Tanshinone IIA exhibits anticonvulsant activity in zebrafish and mouse seizure models
- Authors
- Buenafe, O.E., Orellana Paucar, A.M., Maes, J., Huang, H., De Borggraeve, W.M., Crawford, A.D., Luyten, W., Esguerra, C.V., and de Witte, P.
- ID
- ZDB-PUB-130903-27
- Date
- 2013
- Source
- ACS Chemical Neuroscience 4(11): 1479-87 (Journal)
- Registered Authors
- Buenafe, Olivia Erin, Crawford, Alexander, de Witte, Peter, Esguerra, Camila V.
- Keywords
- none
- MeSH Terms
-
- Abietanes/administration & dosage*
- Abietanes/physiology
- Abietanes/therapeutic use
- Alzheimer Disease/drug therapy
- Animals
- Anticonvulsants/administration & dosage*
- Anticonvulsants/therapeutic use
- Brain Ischemia/drug therapy
- Disease Models, Animal
- Disease Progression
- Drugs, Chinese Herbal/therapeutic use*
- Fertilization in Vitro/drug effects
- Injections, Intraventricular
- Larva/drug effects
- Male
- Medicine, Chinese Traditional/methods*
- Mice
- Microinjections
- Neuroprotective Agents/administration & dosage
- Neuroprotective Agents/therapeutic use
- Pentylenetetrazole/administration & dosage
- Pentylenetetrazole/antagonists & inhibitors*
- Pentylenetetrazole/toxicity
- Plant Extracts/administration & dosage
- Plant Extracts/therapeutic use
- Plant Roots/chemistry
- Proto-Oncogene Proteins c-fos/antagonists & inhibitors
- Proto-Oncogene Proteins c-fos/biosynthesis
- Salvia miltiorrhiza/chemistry
- Seizures/diagnosis
- Seizures/drug therapy*
- Seizures/mortality
- Small Molecule Libraries/administration & dosage
- Small Molecule Libraries/therapeutic use
- Zebrafish/embryology
- PubMed
- 23937066 Full text @ ACS Chem. Neurosci.
Danshen or Chinese red sage (Salvia miltiorrhiza, Bunge) is used by traditional Chinese medicine (TCM) practitioners to treat neurological, cardio- and cerebrovascular disorders, and is included in TCM formulations to control epileptic seizures. In this study, acetonic crude extracts of danshen inhibited pentylenetetrazol (PTZ)-induced seizure activity in zebrafish larvae. Subsequent zebrafish bioassay-guided fractionation of the extract resulted in the isolation of four major tanshinones present which suppressed PTZ-induced activity to varying degrees. One of the active tanshinones, tanshinone IIA, also reduced c-fos expression in the brains of PTZ-exposed zebrafish larvae. In rodent seizure models, tanshinone IIA showed anticonvulsive activity in the mouse 6-Hz psychomotor seizure test in a bi-phasic manner, and modifies seizure thresholds in a complex manner for the mouse i.v. PTZ seizure assay. Interestingly, tanshinone IIA is used as a prescription drug in China to address cerebral ischemia in patients. Here, we provide the first in vivo evidence demonstrating that tanshinone IIA has anticonvulsant properties as well.