Paeoniflorin, a Monoterpene Glycoside, Protects the Brain from Cerebral Ischemic Injury via Inhibition of Apoptosis.

Paeoniflorin (PF) is a principal bioactive component, which exhibits many pharmacological effects, including protection against ischemic injury. This paper aimed to investigate the protective effect of PF both in vivo and in vitro. Middle cerebral artery occlusion (MCAO) was performed on male Sprague-Dawley (SD) rat for 2 h, and different doses of PF or vehicle were administered 2 h after reperfusion. Rats were sacrificed after 7 days treatment of PF/vehicle. PF treatment for 7 days ameliorated MCAO-induced neurological deficit and decreased the infarct area. Further study demonstrated that PF inhibited the over-activation of astrocytes and apoptosis of neurons, and PF promoted up-regulation of neuronal specific marker neuron-specific nuclear (NeuN) and microtubule-associated protein 2 (MAP-2) in brain. Moreover, NMDA-induced neuron apoptosis was employed. The in vitro study revealed that PF treatment protected against NMDA-induced cell apoptosis and neuronal loss via up-regulation of neuronal specific marker NeuN, MAP-2 and Bcl-2 and the down-regulation Bax. Taken together, the present study demonstrates that PF produces its protective effect by inhibiting the over-activation of astrocytes, apoptosis of neurons and up-regulation of neuronal specific marker NeuN, MAP-2, and B-cell lymphoma-2 (Bcl-2), and down-regulation Bax. Our study reveals that PF may be a potential neuroprotective agent for stroke and can provide basic data for clinical use.

Blood-brain barrier permeability of Gualou Guizhi granules and neuroprotective effects in ischemia/reperfusion injury.

The present study aimed to estimate the blood-brain barrier (BBB) permeability of Gualou Guizhi granules (GLGZG) in normal rats and in rat models of ischemia/reperfusion (I/R) injury, and to examine the neuroprotective effects of GLGZG. A sensitive high­performance liquid chromatography-quadrupole-time of flight-mass spectrometry analytical method was developed to determinate the components of GLGZG in the plasma and brain tissue. Middle cerebral artery occlusion (MCAO) in rats served as a model of in vivo I/R. Citrulline, gallic acid, albiflorin, peoniflorin, liquiritin apioside, liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, isoliquiritigenin and glycyrrhizinic acid rapidly passed into the bloodstream. Citrulline, albiflorin, peoniflorin, liquiritin apioside, liquiritin, liquiritigenin, isoliquiritigenin and glycyrrhizinic acid also passed the BBB and reached the brain tissue of MCAO rats, while isoliquiritigenin and glycyrrhizinic acid were not detected in the brain tissue of the normal rats. The potential neuroprotective effect of GLGZG was determined in MCAO rats. The intragastric administration of GLGZG following reperfusion of rats for 2 h decreased the neurological defects and infarction volume, attenuated pathological changes of brain tissue and exerted a significant protective effect in cerebral ischemia injury. In conclusion, certain components of GLGZG passed through the BBB, particularly following cerebral ischemia injury, and this may be therapeutically effective for the treatment of cerebral ischemia injury in the human brain.

Neuroprotective effects of Gualou Guizhi decoction in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Gualou Guizhi decoction (GLGZD) prescribed in traditional Chinese medicine has been reported to have protective effects on ischemic stroke. The present study is to investigate the therapeutic effect of GLGZD on ischemic stroke and explore its mode of action. MATERIALS AND METHODS: GLGZD was studied on transient middle cerebral artery occlusion (MCAO) followed by reperfusion in vivo, as well as on hippocampal primary neuron cultures in vitro. RESULTS: In vivo, it was shown that GLGZD treatment for 7 days could ameliorate transient middle cerebral artery occlusion (MCAO)-induced neurological deficit, histopathology changes and decrease infarct area. Further study demonstrated that GLGZD inhibited over-activation of astrocytes and apoptosis of neurons and GLGZD promoted up-regulation of neuronal specific marker neuron-specific nuclear (NeuN) and microtubule-associated protein 2 (MAP-2) in brain. Moreover, the in vitro study revealed that GLGZD treatment protected against NMDA-induced cell apoptosis and neuronal loss, and promoted up-regulation of neuronal specific marker NeuN. CONCLUSIONS: Taken together, the present study demonstrates that GLGZD produces a protection in the MCAO model rats via inhibiting over-activation of astrocytes, apoptosis of neurons and up-regulation of neuronal specific marker NeuN and MAP-2. Our study reveals that GLGZD might be a potential neuroprotective agent for stroke and can provide basic data for clinical use.