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Journal of Traditional Chinese Medicine >

2023 , Vol. 43 >Issue 2: 286 - 294

DOI: https://doi.org/10.19852/j.cnki.jtcm.20220928.002

Original articles

Efficacy and mechanisms of Dingxian pill (定痫丸) combined with valproic acid on pentylenetetrazol-induced chronic epilepsy in rats

  • Dongxiao QU ,
  • Yiqin GE ,
  • Limin ZHUO ,
  • Liji CHEN ,
  • Yonghua XUE ,
  • Jiwei CHENG ,
  • Jie TAO ,
  • Guoyi LI ,
  • Yudan ZHU ,
  • Qian XIAO
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  • 1 Department of Neurology and Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
    2 Department of Neurosurgery, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
    3 Department of Neurology and Central Laboratory, Putuo Clinical Medical School, Anhui Medical University, Shanghai 200062, China
    4 College of Sciences, Shanghai University, Shanghai 200442, China

Received date: 2022-01-29

  Accepted date: 2022-04-29

  Online published: 2023-03-14

Supported by

National Natural Science Foundation of China: Molecular Mechanism Underlying the Intervention of Scorpion Extract BmK IT2 on Epileptogenesis via Voltage-gated Nav1.6 Channels in Hippocampal Neurons(81903995);Molecular Mechanism Underlying the Intervention of Scorpion Polypeptide MarTX on Temporal Lobe Epileptogenesis by Inhibiting Mechanosensitive Channel Piezo1(82074162);Youth Talent Promotion Project of China Association of Chinese Medicine(CACM-2019-QNRC2-C10);Project for Capacity Promotion of Putuo District Clinical Special Disease(Stroke, 2019tszb02);Science and Technology Innovation Project of Putuo District Health System: Molecular Mechanism of Aerobic Exercise Intervention on Post-epileptic Depression Through "Bone-brain Axis"(ptkwws202107);Antiepileptic Mechanism of Scorpion Active Extract BmK AS Regulating Nav1.6 Sodium Channel in Hippocampal Pyramidal Neurons(ptkwws201902);Evaluation of Microglial Lysosomal BK Channels as Molecular Targets for Clinical Treatment of Temporal Lobe Epilepsy(ptkwws201908);Molecular Mechanism of Sodium Channel SCN8A (Nav1.6) Mutation Mediating Epilepsy and Sodium Valproate Resistance in Children the Research Project of Putuo Hospital, Shanghai University of Traditional Chinese Medicine(2019308);Molecular Mechanism of Sodium Channel SCN8A (Nav1.6) Mutation Mediating Epilepsy and Sodium Valproate Resistance in Children the Research Project of Putuo Hospital, Shanghai University of Traditional Chinese Medicine(2019307)

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Abstract

OBJECIVE: To investigate the efficacy and mechanisms of Dingxian pill (定痫丸) combined with valproic acid (VPA) on pentylenetetrazol-induced chronical epilepsy in rats.

METHODS: A rat model of epilepsy was established by administering pentylenetetrazol (PTZ) water solution (35 mg/kg). Rats were divided into 4 groups, among which three groups were treated with different drugs once a day for 28 d including Dingxian pill (2.4 g/kg), VPA (0.2 g/kg), or a combination of Dingxian pill (2.4 g/kg) and VPA (0.2 g/kg) respectively, and the control group was given the same volume of saline. Rats in different groups were compared based on animal behavior, electroencephalograms, Morris water maze, immunohistochemistry, transcriptomics and real-time polymerase chain reaction.

RSULTS: The combination therapy of Dingxian pill and VPA inhibited PTZ-induced seizure-like behavior and reduced seizure grades more significantly than VPA alone. Compared with the control group, the learning and memory ability of chronic PTZ-induced epileptic rats was improved in all the drug treatment groups, especially in the group that received both Dingxian pill and VPA. Similar to the results of MWM tests, expression of the neuroexcitability marker gene c-Fos was reduced after Dingxian pill and/or VPA treatment, and the effect was most pronounced in the combined treatment group. Transcriptomic analysis revealed that gene expression in the rodent hippocampus, which is involved in epilepsy, was upregulated by combined treatment with Dingxian pill and VPA, compared with VPA treatment alone.

CONCLUSION: Our results not only highlight the anti-epileptic effects of combined Dingxian pill and VPA treatment, but also shed light on the underlying molecular mechanisms and provide a way to apply Traditional Chinese Medicine in the treatment of epilepsy.

Key words： epilepsy; Valproic Acid; learning; memory; transcriptome; Dingxian pill

Cite this article

Dongxiao QU , Yiqin GE , Limin ZHUO , Liji CHEN , Yonghua XUE , Jiwei CHENG , Jie TAO , Guoyi LI , Yudan ZHU , Qian XIAO . Efficacy and mechanisms of Dingxian pill (定痫丸) combined with valproic acid on pentylenetetrazol-induced chronic epilepsy in rats[J]. Journal of Traditional Chinese Medicine, 2023 , 43(2) : 286 -294 . DOI: 10.19852/j.cnki.jtcm.20220928.002

References

1. Kang JT, Lee CF, Chen CF, Chou P. Factors related to the choice of clinic between Chinese traditional medicine and Western Medicine. J Formos Med Assoc 1994; 93 Suppl 1: S49-55.
2. Lam TP, Sun KS. Dilemma of integration with Western Medicine -views of Traditional Chinese Medicine practitioners in a predominant western medical setting. Complement Ther Med 2013; 21: 300-5.
3. Xue CC, Li CG, Hügel HM, Story DF. Does acupuncture or Chinese herbal medicine have a role in the treatment of allergic rhinitis? Curr Opin Allergy Clin Immunol 2006; 6: 175-9.
4. Guo H, Liu MP. Mechanism of Traditional Chinese Medicine in the treatment of allergic rhinitis. Chin Med J (Engl) 2013; 126: 756-60.
5. Zhang MM, Liu XM, He L. Effect of integrated Traditional Chinese and Western Medicine on SARS: a review of clinical evidence. World J Gastroenterol 2004; 10: 3500-5.
6. Liu M, Gao Y, Yuan Y, et al. Efficacy and safety of integrated Traditional Chinese and Western Medicine for corona virus disease 2019 (COVID-19): a systematic review and Meta-analysis. Pharmacol Res 2020; 158: 104896.
7. Huang SK, Ho YL, Chang YS. Prescriptions of Traditional Chinese Medicine, Western Medicine, and integrated Chinese-Western Medicine for allergic rhinitis under the National Health Insurance in Taiwan. J Ethnopharmacol 2015; 173: 212-6.
8. Yanli W, Fuquan L, Xia H. Research progress in the diagnosis and treatment of insomnia by Chinese and Western Medicine. Shi Jie Shui Mian Yi Xue Za Zhi 2019; 6: 523-8.
9. Bo H, Sun SG, Mei YW. Protective effect of ginkgo biloba extract on cerebral ischemia/reperfusion injury in rats. Zhong Guo Zhong Xi Yi Jie He Za Zhi 2003; 23: 436-40.
10. Terrone G, Pauletti A, Pascente R, Vezzani A. Preventing epileptogenesis: a realistic goal? Pharmacol Res 2016; 110: 96-100.
11. Talos DM, Jacobs LM, Gourmaud S, et al. Mechanistic target of rapamycin complex 1 and 2 in human temporal lobe epilepsy. Ann Neurol 2018; 83: 311-27.
12. Upadhya D, Castro OW, Upadhya R, Shetty AK. Prospects of cannabidiol for easing status epilepticus-induced epileptogenesis and related comorbidities. Mol Neurobiol 2018; 55: 6956-64.
13. Namvar S, Fathollahi Y, Javan M, et al. The antiepileptogenic effect of low-frequency stimulation on perforant path kindling involves changes in regulators of G-protein signaling in rat. J Neurol Sci 2017; 375: 450-9.
14. Akhondian J, Ashrafzadeh F, Eslamiyeh H. Levetiracetam (levebel) versus carbamazepine monotherapy for focal epilepsy in children: a randomized clinical trial. Iran J Child Neurol 2020; 14: 69-77.
15. Romoli M, Mazzocchetti P, D'Alonzo R, et al. Valproic acid and epilepsy: from molecular mechanisms to clinical evidences. Curr Neuropharmacol 2019; 17: 926-46.
16. Schmeiser B, Zentner J, Steinhoff BJ, et al. The role of presurgical EEG parameters and of reoperation for seizure outcome in temporal lobe epilepsy. Seizure 2017; 51: 174-9.
17. Salehi F, Sharma M, Peters TM, Khan AR. White matter tracts in patients with temporal lobe epilepsy: Pre- and postoperative assessment. Cureus 2017; 9: e1735.
18. Vrinda M, Sasidharan A, Aparna S, Srikumar BN, Kutty BM, Shankaranarayana Rao BS. Enriched environment attenuates behavioral seizures and depression in chronic temporal lobe epilepsy. Epilepsia 2017; 58: 1148-58.
19. Zhu Y, Zhang S, Feng Y, Xiao Q, Cheng J, Tao J. The Yin and Yang of BK channels in epilepsy. CNS Neurol Disord Drug Targets 2018; 17: 272-9.
20. Zhu Y, Zhang S, Shen M, et al. Anticonvulsant effects of Dingxian pill in pentylenetetrazol-kindled rats. Evid Based Complement Alternat Med 2019; 2019: 4534167.
21. Paulose CS, Chathu F, Khan SR, Krishnakumar A. Neuroprotective role of Bacopa monnieri extract in epilepsy and effect of glucose supplementation during hypoxia: glutamate receptor gene expression. Neurochem Res 2008; 33: 1663-71.
22. Shashkov AS, Wang M, Turdymuratov EM, et al. Structural and genetic relationships of closely related O-antigens of Cronobacter spp. and Escherichia coli: C. sakazakii G2594 (serotype O4)/E. coli O103 and C. malonaticus G3864 (serotype O1)/E. coli O29. Carbohydr Res 2015; 404: 124-31.
23. Barker-Haliski ML, Vanegas F, Mau MJ, Underwood TK, White HS. Acute cognitive impact of antiseizure drugs in naive rodents and corneal-kindled mice. Epilepsia 2016; 57: 1386-97.
24. Williams PA, Larimer P, Gao Y, Strowbridge BW. Semilunar granule cells: glutamatergic neurons in the rat dentate gyrus with axon collaterals in the inner molecular layer. J Neurosci 2007; 27: 13756-61.
25. Wieser HG, Epilepsy ICoNo. ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsia 2004; 45: 695-714.
26. Du TT, Zhu G, Chen Y, et al. Anterior thalamic nucleus stimulation protects hippocampal neurons by activating autophagy in epileptic monkeys. Aging (Albany NY) 2020; 12: 6324-39.
27. Paolone G, Falcicchia C, Lovisari F, et al. Long-term, targeted delivery of GDNF from encapsulated cells Is neuroprotective and reduces seizures in the pilocarpine model of epilepsy. J Neurosci 2019; 39: 2144-56.
28. Brandt MC, Endres-Becker J, Zagidullin N, et al. Effects of KCNE2 on HCN isoforms: distinct modulation of membrane expression and single channel properties. Am J Physiol Heart Circ Physiol 2009; 297: H355-63.
29. Decher N, Bundis F, Vajna R, Steinmeyer K. KCNE2 modulates current amplitudes and activation kinetics of HCN4: influence of KCNE family members on HCN4 currents. Pflugers Arch 2003; 446: 633-40.
30. Lussier Y, Furst O, Fortea E, et al. Disease-linked mutations alter the stoichiometries of HCN-KCNE2 complexes. Sci Rep 2019; 9: 9113.
31. Manville RW, Abbott GW. Cilantro leaf harbors a potent potassium channel-activating anticonvulsant. FASEB J 2019; 33: 11349-63.
32. Barbuti A, Scavone A, Mazzocchi N, Terragni B, Baruscotti M, Difrancesco D. A caveolin-binding domain in the HCN4 channels mediates functional interaction with caveolin proteins. J Mol Cell Cardiol 2012; 53: 187-95.
33. Avchalumov Y, Kirschstein T, Kohling R. Altered physiology and pharmacology in the corticostriatal system in a model of temporal lobe epilepsy. Epilepsia 2011; 52: 151-7.
34. Lai CL, Lu CC, Lin HC, et al. Valproate is protective against 6-OHDA-induced dopaminergic neurodegeneration in rodent midbrain: a potential role of BDNF up-regulation. J Formos Med Assoc 2019; 118: 420-8.
35. Ko HM, Jin Y, Park HH, et al. Dual mechanisms for the regulation of brain-derived neurotrophic factor by valproic acid in neural progenitor cells. Korean J Physiol Pharmacol 2018; 22: 679-88.
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