Ethanol extract of the seed of Zizyphus jujuba var. spinosa potentiates hippocampal synaptic transmission through mitogen-activated protein kinase, adenylyl cyclase, and protein kinase A pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: As the seed of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) has been used to sleep disturbances in traditional Chinese and Korean medicine, many previous studies have focused on its sedative effect. AIM OF THE STUDY: Recently, we reported the neuroprotective effect of the effect of Z. jujuba var. spinosa. However, its effects on synaptic function have not yet been studied. In this project, we examined the action of ethanol extract of the seed of Z. jujuba var. spinosa (DHP1401) on synaptic transmission in the hippocampus. MATERIALS AND METHODS: To investigate the effects of DHP1401, field recordings were conducted using hippocampal slices (400µm). Object recognition test was introduced to examine whether DHP1401 affect normal recognition memory. RESULTS: DHP1401 (50µg/ml) induced a significant increase in synaptic activity in Shaffer collateral pathway in a concentration-dependent manner. This increase of synaptic responses was blocked by NBQX, a broad spectrum α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, but not IEM-1460, a Ca2+-permeable AMPAR blocker. Moreover, U0126, a mitogen-activated protein kinase inhibitor, SQ22536, an adenylyl cyclase inhibitor, and PKI, a protein kinase A inhibitor, blocked DHP1401-induced increase in synaptic transmission. Finally, DHP1401 facilitated object recognition memory. CONCLUSIONS: These results suggest that DHP1401 increase synaptic transmission through increase of synaptic AMPAR transmission via MAPK, AC and PAK.

Cassia obtusifolia seed ameliorates amyloid ß-induced synaptic dysfunction through anti-inflammatory and Akt/GSK-3ß pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Tea infused with the seed of Cassia obtusifolia has been traditionally used as an herbal remedy for liver, eye, and acute inflammatory diseases. Recent pharmacological reports have indicated that Cassiae semen has neuroprotective effects, attributable to its anti-inflammatory actions, in ischemic stroke and Parkinson's disease models. AIM OF THE STUDY: Previously, the ethanol extract of C. obtusifolia seeds (COE) was reported to have memory enhancing properties. However, the effects of COE in an Alzheimer's disease (AD) model are currently unknown. In this study, we investigated the effect(s) of COE on aberrant synaptic plasticity and memory impairment induced by amyloid ß (Aß), a key toxic component found in the AD brain. MATERIALS AND METHODS: To determine the effect of COE on Aß-induced aberrant synaptic plasticity, we used acute mouse hippocampal slices and delivered theta burst stimulation to induce long-term potentiation (LTP). Western blots were used to detect Aß- and/or COE-induced changes in signaling proteins. The novel object location recognition test was conducted to determine the effect of COE on Aß-induced recognition memory impairment. RESULTS: COE was found to ameliorate Aß-induced LTP impairment in the acute hippocampal slices. Glycogen synthase kinase-3ß (GSK-3ß), a key molecule in LTP impairment, was activated by Aß. However, this process was inhibited by COE via Akt signaling. Moreover, COE was found to attenuate Aß-induced microglia, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX) activation. In the in vivo studies performed, COE ameliorated the Aß-induced object recognition memory impairment. CONCLUSION: These results suggest that COE exhibits neuroprotective activities against Aß-induced brain disorders.

Danggui-Jakyak-San enhances hippocampal long-term potentiation through the ERK/CREB/BDNF cascade.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui-Jakyak-San (DJS), a traditional herbal prescription, has long been used to treat gerontological disorders due to insufficient blood supply. AIM OF THE STUDY: Previously, we reported that DJS increased hippocampal neurogenesis and enhanced learning and memory. However, the precise mechanism of DJS and its effects on learning and memory are still not well understood. In this study, we investigated the effect of DJS on hippocampal long-term potentiation (LTP), a cellular mechanism thought to underlie learning and memory. MATERIALS AND METHODS: To understand the effect of DJS on LTP, we used acute mouse hippocampal slices and delivered one train of high frequency stimulation (100 Hz, 100 pulses). Western blots were used to analyze the changes in protein levels induced by DJS. Morris water maze test was used to evaluate the effect of DJS on spatial long-term memory. RESULTS: DJS enhanced LTP in the Schaffer-collateral pathway of the hippocampus in a concentration-dependent manner. Extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB) were activated by DJS. Moreover, brain-derived neurotropic factor (BDNF) was also increased by DJS. Blockade of ERK1/2 activation with PD198306 blocked the DJS-induced activation of the ERK1/2/CREB/BDNF cascade and LTP enhancement. In vivo, DJS improved spatial long-term memory and upregulated the hippocampal CREB/BDNF cascade. CONCLUSION: These results suggest that DJS enhances hippocampal LTP and spatial memory through the ERK/CREB/BDNF cascade.