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http://dx.doi.org/10.4062/biomolther.2019.130

Catalpol and Mannitol, Two Components of Rehmannia glutinosa, Exhibit Anticonvulsant Effects Probably via GABAA Receptor Regulation  

Kim, Mikyung (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University)
Acharya, Srijan (Department of Pharmacology, College of Pharmacy, Chonnam National University)
Botanas, Chrislean Jun (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University)
Custodio, Raly James (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University)
Lee, Hyun Jun (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University)
Sayson, Leandro Val (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University)
Abiero, Arvie (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University)
Lee, Yong Soo (Department of Pharmacology, College of Pharmacy, Duksung Women's University)
Cheong, Jae Hoon (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University)
Kim, Kyeong-man (Department of Pharmacology, College of Pharmacy, Chonnam National University)
Kim, Hee Jin (Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University)
Publication Information
Biomolecules & Therapeutics / v.28, no.2, 2020 , pp. 137-144 More about this Journal
Abstract
Epilepsy is a brain disorder that affects millions of people worldwide and is usually managed using currently available antiepileptic drugs, which result in adverse effects and are ineffective in approximately 20-25% of patients. Thus, there is growing interest in the development of new antiepileptic drugs with fewer side effects. In a previous study, we showed that a Rehmannia glutinosa (RG) water extract has protective effects against electroshock- and pentylenetetrazol (PTZ)-induced seizures, with fewer side effects. In this study, the objective was to identify the RG components that are responsible for its anticonvulsant effects. Initially, a number of RG components (aucubin, acteoside, catalpol, and mannitol) were screened, and the anticonvulsant effects of different doses of catalpol, mannitol, and their combination on electroshock- and chemically (PTZ or strychnine)-induced seizures in mice, were further assessed. Gamma-aminobutyric acid (GABA) receptor binding assay and electroencephalography (EEG) analysis were conducted to identify the potential underlying drug mechanism. Additionally, treated mice were tested using open-field and rotarod tests. Catalpol, mannitol, and their combination increased threshold against electroshock-induced seizures, and decreased the percentage of seizure responses induced by PTZ, a GABA antagonist. GABA receptor binding assay results revealed that catalpol and mannitol are associated with GABA receptor activity, and EEG analysis provided evidence that catalpol and mannitol have anticonvulsant effects against PTZ-induced seizures. In summary, our results indicate that catalpol and mannitol have anticonvulsant properties, and may mediate the protective effects of RG against seizures.
Keywords
Rehmannia glutinosa; Catalpol; Mannitol; Anticonvulsant; Epilepsy; Gamma-aminobutyric acid (GABA);
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1 Gao, J., An, L., Xu, Y. and Huang, Y. (2018) Catalpol exerts an antiepilepticus effect, possibly by regulating the Nrf2-Keap1-ARE signaling pathway. Med. Sci. Monit. 24, 9436-9441.   DOI
2 Grauncke, A. C., Souza, T. L., Ribeiro, L. R., Brant, F., Machado, F. S. and Oliveira, M. S. (2016) Increased susceptibility to pentylenetetrazol following survival of cerebral malaria in mice. Epilepsia 57, e140-e145.   DOI
3 Haglund, M. M. and Hochman, D. W. (2005) Furosemide and mannitol suppression of epileptic activity in the human brain. J. Neurophysiol. 94, 907-918.   DOI
4 Hamoy, M., dos Santos Batista, L., de Mello, V. J., Gomes-Leal, W., Farias, R. A. F., dos Santos Batista, P., do Nascimento, J. L. M., Marcondes, H. C., Taylor, J. G., Hutchison, W. D., Torres, M. F. and Barbas, L. A. L. (2018) Cunaniol-elicited seizures: behavior characterization and electroencephalographic analyses. Toxicol. Appl. Pharmacol. 360, 193-200.   DOI
5 Hansen, S. L., Sperling, B. B. and Sanchez, C. (2004) Anticonvulsant and antiepileptogenic effects of GABAA receptor ligands in pentylenetetrazole- kindled mice. Prog. Neuropsychopharmacol. Biol. Psychiatry 28, 105-113.   DOI
6 Hauser, W. A. (1992) Seizure disorders: the changes with age. Epilepsia 33, 6-14.   DOI
7 Heaulme, M., Chambon, J. P., Leyris, R., Wermuth, C. G. and Biziere, K. (1987) Characterization of the binding of [3H] SR 95531, a GA-BAA antagonist, to rat brain membranes. J. Neurochem. 48, 1677-1686.   DOI
8 Huang, R. Q., Bell-Horner, C. L., Dibas, M. I., Covey, D. F., Drewe, J. A. and Dillon, G. H. (2001) Pentylenetetrazole-induced inhibition of recombinant ${\gamma}$-aminobutyric acid type A (GABAA) receptors: mechanism and site of action. J. Pharmacol. Exp. Ther. 298, 986-995.
9 Kim, M., Kim, H. J., Kim, S. M., De La Pena, J. B., Botanas, C. J., Woo, T., Lee, Y. S., Ryu, J. H. and Cheong, J. H. (2017) Protection against electroshock-and pentylenetetrazol-induced seizures by the water extract of rehmannia glutinous can be mediated through GABA receptor-chloride channel complexes. Nat. Prod. Sci. 23, 40-45.   DOI
10 Kim, H., An, C. S., Jung, K. Y., Choo, Y. K., Park, J. K. and Nam, S. Y. (1999) Rehmannia glutinosa inhibits tumour necrosis factor-${\alpha}$ and interleukin-1 secretion from mouse astrocytes. Pharmacol. Res. 40, 171-176.   DOI
11 Kim, S. S., Son, Y. O., Chun, J. C.,Kim, S. E., Chung, G. H., Hwang, K. J. and Lee, J. C. (2005) Antioxidant property of an active component purified from the leaves of paraquat-tolerant Rehmannia glutinosa. Redox Rep. 10, 311-318.   DOI
12 Larson, A. A. and Beitz, A. (1988) Glycine potentiates strychnine-induced convulsions: role of NMDA receptors. J. Neurosci. 8, 3822-3826.   DOI
13 Lee, S., Yean, M., Kim, J., Lee, J. and Kang, S. (2011) Phytochemical studies on rehmanniae radix preparata. Korean J. Pharmacogn. 42, 127-137.
14 Loscher, W., Fassbender, C. P. and Nolting, B. (1991) The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. II. Maximal electroshock seizure models. Epilepsy Res. 8, 79-94.   DOI
15 Pontes, J. C., Lima, T. Z., Queiroz, C. M., Cinini, S. M., Blanco, M. M. and Mello, L. E. (2016) Seizures triggered by pentylenetetrazol in marmosets made chronically epileptic with pilocarpine show greater refractoriness to treatment. Epilepsy Res. 126, 16-25.   DOI
16 Luttjohann, A., Fabene, P. F. and van Luijtelaar, G. (2009) A revised Racine's scale for PTZ-induced seizures in rats. Physiol. Behav. 98, 579-586.   DOI
17 Lynch, J. W. (2004) Molecular structure and function of the glycine receptor chloride channel. Physiol. Rev. 84, 1051-1095.   DOI
18 Pellmar, T. and Wilson, W. (1977) Synaptic mechanism of pentylenetetrazole: selectivity for chloride conductance. Science 197, 912-914.   DOI
19 Quintans Junior, L. J., Almeida, J. R., Lima, J. T., Nunes, X. P., Siqueira, J. S., Oliveira, L. E. G. D., Almeida, R. N., Athayde-Filho, P. F. D. and Barbosa-Filho, J. M. (2008) Plants with anticonvulsant properties: a review. Rev. Bras. Farmacogn. 18, 798-819.   DOI
20 Rogawski, M. A. and Porter, R. J. (1990) Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. Pharmacol. Rev. 42, 223-286.
21 Schmidt, D. and Schachter, S. C. (2014) Drug treatment of epilepsy in adults. BMJ 348, 130-136.   DOI
22 Serafini, R. (2017) A comparison of anticonvulsant efficacy and action mechanism of Mannitol vs Phenytoin in adult rat neocortical slices. IBRO Rep. 3, 55-64.   DOI
23 Berezhnoy, D., Nyfeler, Y., Gonthier, A., Schwob, H., Goeldner, M. and Sigel, E. (2004) On the benzodiazepine binding pocket in GABAA receptors. J. Biol. Chem. 279, 3160-3168.   DOI
24 Tan, K. R., Baur, R., Charon, S., Goeldner, M. and Sigel, E. (2009) Relative positioning of diazepam in the benzodiazepine-binding-pocket of GABA receptors. J. Neurochem. 111, 1264-1273.   DOI
25 Tomoda, M., Kato, S. and Mie, O. (1971) Water-soluble constituents of rehmanniae radix. I. Carbohydrates and acids of Rehmannia glutinosa f. hueichingensis. Chem. Pharm. Bull. 19, 1455-1460.   DOI
26 Woo, T. S., Yoon, S. Y., dela Pena, I. C., Choi, J. Y., Lee, H. L., Choi, Y. J. and Cheong, J. H. (2011) Anticonvulsant effect of Artemisia capillaris Herba in mice. Biomol. Ther. (Seoul) 19, 342-347.   DOI
27 Yoon, S. Y., dela Pena, I. C., Shin, C. Y., Son, K. H., Lee, Y. S., Ryu, J. H., Cheong, J. H. and Ko, K. H. (2011) Convulsion-related activities of Scutellaria flavones are related to the 5, 7-dihydroxyl structures. Eur. J. Pharmacol. 659, 155-160.   DOI
28 Zhang, R. X., Li, M. X. and Jia, Z. P. (2008) Rehmannia glutinosa: review of botany, chemistry and pharmacology. J. Ethnopharmacol. 117, 199-214.   DOI
29 Baek, G. H., Jang, Y. S., Jeong, S. I., Cha, J., Joo, M., Shin, S. W., Ha, K. T. and Jeong, H. S. (2012) Rehmannia glutinosa suppresses inflammatory responses elicited by advanced glycation end products. Inflammation 35, 1232-1241.   DOI
30 Begley, C. E., Famulari, M., Annegers, J. F., Lairson, D. R., Reynolds, T. F., Coan, S., Dubinsky, S., Newmark, M. E., Leibson, C., So, E. L. and Rocca, W. A. (2000) The cost of epilepsy in the United States: an estimate from population-based clinical and survey data. Epilepsia 41, 342-351.   DOI
31 Cheng, Y. C. and Prusoff, W. H. (1973) Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem. Pharmacol. 22, 3099-3108.   DOI
32 Chou, T. C. and Talalay, P. (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Enzym. Regul. 22, 27-55.   DOI
33 Deyn, P. P. D., Marescau, B. and MacDonald, R. (1989) Epilepsy and the GABA-hypothesis a brief review and some examples. Acta Neurol. Belg. 90, 65-81.
34 Fisher, R. S., Vickrey, B. G., Gibson, P., Hermann, B., Penovich, P., Scherer, A. and Walker, S. (2000) The impact of epilepsy from the patient's perspective II: views about therapy and health care. Epilepsy Res. 41, 53-62.   DOI
35 Fisher, R. S., van Emde Boas, W., Blume, W., Elger, C., Genton, P., Lee, P. and Engel, J., Jr. (2005) Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 46, 470-472.   DOI