The fruit of Crataegus pinnatifida ameliorates memory deficits in ß-amyloid protein-induced Alzheimer's disease mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Crataegus pinnatifida is a traditional medicine widely used as digestive drug in East Asia. Although Chinese herbal medicine used it for mental health, scientific evidence does not exist, yet. AIMS OF STUDY: The aim of this study is to show that the ethanol extract of the fruit of Crataegus pinnatifida (CPE) has neuroprotective effect on Alzheimer' disease model mice. MATERIALS AND METHODS: Intracerebroventricular injection of Aß was used to induce Alzheimer's disease-like pathology. Passive avoidance and Y-maze tasks were used to examine the effect of CPE on memory impairments by Aß. Immunohistochemistry was used to examine the effect of CPE on glial activation. ThT assay was used to observe the effect of CPE on Aß aggregation. MTT and LDH release assays were utilized to examine effects of CPE on Aß-induced cytotoxicity. RESULTS: CPE prevented memory deficit in Aß-induced memory impairment model. Moreover, CPE prevented glial activation in the hippocampus of Aß-injected model. In in vitro test, CPE inhibited Aß fibril formation in a concentration-dependent manner. CPE also caused disaggregation of Aß fibrils. Along with this, CPE blocked neuronal cell death induced by Aß. CONCLUSIONS: Collectively, these experimental findings demonstrated that CPE could be a candidate for development of AD therapy.

The ethanol extract of Zizyphus jujuba var. spinosa seeds ameliorates the memory deficits in Alzheimer's disease model mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) have long been treated as hypnotic agent for sleep disturbances in traditional Chinese and Korean medicine and many previous studies have focused on its effect in central nervous system. AIMS OF STUDY: The present study aimed to provide evidence showing that the ethanol extract of Zizyphus jujuba var. spinosa seeds (EEZS), which may regulate plasmin activity, has the potential to serve as a therapeutic agent for AD. MATERIALS AND METHODS: Synaptic function was determined by measuring long-term potentiation (LTP) in Shaffer-collateral pathway of the hippocampus. Protein levels of plasmin or plasminogen were examined using western blotting. Plasmin activity was measured using ELISA. Cognitive functions were measured using passive avoidance and object recognition tests in the 5XFAD mice. RESULTS: Our in vitro analysis revealed that EEZS-treated hippocampal slices from 5XFAD mice, a mouse model of AD, showed significantly higher long-term potentiation levels than did vehicle-treated hippocampal slices from 5XFAD mice (P < 0.05). Additionally, EEZS significantly elevated the plasmin level and activity in the hippocampal slices from 5XFAD mice (P < 0.05). Co-treating the slices with EEZS and 6-aminocaproic acid, a plasmin inhibitor, blocked the ameliorating effects of EEZS on the synaptic deficits that were present in 5XFAD mice. Compatible with the in vitro study, the results of our in vivo investigation showed that administering EEZS orally to 5XFAD mice ameliorated their memory impairments. Orally administered EEZS also elevated the plasmin level and activity in the hippocampus of 5XFAD mice. CONCLUSIONS: Collectively, our findings suggest that EEZS alleviates the AD-like symptoms in 5XFAD mice by regulating of plasmin activity and EEZS may be a suitable treatment for AD.

Neuroprotective effect of the ethanol extract of Artemisia capillaris on transient forebrain ischemia in mice via nicotinic cholinergic receptor.

Artemisia capillaris Thunberg is a medicinal plant used as a traditional medicine in many cultures. It is an effective remedy for liver problems including hepatitis. Recent pharmacological reports have indicated that Artemisia species can exert various neurological effects. Previously, we reported a memory-enhancing effect of Artemisia species. However, the mechanisms underlying the neuroprotective effect of A. capillaris (AC) are still unknown. In the present study, we investigated the effect of an ethanol extract of AC on ischemic brain injury in a mouse model of transient forebrain ischemia. The mice were treated with AC for seven days, beginning one day before induction of transient forebrain ischemia. Behavioral deficits were investigated using the Y-maze. Nissl and Fluoro-jade B staining were used to indicate the site of injury. To determine the underlying mechanisms for the drug, we measured acetylcholinesterase activity. AC (200 mg·kg-1) treatment reduced transient forebrain ischemia-induced neuronal cell death in the hippocampal CA1 region. The AC-treated group also showed significant amelioration in the spontaneous alternation of the Y-maze test performance, compared to that in the untreated transient forebrain ischemia group. Moreover, AC treatment showed a concentration-dependent inhibitory effect on acetylcholinesterase activity in vitro. Finally, the effect of AC on forebrain ischemia was blocked by mecamylamine, a nonselective nicotinic acetylcholine receptor antagonist. Our results suggested that in a model of forebrain ischemia, AC protected against neuronal death through the activation of nicotinic acetylcholine receptors.

The enhancing effect of Aubang Gahl Soo on the hippocampal synaptic plasticity and memory through enhancing cholinergic system in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aubang Gahl Soo (AGS) is a Korean traditional drink manufactured from medicinal plants and fruits using sugar or honey. Although traditional old book stated its effects on body, there is no scientific evidence yet. Therefore, in the present study, we tested AGS on brain functions. AIM OF THIS STUDY: In this study, we tried to uncover the effect of on brain functions. To do this we examined the action of AGS on the hippocampal synaptic function and memory in mice. MATERIALS AND METHODS: To examine the effect of AGS on synaptic plasticity, we observed input-output curves (I/O curve), paired-pulse facilitation (PPF), and long-term potentiation (LTP) using mouse hippocampal slices. Moreover, to investigate the functional relevance of the effect of AGS on synaptic plasticity, we conducted passive avoidance, Y-maze and Morris water maze tests. To examine relevant mechanism, acetylcholinesterase (AChE) activity and acetylcholine (ACh) level assay were also conducted. RESULTS: In the basal synaptic transmission study, we found that AGS did not affect I/O curves and PPF. However, AGS facilitated hippocampal LTP in a concentration-dependent manner. Moreover, AGS blocked AChE activity (IC50 = 485 µg/ml). Moreover, ACh level was increased by AGS (100 µg/ml) treatment. Along with this, facilitating effect of AGS on hippocampal LTP also blocked by scopolamine, a muscarinic acetylcholine receptor antagonist. Moreover, AGS also ameliorated memory impairments induced by scopolamine in passive avoidance, Y-maze, and Morris water maze tests. CONCLUSIONS: These results suggest that AGS facilitates hippocampal LTP through activating cholinergic system and ameliorates cholinergic dysfunction-induced memory deficit.

The Seed of Zizyphus jujuba var. spinosa Attenuates Alzheimer's Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling.

Ziziphus jujuba is a plant, which bears fruits and seeds that are used for medicinal purposes in Traditional oriental medicine. The seed of Zizyphus jujuba var. spinosa (EZJ) has been also traditionally used for psychiatric disorders in Chinese and Korean medicines. Recent findings have indicated that EZJ improves memory impairment, a common symptom of various neurological diseases. However, the effects of EZJ on amyloid ß (Aß) toxicity, which is a main cause of Alzheimer's disease (AD), remain to be elucidated. To illuminate the potential anti-AD effect and mechanism in the mouse hippocampal tissue, we examined the effect of standardized EZJ on Aß-induced synaptic long-term potentiation (LTP) deficit in the hippocampal tissue. EZJ blocked Aß-induced LTP deficits in a concentration-dependent manner. Moreover, EZJ increased brain-derived neurotrophic factor (BDNF) level in naïve hippocampal slices. The finding that the blockade of BDNF receptor reduced the effect of EZJ suggests that EZJ ameliorates the Aß-induced LTP deficit through BDNF/topomyosin receptor kinase B (TrkB) signaling. However, transcription or translation inhibitors failed to block the effect of EZJ, suggesting that BDNF synthesis is not required for the action of EZJ on LTP. Finally, we found that EZJ stimulates plasmin activity. In contrast, plasmin inhibitor blocked the effect of EZJ on the Aß-induced LTP deficit. Our findings indicate that EZJ ameliorates Aß-induced LTP deficits through BDNF/TrkB signaling. This phenomenon is induced by a regulatory effect of EZJ on the post-translation modification of BDNF.