Abstract
The earliest records of traditional Chinese medicine (TCM) prevention and treatment of epilepsy dated back to famous “Huang Di Nei Jing.” TCM “spasmolytic powder” (equal-ratio compatibility of scorpion and centipede) is a famous prescription which was recognized as a useful add-on drug for refractory epilepsy in clinical observations. Multidrug resistance gene (mdr1) product Pgp overexpression in blood–brain barrier and blood–cerebrospinal fluid barrier is well recognized as the drug resistance mechanism of refractory epilepsy. Here, we established the drug-resistant epilepsy Sprague–Dawley rat model induced by Coriaria Lactone and treated these rats with topiramate and verapamil and low dose, middle dose, and high dose of spasmolytic powder by intragastric administration for 1 week. Electroencephalogram, real-time PCR, and immunohistochemistry were respectively used to detect epileptic discharge frequencies and amplitudes and expression of mdrl mRNA and Pgp on hippocampus and temporal lobe of rats. The results showed that the seizure decreases significantly in the high- and middle-dose groups of spasmolytic powder and topiramate group; in addition, mdr1 mRNA and Pgp expressions on hippocampus and temporal lobe of these drug intervention groups were significantly less than the model group (P < 0.05). These findings indicate that inhibition of intracephalic Pgp expression is possibly one of mechanisms of spasmolytic powder treating refractory epilepsy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aronica E, Gorter JA, Ramkema M et al (2004) Expression and cellular distribution of multidrug resistance-related proteins in the hippocampus of patients with mesial temporal lobe epilepsy. Epilepsia 45(5):441–451
Bates SF, Chen C, Robey R, Kang M, Figg WD, Fojo T (2002) Reversal of multidrug resistance: lessons from clinical oncology. Novartis Found Symp 243:83–96
Bazil CW (2002) New antiepileptic drugs. Neurologist 8(2):71–81
Chen CJ, Chin JE, Ueda K et al (1986) Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47(3):381–389
Cao J, Fan Y (2006) Experiment research articles overview about single traditional Chinese medicine with anti-epilepsy function. Chinese Journal of Basic medicine in traditional Chinese Med 12:875–878
Chen L, Tian L, Yang T, Cheng X, Hermann S, Zhou D (2008) Reversal of Mdr1b-dependent multidrug resistance in a rat astrocyte model by adenoviral-delivered short hairpin RNA. Cell Mol Neurobiol 28(8):1057–1066
Deffie AM, Batra JK, Goldenberg GJ (1989) Direct correlation between DNA topoisomerase II activity and cytotoxicity in adriamycin-sensitive and -resistant P388 leukemia cell lines. Cancer Res 49(1):58–62
Huang Y, Zuo P (2006) The inhibiting effect of Buthus martensic Karsch extract (Bm KE) on NM DA receptor in epileptic mice. Beijing Union Univers J (natural science edition) 20(4):50–52
Huang J, Huang X, Chen Z, Zheng Q, Sun R (2004) Dose conversion among different animals and healthy volunteers in pharmacological study. Chinese Journal of Clinical Pharmacology and Therapeutics 9(9):1069–1072
Jiao S (1977) Ten lectures of drug use experiences, 1st edn. People's Medical Publishing House, Beijing
Jallon P (1997) Epilepsy in developing countries. Epilepsia 38(10):1143–1151
Kudo Y, Niwa H, Tanaka A (1984) Actions of picrotoxin and related compound on the frog spinal cord: the role of a hydroxylgroup at the 6-position in antagonizing the actions of amino acids and presynaptic inhibition. Br J Pharmacol 81:373–380
Kotsopoulos IA, van Merode T, Kessels FG, de Krom MC, Knottnerus JA (2002) Systematic review and meta-analysis of incidence studies of epilepsy and unprovoked seizures. Epilepsia 43(11):l402–l1409
Lei Z (1998) Science of Chinese materia medica, 2nd edn. Shanghai Scientific & Technical Publishers, Shanghai
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta C(T)). Method Meth 25:402–408
Löscher W, Schmidt E (2002) New horizons in the development of antiepileptic drugs. Epilepsy Res 50(1–2):3–16
Li Q, Chen X, He L, Zhou D. (2009) Traditional Chinese medicine for epilepsy. Cochrane Database of Systematic Reviews 8(3):CD006454
Miller JW (2008) Of race, ethnicity, and rash: the genetics of antiepileptic drug-induced skin reactions. Epilepsy Curr 8(5):120–121
Morrow CS, Cowan KH (1988) Mechanisms and clinical significance of multidrug resistance. Oncology 2:55–63
Potschka H, Löscher W (2001) In vivo evidence for P-glycoprotein-mediated transport of phenytoin at the blood–brain barrier of rats. Epilepsia 42(10):1231–1240
Potschka H, Baltes S, Löscher W (2004) Inhibition of multidrug transporters by verapamil or probenecid does not alter blood-barrier penetration of levetiracetam in rat. Epilepsy Res 58(2–3):85–91
Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32:281–294
Sills GJ, Kwan P (2001) P-Glycoprotein-mediated anti epileptic drug transport: a role in refractory epilepsy? Epilepsia 42(s7):83
Tishler DM, Weinberg KI, Hinton DR, Barbaro N, Annett GM, Raffel C (1995) MDR1 gene expression in brain of patients with medically intractable epilepsy. Epilepsia 36(1):1–6
Thomas H, Coley HM (2003) Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glycoprotein. Cancer Control 10:159–165
Tian L, Chen L, Yang T, Zhang Q, Zhou D (2009) RNAi inhibits Coriaria Lactone-induced MDR1b overexpression in rat brain microvascular endothelial cells. J Mol Neurosci 39(1–2):284–293
Wang WZ, Wu JZ, Wang DS (2003a) The prevalence and treatment gap in epilepsy in China: an ILAE/IBE/WHO study. Neurology 60(9):1544–1545
Wang Y, Zhou D, Wang B, Li H, Chai H, Zhou Q, Zhang S, Stefen H (2003b) A kindling model of pharmacoresistant temporal lobe epilepsy in Sprague–Dawley rats induced by Coriaria Lactone and its possible mechanism. Epilepsia 44:475–488
Wang Y, Zang X, Li S, Zhang J, Zhao J, Zhang W (2007) Inhibitory effects of scorpion venom heat resistant protein on the excitability of acutely isolated rat hippocampal neurons. Acta Physiologica Sinica 59(1):87–93
Wang B, Li Y, Huang G (2006) Pathology technology. People's Medical Publishing House, Beijing
Xu J (1985) Pharmacology of traditional Chinese medical formulae, 1st edn. Shanghai Scientific & Technical Publishers, Shanghai
Zhang B (1985) Chinese internal medicine, 1st edn. Shanghai Scientific & Technical Publishers, Shanghai
Zhou H, Cai H, Xie Y, Tang Y (2002) Effects of scorpion toxin on Coriaria Lactone induced epilepsy in rats. J Clin Electroneurophysiology 11(1):31–33
Acknowledgments
This work was supported by the Chinese Country Natural Science Fund (30900470/C090301) and Chengdu City Science and Technology Bureau fund (12DXYB209JH-002). We thank Dr Liang Wang for technical assistance.
Author information
Authors and Affiliations
Corresponding author
Additional information
Lei Chen and Peimin Feng contributed equally to this paper.
Rights and permissions
About this article
Cite this article
Chen, L., Feng, P., Li, Y. et al. Influences of “Spasmolytic Powder” on Pgp Expression of Coriaria Lactone-Kindling Drug-Resistant Epileptic Rat Model. J Mol Neurosci 51, 1–8 (2013). https://doi.org/10.1007/s12031-012-9935-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-012-9935-x