ABSTRACT
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.
Subject(s)
Abietanes/administration & dosage , Anticonvulsants/administration & dosage , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional/methods , Pentylenetetrazole/antagonists & inhibitors , Seizures/drug therapy , Abietanes/physiology , Abietanes/therapeutic use , Alzheimer Disease/drug therapy , Animals , Anticonvulsants/therapeutic use , Brain Ischemia/drug therapy , Disease Models, Animal , Disease Progression , Fertilization in Vitro/drug effects , Injections, Intraventricular , Larva/drug effects , Male , Mice , Microinjections , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/therapeutic use , Pentylenetetrazole/administration & dosage , 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/mortality , Small Molecule Libraries/administration & dosage , Small Molecule Libraries/therapeutic use , Zebrafish/embryologyABSTRACT
Phosphorus-31 nuclear magnetic resonance spectroscopy ( (31)P NMR) was used to differentiate virgin coconut oil (VCO) from refined, bleached, deodorized coconut oil (RCO). Monoglycerides (MGs), diglycerides (DGs), sterols, and free fatty acids (FFAs) in VCO and RCO were converted into dioxaphospholane derivatives and analyzed by (31)P NMR. On the average, 1-MG was found to be higher in VCO (0.027%) than RCO (0.019%). 2-MG was not detected in any of the samples down to a detection limit of 0.014%. On the average, total DGs were lower in VCO (1.55%) than RCO (4.10%). When plotted in terms of the ratio [1,2-DG/total DGs] versus total DGs, VCO and RCO samples grouped separately. Total sterols were higher in VCO (0.096%) compared with RCO (0.032%), and the FFA content was 8 times higher in VCO than RCO (0.127% vs 0.015%). FFA determination by (31)P NMR and titration gave comparable results. Principal components analysis shows that the 1,2-DG, 1,3-DG, and FFAs are the most important parameters for differentiating VCO from RCO.
