• 동의신경정신과학회지
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• 제16권1호
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• pp.171-183
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• 2005

Objective : The Korean famous medicinal prescription of Subi-jeon was investigated for their antidepressant effects by tail suspension test, hot plate test, reserpine-induced hypothermia test. In addition, the monoamine oxidase activity was determined in vivo. Methods : The methanol extract reduced dose-dependently the duration of immobility in the tail suspension test, by 31.4 and 34%(p<0.05) at doses of 500mg/kg and 1g/kg, respectively, compared with control group. In comparison with this, the effect of the water extract was very weak. Results : 1. In the hot plate test, the methanol extract potently increased the jump latency time(p<0.05) compared to the control group, exhibiting the inhibition rate of 197% and 256% at doses of 500mg/kg and 1g/kg(per os), respectively, which is more effective than the water extract. 2. Both extracts suppressed the fall of body temperature induced by reserpine(reserpine-induced hypothermia) in a dose-dependent manner, showing the less effect at lower doses and better effect at higher doses compared to the water extract. 3. Both extracts inhibited the brain monoamine oxidase activity in an in vivo assay compared to the control group, the activity of water extract was better than that of the methanol extract. Conclusion : The prescription of Subi-jeon can be useful for the prevention and treatment of depression.

• 생물정신의학
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• 제9권1호
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• pp.25-33
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• 2002

우울증 환자들에게 항우울제를 처방하는 임상의들이 흔히 겪게 되는 두 가지 어려움은 약물의 치료 반응 유무를 판단하기 위하여 처음 약물을 투여한 후 4~6주 이상을 기다려야 하는 것과 어떤 종류의 항우울제라도 처음 4~6주 이후에도 반응을 보이지 않는 환자들이 30~40% 이상이 된다는 것이다. 이와 같은 어려움을 극복하기 위해서는 환자 개개인의 항우울제에 대한 반응성을 미리 예측하는 것이 필요하다. 이 논문에서는 연구자들의 과거 실험들과 이미 발표된 연구들을 중심으로 하여 항우울제에 대한 치료 반응성을 예측하는데 약리유전학적 방법을 이용한 현재까지의 연구들과 연구 결과를 해석 할때 고려해야 할 사항을 살펴보고자 한다. 세로토닌 수송체(serotonin transporter, 5-HTT)는 항우울제가 신경세포에 작용하는 주요 작용부위 중 하나이다. 최근의 연구들에 의하면 5-HTT 유전자 promoter 부위의 기능적인 다형성(5-HTT linked polymorphism repetitive element in promoter region, 5-HTTLPR)이 항우울제에 대한 치료 반응성과 관련이 있는 것으로 알려져 있으며, 5-HTTLPR 유전형의 분포빈도는 인종들 간에서 차이가 있는 것으로 알려져 있다. 연구자들은 최근의 실험을 통하여 5-HTTLPR 유전형들의 endophenotype을 혈소판 막에 분포하는 5-HTT의 약동학적 특성으로 측정할 수 있음을 발견하였다. 흥미로운 사실은 5-HTTLPR 유전형의 분포가 인종적으로 다른 양상으로 나타났듯이, 그 endophenotype인 혈소판막의 5-HTT의 약동학적 특성 역시 전혀 반대되는 양상으로 나타났다. 하지만 이 endophenotype의 특성만으로 항우울제의 치료반응을 예측하는 것은 아직까지 한계가 있으며, 향후 이러한 과제를 해결하기 위한 방법중 약리유전학적 방법을 사용할 수 있음을 제안하였다. 예비적으로 시행한 실험을 통하여 연구자들은 세로토닌 수송체의 구조와 특징이 비슷한 생체아민 수송체들의 유전자 다형성들 간에 유의한 상관관계가 있음을 발견하였으며, 이들 유의한 상관관계가 있는 유전자형을 연합하여 조합할 때 세로토닌 수송체의 유전형만의 기여도보다도 항우울제에 대한 반응 예측도의 odds ratio가 유의하게 상승함을 발견하였다. 이러한 연구 결과들은 임상의가 항우울제를 처방 할 때에 환자들의 유전적 그리고 인종적인 배경을 고려하여 개별화된 전략을 사용하여야 한다는 가설을 뒷받침한다. 앞으로 항우울제의 작용기전과 그 대사과정에 관여하는 유전자들들 중심으로 유전자 간의 상호 작용을 밝히고 그 표현형이 약물의 치료 반응도에 미치는 기여도를 평가하는 작업들은 항우울제의 치료 반응과 그 부작용을 미리 예측할 수 있는 평가 도구를 개발할 수 있는 가장 최선의 길이 될 수 있을 것이다.

• 대한본초학회지
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• 제29권2호
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• pp.7-13
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• 2014

Objectives : Chronic mild stress (CMS) model is currently recognized as a better animal model of depression. The purpose of this study was to investigate the antidepressant-like effects of the Nelumbo nucifera leave extract using CMS model. Methods : The antidepressant-like effects of Nelumbo nucifera leaves extract was determined by using animal models of depression. Male ICR mice were divided into four groups: saline-treated normal, without CMS; saline-treated stress control; CMS+ Imipramine(20mg/kg); CMS+Nelumbo nucifera leaves extract(200mg/kg). All mice except the normal group exposed an unpredicted sequence of chronic mild stressors for 5 weeks. The behavior of mice were detected by sucrose preference test, forced swim test and tail suspension test. Then concentration of corticosterone in serum was detected by enzyme immunoassay. Results : Nelumbo nucifera leaves extract administration by daily gavage from the 3rd week exhibited an antidepressant-like effect on CMS-induced depression in mice. Nelumbo nucifera leaves extract administration at dose of 200 mg/kg significantly increased the sucrose consumption, and decreased the immobility durations in forced swim test and tail suspension test. Furthermore the corticosterone level decreased than control group. Conclusions : Chronic mild stress can affect mouse behavior and corticosterone level and cause depression. The present experiments not only further confirm the antidepressant-like effects of Nelumbo nucifera leaves extract in the sucrose preference test, forced swimming test and tail suspension test, but also the improving effects of Nelumbo nucifera leaves extract on the depression-like symptoms in the CMS model. Nelumbo nucifera leaves extract has the antagonism on CMS and produce antidepressive effects.

• 한국약용작물학회지
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• 제22권3호
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• pp.196-202
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• 2014

Depression is one of the most common neuropsychiatric disorders and has been associated with the neuroendocrine system and alterations in behavior. Schisandra chinensis Baillon is one of major medicinal plants used as a Korea medicine and food sources, and has been processed in the fields of various food products and medicinal herbs. The chronic mild stress (CMS) protocol is widely used to evoke depressive-like behaviors in laboratory mice or rat. The CMS procedure induced some behavioral changes that are compatible with the common expectations, i.e. 'anhedonic' behavior and can affect corticosterone level. The present study, Schisandra chinensis extract administration by daily gavage from the 3 weeks exhibited an antidepressant-like effect on CMS-induced depression in mice. Schisandra chinensis extract administration at dose of 200mg/kg significantly increased the sucrose consumption, and decreased the immobility durations in forced swim test and tail suspension test. Furthermore the corticosterone level decreased than control group. In conclusion, Schisandra chinensis extract showed antidepressant-like effects on sucrose preference test, forced swimming test and tail suspension test based on CMS model.

• 정신신체의학
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• 제21권2호
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• pp.81-92
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• 2013

새로운 항우울제가 개발되고 임상에서 정신과적 질환뿐만이 아니라 만성통증증후군, 섬유근통증증후군, 두통 등의 많은 정신신체질환 그리고 신체질환자의 적응장애 및 우울증 등의 자문조정정신의학 영역에서도 다양하게 자주 사용되고 있다. 다양한 정신의학적 질환을 치료하기 위해 처방하는 새로운 항우울제의 사용 시 치료중단의 가장 큰 원인은 약물부작용이다. 이 논문은 현재 우리나라에서 널리 사용되고 있는 새로운 항우울제 사용 시 나타나는 부작용들 중 정신신체의학과 자문조정정신의학영역에서 관심을 가져야 할 매우 빈번하게 나타나는 세 가지 부작용인 오심과 구토, 체중증가, 성기능장애에 대한 발생기전, 발생빈도, 그리고 약물학적 처치를 위주로 한 해결방안을 알아보았다. 저자는 이 논문을 통하여 정신건강의학과 의사만이 아니라 정신신체의학 영역에 관심을 가지거나 자문조정정신의학과 연계되는 타과 영역의 의사들이 새로운 항우울제를 사용할 때 빈번하게 나타나서 삶의 질을 떨어뜨리고 치료중단을 일으킬 수 있는 이 약물들의 부작용을 잘 인지함으로써 이를 조기에 발견하고 적절히 해결하여 환자 치료에 도움을 주고자 하였다.

• 대한약침학회지
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• 제21권1호
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• pp.35-40
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• 2018

Objective: The role of BDNF (brain-derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide has been proved in antidepressant activity of long term saffron administration in the rat hippocampus. In this study we evaluated the role of these proteins in antidepressant activity of saffron in long term administration in the rat cerebellum. Methods: Saffron aqueous extract (40 and 80 mg/kg/day) and imipramine (10 mg/kg/day) were administered intraperitoneally for 21 days to rats. At the end of experiment, animals were sacrificed and cerebellums were separated. The protein levels of BDNF, VGF, CREB and P- CREB in the rat cerebellum were evaluated using western blot analysis. Results: Saffron aqueous extract (80mg/kg/day) caused significant increase in protein level of P-CREB in long term treatment in the rat cerebellum. The increases in the protein levels of VGF, CREB and BDNF were not significant. Conclusion: In summary, our results showed that antidepressant effect of saffron in rat cerebellum might be due to the enhanced phosphorylation of CREB.

• 약학회지
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• 제50권6호
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• pp.429-435
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• 2006

The antidepressant effects of Cirsium japonicum compositae was investigated using open field test and forced swimming test. Total extract of Cirsium japonicum (CJ) was orally administered at dose of 20, 100, 300, 500 mg/kg bodyweight. Supplementation of CJ increased dose-dependently movement, rearing frequency and total turn angle in the center area of open field in mice. Treatment of Cirsium japonicum's extract (300 mg/kg, CJ) decreased immobile duration and increased mobile and strong mobile duration significantly; and it is comparable to that of imipramine and fluoxetine. These results indicate that CJ has antidepressant effect. Treatment of CJ did not induced any impairment in motor coordination and myorelaxation. These results indicate that the constituents or its complex of Cirsium japonicum could be a candidate of new antidepressant drug.

• 한국산학기술학회논문지
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• 제15권11호
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• pp.6739-6745
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• 2014

은행속에 속하는 산청목은 중국과 한국 북동부지역에 널리 분포하는 자생 식물로 전통적으로 항염증제로 사용되었으며 현재까지 항우울에 대한 효능과 그에 대한 면역변화에 대한 연구는 미흡한 실정이다. 본 연구실에서는 100, 200, 그리고 400 mg/kg 농도의 산청목추출물을 실험쥐에게 경구투여를 실행하였으며 강제수영실험을 통하여 항우울효과를 평가 그리고 혈 중 코티솔, ACTH, 그리고 사이토카인의 농도를 측정하였다. 실험 결과 실험쥐에 경구투여한 산청목 투입량이 증가함에 따라 강제수영실험에서의 행동불능시간이 감소하였으며 수중공포에 의해 분비유도된 사이토카인 농도 또한 감소함을 볼 수 있었다. 특히 코티솔, IL-6 과 $IL-1{\beta}$농도가 산청목 투입군에서 유의하게 감소함을 알 수 있었다. 산청목 경구투여군에서의 부동시간의 감소와 전염증성 사이토카인의 저하를 종합하여 볼 때 산청목의 항염증 효능으로 인한 작용에 의하여 강제수영 실험에서 항우울효과가 발현했다고 간주된다.

• Biomolecules & Therapeutics
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• 제21권1호
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• pp.79-83
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• 2013

The purpose of the present study was to examine the effect of Lycii Radicis Cortex (LRC) and betaine (BT) on immobility and neurochemical change in the forced swimming test (FST) in the rat. LRC, BT or fluoxentine was administered intraperitoneally to Sprague-Dawley rats three times (1, 5 and 23.5 h) before the FST. To investigate antidepressant-like effect, serotonin (5-HT) and norepinephrine (NE) were examined in the hippocampus and hypothalamus of rats. LRC (100 mg/kg) and BT (30, 100 mg/kg) significantly decreased the immobility time in the FST. LRC (100 mg/kg) significantly increased both 5-HT and NE levels in the hypothalamus of rats exposed to FST. BT (100 mg/kg) significantly increased 5-HT levels in the hypothalamus and hippocampus of rats. Taken together, these results demonstrated that improvement in the behavioral changes after LRC and BT administration may be mediated by elevation of 5-HT level in the hypothalamus and hippocampus, indicating a possible antidepressant-like activity. The present results suggest that the efficacy of LRC and BT in an animal model of depression may provide anti-depressant effects in human, which remains to be determined.

• 한국식품영양과학회:학술대회논문집
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• 한국식품영양과학회 2001년도 International Symposium on Food,Nutrition and Health for 21st Century
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• pp.22-37
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• 2001

Melatonin is secreted during the hours of darkness and is thought to influence the circadian and seasonal timing of a variety of physiological processes. Serotonin N-acetyltransferase (AA-NAT) which is found to be expressed in pineal gland, retina, and various tissues, catalyses the conversion of serotonin to N-acetylserotonin and is known as the rate-limiting enzyme in the biosynthetic pathway of melatonin. The compounds that modulate the activity of AA-NAT can be used to treat serotonin-and melatonin-related diseases such as insomnia, depression and seasonal affective disorders (SAD). Several assay methods have been developed by which to measure AA-NAT activity. We have also developed a simple, rapid and sensitive AA-NAT assay method that takes advantage of differences in the organic solubilities between acetyl CoA and N-acetyltryptamine. We screened modulators of AA-NAT activity from the water extracts of the medicinal plants. We found MNP1005 which strongly inhibited the activity of AA-NAT ($IC_{50}$=2.2$\mu$M). Enzyme inhibitory kinetic studies revealed that MNP1005 exhibited a noncompetitive inhibition toward tryptamine. The antidepressant effect of MNP1005 was investigated on behavioral despair test so called forced swimming test (FST). MNP1005 significantly increased swimming behavior by reducing immobility with treatment of 10 mg/kg when compared to the vehicle-treated control group (P < 0.05). This suggests that MNP1005 possesses antidepressant activity. The influence of chronic MNP1005 treatment on the expression of brain-derived neurotrophic factor (BDNF) was examined by in situ hybridization and Northern blot. Chronic treatment of MNP1005 blocked the downregulation of BDNF mRNA in the frontal cortex and other cortex regions in response to restraint stress.