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Sci Rep. 2017 May 10;7(1):1701. doi: 10.1038/s41598-017-01734-z.

DV21 decreases excitability of cortical pyramidal neurons and acts in epilepsy.

Author information

1
Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. xumin8121@hotmail.com.
2
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming, China. xumin8121@hotmail.com.
3
Center for Pharmaceutical Sciences, Faculty of Life Science and Technology, Kunming University of Technology and Science, Kunming, China. xumin8121@hotmail.com.
4
Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
5
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming, China.
6
Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. lixm@zju.edu.cn.

Abstract

Epilepsy is one of the most common neurological disorders and the administration of antiepileptic drugs (AEDs) is the most common treatment. Although there are more than 15 AEDs available, a third of epilepsy patients remain refractory to available drugs, so novel effective drugs are needed. Here, we found that DV21, which is a natural triterpenoid compound extracted from plants of the Asclepiadaceae family, significantly decreased the incidence and stages of seizures in three classical drug-induced acute seizure models in C57BL/6 mice. Furthermore, we also found that the antiepileptic effect of DV21 might be partly mediated through reducing the excitability of cortical pyramidal neurons by increasing M current, which are low-threshold non-inactivating voltage-gated potassium currents. Moreover, the application of XE991, an inhibitor of M current, could block most the antiepileptic effect of DV21. Taken together, our results indicated that DV21 might be a novel leading compound for the treatment of epilepsy.

PMID:
28490750
PMCID:
PMC5431874
DOI:
10.1038/s41598-017-01734-z
[Indexed for MEDLINE]
Free PMC Article

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