• The Korean Journal of Pharmacology
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• v.19 no.2
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• pp.45-55
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• 1983

A role for brain serotonin(5-HT) in regulation of the HPA axis has been suggested but remains contoversial and poorly defined. The present experiments were designed to check kinetic parameters of 5-HT turnover in rat hypothalamus and remainder brain areas before and after stress and to test whether using various different pharmacologic approaches to stimulate or eliminate the control serotonergic system have any consistent effect on the stress-induced activation of HPA system. Steady state brain serotonin and 5-HIAA concentrations during 1 min ether stress were significantly elevated without significant rise in the levels of plasma corticosterone, which highly increased 2 minutes after stress. This suggests that the increase in serotonergic neuron activity precede that in HPA activity. Furthermore, during 1 ruin-ether stress or 30 min immobilization stress there is a marked increase in hypothalamic and remainder brain serotonin (5-HT) turnover or synthesis rates assessed by both the pargline/5-HT method and pargyline/5-HIAA method. The stress-induced corticosterone levels were increased by serotonin precursors and serotonin agonist in a dose-related fashion. The stress- induced corticosterone levels were highly elevated by L-tryptophan (100 mg/kg) and Potentiated by monoamine oxidase inhibitor, pargyline or serotonin agonist, 5-MeoDMT. The stress-induced elevation of corticosterone and 5-HT levels in rat brain were not significantly decreased by the administration of 5-HT synthesis inhibitor, PCPA and 5-HT neurotoxin, 5,7-DHT. However, the stress-induced elevation of corticosterone and 5-HT levels were decreased by the destruction of midline raphe nuclei. There was a strong positive correlation between plasma corticosterone and 5-HT concentrations changed by drugs which mainly manipulating 5-HT system in the hyhothalamus and in the remainder of the brain. In conclusion, our present data stongly suggest that 5-HT is an important key neurotransmitter involved in the stress-induced activation of the HPA system.

• CELLMED
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• v.2 no.2
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• pp.19.1-19.6
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• 2012

$Capparis$ $zeylanica$ Linn. a 'Rasayana' drug is used for its memory enhancing effects in the traditional Ayurvedic system of medicine. The aim of this study was to evaluate acetylcholinesterase (AChE) inhibitory and memory enhancing activities of $Capparis$ $zeylanica$ Linn. The$in-vitro$ and $ex-vivo$ models of AChE inhibitory activity were used along with Morris water maze test to study the effect on memory in rats. The anticholinesterase effect of methanolic and aqueous extracts of $Capparis$ $zeylanica$ was measured by spectrophotometric Ellman method at 0.1, 0.3, 1.0, 3.0, 10 and 30 mg/ml and brain monoamine oxidase (MAO-A and MAO-B) activity was assessed by Naoi's method. The results $in-vitro$ and $ex-vivo$ AChE assay revealed that methanolic and aqueous extracts of $Capparis$ $zeylanica$ inhibit AChE activity, whereas these extracts did not alter MAO activity at any concentration tested as compared to moclobemide and L-deprenyl. The results indicate that $Capparis$ $zeylanica$ improves scopolamine-induced memory deficits through inhibition of AChE activity, and not by direct MAO inhibition.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.9-14
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• 2002

In the present study, we used the microdialysis technique combined with high performance liquid chromatography (HPLC) and electrochemical detection to measure the extracellular levels of norepinephrine (NE) in the posterior hypothalamus in vivo, and to examine the effects of various drugs, affecting central noradrenergic transmission, on the extracellular concentration of NE in the posterior hypothalamus. Microdialysis probes were implanted stereotaxically into the posterior hypothalamus (coordinates: posterior 4.3 mm, lateral 0.5 mm, ventral 8 mm, relative to bregma and the brain surface, respectively) of rats, and dialysate collection began 2 hr after the implantation. The baseline level of monoamines in the dialysates were determined to be: NE $0.17{\pm}0.01,$ 3,4-dihydroxyphenylacetic acid (DOPAC) $0.94{\pm}0.07,$ homovanillic acid (HVA) $0.57{\pm}0.05$ pmol/sample (n=8). When the posterior hypothalamus was perfused with 90 mM potassium, maximum 555% increase of NE output was observed. Concomitantly, this treatment significantly decreased the output of DOPAC and HVA by 35% and 28%, respectively. Local application of imipramine $(50\;{\mu}M)$ enhanced the level of NE in the posterior hypothalamus (maximum 200%) compared to preperfusion control values. But, DOPAC and HVA outputs remained unchanged. Pargyline, an irreversible monoamine oxidase inhibitor, i.p. administered at a dose of 75 mg/kg, increased NE output (maximum 165%), while decreased DOPAC and HVA outputs (maximum 13 and 12%, respectively). These results indicate that NE in dialysate from the rat posterior hypothalamus were neuronal origin, and that manipulations which profoundly affected the levels of extracellular neurotransmitter had also effects on metabolite levels.

• Journal of Oriental Neuropsychiatry
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• v.17 no.3
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• pp.21-43
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• 2006

This study was designed to assess Effects of jingansikpungtanggagam-bang on Central Nerve System. Method : jingansikpungtanggagam-bang, a Korean traditional prescription, was evaluated for its anticonvulsant effect, hypnotic activity, analgesic action, anxiolytic effect, memory enhancement, and MAO inhibitory activity and detennined the content of neurotransmitter in brain by HPLC method. Result : 1. The extract increased potently anticonvulsant effect at 1g/kg by 5.6-fold extention of onset time against control group. 2. The extract increased hvrmsis at 500mg/kg by over twofold length of sleeping time compared to control. 3. The extract showed a significant analgesic effect with 86.0% inhibition on writhing frequency at 500mg/kg by phenylquinone-induced writhing test. 4. The extract inhibited dose-dependently the activity of monoamine oxidase in vitro. 5. This prescription increased the brain levels of serotonin and 5-hydroxyindoleacetic acid by 3.3% and 1.4%, respectively. 6. the extract exhibited the anxiolytic effect with 21.3% decrease of the immobility duration against control group. 7. the extract enhanced memory recovery on scopolamine-induced impairment of passive avoidance performance at 1g/kg pretreatment with 20.2% increase of latency time. Conclusion : The result sugguest that jiugansikpungtanggagam-bang can be used effectively as a sedative prescription in Korean traditional medicine.

• Journal of Nutrition and Health
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• v.37 no.3
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• pp.176-181
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• 2004

This study was designed to investigate the effects of buthanol (BuOH) fraction of pine (Pinus densiflora Sieb et Zucc) needle on cholesterol and lipofuscin (LF) accumulations, acetylcholine (ACh) and its related enzyme activities such as choline acetyltransferase (CAhT) and acetylcholinesterase (AChE), and monoamone oxidase-B (MAO-B) activity, which destroyed the catecholamine-related neurotransmitters in brain membranes of Sprague-Dawley (SD) rats. Male SD rats were fed basic diets (control group) or experimental diets (BuOH-25, BuOH-50 and BuOH-100) for 45 days. Cholesterol accumulations in mitochondria and microsomes were significantly inhibited (about 14 - 17％ and 23 - 34％, respectvely) in BuOH-50 and BuOH-100 groups, whereas LF levels were significantly inhibited (about 10 - 14％) in BuOH-50 and BuOH-100 groups compared with control group. ACh levels and ChAT activities were significantly increased (about 11 - 17％ and 11 - 23％, respectively) in membranes of BuOH-50 and BuOH-100 groups compared with control group. AChE activities were significantly increased (about 14 - 17％) in membranes of BuOH-50 and BuOH-100 groups. There was no significant difference in MAO-B activities between control and experimental diet groups. The results suggest that butanol fraction of pine needle may play an effective role in an antiaging effect and improving a learning and memory impairments.

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.1
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• pp.109-115
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• 1997

This study was designed to investigate the effects of methionine(Met) on the activities of brain lipid peroxidation related enzymes in ethanol administrated rats of selenium(Se) deficiency. Male Sprague-Dawley rats were fed Se deficiency diets containing one of the three levels of Met (0, 3, 9g/kg diet) and ethanol(2.5g/kg of body weight) was administrated as 25v/v% ethanol treated groups orally. The rats sacrificed after 5 and 10 weeks of feeding periods. Alcohol dehydrogenase activity was increased in ethanol treated groups and was higher Met normal group than Met deficiency and excessive groups at 5 and 10 weeks dieting. Aldehyde dehydrogenase activity was decreased in ethanol treated groups and significantly decreased in Met deficiency group. Monoamine oxidase activity in brain was increased in ethanol treated groups and was predominently increased in Met deficiency groups. Superoxide dismutase and glutathione peroxidase activities were decreased in ethanol treated groups and tended to increase in proportion to level of dietary methionine. Glutathione S-transferase and catalase activities and lipid peroxide content were increased by ethanol administration and were higher Met deficiency group than normal and excessive groups.

• YAKHAK HOEJI
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• v.49 no.4
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• pp.355-364
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• 2005

A neurotoxin, 6-hydroxydopamine (6-OHDA) has long been used to form a Parkinson's disease (PD) model by inducing the lesion in catecholaminergic pathways, particularly the nigrostriatal dopamine (DA) pathway. Whereas l-deprenyl, a selective inhibitor of monoamine oxidase (MAO) type B, is now widely used in the treatment of PD, the precise action mechanism of the drug remains elusive. In this study, we investigated whether l-deprenyl shows protective effect against the DA depletion induced by 6-OHDA in rat brain, and against 6-OHDA-induced neurotoxicity and oxidative stress in catecholaminergic neuroblastoma SH-SY5Y cells that are known to lack MAO-B activity. Pretreatment of l-deprenyl significantly enhanced the striatal DA, 3,4-dihydroxyphenylacetic acid, homovanilic acid, and 3-methoxytyramine levels compared to the untreated 6-OHDA-lesioned rat, indicating that l-deprenyl pretreatment prevents 6-OHDA-induced depletion of not only striatal dopamine but also its metabolites. Treatment of 6-OHDA for 24hrs decreased the cell viability and increase the generation of ROS in dose-dependent manners. We further investigated whether caspase activity is involved in the action of l-deprenyl. Treatment of l-deprenyl $(0.1\~100{\mu}M)$ did not produce any changes in 6-OHDA-induced cleavage of poly (ADP-ridose) polymerase in SH-SY5Y cells. Our results suggest that the neuroprotective effect of l-deprenyl against 6-OHDA is due to its increased scavenger activity, but independent of inhibition of MAO-B or caspase-3 activation.

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.1-6
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• 1990

We established an in vitro system of central serotonergic neurons by culturing dissociated rat embryonic (El4) brainstem cells to 14 days in vitro and monitored the serotonergic neuronal growth by measuring 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents in the cells with hish performance liquid chromatography with electrochemical detection (HPLC-EC). We studied also tile effects of various drugs on the contents of 5-HT and 5-HIAA, confirming in vivo reports. The 5-HT content (13 ng/mg protein) and 5-HT turnover rate (17 pmol/mg protein/h) at 14 days in vitro were in good agreement with those reported in the adult rat brain. The 5-HT content was more easily depleted with p-chlorophenylalanine, a tryptophan hydroxylase inhibitor than with NSD 1015 (3-hydroxybenzylhydrazine), an aromatic L-amino acid decarboxylase (AADC) inhibitor. Incubation of the cultures with tryptophan or 5-hydroxytryptophan increased the rate of serotonin formation implying that neither tryptophan hydroxylase nor AADC is saturated with its amino acid substrate in this in vitro system . The 5-HT content was depleted by reserpine. The 5-HT and 5-HIAA contents were increased and decreased, respectively, by monoamine oxidase inhibitors. All the above results indicate that the biochemical properties of the central serotonergic neurons in this culture system reflect reliably those of central serotonergic neurons in vivo. We suggest that measuring 5-HT and 5-HIAA contents in the primary cultured dissociated brainstem-cells with HPLC-EC is useful in the study of pharmacology as well as toxicolgy of the central serotonergic neurons.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.1
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• pp.92-97
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• 2002

The effects of Pueraria flos (PF) and Pueraria radix (PR) water extract on the hepatic alcohol metabolic enzyme activities were examined in rats that were orally administered ethanol (25% v/v, 5g/kg body weight/day) for 5 weeks. The PF and PR water extract were supplemented in a diet, based on 1.2 g or 2.4 g of raw PF or PR/kg body weight/body. Alcohol administration without the PF or PR supplementation significantly decreased net weight gain, feed intake and feed efficiency ratio. However. both dose of the PF of PR supplementation resulted in significant enhancement of growth and suppression of increased relative weight of liver, brain and heart by alcohol administration. Activities of hepatic alcohol dehydrogenase and microsomal ethanol oxidizing system were higher in the alcohol treated group than in the normal group, while aldehyde dehydrogenase activity was significantly lowered in the alcohol treated group. The hepatic metabolic enzyme activities altered by alcohol administration were normalized by both doses of PF or PR supplement. Hepatic monoamine oxidase activity and hydrogen peroxide, which were significantly higher in the alcohol treated group than in the normal group, were also decreased by the supplementation with either PF or PR. These results indicate that low-or high-supplementation of either water extract PF or PR may alleviate ethanol-induced hepatotoxicity by altering alcohol metabolic enzyme activities.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.4
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• pp.409-414
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• 2009

The aim of this study was to investigate the ameliorating effects of deer antler extract on the learning and memory impairments induced by the administration of scopolamine (2 mg/kg, i.p.) in rats. Tacrine was used as a positive control agent for evaluating the cognition enhancing activity of deer antler extract in scopolamine-induced amnesia models. The results showed that the deer antler extract-treated group (200 mg/kg, p.o.) and the tacrine-treated group (10 mg/kg, p.o.) significantly ameliorated scopolamine-induced amnesia based on the Morris water maze test. Although there was no statistical significance of brain ACh contents among the experimental groups, the brain ACh contents of the deer antler extract-treated group was slightly higher than that of the scopolamine-treated group. The inhibitory effect of deer antler extract on the acetylcholinesterase activity in the brain was significantly lower than that of scopolamine-treated group. The tacrine- and the deer antler-treated groups reduced the MAO-B activity compared to the scopolamine-treated group, but not significantly. These results suggest that the deer antler extract could be an effective agent for the prevention of the cognitive impairment induced by cholinergic dysfunction.