

De Smet, Peter A. G. M. (1995). Health risks of herbal remedies. Drug Safety, 13(2), 81-93. doi: 10.2165/00002018-199513020-00003

Dias Souza, R. K., Mendonça, A. C. A. M., & Silva, M. A. P. (2013). Aspectos etnobotânicos, fitoquímicos e farmacológicos de espécies de rubiaceae no brasil. Revista Cubana de Plantas Medicinales, 18(1), 140-156.

Do, Q. D., Angkawijaya, A. E., Tran-Nguyen, P. L., Huynh, L. H., Soetaredjo, F. E., Ismadji, S., & Ju, Yi-Hsu. (2014). Effect of extraction solvent on total phenol content, total flavonoid content, and antioxidant activity of Limnophila aromatica. Journal of Food and Drug Analysis, 22(3), 296-302. doi: https://doi.org/10.1016/j.jfda.2013.11.001

dos Santos, R.G. (2013). Safety and side effects of ayahuasca in humans - an overview focusing on developmental toxicology. Journal os Psychoactive Drugs, 45(1), 68-78. doi: 10.1080/02791072.2013.763564

Faria, R. R., & Araujo, A. C. (2015). Fruit set of distylous Psychotria carthagenensis jacq. (rubiaceae) mediated by Apis mellifera (apidae) and species of Augochloropsis (halictidae). Acta Botanica Brasiliensis, 29(2), 278-281. doi: 10.1590/0102-33062014abb0006

Faria, R. R., Ferrero, V., Navarro, L., & Araujo, A. C. (2012). Flexible mating system in distylous populations of Psychotria carthagenensis jacq. (rubiaceae) in brazilian cerrado. Plant Systematics and Evolution, 298(3), 619-627. doi: 10.1007/s00606-011-0571-7

Faria, R. R., & Lima, T. N. (2008). Spiders associated with Psychotria carthagenensis jacquin. (rubiaceae): Vegetative branches versus inflorescences, and the influence of Crematogaster sp. (Hymenoptera, formicidae), in south-pantanal, brazil. Brazilian Journal of Biology, 68(2), 229-232. doi: 0.1590/S1519-69842008000200002

Fontoura, F. M., Matias, R., Ludwig, J., Oliveira, A. K. M., Bono, J. A. M., Martins, P. F. R. B., Guedes, N. M. R. (2015). Seasonal effects and antifungal activity from bark chemical constituents of Sterculia apetala (malvaceae) at pantanal of miranda, mato grosso do sul, brazil. Acta Amazonica, 45, 283-292.

Formagio, A. S. N., Volobuff, C. R. F., Santiago, M., Cardoso, C. A. L., Vieira, M. C., & Pereira, Z. V. (2014). Evaluation of antioxidant activity, total flavonoids, tannins and phenolic compounds in Psychotria leaf extracts. Antioxidants, 3(4), 745-757. doi: 10.3390/antiox3040745

Fox, J. G, Barthold, Stephen, D., Muriel, Newcomer, C. E, Quimby, F. W., & Smith, A. (2006). The mouse in biomedical research: Normative biology, husbandry, and models (2nd ed. Vol. 3). London: Elsevier (Academic Press).

Frecska, E., Bokor, P., & Winkelman, M. (2016). The therapeutic potentials of ayahuasca: Possible effects against various diseases of civilization. Frontiers in Pharmacology, 7, 35. doi: 10.3389/fphar.2016.00035

Gambelunghe, C., Aroni, K., Rossi, R., Moretti, L., & Bacci, M. (2008). Identification of n,n-dimethyltryptamine and β-carbolines in psychotropic ayahuasca beverage. Biomedical Chromatography, 22(10), 1056-1059. doi: 10.1002/bmc.1023

Hall, E. J. (2013). Small intestine. In R. J. Washabau & M. J. Day (Eds.), Canine and feline gastroenterology (pp. 651-728). Saint Louis: W.B. Saunders.

Harborne, A.B. (Ed). (1998). Phytochemical methods: A guide to modern techniques of plant analysis. Dordrecht: Springer.

Idoh, K., Agbonon, A., Potchoo, Y., & Gbeassor, M. (2016). Toxicological assessment of the hydroethanolic leaf extract of Clerodendrum capitatum in wistar rats. Pan African Medical Journal, 24, 66. doi: 10.11604/pamj.2016.24.66.8771

Jackson, J. K., & Derleth, D. P. (2000). Effects of various arterial infusion solutions on red blood cells in the newborn. Archives of Disease in Childhood - Fetal and Neonatal Edition, 83(2), F130-F134. doi: 10.1136/fn.83.2.F130

Koch, A. K., Silva, P. C., & Silva, C. A. (2010). Biologia reprodutiva de Psychotria carthagenensis (rubiaceae), espécie distílica de fragmento florestal de mata ciliar, centro-oeste do brasil. Rodriguésia, 61, 551-558. doi: 10.1590/2175-7860201061314

Leal, M. B., & Elisabetsky, E. (1996). Absence of alkaloids in Psychotria carthagenensis jacq. (rubiaceae). Journal of Ethnopharmacology, 54(1), 37-40. doi: 10.1016/0378-8741(96)01448-1

Lionetto, M. G., Caricato, R., Calisi, A., Giordano, M. E., & Schettino, .T. (2013). Acetylcholinesterase as a biomarker in environmental and occupational medicine: New insights and future perspectives. Biomed Research International, 2013, 321213-321213. doi: 10.1155/2013/321213

Liu, W., Yin, D., Li, N., Hou, X., Wang, D., Li, D., & Liu, J. (2016). Influence of environmental factors on the active substance production and antioxidant activity in Potentilla fruticosa l. And its quality assessment. Science Reports, 6(1), 28591. doi: 10.1038/srep28591

Lopes, S. O., Moreno, P. R. H., & Henriques, A. T. (2000). Growth characteristics and chemical analysis of Psychotria carthagenensis cell suspension cultures. Enzyme and Microbial Technology, 26(2), 259-264. doi: 10.1016/S0141-0229(99)00148-9

Magedans, Y. V. S., Rodrigues-Corrêa, K. C. S., Costa, C. T., Matsuura, H. N., & Fett-Neto, A. G. (2019). Sustainable production of bioactive alkaloids in Psychotria l. of southern brazil: Propagation and elicitation strategies. Acta Botica Brasiliensis, 33(4), 607-617. doi: 10.1590/0102-33062019abb0114

Martins, D., & Nunez, C. V. (2015). Secondary metabolites from rubiaceae species. Molecules, 20(7), 13422-13495. doi: 10.3390/molecules200713422

Matos, F. J. A. (2009). Introdução a fitoquímica experimental. (3 ed.). Fortaleza: Edições UFC.

McKenna, D. J. (2004). Clinical investigations of the therapeutic potential of ayahuasca: Rationale and regulatory challenges. Pharmacol Ther, 102(2), 111-129. doi: 10.1016/j.pharmthera.2004.03.002

McKenna, D. J., Towers, G. H. N., & Abbott, F. (1984). Monoamine oxidase inhibitors in south american hallucinogenic plants: Tryptamine and β-carboline constituents of ayahuasca. Journal of Ethnopharmacology, 10(2), 195-223. doi: 10.1016/0378-8741(84)90003-5

Melo, S. K. Mendes, L., Batista, L., Almeida, T. L. A. Craveiro, R., Willcox, E., Manso, H. E. C. C. C. , & Manso Filho, H. C. (2013). Índices hematimétricos e bioquímica sanguínea no cavalo de cavalgada em condições tropicais. Ciência Animal Brasileira, 14(2), 208-215.

Morado, C. M., Araújo, F. G., & Gomes, I. D. (2017). The use of biomarkers for assessing effects of pollutant stress on fish species from a tropical river in southeastern brazil. Acta Scientiarum Biological Science, 39(4), 431-439. doi: 10.4025/actascibiolsci.v39i4.34293

Moraes, T. M., de Araújo, M. H., Bernardes, N. R., de Oliveira, D. B., Lasunskaia, E. B., Muzitano, M. F., & Da Cunha, M. (2011). Antimycobacterial activity and alkaloid prospection of Psychotria species (rubiaceae) from the brazilian atlantic rainforest. Planta Medica, 77(9), 964-970. doi: 10.1055/s-0030-1250656

Morais, J. A. (2014). Toxicidade aguda e crônica do chá ayahuasca (banisteriopsis caapi e psychotria viridis), por análise histológica em ratas wistar. (Mestrado Dissertação), Universidade de Brasília

Brasília/Brasil.

Moreira, C. N., Souza, S. N., Barini, A. C., Araújo, E. G., & Fioravanti, M. C. S. (2012). Serum γ-glutamyltransferase activity as an indicator of chronic liver injury in cattle with no clinical signs. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, 64(6), 1403-1410. doi: 10.1590/S0102-09352012000600001

Motta, V. T. (2009). Bioquímica clínica para o laboratório: Princípios e interpretações. (5ª ed.). Curitiba: Medbook.

Narra, M. R. (2016). Single and cartel effect of pesticides on biochemical and haematological status of Clarias batrachus: A long-term monitoring. Chemosphere, 144, 966-974. doi: 10.1016/j.chemosphere.2015.09.065

Oh, M. H., Houghton, P. J., Whang, W. K., & Cho, J. H. (2004). Screening of korean herbal medicines used to improve cognitive function for anti-cholinesterase activity. Phytomedicine, 11(6), 544-548. doi: 10.1016/j.phymed.2004.03.001

Oliveira, R. A. G., Takadachi, M. M., Nonoyama, K., & Barretto, O. C. O. (2003). The absolute recommendation of chamber neubauer method for platelets counting instead of indirect methods in severe thrombocytopenic patients. Jornal Brasileiro de Patologia e Medicina Laboratorial, 39(2), 139-141. doi: 10.1590/S1676-24442003000200008

Pohanka, M. (2011). Cholinesterases, a target of pharmacology and toxicology. Biomedical Paper of the Medical Faculty of the University Palacky Olomouc Czech Repub, 155(3), 219–230. doi: 10.5507/bp.2011.036

Porto, D., Henriques, A., & Fett-Neto, A. (2009). Bioactive alkaloids from south american Psychotria and related species. The Open Bioactive Compounds Journal, 2, 29-36. doi: 10.2174/1874847300902010029

Ramaiah, SK. (2007). A toxicologist guide to the diagnostic interpretation of hepatic biochemical parameters. Food Chemistry and Toxicology, 45(9), 1551-1557.

Rang, H. P., Ritter, J. M., Flower, R. J., & G., Henderson. (2016). Rang & dale's pharmacology. (8th Edition ed.). London: Churchill Livingstone Elsevier.

Reflora. (2020). Psychotria in flora do brasil 2020 em construção: Psychotria carthagenensis jacq. Retrieved 03 Fev. 2020, from http://reflora.jbrj.gov.br/reflora/listaBrasil/FichaPublicaTaxonUC/FichaPublicaTaxonUC.do?id=FB14167

Rivier, L., & Lindgren, Jan-Erik. (1972). “Ayahuasca,” the south american hallucinogenic drink: An ethnobotanical and chemical investigation. [journal article]. Economic Botany, 26(2), 101-129. doi: 10.1007/bf02860772

Santos, A., & Mostardeiro, C. (2013). Padronização de metodologia analítica para avaliação da colinesterase plasmática. Revista Contexto & Saúde, 8(14-15), 23-30. doi: 10.21527/2176-7114.2008.14/15.23-30

Sanz-Biset, J., Campos-de-la-Cruz, J., Epiquién-Rivera, M. A., & Cañigueral, S. (2009). A first survey on the medicinal plants of the chazuta valley (Peruvian amazon). Journal of Ethnopharmacology, 122(2), 333-362. doi: 10.1016/j.jep.2008.12.009

Sharma, T., & Kanwar, S. (2018). Phytomolecules for obesity and body weight management. Journal of Biochemistry & Cell Biology, 1(1), 101.

Shukla, S., & Singh, S. (2001). Alkaloid profile in relation to different developmental stages of Papaver somniferum l. Phyton - Annales Rei Botanicae, 41, 87-96.

Silva, T. D. P., Lacerda, L. A., Carvalho, L. S., Souza, S. N., Arnhold, E., Sant’Ana, F. J. F., & Fioravanti, M. C. S. (2017). Manual and automated blood cells count in ocelots (Leopardus pardalis - Linnaeus, 1758). Arquivo Brasileiro de Medicina Veterinária e Zootecnia, 69(5), 1191-1197. doi: 10.1590/1678-4162-9299

Simão, A. Y., Gonçalves, J., Duarte, A. P., Barroso, M., Cristóvão, A. C., & Gallardo, E. (2019). Toxicological aspects and determination of the main components of ayahuasca: A critical review. Medicines (Basel), 6(4), pii: E106. doi: 10.3390/medicines6040106

Simpson, D., & Amos, S. (2017). Chapter 12 - other plant metabolites. In S. Badal & R. Delgoda (Eds.), Pharmacognosy (pp. 267-280). Boston: Academic Press.

Sousa, C. M. M., Silva, H. R., Vieira-Jr., G. M., Ayres, M. C. C., Costa, C. L. S. , Araújo, D. S., Chaves, M.H. (2007). Fenóis totais e atividade antioxidante de cinco plantas medicinais. Química Nova, 30, 351-355.

Souza, F. A., Sena, J., Maranho, L. T., Oliveira, C. M. R., & Guimarães, A. T. B. . (2008). Caracterização fitoquímica preliminar de infusões populares obtidas das partes aéreas das espécies Apium leptophylum (pers.) f. Muell. Ex benth. (apiaceae), Elvira biflora l. (dc.) e Vernonia polyanthes less. (asteraceae). Revista Brasileira de Farmacognosia, 89(1), 24-27.

Sreevidya, N., & Mehrotra, S. (2003). Spectrophotometric method for estimation of alkaloids precipitable with dragendorff's reagent in plant materials. Journal of AOAC International, 86(6), 1124-1127. doi: 10.1093/jaoac/86.6.1124

Taylor, F. G. R., Brazil, T. J., & Hillyer, M. H. (2010). Diagnostic techniques in equine medicine. (Second Edition ed.). Edinburgh: W.B. Saunders.

Ventura, A. L. M. , Abreu, P. A., Freitas, .R. C. C., Sathler, P. C., Loureiro, N., & Castro, H. C. (2010). Sistema colinérgico: Revisitando receptores, regulação e a relação com a doença de alzheimer, esquizofrenia, epilepsia e tabagismo. Revista de Psiquiatria Clínica, 37(2), 66-72. doi: 10.1590/S0101-60832010000200007

Vitarelli, N. C., & Santos, M. (2009). Anatomia de estípulas e coléteres de Psychotria carthagenensis jacq. (rubiaceae). Acta Botanica Brasiliensis, 23(4), 923-928. doi: 10.1590/S0102-33062009000400002

Walker, H. K., Hall, W. D., & Hurst, J. W. (1990). Clinical methods: The history, physical, and laboratory examinations. (3rd edition ed.). Boston: Butterworths.

Yang, H., Zhang, H., Yang, C., & Chen, Y. (2016). Chemical constituents of plants from the genus psychotria. Chemistry and Biodiversity, 13(7), 807-820. doi: 10.1002/cbdv.201500259

Yang, L., Wen, Kui-Shan, Ruan, X., Zhao, Ying-Xian, Wei, F., & Wang, Q. (2018). Response of plant secondary metabolites to environmental factors. Molecules, 23(4), 762. doi: 10.3390/molecules23040762

Zhang, Cui-Xian, Zhang, Dong-Mei, Chen, M., Guan, Shan-Yue, Yao, Jun-Hua, H., Xi-Xin, Ye, Wen-Cai. (2013). Antiproliferative triterpenoid saponins from the stem of psychotria sp. Planta Medica, 79, 978-986. doi: 10.1055/s-0032-1328650

Downloads

Published

08/04/2021

How to Cite

NASCIMENTO, G. C. Z. .; RIVERO-WENDT, C. L. G.; MIRANDA-VILELA, A. L. .; DOURADO, D. M. .; FACCO, G. G. .; OLIVON, V. C. .; PORTO, K. R. de A. .; ROEL, A. R. .; NUNES , V. L. B. .; OLIVEIRA, A. K. M. .; MATIAS, R. . Acetylcholinesterase inhibitory potential and lack of toxicity of Psychotria carthagenensis infusions. Research, Society and Development, [S. l.], v. 10, n. 4, p. e22810414059, 2021. DOI: 10.33448/rsd-v10i4.14059. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/14059. Acesso em: 23 dec. 2024.

Issue

Section

Agrarian and Biological Sciences