• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.233-233
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• 2002

• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.525-538
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• 2018

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, and anxiety that may involve the release of monoamines in the fear circuit. The reported pharmacological properties of tetramethylpyrazine (TMP) include anti-cancer, anti-diabetic, anti-atherosclerotic, and neuropsychiatric activities. However, the anxiolytic-like effects of TMP and its mechanism of action in PTSD are unclear. This study measured several anxiety-related behavioral responses to examine the effects of TMP on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Rats were given TMP (10, 20, or 40 mg/kg, i.p.) for 14 days after SPS exposure. Administration of TMP significantly reduced grooming behavior, increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. TMP administration significantly reduced the freezing response to contextual fear conditioning and significantly restored the neurochemical abnormalities and the SPS-induced decrease in 5-HT tissue levels in the prefrontal cortex and hippocampus. The increased 5-HT concentration during TMP treatment might be partially attribute to the tryptophan and 5-hydroxyindoleacetic acid mRNA level expression in the hippocampus of rats with PTSD. These findings support a role for reducing the altered serotonergic transmission in rats with PTSD. TMP simultaneously attenuated the HPA axis dysfunction. Therefore, TMP may be useful for developing an agent for treating psychiatric disorders, such those observed in patients with PTSD.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.390-395
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• 2017

The present study investigated the sedative effects of Sophora flavescens (SF) and its bioactive compound, matrine through performing locomotor activity test and the electroencephalography (EEG) analysis in the rat. The underlying neural mechanism of their beneficial effects was determined by assessing c-Fos immunoreactivity and serotonin (5-HT) in the brain utilizing immunohistochemical method and enzyme-linked immunosorbent assay. The results showed that SF and matrine administration had an effect on normalization of caffeine-induced hyperactivity and promoting a shift toward non-rapid eye movement (NREM) sleep. c-Fos-immunoreactivity and 5-HT level in the ventrolateral preoptic nucleus (VLPO), a sleep promoting region, were increased in the both SF and matrine-injected groups. In conclusion, SF and its bioactive compound, matrine alleviated caffeine-induced hyperactivity and promoted NREM sleep by activating VLPO neurons and modulating serotonergic transmission. It is suggested that SF might be a useful natural alternatives for hypnotic medicine.

• 대한한의학회지
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• 제26권4호
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• pp.62-73
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• 2005

Objectives: This study was designed to identify the ergogenic effects of Red ginseng and Paeonia radix mixtures and optimal ratios. Materials and Methods: This study was conducted by administering treatments of Red ginseng and Paeonia radix mixtures to rats and by measuring the time to exhaustion by treadmill running. Results: The treatment of Red ginseng and Paeonia radix mixtures to the rats increased the time to exhaustion by treadmill running. The most potent inhibition of Red ginseng and Paeonia radix mixtures on the 5-HT synthesis and the TPH expression in the dorsal raphe was observed at the dose of 200 mg/kg and the optimal ratio of Red ginseng and Paeonia radix for the maximum efficacy was 50:50. Under normal conditions (not exercise), long-term treatment of Red ginseng and Paeonia radix mixtures did not affect the 5-HT synthesis and the TPH expression in the dorsal raphe, suggesting that Red ginseng and Paeonia radix mixtures does not alter serotonin level in the normal rats. The suppressive effect of Red ginseng and Paeonia radix mixtures on the 5-HT synthesis and the TPH expression during exercise is a possible ergogenic mechanism of these mixtures. Conclusions : Red ginseng and Paeonia radix mixtures reduce exercise-induced fatigue, and have the effect of acting as ergogenic aids on the time to exhaustion by treadmill exercise and on 5-HT synthesis and TPH expression.

• Journal of Animal Science and Technology
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• 제64권5호
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• pp.922-936
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• 2022

5-Hydroxytryptamine (5-HT), a monoamine, as a local regulator in the mammary gland is a chemical signal produced by the mammary epithelium cell. In cows, studies have shown that 5-HT is associated with epithelial cell apoptosis during the degenerative phase of the mammary gland. However, studies in other tissues have shown that 5-HT can effectively promote cell viability. Whether 5-HT could have an effect on mammary cell viability in dairy cows is still unknown. The purpose of this study was to determine: (1) effect of 5-HT on the viability of bovine mammary epithelial cells and its related signaling pathways, (2) interaction between prolactin (PRL) and 5-HT on the cell viability. The bovine mammary alveolar cell-T (MAC-T) were cultured with different concentrations of 5-HT for 12, 24, 48 or 72 hours, and then were assayed using cell counting kit-8, polymerase chain reaction (PCR) and immunobloting. The results suggested that 20 μM 5-HT treatment for 12 or 24 h promote cell viability, which was mainly induced by the activation of 5-HT receptor (5-HTR) 1B and 4, because the increase caused by 5-HT vanished when 5-HTR 1B and 4 was blocked by SB224289 and SB204070. And protein expression of mammalian target of rapamycin (mTOR), eukaryotic translation elongation factor 2 (eEF2), janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) were decreased after blocking 5-HT 1B and 4 receptors. When MAC-T cells were treated with 5-HT and PRL simultaneously for 24 h, both the cell viability and the level of mTOR protein were significantly higher than that cultured with 5-HT or PRL alone. In conclusion, our study suggested that 5-HT promotes the viability of MAC-T cells by 5-HTR 1B and/or 4. Furthermore, there is a reciprocal relationship between PRL and 5-HT.

• Journal of Ginseng Research
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• 제44권4호
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• pp.644-654
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• 2020

Background: Posttraumatic stress disorder (PTSD), a mental disorder induced by traumatic stress and often accompanied by depression and/or anxiety, may involve an imbalance in the neurotransmitters associated with the fear response. Korean Red Ginseng (KRG) has long been used as a traditional medicine and is known to be involved in a variety of pharmacological activities. We used the open field test and forced swimming test to examine the effects of KRG on the depression-like response of rats after exposure to single prolonged stress (SPS), leading to activation of the serotonergic system. Methods: Male rats received KRG (30, 50, and 100 mg/kg, intraperitoneal injection) once daily for 14 days after exposure to SPS. Results: Daily KRG administration significantly improved depression-like behaviors in the forced swimming test, increased the number of lines crossed and time spent in the central zone in the open field test, and decreased freezing behavior in contextual and cued fear conditioning. KRG treatment attenuated SPS-induced decreases in serotonin (5-HT) tissue concentrations in the hippocampus and medial prefrontal cortex. The increased 5-HT concentration during KRG treatment may be partially attributable to the 5-hydroxyindoleacetic acid/5-HT ratio in the hippocampus of rats with PTSD. These effects may be caused by the activation of hippocampal genes encoding tryptophan hydroxylase-1 and 2 mRNA levels. Conclusion: Our findings suggest that KRG has an antidepressant effect in rats subjected to SPS and may represent an effective use of traditional medicine for the treatment of PTSD.

• 대한한의학회지
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• 제28권3호통권71호
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• pp.165-172
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• 2007

Objectives : To find antipruritic herbal medicines, we screened the water extracts of four herbal medicines which have been frequently prescribed to treat dermatologic diseases in oriental medicine. Methods : Water extracts of Bupleuri Radix, Scutellariae Radix, Cimicifugae Rhizoma and Puerariae Radix were administered at a dose of 300 mg/kg to male ICR mice. 1 hour later, serotonin hydrochloride dissolved in physiologic saline at a concentration of 100 nmol / 50${\mu}{\ell}$ was administered intradermally to the nape of the neck at a dose of 50${\mu}{\ell}$. Then the scratching behavior was observed. Dry skin pruritus was induced with cutaneous application of acetone / ether (1:1) mixture and water (AEW) to the rostral back of male ICR mice, twice a day for 5 days. 14 hours after the last application, the most effective material in the first experiment was administered perorally at doses of 75, 150, 300, 600 and 1200 mg/kg. 1 hour later, the scratching behavior was observed. Results : Water extracts of Puerariae Radix significantly inhibited the serotonin-induced scratching behavior and the mean of scratching bouts was reduced by half compared with the control group. Bupleuri Radix group also showed a 29% decrease in the mean of scratching bouts, but there was no statistical significance. Water extracts of Puerariae Radix also inhibited the AEW-induced scratching behavior, in a dose-dependent manner. The dose of 150 mg/kg showed the highest and statistically significant antipruritic effect. Conclusions : These results suggest that Puerariae Radix and its constituents have antipruritic effect, and are new candidates as antipruritic agents.

• 대한수의학회지
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• 제36권3호
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• pp.513-519
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• 1996

The development of calcitonin, serotonin(5-HT) and bovine chromogranin (BCG)-immunoreactive cells was investigated in the thyroid glands of Korean native goat from fetus to adult, using an immunohistochemical method. Moderate number of calcitonin-immunoreactive cells were present in the thyroid glands from 1 month to 6 months after birth, whereas a few in the adult. They were not present in the thyroid glands of fetus and 1 day after birth. A number of 5-HT- and BCG-immunoreactive cells were present in the thyroid glands of Korean native goat from fetus to adult. They were increased in number with age. BCG-immunoreactive cells were weakly reacted in fetus and 1 day after birth, while these cell were strongly stained from 1 month to adult. These findings suggest that calcitonin-, 5-HT- and BCG-immunoreactive cells were present in the thyroid gland of Korean native goat.

• EDISON SW 활용 경진대회 논문집
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• 제6회(2017년)
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• pp.46-53
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• 2017

알츠하이머병은 치매를 유발하는 가장 주된 원인 질환으로 환자들은 인지장애를 겪게 된다. 현재 치료약으로 사용되는 약으로는 acetylcholinesterase 저해재가 있지만 이 약들의 효과는 미비하다. 그래서 인지기능에 영향을 미친다고 알려진 신경전달물질인 GABA, Glutamate, acetylcholine의 수치를 조절 할 수 있는 $5-HT_6$ receptor antagonist가 현재 개발되고 있다. 현재 여러 antagonist들이 임상실험 되었고, 인지 능력향상에 효과를 보이고 있다. 그러나, $5-HT_6$ receptor의 구조가 밝혀지지 않아 아직 원자적 수준의 결합 분석이 이루어지지 않았으므로 이 부분에 대한 연구가 필요하다. 따라서 본 연구에서는 Homology modeling을 통해 receptor의 구조를 예측하고, 현재 임상실험 중인 antagonist들 중 7개를 docking을 통해 단백질과 리간드의 결합을 예측하였다. Edison에서 Galaxy TBM과 Galaxy Refine을 사용하여 Homology modeling 한 결과 GPCR의 전형적인 모델에 특징적으로 긴 cterminal을 가졌다는 것을 확인 할 수 있었다. 생성된 구조를 가지고 Edison의 Dock 프로그램으로 7개의 antagonist가 어떠한 결합을 하는지 분석하였다. 그 결과, binding pose에 공통적으로 Trp102, Asp106, Val107, Pro177, Phe188, Val189, Ala192, Phe284, Phe285, Asn288, Thr306, Tyr310이 관여하는 것을 docking을 통해 알 수 있었다. 특히, Phe285는 7개의 antagonist 중에 4개와의 interaction을 하고 있는 것을 관찰하였다. 이 연구를 통하여 $5-HT_6$에 효과적으로 결합하여 치료효과를 낼 수 있는 신약을 개발할 수 있다.

• 생물정신의학
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• 제14권4호
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• pp.262-267
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• 2007

The serotonin 6(5-HT6) receptor gene is a candidate gene for influencing the clinical response to treatment with antidepressants. The purpose of this study was to determine the relationship between the C267T polymorphism in the 5-HT6 receptor gene and the treatment response to citalopram in a Korean population with major depressive disorder(MDD). Methods : Citalopram was administered for 8 weeks to the 90 patients who completed study. 21-item Hamilton depression rating scale(HAMD-21) was used as a outcome measure. Results : We found that the genotype, allele, and allele-carrier distributions did not differ significantly between MDD patients and normal controls. A main effect of an interaction of genotype with time on the decrease in the HAMD-21 score during the 8 weeks study period was not found. ANOVA revealed no significant effects of the C825T polymorphism on the decrease in the HAMD-21 score at each time period. Conclusions : These results suggest that the C267T polymorphism in the 5-HT6 receptor gene is not associated with the treatment response to citalopram.