Tanshinone IIA exhibits anticonvulsant activity in zebrafish and mouse seizure models.
Danshen or Chinese red sage (Salvia miltiorrhiza, Bunge) is used by traditional Chinese medicine (TCM) practitioners to treat neurological, cardiovascular, and cerebrovascular disorders and is included in some 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, 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 biphasic manner and modified 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.
Laboratory for Molecular Biodiscovery, Department of Pharmaceutical & Pharmacological Sciences, KU Leuven - University of Leuven , 3000 Leuven, Belgium.
Olivia Erin
OE
Buenafe
Adriana
A
Orellana-Paucar
Jan
J
Maes
Hao
H
Huang
Xuhui
X
Ying
Wim
W
De Borggraeve
Alexander D
AD
Crawford
Walter
W
Luyten
Camila V
CV
Esguerra
Peter
P
de Witte
D045784:Abietanes / Q000008:administration & dosage* / Q000502:physiology / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000627:therapeutic use; D002545:Brain Ischemia / Q000188:drug therapy; D004195:Disease Models, Animal; D018450:Disease Progression; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005307:Fertilization in Vitro / Q000187:drug effects; D007276:Injections, Intraventricular; D007814:Larva / Q000187:drug effects; D008297:Male; D008516:Medicine, Chinese Traditional / Q000379:methods*; D051379:Mice; D008845:Microinjections; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010936:Plant Extracts / Q000008:administration & dosage / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D027561:Salvia miltiorrhiza / Q000737:chemistry; D012640:Seizures / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D054852:Small Molecule Libraries / Q000008:administration & dosage / Q000627:therapeutic use; D015027:Zebrafish / Q000196:embryology
D045784:Abietanes; D000927:Anticonvulsants; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D054852:Small Molecule Libraries; C021751:tanshinone; D010433:Pentylenetetrazole