Acute toxicity and potentiation of barbiturate-induced sleep in mice orally treated with hydro-alcoholic extract of Cyclolepis genistoides D. Don. (Asteraceae)

Yenny Montalbetti Moreno; Derlis A. Ibarrola; Olga Heinichen; Nelson Alvarenga; Julio. H. Dolz Vargas; Maria C. Hellion-Ibarrola

doi:10.7324/JAPS.2018.81106

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Abstract

The aims of this work were to determine the acute toxicity, the influence on general behavior, motor coordination, barbiturate-induced sleeping time in mice, and the chemical constituents of a hydro-alcoholic extract of the Cyclolepis genistoides D. Don. (Asteraceae) (CE-Cg). The presence of triterpenes, sesquiterpene lactones, and saponins was detected by preliminary phytochemical testing of CE-Cg. No lethal sign was observed up to 3,000.0 mg/kg (po) or 1,500.0 mg/kg bw (ip) of CE-Cg administered to mice. Oral doses of 10.0, 100.0, and 1,000.0 mg/kg bw of the CE-Cg significantly prolong the sleeping time induced by barbiturate and ethyl ether when compared with the control group. Motor coordination performance in rota-rod and chimney test was not modified by oral treatment with CE-Cg (1.0, 10.0, 100.0, and 1,000.0 mg/kg bw) when compared with the control group. Therefore, based on these findings, we concluded that the hydro-alcoholic extract of the C. genistoides D. Don. is safe, well tolerated without disturbing motor coordination orally and shows significant hypnotic property in mice. Consequently, C. genistoides is potentially a good candidate to develop a phytotherapeutic agent for a complementary treatment of insomnia and encourages us to pursue specific and complementary chemical and pharmacological evaluation at Central nervous system (CNS) level.

Keyword: Cyclolepis genistoides D. Don. Palo azul LD50 general behavior sleep time.

Citation:

Montalbetti Y, Ibarrola DA, Heinichen O, Alvarenga N, Dolz-Vargas JH, Hellion-Ibarrola MC. Acute toxicity and potentiation of barbiturate-induce sleep in mice orally treated with hydro-alcoholic extract of Cyclolepis genistoides D. Don. (Asteraceae). J App Pharm Sci, 2018; 8(11): 042–047.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Reference

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Boissier JR, Simon P. La reaction d’exploration chez la souris. Therapie, 1962; 17:1225–32.

British Toxicology Society Working Party on Toxicity. Special report: a new approach to the classification of substances and preparations on the basis of their acute toxicity. Hum Toxicol, 1984; 3(2):85–92.https://doi.org/10.1177/096032718400300202

Cabrera AL. 1978. Flora de la Provincia de Jujuy: República Argentina Vol. X, 590–592

Cabrera AL, Freire SE. Flora del Paraguay Compositae V Conservatoire et jardin botaniques de la Ville de Genève. Missouri Botanical Garden, 1998; 27:118–21.

Carlini EA, Contar JDP, Silva-Filho AR, Silveira-Filho NG, Frochtengarten ML, Bueno OFA. Pharmacology of lemongrass (Cymbopogon citratus Stapf) I Effects of teas prepared from the leaves on laboratory animals. J Etnopharmacol, 1986; 17(1):37–64.https://doi.org/10.1016/0378-8741(86)90072-3

Chambers DM, Jefferson GC, Ruddick CA. Halothane-induced sleeping time in the mouse: its modification by benzodiazepines. Eur J Pharmacol, 1978; 50(2):103–12.https://doi.org/10.1016/0014-2999(78)90004-3

CYTED. Manual de Técnicas de Investigación: Subprograma X: Química Fina Farmacéutica. Proyecto X-1: Búsqueda de Principios Bioactivos en Plantas de la Región. Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo. Editor: CYTED, Madrid, Espa-a, 1995.

De Heluani CS, De Boggiato MV, Catalan CAN, Díaz JG, Gedris TE, Herz W. Triterpenes and sesquiterpene lactones from Cyclolepis genistoides. Phytochemistry, 1997; 45(4):801–5.https://doi.org/10.1016/S0031-9422(97)00021-6

De Lima TCM. Evaluación de la actividad y desempe-o motor. In: Lapa AJ, Souccar C, Lima-Landman MTR, Monteiro de Lima TC (eds.). Métodos de Evaluación de la Actividad Farmacológica de Plantas Medicinales. Editograf, CYTED/CNPq, Florianópolis, Brasil, pp 78–9, 2002.

Dunham NW, Miya TS. A note on to simple apparatus for detecting neurological deficits in rats and mice. J Amer Pharm Assoc, 1957; 46:208–10.https://doi.org/10.1002/jps.3030460322

Esteves JE, Wheatley L, Mayall C, Abbey H. Emotional processing and its relationship to chronic low back pain: Results from a case-control study. Manual Ther, 2013; 18(6):541–6.https://doi.org/10.1016/j.math.2013.05.008

Filipov A. Medical plants of the Pilagá of central Chaco. J Ethnopharmacol 1994; 44(3):181–93.https://doi.org/10.1016/0378-8741(94)01185-0

Giberti GC. Herbal Folk Medicine in Northwestern Argentina: Compositae. J Ethnopharmacol, 1983; 7(3):321–41.https://doi.org/10.1016/0378-8741(83)90006-5

González Torres DM. Catálogo de Plantas Medicinales (y Alimenticias y Útiles) usadas en Paraguay, Ed. El País Asunción, Paraguay, p 322.

Hasegawa H. Alpha glucosidase inhibitor comprising Palo Azul as active ingredient. Patent Abstracts of Japan, Bibliographic data: JP2005263629 (A)-2005-09-29. Available via https://worldwide. e s p a c e n e t . c o m / p u b l i c a t i o n D e t a i l s / b i b l i o ? C C = J P & N R = 2005263629&KC=&FT=E&locale=en_EP#

Ibarrola D, Degen R, Ferro EA, Alvarenga N, Ibarrola-Hellion MC. Catalogo Illustrado de 80 plantas medicinales del Paraguay. 1st edition, Facultad de Ciencias Químicas, Universidad Nacional de Asunción and Agencia de Cooperación International del Japón (JICA), Asunción, Paraguay, pp 125–6, 2011.

Irwin S. Drug screening and evaluation of new compounds in animals. In: Nodine JH, Siegler PE (eds.). Animal and pharmacologic techniques in drug clinical evaluation. 1st edition, Year Book Medical Publischers Inc., Chicago, IL, pp 36–54, 1964.

OECD. Test No. 425: acute oral toxicity: up-and-down procedure, OECD guidelines for the testing of chemicals, Section 4. OECD Publishing, Paris, France, 2008. Available via https://doi.org/10.1787/9789264071049-enhttps://doi.org/10.1787/9789264071049-en

Pin A, González G, Marin G, Céspedes G, Cretton S, Christen P, et al. Plantas Medicinales del Jardín Botanico de Asuncion. Editoras: Ana Pin y Gloria Céspedes. Financiamiento: Municipalidad de Asunción, Municipalidad de Ginebra, Conservatorio y Jardín Botánicos de Ginebra Suiza y la Asociación Etnobotánica Paraguaya. Editorial AGR Servicios Gráficos. Primera Edición, p 224, 2009.

Rondina R, Bandoni AL, Coussio JD. Especies medicinales Argentinas con potencial actividad analgésica. Dominguezia, 2008; 24(1):47–69.

Sanabria-Galindo A. Análisis fitoquímico preliminar: metodología y su aplicación en la evaluación de 40 plantas de la familia Compositae. Departmento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia, Bogotá, Colombia, pp 62–77, 1983.

Sato H, Ishikawa M, Funaki A, Kimura Y, Yoshida H, Fukata H, Hasegawa H, Ueno K. Cyclolepis genistoides D. Don (palo azul) promotes differentiation of adipocytes and regulates adipokine expression. Nutr Res, 2013; 33(11):922–31.https://doi.org/10.1016/j.nutres.2013.07.012

Sato H, Funaki A, Kimura Y, Sumitomo M, Yoshida H, Fukata H, Ueno K. Ethanol extract of Cyclolepis genistoides D. Don (palo azul) induces formation of myotubes, which involves differentiation of C2C12 myoblast cells. Nutr Res, 2016; 36(7):731–41.https://doi.org/10.1016/j.nutres.2016.02.011

Sosa A, Fusco MR, Petenatti ME, Juarez A, Del Vitto LA, Petenatti E. Estudios farmacognósticos y farmacológicos comparativos sobre tres especies diuréticas de amplio uso popular en el centro-oeste argentino. Bol Latinoam Caribe, 2007; 6(6):386–7.

Sosa A, Fusco MR, Rossomando P, Juárez A, Robles S, Petenatti E, Pelzer L. Anti-inflammatory properties from isolated compounds of Cyclolepis genistoides. Pharm Biol, 2011; 49(7):675–8.https://doi.org/10.3109/13880200903431467

Stallard N, Whitehead A. A statistical evaluation of the fixed dose procedure. Alter Lab Anim, 2004; 32 Suppl 2:13–21.

Sung HY, Kang SW, Kim JL, Li J, Lee ES, Gong JH, Peng J, Cao PP, Liang X, Hai CX. Oleanolic acid reduces markers of differentiation in 3T3-L1 adipocytes. Nutr Res, 2010; 30(12):831–9.https://doi.org/10.1016/j.nutres.2010.10.001

Wang X, Li YL, Wu H, Liu JZ, Hu JX, Liao N, et al. Antidiabetic effect of oleanolic acid: a promising use of a traditional pharmacological agent. Phytother Res, 2011; 25(7):1031–40.https://doi.org/10.1002/ptr.3385

WHO. Safety and security on the Internet: challenges and advances in Member States: based on the findings of the second global survey on e-Health. (Global Observatory for e-Health Series, v. 4). Available via http://www.who.int/goe/publications/ehealth_series_vol4/en/

WHO. Traditional medicine strategy: 2014–2023. World Health Organization, 2013. Available via http://www.who.int/medicines/ publications/traditional/trm_strategy14_23/en/