Spasmolytic activity of essential oil from Lippia microphylla Cham. (Verbenaceae) is mediated by modulation of Ca2+ signaling on animal and cellular models
DOI:
https://doi.org/10.33448/rsd-v10i7.16060Keywords:
Lippia microphylla Cham; Verbenaceae; Essential oil; Timol; Carvacrol; Músculo liso intestinal.Abstract
Lippia species (Verbenaceae) are widely used on folk medicine to treat respiratory and gastrointestinal disorders. In this work, we evaluated the relaxant effect of the essential oil from Lippia microphylla Cham. (LM‑EO) and its major components on guinea pig ileum as well as elucidate the involved mechanisms. LM-EO inhibited phasic contractions as well as relaxed tonic contractions induced by several contractile agents on guinea pig ileum. Similar results were observed in tests using thymol and carvacrol, the major constituents of LM-EO. Voltage-dependent calcium channel (CaV) blockade was suggested since LM-EO shifted to the right non parallelly CaCl2-induced cumulative contractions and confirmed when LM-EO relaxed the ileum pre contracted by S-(-)-Bay K8644, a selective CaV agonist. On circular layer, LM-EO inhibited phasic contractions, being equipotent to the effect observed in the intact ileum. In the myocytes from ileum longitudinal layer, LM-EO reduced fluorescence intensity induced by histamine, similarly to verapamil (CaV blocker), indicating a decrease in cytosolic concentration of Ca2+ ([Ca2+]c). In conclusion, LM-EO presents a spasmolytic activity on guinea pig ileum by CaV blockade and [Ca2+]c reduction. These results present a rationale for the use of L. microphylla as a potential product to intestinal disorders.
References
Agra, M. F., Silva, K. N., Basílio, I. J. L. D. et al. (2008). Survey of medicinal plants used in the region Northeast of Brazil. Brazilian Journal of Pharmacognosy, 18, 472.
Alexander, S. P. H., Striessnig, J., Kelly, E. et al. (2017). The Concise Guide to Pharmacology 2017/18: Voltage-gated ion channels. British Journal of Pharmacology, 174, 160.
Alonso, J., & Desmarchelier C. (2015). Plantas medicinales autóctonas de la Argentina. Bases científicas para su aplicación en atención primaria de salud, first ed. Corpus Editorial y Distribuidora Buenos Aires.
Begrow, F., Engelbertz, J., Feistel, B. et al. (2010). Impact of thymol in thyme extracts on their antispasmodic action and ciliary clearance. Planta Medica, 76, 311.
Blanco, M. A., Colareda, G. A., & Van-Baren, C. (2013). Antispasmodic effects and composition of the essential oils from two South American chemotypes of Lippia alba. Journal of Ethnopharmacology, 149, 803.
Catterall, W. A. (2011). Voltage‑gated calcium channels. Cold Spring Harbor Perspectives in Biology, 3, a003947.
Cecchi, X., Wolff, D., Alvarez, A. et al. (1987). Mechanisms of Cs+ blockade in a Ca2+-activated K+ channel from smooth muscle. Biophysical Journal, 52, 707.
Cheng, J. T., & Shinokuza K. (1987). Prostaglandin E2 induced the cyclic AMP‑dependent release of acetylcholine in circular muscles of the isolated guinea pig ileum. Neuroscience Letters, 83, 293.
Claro, S., Kanashiro, C. A., Oshiro, M. E. M. et al. (2007). α- and ε‑protein kinase C activity during smooth muscle apoptosis in response to γ-radiation. Journal of Pharmacology and Experimental Therapeutics, 322, 964.
Costa, S. M., Santos, H. S., Pessoa, O. D. et al. (2005). Constituents of the essential oil of Lippia microphylla Cham. from Northeast Brazil. Journal of Essential Oil Research, 17, 378.
Coutinho, H. D., Rodrigues, F. F., Nascimento, E. M. et al. (2011). Synergism of gentamicin and norfloxacin with the volatile compounds of Lippia microphylla Cham. (Verbenaceae). Journal of Essential Oil Research, 23, 24.
Daniel, E. E., Kwan, C. Y., & Janssen, L. (2001). Pharmacological techniques for the in vitro study of intestinal smooth muscle. Journal of Pharmacology and Toxicology, 45, 141.
De Souza, E. L. D., Lima, E. D. O., Freire, K. R. D. L. et al. (2005). Inhibitory action of some essential oils and phytochemicals on the growth of various moulds isolated from foods. Brazilian Archives of Biology and Technology, 48, 245.
Denizot, F., & Lang, R. (1986). Rapid colorimetric assay for cell growth and survival – modification to the tetrazolium dye procedure giving improved sensitivity and reliability. Journal of Immunological Methods, 89, 271.
Ferrante, J., Luchowski, E., Rutledge, A. et al. (1989). Binding of a 1,4‑dihydropyridine calcium channel activator, S-(-)-Bay K8644, to cardiac preparations. Biochemical and Biophysical Research Communications, 158, 149.
Görnemann, T., Nayal, R., Pertz, H. H. et al. (2008). Antispasmodic activity of essential oil from Lippia dulcis Trev. Journal of Ethnopharmacology, 117, 166.
Honda, K., Takano, Y., & Kamiya, H. (1996). Involvement of protein kinase C in muscarinic agonist‑induced contractions of guinea pig ileal longitudinal muscle. General Pharmacology, 27, 957.
Horie, S., Tsurumaki, Y., Someya, A. et al. (2005). Involvement of cyclooxygenase-dependent pathway in contraction of isolated ileum by urotensin II. Peptides, 26, 323.
Knot, H. T., Brayden, E. J., & Nelson, M. T. (1996). Calcium channels and potassium channels, in: Bárány, M. (ed.) Biochemistry of smooth muscle contraction. Academic Press, 203.
Lemos, T. L., Monte, F. J., Santos, A. K. L. et al. (2007) Quinones from plants of northeastern Brazil: structural diversity, chemical transformations, NMR data and biological activities. Natural Product Research, 21, 529.
Makhlouf, G. M., & Murthy, K. S. (1997). Signal transduction in gastrointestinal smooth muscle. Cell Signal, 9, 269.
Marx, H. E., Leary, N. O., Yuan, Y-W. et al. (2010). A molecular phylogeny and classification of Verbenaceae. American Journal of Botany, 97, 1647.
Morais, S. M., Lima, K, S, B., Siqueira, S. M. C. et al. (2013). Correlação entre as atividades antiradical, antiacetilcolinesterase e teor de fenóis totais de extratos de plantas medicinais de farmácias vivas. Revista Brasileira de Plantas Medicinais, 15, 575.
Murthy, K. (2006). Signaling for contraction and relaxation in smooth muscle of the gut. Annual Review of Physiology, 68, 345.
Neubig, R. R., Spedding, M., Kenakin, T. et al. (2003). International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacological Reviews, 55, 597.
Paredes, R. M., Etzler, J. C., Watts, L. T. et al. (2008). Chemical calcium indicators. Methods, 46, 143.
Pascual, M. E., Slowing, K., Carretero, E. et al. (2001). Lippia: traditional uses, chemistry and pharmacology: a review. Journal of Ethnopharmacology, 76, 201.
Peixoto-Neves, D., Silva-Alves, K. S., Gomes, M. D. M. et al. (2010). Vasorelaxant effects of the monoterpenic phenol isomers, carvacrol and thymol, on rat isolated aorta. Fundamental & Clinical Pharmacology, 24, 341.
Rembold, C. M. (1992) Regulation of contraction and relaxation in arterial smooth muscle. Hypertension, 20, 129.
Rivero‐Cruz, I., Duarte, G., Navarrete, A. et al. (2011). Chemical composition and antimicrobial and spasmolytic properties of Poliomintha longiflora and Lippia graveolens essential oils. Journal of Food Science, 76, C309.
Rodrigues, F. F. G., Coutinho, H. D. M., Campos, A. R. et al. (2011). Antibacterial activity and chemical composition of essential oil of Lippia microphylla Cham. Acta Scientiarum. Biological Sciences, 33, 141.
Santos, J. S., Melo, J. I. M., Abreu, M. C. et al. (2009). Verbenaceae sensu stricto na região de Xingó: Alagoas e Sergipe, Brasil. Rodriguésia, 60, 985.
Santos, M. R., Moreira, F. V., Fraga, B. P., Souza, D. P. D. et al. (2011). Cardiovascular effects of monoterpenes: a review. Revita Brasileira de Farmacognosia, 21, 764.
Scarpa, G. F. (2004). Medicinal plants used by the Criollos of Northwestern Argentine Chaco. Journal of Ethnopharmacology, 91, 115.
Shimuta, S. I., Kanashiro, C. A., Oshiro, M. E. M. et al. (1990). Angiotensin II desensitization and Ca2+ and Na+ fluxes in cultured intestinal smooth muscle cells. Journal of Pharmacology and Experimental Therapeutics, 253, 1215.
Silva, F. S., Menezes, P. M. N., Sá, P. G. S. D. et al. (2016). Chemical composition and pharmacological properties of the essential oils obtained seasonally from Lippia thymoides. Pharmaceutical Biology, 54, 25.
Somlyo, A. P., & Somlyo, A. V. (1994). Signal transduction and regulation in smooth muscle. Nature, 372, 231.
Soraru, S. B., & Bandoni, A. L. (1978). Plantas de la medicina popular argentina. Editorial Albatros, Buenos Aires.
Spedding, M., & Paoletti, R. (1992). Classification of calcium channels and the sites of action of drugs modifying channel function. Pharmacological Reviews, 44, 363.
Sun, Y. D., & Benishin, C. G. (1994). K+ channel openers relax longitudinal muscle of guinea-pig ileum. European Journal of Pharmacology, 271, 453.
Tanahashi, Y., Unno, T., Matsuyama, H. et al. (2009). Multiple muscarinic pathways mediate the suppression of voltage-gated Ca2+ channels in mouse intestinal smooth muscle cells. British Journal of Pharmacology, 158, 1874.
Tepe, A. S., & Tepe, B. (2015). Traditional use, biological activity potential and toxicity of Pimpinella species. Industrial Crops and Products, 69, 153.
Thorneloe, K. S., & Nelson, M. T. (2005). Ion channels in smooth muscle: regulators of intracellular calcium and contractility. Canadian Journal of Physiology and Pharmacology, 83, 215.
Usowicz, M. M., Gigg, M., Jones, L. M. E. et al. (1995). Allosteric interactions at L‑type calcium channels between FPL 641 76 and the enantiomers of the dihydropyridine Bay K8644. Journal of Pharmacology and Experimental Therapeutics, 275, 638.
Van Rossum, J. M. (1963). Cumulative dose-response curves. Archives Internationales de Pharmacodynamie et de Therapie, 143, 299.
Webb, R. C. (2003). Smooth muscle contraction and relaxation. Advances in Physiology Education, 27, 201.
Wray, S., Burdyga, T., & Noble, K. (2005). Calcium signalling in smooth muscle. Cell Calcium, 38, 397.
Xavier, A. L, Pita, J. C. L., Brito, M. T. et al. (2015). Chemical composition, antitumor activity, and toxicity of essential oil from the leaves of Lippia microphylla. Zeitschrift für Naturforschung C, 70, 129.
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Copyright (c) 2021 Gislaine Alves de Oliveira; Joedna Cavalcante Pereira; Italo Rossi Roseno Martins; Ana Carolina de Carvalho Correia; Rafael de Almeida Travassos; Maria da Conceição Correia Silva; Iara Leão Luna de Souza; Josean Fechine Tavares; Edgar Julian Paredes-Gamero; Bagnólia Araújo da Silva
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