Abstract
This experiment was performed to investigate whether apigenin has hypnotic effects and/or enhances pentobarbital-induced sleep behaviors through the GABAergic systems. Apigenin prolonged sleep time induced by pentobarbital similar to muscimol, a GABAA receptors agonist. Apigenin also increased sleep rate and sleep time in the combined administration with pentobarbital at the sub-hypnotic dosage, and showed synergic effects with muscimol in potentiating sleep onset and enhancing sleep time induced by pentobarbital. In addition, both of apigeinin and pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Apigenin increased glutamate decarboxylase (GAD) and had no effect on the expression of GABAA receptorα-, β-, γ-subunits in n hippocampus of mouse brain, showing different expression of subunits from pentobarbital treatment group. In conclusion, it is suggested that apigenin augments pentobarbital-induced sleep behaviors through chloride ion channel activation.
Similar content being viewed by others
References
Avallone, R., Zanoli, P., Puia, G., Kleinschnitz, M., Schreier, P., and Baraldi, M., Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla. Biochem. Pharmacol., 59, 1387–1394 (2000).
Brailowsky, S. and Garcia, O., Ethanol, GABA and epilepsy. Arch. Med. Res., 30, 3–9 (1999).
Buddhala, C., Hsu, C. C., and Wu, J. Y., A novel mechanism for GABA synthesis and packaging into synaptic vesicles. Neurochem. Int., 55, 9–12 (2009).
Chebib, M. and Johnston, G. A., GABA-Activated ligand gated ion channels: medicinal chemistry and molecular biology. J. Med. Chem., 43, 1427–1447 (2000).
Chistina Grobin, A., Inglefield, J. R., Schwartz-Bloom, R. D., Devaud, L. L., and Morrow, A. L., Fluorescence imaging of GABAA receptor-mediated intracellular [Cl-] in P19-N cells reveals unique pharmacological properties. Brain Res., 827, 1–11 (1999).
Darias, V., Abdala, S., Martin-Herrera, D., Tello, M. L., and Vega, S., CNS effects of a series of 1,2,4-triazolyl heterocarboxylic derivatives. Pharmazie, 53, 477–481 (1998).
Davies, M., Bateson, A. N., and Dunn, S. M., Molecular biology of the GABA(A) receptor: functional domains implicated by mutational analysis. Front. Biosci., 1, d214–d233 (1996).
De Sousa, F. C., Pereira, B. A., Lima, V. T., Lacerda, C. D., Melo, C. T., Barbosa-Filho, J. M., Vasconcelos, S. M., and Viana, G. S., Central nervous system activity of yangambin from Ocotea duckei Vattimo (Lauraceae) in mice. Phytother. Res., 19, 282–286 (2005).
Doghramji, K., The epidemiology and diagnosis of insomnia. Am. J. Manag. Care, 12, S214–S220 (2006).
Follesa, P., Porcu, P., Sogliano, C., Cinus, M., Biggio, F., Mancuso, L., Mostallino, M. C., Paoletti, A. M., Purdy, R. H., Biggio, G., and Concas, A., Changes in GABAA receptor gamma 2 subunit gene expression induced by long-term administration of oral contraceptives in rats. Neuropharmacology, 42, 325–336 (2002).
Ganzera, M., Pocher, A., and Stuppner, H., Differentiation of Cirsium japonicum and C. setosum by TLC and HPLCMS. Phytochem. Anal., 16, 205–209 (2005).
Glowinski, J. and Iversen, L. L., Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J. Neurochem., 13, 655–669 (1966).
Han, H., Ma, Y., Eun, J. S., Hong, J. T., and Oh, K. W., Anxiolytic-like effects of cyclopeptide fraction alkaloids of Zizyphi Spinosi Semen: possible involvement of GABAA receptors. Biomol. Ther., 16, 261–269 (2008).
Jager, A. K., Krydsfeldt, K., and Rasmussen, H. B., Bioassayguided isolation of apigenin with GABA-benzodiazepine activity from Tanacetum parthenium. Phytother. Res., 23, 1642–1644 (2009).
Kumar, S., Alam, M. N., Rai, S., Bashir, T., Mcginty, D., and Szymusiak, R., Central nervous system sites of the sleep promoting effects of eszopiclone in rats. Neuroscience, 181, 67–78 (2011).
Ma, Y., Han, H., Eun, J. S., Kim, H. C., Hong, J. T., and Oh, K. W., Sanjoinine A isolated from Zizyphi Spinosi Semen augments pentobarbital-induced sleeping behaviors through the modification of GABA-ergic systems. Biol. Pharm. Bull., 30, 1748–1753 (2007).
Ma, Y., Ma, H., Jo, Y. J., Kim, D. S., Woo, S. S., Li, R., Hong, J. T., Moon, D. C., Oh, K. W., and Eun, J. S., Honokiol potentiates pentobarbital-induced sleeping behaviors through GABAA receptor Cl- channel activation. Biomol. Ther., 16, 328–335 (2008).
Ma, Y., Ma, H., Eun, J. S., Nam, S. Y., Kim, Y. B., Hong, J. T., Lee, M. K., and Oh, K. W., Methanol extract of Longanae Arillus augments pentobarbital-induced sleep behaviors through the modification of GABAergic systems. J. Ethnopharmacol., 122, 245–250 (2009).
Macdonald, R. L. and Olsen, R. W., GABAA receptor channels. Annu. Rev. Neurosci., 17, 569–602 (1994).
Marder, M. and Paladini, A. C., GABA(A)-receptor ligands of flavonoid structure. Curr. Top. Med. Chem., 2, 853–867 (2002).
Martinez, A. L., Dominguez, F., Orozco, S., Chavez, M., Salgado, H., Gonzalez, M., and Gonzalez-Trujano, M. E., Neuropharmacological effects of an ethanol extract of the Magnolia dealbata Zucc. leaves in mice. J. Ethnopharmacol., 106, 250–255 (2006).
Möhler, H., Fritschy, J. M., and Rudolph, U., A new benzodiazepine pharmacology. J. Pharmacol. Exp. Ther., 300, 2–8 (2002).
Nazaruk, J. and Jakoniuk, P., Flavonoid composition and antimicrobial activity of Cirsium rivulare (Jacq.) All. flowers. J. Ethnopharmacol., 102, 208–212 (2005).
Ohayon, M. M., Methodology of a study on insomnia in the general population. Encephale, 28, 217–226 (2002).
Park, J. C., Lee, J. H., and Choi, J. S., A flavone diglycoside from Cirsium japonicum var. ussuriense. Phytochemistry, 39, 261–262 (1995).
Rudolph, U., Crestani, F., and Möhler, H., GABA(A) receptor subtypes: dissecting their pharmacological functions. Trends Pharmacol. Sci., 22, 188–194 (2001).
Rudolph, U. and Möhler, H., GABA-based therapeutic approaches: GABAA receptor subtype functions. Curr. Opin. Pharmacol., 6, 18–23 (2006).
Segal, D. S. and Kuczenski, R., Tyrosine hydroxylase activity: regional and subcellular distribution in the brain. Brain Res., 68, 261–266 (1974).
Shukla, S. and Gupta, S., Apigenin: a promising molecule for cancer prevention. Pharm. Res., 27, 962–978 (2010).
Tillakaratne, N. J. K., Medina-Kauwe, L., and Gibson, K. M., Gamma-aminobutyric acid (GABA) metabolism in mammalian neural and nonneural tissues. Comp. Biochem. Physiol. A Physiol., 112, 247–263 (1995).
Tobler, I., Kopp, C., Deboer, T., and Rudolph, U., Diazepam-induced changes in sleep: role of the alpha 1 GABA(A) receptor subtype. Proc. Natl. Acad. Sci. U. S. A., 98, 6464–6469 (2001).
Viola, H., Wasowski, C., Levi De Stein, M., Wolfman, C., Silveira, R., Dajas, F., Medina, J. H., and Paladini, A. C., Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects. Planta Med., 61, 213–216 (1995).
West, M. R. and Molloy, C. R., A microplate assay measuring chloride ion channel activity. Anal. Biochem., 241, 51–58 (1996).
Wolfman, C., Viola, H., Marder, M., Wasowski, C., Ardenghi, P., Izquierdo, I., Paladini, A. C., and Medina, J. H., Anxioselective properties of 6,3′-dinitroflavone, a high-affinity benzodiazepine receptor ligand. Eur. J. Pharmacol., 318, 23–30 (1996).
Yang, C. S., Landau, J. M., Huang, M. T., and Newmark, H. L., Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu. Rev. Nutr., 21, 381–406 (2001).
Zhu, S. and Baker, R. C., Effects of inhalation anesthetics of Kainate-induced glutamate release from cerebellar granule cells. Life Sci., 58, 1359–1366 (1996).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, JW., Kim, CS., Hu, Z. et al. Enhancement of pentobarbital-induced sleep by apigenin through chloride ion channel activation. Arch. Pharm. Res. 35, 367–373 (2012). https://doi.org/10.1007/s12272-012-0218-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-012-0218-4