Inhibition Of Chiral 3-n-Butylphthalide On Cerebral Ischemia Induced Apoptosis And Studies Of Racemic 3-n-Butylphthalide On Ion Channels

s-(-)- 3-n-butylphthalide [s-(-)- NBP] was extracted as a pure component from seeds of Apium graveolens Linn. Then, (±)- NBP was synthesized and developed as an anti-cerebral ischemic agent by Institute of Materia Medica. Recently, it has been finished phase III clinical trial. There is a chiral center in the molecule of NBP, and a pair of enantiomers have been successfully synthesized. It has been reported that NBP have many anti-ischemic effects, including: reducing cerebral infarct area, improving energy metabolism, enhancing regional cerebral blood flow, ameliorating brain edema and blood-brain barrier damage, ameliorating mitochondria dysfunction, improving microcirculation, etc. A number of studies have provided evidence that apoptosis might be an important factor in the progression of tissue damage resulting from cerebral ischemia. The participation of mitochondria in the mechanism of cell death has received much attention in recent years. The Bcl-2 family proteins could regulate the mitochondrial permeability transition, and/or the release of apoptogenic proteins, such as cytochrome c, to the cytoplasm where it activates caspase-3, which has been reported to trigger apoptosis. The effects of (±)- NBP on hypoxia/hypoglycemia induced apoptosis of rat cortical neurons have been previously reported. Based on the fact that the biological activities and toxicities of drugs are closely related to their optical activities, the present study was designed to compare the action potency of s-(-)-, r-(+)- and (±)- NBP on apoptosis in a transient middle cerebral artery occlusion (MCAO) model imitating human...