Ethanolic Extract of the Seed of Zizyphus jujuba var. spinosa Ameliorates Cognitive Impairment Induced by Cholinergic Blockade in Mice.

In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activity. The ameliorating effect of EEZS on scopolamine-induced memory impairment was significantly reversed by a sub-effective dose of MK-801 (0.0125 mg/kg, s.c.). In addition, single administration of EEZS in normal naïve mouse enhanced latency time in the passive avoidance task. Western blot analysis was employed to confirm the mechanism of memory-ameliorating effect of EEZS. Administration of EEZS (200 mg/kg) increased the level of memory-related signaling molecules, including phosphorylation of extracellular signal-regulated kinase or cAMP response element-binding protein in the hippocampal region. Also, the time-dependent expression level of brain-derived neurotrophic factor by the administration of EEZS was markedly increased from 3 to 9 h. These results suggest that EEZS has memory-ameliorating effect on scopolamine-induced cognitive impairment, which is mediated by the enhancement of the cholinergic neurotransmitter system, in part, via NMDA receptor signaling, and that EEZS would be useful agent against cognitive dysfunction such as Alzheimer's disease.

Prunella vulgaris attenuates prepulse inhibition deficit and attention disruption induced by MK-801 in mice.

Prunella vulgaris var. lilacina is widely distributed in Korea, Japan, China, and Europe, and it has been traditionally used to treat inflammation or hypertension. In the present study, we investigated the effects of the ethanolic extract of the spikes of Prunella vulgaris var. lilacina (EEPV) on dizocilpine (MK-801)-induced schizophrenia-like phenotype behaviors such as the disruption of prepulse inhibition and attention deficits in mice. We also determined the effect of EEPV on MK-801-induced alterations in phosphorylated extracellular signal-regulated kinase, phosphorylated protein kinase B, phospho-glycogen synthase kinase 3-ß, and phosphorylated cAMP response element-binding protein levels in the cortex and hippocampus of mice. MK-801-induced prepulse inhibition deficits were ameliorated by the administration of EEPV, as shown in the acoustic startle response test. Furthermore, EEPV attenuated the MK-801-induced attention deficits in the water finding test. We also found that EEPV attenuated the increased phosphorylated extracellular signal-regulated kinase, phosphorylated protein kinase B, or phospho-glycogen synthase kinase 3-ß levels induced by MK-801 in the cortex but not in the hippocampus. These results suggest that EEPV could be useful for treating schizophrenia because EEPV ameliorates prepulse inhibition disruption and attention deficits induced by MK-801.

Neuroprotective effects of a traditional herbal prescription on transient cerebral global ischemia in gerbils.

AIM OF THE STUDY: Kyung-Ok-Ko (KOK), a traditional herbal prescription composed of Rehmannia glutinosa var. purpurae, Panax ginseng, Poria cocos, Lycium chinense, Aquillaria agallocha and honey, has been used to treat age-related symptoms, such as amnesia or dementia, and has been shown to ameliorate scopolamine-induced memory impairment in mice. However, the effects of KOK on transient cerebral global ischemia-induced brain damage are unclear. MATERIALS AND METHODS: Transient cerebral global ischemia was induced by occluding the bilateral common carotid artery for 5 min followed by reperfusion for 7 days. KOK (0.25, 0.5, 1, or 2 g/kg) was administered orally immediately after reperfusion and once a day over the next 7 days. Y-maze or novel object recognition tasks were to analyze learning and memory capabilities at 4 or 5 days after reperfusion, respectively. Histochemistry and immunohistochemistry were used for evaluation of the effect of KOK on neuronal degeneration. RESULTS: Histochemical studies showed that KOK increased the number of viable cells detected by Nissl staining and decreased the number of degenerated neuronal cells detected by Fluoro-Jade B staining in the hippocampal CA1 region. In the immunohistochemical study, the sub-chronic KOK administration attenuated the ischemia-induced activation of microglia and astrocytes and the increase of cytokine IL-1ß (P<0.05). In addition, KOK administration significantly attenuated the ischemia-induced cognitive impairments observed in the Y-maze and novel object recognition tasks (P<0.05). CONCLUSION: These findings suggest that the neuroprotective effects of KOK may be mediated by its anti-inflammatory activities, resulting in the attenuation of memory impairment.

Alaternin attenuates delayed neuronal cell death induced by transient cerebral hypoperfusion in mice.

The aim of this study was to determine whether alaternin exhibits neuroprotective activity after transient cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAO). Mice were subjected to BCCAO, and circulation was restored after 20 min. Alaternin (10 mg/kg, p.o) treatment significantly prevented nitrotyrosine and lipid peroxidation, as well as BCCAO induced-inducible nitric oxide synthase (iNOS) expression. Alaternin also significantly reduced microglial activation (a marker of inflammation). The number of viable neurons detected by Nissl staining increased with alaternin (10 mg/kg, p.o) treatment at 7 days post-BCCAO. In the passive avoidance task, alaternin significantly ameliorated BCCAO-induced cognitive impairments (P<0.05). These results suggest that the neuroprotective effects of alaternin are mediated by its anti-inflammatory and radical scavenging activities.

[Structrue identification of biflavones and determination of Taxol from Taxus Madia].

OBJECTIVE: To study the flavonoids from Taxus Madia and determine the content of Taxol from different parts of Taxus Madia. METHODS: Various column chromatographic techniques were applied for isolation and purification. The structrues were elucidated by physico-chemical property and spectral evidence. The analysis of Taxol was carried out on C18 (150 mm x 4.6 mm i. d. 5 microm). The mobile phase was MeOH-H2O (3:1). The flow-rate was 0.8 ml/min. The detection wave-length was 228 nm. RESULTS: Three bifiavonyl compounds were isolated and identified as Sciadopitysin (Compound I), Ginkgetin (Compound II), 7,7",4'-Tri-O-Methylamentoflavone (Compound III). The contents of Taxol from branches and leaves, main root, fibrous root was 0.0308 mg/g, 0.02191 mg/g, 0.01983 mg/g respectively. CONCLUSION: Compound I-III are obtained from Taxus Madia for the first time. The contents of Taxol is the highest in the part of branches and leaves, and then is the main root, the lowest is the fibrous root.

The seed extract of Cassia obtusifolia ameliorates learning and memory impairments induced by scopolamine or transient cerebral hypoperfusion in mice.

In the present study, we assessed the effect of the ethanolic extract of the seeds of Cassia obtusifolia (COE) on the learning and memory impairments induced by scopolamine or transient bilateral common carotid artery occlusion (2VO). In a study of the cholinergic dysfunction induced by scopolamine, single COE (25, 50, or 100 mg/kg, p.o.) administration significantly attenuated scopolamine-induced cognitive impairments as determined by the passive avoidance and Y-maze tasks (P<0.05) and also reduced escape-latency on the Morris water maze task (P<0.05). In the 2VO study, COE (50 mg/kg, p.o.) significantly reversed 2VO-induced cognitive impairments in mice by the passive avoidance and the Y-maze tasks (P<0.05). Moreover, COE (50 mg/kg, p.o.) also reduced escape-latency and prolonged swimming time in the target quadrant during a probe trial of the Morris water maze task (P<0.05). In an in vitro study, COE was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC(50) value: 81.6 microg/ml). Furthermore, COE also inhibited acetylcholinesterase activity in an ex vivo study. These results suggest that COE attenuates memory impairment induced by scopolamine or 2VO and that these effects are mediated by enhancing the cholinergic nervous system via acetylcholinesterase inhibition.

Tanshinone congeners improve memory impairments induced by scopolamine on passive avoidance tasks in mice.

Tanshinones are a group of diterpenoids found in the roots of Salvia miltiorrhiza Bunge which has been used to treat cardiac disease. In the present study, we investigated the effect of the tanshinone congeners, tanshinone I, tanshinone IIA, cryptotanshinone, and 15, 16-dihydrotanshinone I, on learning and memory impairments induced by scopolamine (1 mg/kg, i.p.), a muscarinic antagonist, using passive avoidance tasks in mice. Tacrine was used as a positive control. Tanshinone I (2 or 4 mg/kg, p.o.), tanshinone IIA (10 or 20 mg/kg, p.o.), cryptotanshinone (10 mg/kg, p.o.), and 15, 16-dihydrotanshinone I (2 or 4 mg/kg, p.o.) significantly reversed scopolamine-induced cognitive impairments (P<0.05). Tanshinone I (2 mg/kg, p.o.) and tanshinone IIA (10 or 20 mg/kg, p.o.) were also reversed diazepam-induced cognitive dysfunctions (P<0.05). In addition, cryptotanshinone and 15, 16-dihydrotanshinone I were found to have an inhibitory effect on acetylcholinesterase in vitro with IC(50) values 82 and 25 microM, respectively. Furthermore, cryptotanshinone inhibited acetylcholinesterase activity for 3 h and 15, 16-dihydrotanshinone I for 6 h in an ex-vivo study. These results suggest that tanshinone congeners may be useful for the treatment of cognitive impairment and that their beneficial effects are mediated, in part, by cholinergic signaling enhancement.