• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.6
• /
• pp.1151-1156
• /
• 2002

This research was done to make the effective prescription and cope with various senile dementia. Sprague-Dawley rats were injured by ibotenic acid to make a damage on learning and memory functions of model rats. At first acquisition test and retention rest were done in the Morris water maze. And to evaluate the effects of the sample drug(GSD) on choline acetyltranferase and acetylcholine esterase, immunoreactive measurement and enzymatic activity measuring were carried out. The ibotenic acid were injected to hippocampus CA1 and CA3 area. Conclusion : GSD improved the learning ability in the acquisition test and memory function in the retention test significantly. And GSD increased the level of ChAT which is synthesizing acetylcholine in CA1 area, and at the same time it increased the level of AChE which is resolving acetylcholine. These results show that GSD improved the cholinergic catabolism and anabolism, and the increment of metabolic activity of cholinergic system. In other words, it contributes to the recovery of damaged learning and memory function by ibotenic acid. So it can be concluded that GSD will be helpful to cholinergic brain damage induced by primary or senile reduction of acetylcholine secretive activity.

• The Journal of Korean Medicine
• /
• v.23 no.2
• /
• pp.125-138
• /
• 2002

Learning and memory are essential requirements for every living organism in order to cope with environmental demands, and cholinergic systems are known to be involved in learning and memory. Scutellaria baicalensis (SB) and Gastrodia elata (GE) as a traditional Oriental medicine have been clinically used to treat or prevent memory deficits, including Alzheimer's disease. In the present study, we investigated the effects of SB and GE on learning and memory in the Morris water maze task and the central cholinergic system of the rats with excitotoxic medial septum lesions. In the water maze test, the animals were trained to find a platform at a fixed position over 6 days and then received a 60-s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesion of the medial septum (MS) impaired their performance in the maze test (latency of acquisition test on the 3rd day, $27.6{\pm}$4.4 sec vs. $61.7{\pm}17.7$ sec; retention test, $7.9{\pm}1.3%$ vs. $5.7{\pm}1.0%$: sharn vs. ibotenic lesioned groups, respectively) and reduced choline acetyltransferase (ChAT) - immunoreactivity in the MS and the hippocarnpus, which is a marker for degeneration of the central cholinergic system (number of cells, $21.1{\pm}1.1$ vs. $13.2{\pm}1.3$: sham vs. ibotenic lesioned group). Daily administrations of SB (100mg/kg, p.o.) and GE (100mg/kg, p.o.) for 21 consecutive days produced significant reversals of ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of cholinergic immunoreactivity in the MS and the hippocarnpus induced by ibotenic acid. These results demonstrated that SB and GE ameliorated learning and memory deficits through effects on the central nervous system, partly through effect on the acetylcholine system. Our studies suggest an evidence of SB and GE as treatment for Alzheimer's disease.

• Animal cells and systems
• /
• v.12 no.4
• /
• pp.203-209
• /
• 2008

Berberine, an isoquinoline alkaloid found in Coptidis Rhizoma(goldenthread) extract, has multiple pharmacological effects such as anti-inflammatory, antimicrobial and anti-ischemic effects. In the present study, we examined the effects of berberine on neuronal survival and differentiation in a hippocampal precursor cell line and in the memory deficient rat model. Berberine increased in a dose dependent manner the survival of hippocampal precursor cells as well as differentiated cells. In addition, berberine promoted neuronal differentiation of hippocampal precursor cells. In the memory deficient rat model induced by stereotaxic injection of ibotenic acid into entorhinal cortex(Ibo model), hippocampal cells were increased about 2.7 fold in the pyramidal layer of CA1 region and about 2 fold in the dentate gyrus by administration of berberine after 2 weeks of ibotenic acid injection. Furthermore, neuronal cells immunoreactive to calbindin were increased in the hippocampus and entorhinal cortex area by administration of berberine. Taken together, these results suggest that berberine has neuroprotective effect in the Ibo model rat brain by promoting the neuronal survival and differentiation.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.17 no.2
• /
• pp.553-559
• /
• 2003

In order to make the efficient prescription and cope with various senile dementia, learning and memory functions of Sprague-Dawley model rats were tested with Morris water maze at first. And to evaluate the effects of the sample drug(GM) on choline acetyltranferase and acetylcholine esterase, immunoreactive measurement and enzymatic activity measuring were carried out. Rats were injected with ibotenic acid through hippocampus CA1 and CA3 area. The results are as following. GM improves the learning ability in tile acquisition test and memory function in the retention test significantly. And GM increases the level of ChAT which is synthesizing acetylcholine in CA3 area, and at the same time it increases the level of AChE which is resolving acetylcholine. These results show that GM improve the cholinergic catabolism and anabolism, and the increment of metabolic activity of cholinergic system contributes to the recovery of damaged learning and memory function by ibotenic acid. So it can be concluded that GM will be helpful to cholinergic brain disease induced by primary or senile reduction of acetylcholine secretive activity.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.17 no.1
• /
• pp.50-56
• /
• 2003

This research was done to make the effective prescription and cope with various senile dementia. So Sprague-Dawley rats were injected with ibotenate to make a damage on learning and memory functions. At first acquisition test and retention rest were done in the Morris water maze. And to evaluate the effects of the sample drug(TBM) on choline acetyltranferase and acetylcholine esterase, immunoreactive measurement and enzymatic activity measuring were carried out. The ibotenic acid were injected to hippocampus CA1 and CA3 area. The results were as following. TBM improved the learning ability in the acquisition test and memory function in the retention test significantly. And TBM increased the level of ChAT which is synthesizing acetylcholine in CA3 area, and at the same time it increased the level of AChE which is resolving acetylcholine. These results show that T8M improved the cholinergic catabolism and anabolism, and the increment of metabolic activity of cholinergic system. In other words, it contributes to the recovery of damaged learning and memory function by ibotenic acid. So it can be concluded that TBM will be helpful to cholinergic brain damage induced by primary or senile reduction of acetylcholine secretive activity.

• The Korean Journal of Physiology and Pharmacology
• /
• v.23 no.6
• /
• pp.483-491
• /
• 2019

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. ${\beta}$-Amyloid ($A{\beta}$) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed $A{\beta}$ + IBO-induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in $A{\beta}$ + IBO-induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against $A{\beta}$ + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine $A_1$ receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the $A{\beta}$ + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of $A_1R$ is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.

• Toxicological Research
• /
• v.4 no.2
• /
• pp.85-94
• /
• 1988

In order to elucidate the mechanism of toxic action of a pisonous mushroom, Amanita pantherina, biochemical effects of the mushroom extracts on mice were studied. A hotwater extract of Amanita pantherina injected intraperitoneally into male ICR mice evoked signs similar to those observed clinically upon acute poisoning by the mushroom and also changed the levels of component enzyme activities in blood, liver and urine. The serum cholinesterase activity was decreased significantly during 1-3 h after injection.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.6
• /
• pp.1236-1242
• /
• 2002

In order to make an efficient prescription and cope with dementia, learning and memory functions of Sprague-Dawley model rats were tested with Morris water maze. And to evaluate the effect of the sample drug(CHM) on choline acetyltranferase and acetylcholine esterase, immunoreactive measurement and enzymatic activity measuring were carried out. Rats were injected with ibotenic acid through hippocampus CA1 and CA3 area. The results are as following. CHM improves the learning ability in the acquisition test and memory function in the retention test significantly. And CHM increases the level of AChE which is resolving acetylcholine. Though it doesn't increase the level of ChAT significantly which is synthesizing acetylcholine, but it shows the tendency of increase. So these results show that CHM improve the cholinergic catabolism and anabolism, and the increment of metabolic activity of cholinergic system. Thus it can be concluded that CHM will be helpful to cholinergic brain disease induced by primary or senile reduction of acetylcholine secretive activity.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2004.11a
• /
• pp.124-128
• /
• 2004

We have assessed amyloid ${\beta}-peptide$ $(A{\beta})-induced$ neurotoxicity in primary neurons and organotypic hippocampal slice cultures (OHC) in rat. Exposing cultured hippocampal and cerebellar granule neurons to $A{\beta}$ resulted in a decrease of MTT reduction, and in destruction of neuronal integrity. Treatment of these neurons with tunicamycin, an inhibitor of N-glycosylation in the endoplasmic reticulum (ER), also decreased MTT reduction in these neurons. S-allyl-L-cysteine (SAC), an active organosulfur compound in aged garlic extract, protected hippocampal but not cerebellar granule neurons against $A{\beta}$- or tunicamycin-induced toxicity. In the hippocampal neurons, protein expressions of casapse-12 and GRP 78 were significantly increased after $A{\beta}_{25-35}$ or tunicamycin treatment. The increase in the expression of caspase-12 was suppressed by simultaneously adding $1{\mu}M$ SAC in these neurons. In contrast, in the cerebellar granule neurons, the expression of caspase-12 was extremely lower than that in the hippocampal neurons, and an increase in the expression by $A{\beta}_{25-35}$ or tunicamycin was not detected. In OHC, ibotenic acid (IBO), a NMDA receptor agonist, induced concentration-dependent neuronal death. When $A{\beta}$ was combined with IBO, there was more intense cell death than with IBO alone. SAC protected neurons in the CA3 area and the dentate gyrus (DG) from the cell death induced by IBO in combination with $A{\beta}$, although there was no change in the CA1 area. Although protein expression of casapse-12 in the CA3 area and the DG was significantly increased after the simultaneous treatment of AI3 and IBO, no increase in the expression was observed in the CA1 area. These results suggest that SAC could protect against the neuronal cell death induced by the activation of caspase-12 in primary cultures and OHC. It is also suggested that multiple mechanisms may be involved in neuronal death induced by AI3 and AI3 in combination with IBO.

• Journal of Oriental Neuropsychiatry
• /
• v.19 no.1
• /
• pp.125-146
• /
• 2008

Objectives : The purpose of this study is to suggest for the following experimental study of dementia by reviewing recent oriental medicine journals that have been published since 2000. Methods: We have investigated various types of studies in relation to dementia through 90 articles that have been published from 2000 to 2007 in recent oriental medicine journals were registered Korea research foundation. Results and Conclusions : 1. Since 2000, 88 articles in relation to dementia have been published and almost of them are herbal medicine-centered studies. Also they show a tendency to increase every year. The journal of oriental neuropsychiatry carries the highest number of studies in relation to dementia. 2. According to the experimental paper, there are 30 cases of using herb simplexes, 48 cases of herb-combined prescription, and 10 cases of other ways. Especially 7 cases of using herb-combined prescription relation to Sasang constitution are all for the Taeumin. 3. There are 85 cases of Animal and cellular experimental, 60 cases of using pathologic model induced cytotoxic activity, a case of using L-NAME, 3 cases of 192 saporin, 4 cases of ibotenic acid, 10 cases of focal cerebral ischemia, 3 cases of alcohol-administered, and one case of natural degradation. 4. Moms water maze, Radial arm maze Passive avoidance learning model were using for examining learning and memory of model animal 5. We propose that following studies of dementia are to he investigated of the applied method of using siRNA with tranceduced gene, sample preparation by water-soaking, oriental medical diagnosis, standardization of differentiating symptom and herb simplexes, building the database by classified prescriptions, and experiment model which are based on precise examining mechanism with cell line as like mouse H19-7 hippocampus, rat HT22 hippocampus, astrocyte, microglia, using the model of animals at APP, PS1, BACE, CT99/PS1, APOE4, Tau, APP/PSI/Tau