• Biomolecules & Therapeutics
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• 제7권3호
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• pp.210-215
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• 1999

Nitric oxide (NO) can mediate numerous physiological processes, including vasodilation, neurotransmission, cytotoxicity, secretion and inflammatory response. The regulation of NO production by inducible NO synthase (iNOS) is considered to be the possible target of the development of anti-inflammatory agent, based on the observation that NO can activate cyclooxygenase, which results in the synthesis of prostaglandins. In an effort to screen new inhibitor of NO production from about 352 species of herbal extracts, we found 9 species with 50% or more inhibitory effect on NO production. Especially, the dose-dependent inhibition of NO production in lipopolysaccharide-treated macrophages by two of the herbal extracts (Artemisiae asiaticae Herba and Saussureae Radix) was due to the decrease in the expression of iNOS.

• Biomolecules & Therapeutics
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• 제27권4호
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• pp.357-362
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• 2019

Limonene is a cyclic terpene found in citrus essential oils and inhibits methamphetamine- induced locomotor activity. Drug dependence is a severe neuropsychiatric condition that depends in part on changes in neurotransmission and neuroadaptation, induced by exposure to recreational drugs such as morphine and methamphetamine. In this study, we investigated the effects of limonene on the psychological dependence induced by drug abuse. The development of sensitization, dopamine receptor supersensitivity, and conditioned place preferences in rats was measured following administration of limonene (10 or 20 mg/kg) and methamphetamine (1 mg/kg) for 4 days. Limonene inhibits methamphetamine- induced sensitization to locomotor activity. Expression of dopamine receptor supersensitivity induced by apomorphine, a dopamine receptor agonist, was significantly reduced in limonenepretreated rats. However, there was no significant difference in methamphetamine-induced conditioned place preferences between the limonene and control groups. These results suggest that limonene may ameliorate drug addiction-related behaviors by regulating postsynaptic dopamine receptor supersensitivity.

• 생물정신의학
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• 제16권3호
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• pp.181-189
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• 2009

Objectives : N100 amplitude slope(the intensity dependence of the cortical auditory evoked potentials) is widely considered as an indirect indicator of central serotonergic neurotransmission. However, there are only a few studies about N100 amplitude slopes of major psychiatric disorders. In this study, we examined N100 amplitude slope differences among major depressive disorder(MDD), bipolar disorder(BD), schizophrenia (SCZ) and normal controls(NC). Methods : We measured the N100 amplitude slopes of 35 patients with MDD, 33 patients with BD, 27 patients with SCZ and 35 NC subjects. Amplitude differences from N1 to P2 at the five different sound intensities(55, 65, 75, 85 and 95dB) were examined at Cz electrode. The N100 amplitude slope was calculated as the linear regression of five N1/P2 peak-to-peak amplitudes across stimulus intensities. Results : BD patients showed significantly reduced N100 amplitude slope compared with NC(0.54${\pm}$0.70 vs. 0.96${\pm}$0.72, p=0.035). N100 amplitude slope of SCZ patients was significantly reduced compared with NC(0.50${\pm}$0.47 vs. 0.96${\pm}$0.72, p=0.027). N100 amplitude slope of BD patients was significantly lower than that of MDD patients(0.54${\pm}$0.70 vs. 0.94${\pm}$0.60, p=0.046). SCZ patients also showed significant reduction of N100 amplitude slope compared with MDD patients(0.50${\pm}$0.47 vs. 0.94${\pm}$0.60, p=0.036). There was no significant difference of N100 amplitude slope between MDD patients and NC(0.94${\pm}$0.60 vs. 0.96${\pm}$0.72, p=1.000). Conclusion : Interestingly, the N100 amplitude slopes of BD and SCZ were reduced compared to NC and MDD patients. Our results suggest the predictive use of N100 amplitude slope in making differential diagnoses of major psychiatric disorders. Clinical implications of N100 amplitude slope in major psychiatric disorders were discussed.

• 동의생리병리학회지
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• 제24권1호
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• pp.143-151
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• 2010

In Vivo and In vitro antispasmodic effects of Jun-Si-Baek-Chul-San, a Traditional Korean Polyherbal Medicineconsisted of 7 types of herbs were observed in the present study. To clarify the effects of Jun-Si-Baek-Chul-San, on accelerating small intestinal movement induced by the stimulation of cholinergic neurotransmission, we evaluated the effects of Jun-Si-Baek-Chul-San on In vivo carbachol (an acetylcholinergic agent)-accelerated mice small intestinal transit and on In vitro contractions induced by low-frequency electrostimulation, KCl, histamine or acetylcholine using isolated guinea pig ileum. To induce the acceleration of mice small intestinal transit, Carbachol 1 mg/kg was once subcutaneously dosed 15min before last administration of the test drugs. In the present study, Jun-Si-Baek-Chul-San 500, 250 and 125 mg/kg or domperidone 20 mg/kg were orally pretreated on the carbachol-accelerated mice small intestinal transit once a day for 7 days and the small intestinal transit rateof activated charcoal powder were monitored. In vitro assays, Jun-Si-Baek-Chul-San1, 0.1, 0.01 and 0.001 mg/ml or domperidone $2{\times}10^{-5}M$ were treated 10min before ileal contraction was induced by filed stimulation, acetylcholine, KCl and histamine, and the % changes of contractions were observed compared to the treatment of inducer alone. In spontaneous contraction, the % changes of contractions were observed compared to treatment of vehicle alone at 10min after Jun-Si-Baek-Chul-San or domperidone treatment. The efficacy of Jun-Si-Baek-Chul-San was compared to those of domperidone. High concentration, 1 mg/ml of Jun-Si-Baek-Chul-San was found to decrease the spontaneous contraction of the isolated guinea-pig ileum. In addition, Jun-Si-Baek-Chul-San decrease contractions induced by electrostimulation, acetylcholine, histamine and KCl in the isolated guinea-pig ileum. In addition, Jun-Si-Baek-Chul-San effectively inhibited the accelerated small intestinal movement induced by carbachol stimulation of cholinergic neurotransmission in In vivo. Based on the results, although the exact molecular or action mechanism and which herbs or compound in Jun-Si-Baek-Chul-San are responsible for actions, it was concluded that Jun-Si-Baek-Chul-San normalization in the accelerated intestinal motility might be interfere with a variety of muscarinic, adrenergic and histaminic receptor activities or with the mobilization of calcium ions required for smooth muscle contraction non-specificly. Therefore, it is expected that Jun-Si-Baek-Chul-San will be promising as a prescription of clinical treatment of digestive tract disorders such as accelerated the motility of intestine, diarrhea or intestinal painful contractions.

• 생명과학회지
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• 제27권5호
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• pp.600-610
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• 2017

가려움증의 분류는 수용체성 가려움증(Pruritoceptive itch), 신경병증 가려움증(Neuropathic itch), 신경성 가려움증(Neurogenic itch), 심인성 가려움증(Psychogenic itch)의 신경생리학적 기전에 따른 4가지 카테고리로 분류하는 것이 일반적이었으나 최근 임상적인 기준을 통해 분류하기도 한다. 가려움증의 신경전달 경로는 히스타민-의존 경로와 히스타민-비의존 경로 2가지로 나뉘며 각 가려움증 매개체마다 서로 다른 수용체와 신경펩티드가 작용한다. 히스타민, BAM8-22, chloroquine 등의 가려움증 매개체는 히스타민-의존 경로를 통해 신호가 전달되며 cowhage spicule, 단백분해효소(protease), TSLP (Thymic stromal lymphopoietin) 등의 매개체가 히스타민-비의존 경로와 관련있다는 보고가 있다. 이러한 가려움증 매개체, 수용체, 신경펩티드는 가려움증 치료의 대상이 된다. 가려움증과 통증은 대표적인 유해자극으로서 과거에는 두 감각이 하나의 유해자극수용체를 통해 전달된다는 주장이 있었지만 최근 밝혀진 바에 따르면 가려움증과 통증은 독립적인 신경전달체계를 가지고 있으며 두 신경체계는 서로 억제작용을 한다. 가려움증 뉴런의 선택적 소집단이 존재한다는 주장을 뒷받침하는 연구들이 이 주장에 무게를 싣고 있다. 또한 가려움증과 통증의 상호 길항작용에 대해서도 다양한 기전으로 설명되고 있다. 최근에도 새롭게 연구되는 매개체와 수용체들이 많은 연구들을 통해 밝혀지고 있다. 특히 최근에는 히스타민 4 수용체에 대한 연구가 활발히 진행되고 있는데, 이는 T 세포 같은 면역세포 자체에 발현되어 있어 이 H4 수용체를 차단하는 치료제는 말초의 매개체를 차단하는 기존의 히스타민 수용체 차단제와는 달리 가려움증 만성화에 중요한 염증 반응 자체를 억제할 수 있다는 점에서 그 유용성이 크다고 할 수 있다. 가려움증의 기본적인 발생 기전에 대한 이해와 새로운 가려움증 매개체에 대한 연구는 효과적인 치료법의 개발로 이어질 것이며 이것이 가려움증 연구가 나아갈 바로 생각한다.

• Biomolecules & Therapeutics
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• 제23권3호
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• pp.245-250
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• 2015

Silibinin, a natural flavonoid antioxidant isolated from extracts of the milk thistle herb, has recently been identified as having anti-hepatotoxic and anticancer properties. In this paper, we investigated the effects of silibinin on behavior and neuroplasticity in mice subjected to chronic unpredictable mild stress (CUMS). After 5 consecutive weeks of CUMS, the mice were treated with silibinin (100 mg/kg, 200 mg/kg and 400 mg/kg by oral gavage) for 3 consecutive weeks. The results showed that silibinin administration significantly alleviated the CUMS-induced depressive-like behavior, including the total number of squares crossed and the frequency of rearing in the open field test, the immobility time in the tail suspension test and the forced swimming test. Furthermore, silibinin treatment increased the levels of brain-derived neurotrophic factor (BDNF), serotonin (5-HT) and norepinephrine (NE) in the prefrontal cortex and hippocampus. Our study provides new insight into the protective effects of silibinin on the depressive status of CUMS mice, specifically by improving neuroplasticity and neurotransmission.

• 생물정신의학
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• 제6권1호
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• pp.3-11
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• 1999

At the beginning, researches on the biology of depression or affective illness have focused mainly on the receptor functions and neuroendocrine activities. And the studies of the past years did not break new theoretical background, but the recent advances in the research on the molecular mechanisms underlying neural communication and signal transduction do add some insights to many established ideas. This article will overview some of the more recent advances in the clinical researches of depression. Our major concerns to be presented here include the followings : (1) alterations in the post-synaptic neural transduction ; (2) changes in the neurons of hypothalamic neuropeptides ; (3) decreased peptidase enzyme activities ; (4) associations of hypothalamic-pituitary-adrenal axis abnormalities with serotonin neurotransmission ; (5) role of serotonin transporter ; (6) changes in the responsiveness of intracellular calcium ion levels ; (7) the inositol deficiency theory of lithium and depression ; (8) the transcription factors including immediate early genes ; (9) recent genetic studies in some families. This brief overview will suggest that changes in DNA occur during antidepressant therapy. These changes at the DNA level initiating a cascade of events underlying antidepressant modality will give us the insights on the molecular biological basis of the pathogenesis of depression and cues for a new class of antidepressants.

• 생물정신의학
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• 제4권1호
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• pp.136-145
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• 1997

We are report on three cases of typical clinical characterstics and treatment response in neuroleptic maligant syndrome(NMS), and reviewed the literatures of NMS. NMS was first recognized as a life-threatening complication of dopamine receptor antagonists, and defined as a catatonic-like states associated with fever, obtundation, muscle rigidity, and unstable vital sign in patients taking neuroleptic agents. Concepts of NMS have changed because medications other than classic neuroleptic drugs have been implicated as triggering agents and syndromes identical to NMS have been observed in other conditions. The important neurochemical features are probably functional dopamine deficiency and ensuing hyperactivity of excitatory amino acid neurotransmission in the basal ganglia and hypothalamus. Recognition of NMS and early discontinuation of neuroleptics are the most important step in its management. Supportive care includes management of hyperthermia and fluid replacement. Controversial therapeutic measures include the application of dopamine receptor agonists, excitatory amino acid antagonists, or dantrolene. Psychiatric patients with a history on NMS and psychotic relapse necessitating antipsycotics do not commonly redevelop NMS.

• Biomolecules & Therapeutics
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• 제12권2호
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• pp.101-107
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• 2004

Repeated administration of psychostimulants such as amphetamines increases locomotor activity in rodents. These drugs, including methamphetamine, enhance dopaminergic neurotransmission and result in hyper-locomotion and behavioral sensitization. It is well known that the existence of a complex balance between the cholinergic and dopaminergic systems in the central nervous system. Thus, behavioral sensitization by methamphetamine may be related to the expression of the M1 muscarinic acetylcholine receptors gene. The present study investigated the changes of M1R mRNA in hyperlocomotor activity and behavioral sensitization by methamphetamine (2 mg/kg) in mice. Our results showed that M1R mRNA expression was increased in the frontal cortex and the hippocampus region (the CA2 region) in the acute methamphetamine administered group compared to the saline administered group. In the chronic group, M1R mRNA expression was increased in the frontal cortex ill1d the hippocampus regions (CA2 and DG regions) in melt1amphetamine administered group compared to saline control group. These results indicate that acute or chronic treatment of mathamphetamine leads to the region-specific changes in mRNA expression levels of M1R. Therefore, Therefore, the present result suggests that M1R may play a role in modulating of methamphetamine-induced behavioral sensitization in mice.

• The Korean Journal of Physiology and Pharmacology
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• 제1권2호
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• pp.117-125
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• 1997

The N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission is involved in synaptic plasticity, developmental processes, learning and memory and many neuropathological disorders including age-related diseases. In the present study, regulation of the NMDA receptor properties by various ligands was investigated using $[^3H]MK-801$ binding studies in the synaptic membranes of young and aged rat forebrains. The binding in the presence of glutamate and glycine increased dramatically with growth between 1 and 6 weeks old, and thereafter declined gradually with aging. Glutamate, glycine or spermine respectively increased the binding with growth. Glutamate maintained the binding during aging, while glycine or spermine significantly decreased the binding in the aged brain. The maximum stimulation by glycine varied depending on the ages of brains. Greater sensitivity to glycine was observed at 1 week and 3 months and the sensitivity was significantly reduced in the aged brain. In contrast, spermine showed similar stimulation patterns in young and aged rats. These results indicated that the functional properties of the NMDA receptor-ion channel complex in young and aged rat forebrains are differentially regulated by agonists, and the reduction of the receptor function with normal aging may be, in some degree, due to the reduction of the receptor sensitivity to glycine.