Sedative Effects of Combined Administration of 4-Hydroxy-3-methoxybenzaldehyde, a Component of Gastrodia elata, and 2,3-Dihydroxybenzaldehyde in Rats

이동웅,최형철,이광윤,이수관,김정애,용철순,김진숙,허근,신손문,구병수,하정희,Lee, Dong-Ung,Choi, Hyung-Chul,Lee, Kwang-Youn,Lee, Soo-Kwan,Kim, Jung-Ae,Yong, Chul-Soon,Kim, Jin-Sook,Huh, Geun,Shin, Son-Moon,Koo, Byung-Soo,Ha, Jeoung-He Korean Society of Life Science 2006 생명과학회지 Vol.16 No.7

The present study was performed to investigate the sedative effects of the combined administration of phenolic compounds. 4-hydroxy-3-methoxybenzaldehyde, a component of Gastrodia elnta, showing positive GABAergic neuromodulation was administered intraperitoneally together with an identical dose of 2,3-dihydroxybenzaldehyde, a potent antioxidant, to the rats and then evaluated for its effects on the convulsion, the hypnosis, the inxiety and the muscle relaxation. Combined administration of both compounds significantly reduced the pentyleneterazole-induced lethality. In addition, this mixture significantly enhanced the pentobarbital-induced sleeping time. Contrary to the anticonvulsive and sedative effects, the combined administration did not exhibit anxiolytic or muscle relaxant activities. These results indicated that the combined treatment of 2,3-dihydroxybenzaldehtyde and 4-hydroxy-3-methoxybenzaldehyde with different effects leads to the anticonvulsion and/or sedation 페놀성 화합물들의 병용투여가 rat의 진정효과에 미치는 영향을 조사하였다. 천마성분으로서 positive GABAergic neuromodulation을 보이는 4-hydroxy-3-methoxybenzaldehyde와 강력한 항산화물질인 2,3-dihydroxlrbenzaldehyde를 동량 투여한 결과, pentyleneterazole에 의해 유발된 사망률이 유의하게 감소되었으며 pentobarbital에 의해 유도된 수면시간은 유의하게 연장되었으나 항불안효과와 근육이완효과는 나타나지 않았다. 이러한 결과로 보아 항경련효과를 가진 화합물과 항산화 효과를 가진 화합물을 병용투여 함으로서 경련이나 불면 등의 신경증상을 효과적으로 억제할 수 있을 것으로 사료된다.

세계 천연가스 수급현황과 전망

이동웅,Lee, Dong-Ung 대한석유협회 1982 석유와 에너지 Vol.1982 No.6

Stereochemistry of the Degradation Product of (-)-α-Narcotine and Its Analogs with Ethyl Chloroformate

이동웅,Lee Dong-Ung Korean Society of Life Science 2005 생명과학회지 Vol.15 No.1

양귀비의 성분중 하나인 $(-)-\alpha-narcotine$은 ethyl chloroformate와 가온반응시 diastereomeric chloro-carbamate 혼한물과 Z/E-enol lactone혼합물을 생성하였는데 이 중에서 Z/E-isomer의 생성비를 HPLC로 측정한 결과 Z:E=1:1.12로 나타나 열역학적으로 불안정한 E-isomer가 다소 많이 생성되었다. 그러나 이 isomer 혼합물을 chromatography로 각각 분리 한 결과, 그 생성 비는 Z:E=7:1로 나타나 분리도중에 column 내 에서 E-isomer가 보다 안정한 Z-isomer로 대부분 변하였음을 알 수 있었다. Z/E-isomer의 생성비가 유사한 구조의 화합물에서 어떻게 변하는지를 관찰하기 위하여 $\beta-narcotine$, deuterated $\beta-narcotine$ 및 $\beta-hydrastine$을 대상으로 동일한 조건하에 반응시킨 결과, 이들의 isomer 생성비율이 구조에 따라 크게 차이가 있음을 알 수 있었으며 그 이유를 설명하였다. 한편, 일반적인 보고와는 달리, narcotine에서 생성된 안정한 Z-isomer는 광화학반응에 의해 불안정한 E-isomer로 쉽게 변한다는 사실도 확인하였다. A$(-)-\alpha$-narcotine from Papaver sommiferum was refluxed with ethyl chloroformate to give the diastereomeric chloro-carbamate mixture and the Z/E-enol lactones as Z:E=1:1.1 ratio in HPLC analysis. After photoisomerization with UV (254 nm), the Z/E ratio was drastically changed to Z:E=7:1, which may indicate that the E-isomer was easily converted to the Z-isomer due to photoisomerization. The photoisomerization of the Z/E-enol lactones and the different stereochemistry of the degradation product of $\beta-narcotine$, deuterated $\beta-narcotine$ and $\beta-narcotine$ with ethyl chloroformate will also be discussed.

흰쥐 기관지평활근에 대한 황련류의 이완효능

이동웅(Dong Ung Lee),장기철(Ki Churl Chang) 대한약학회 1997 약학회지 Vol.41 No.6

Recently we reported that water extracts of Coptidis Rhizomas showed calcium antagonistic action and alpha-adrenoceptor inhibitory action in the vascular smooth muscle. Since calcium antagonistic properties are important in the treatment of various diseases including asthma. In the present study, the bronchodilatory effects of crude extract of three kinds of Coptidis Rhizoma (Coptidis chinensis, Coptis japonica and root hair of Coptis japonica) was investigated using rat isolated trachea. The result showed that all extracts relaxed carbachol-contracted tracheal smooth muscle. Concentration-dependently, in which the root hair of Coptis japonica was the least potent. The inhibitory potency expressed in terms of IC50 against carbachol contraction was 1.8mcg/ml and 2.7mcg/ml for Coptidis chinensis and Coptis japonica, respectively. These extracts also inhibited KCI-contracted tracheal smooth muscle. But the relative potency (IC50) was 3.5 and 4.1 folds weaker than carbachol-induced contraction for Coptidics chinenesis and Coptis japonica, respectively. Pretreatment of crude extracts also inhibited carbachol- or KCI-induced contraction, non-competitively. These findings indicate that the extracts have muscarinic blocking as well as Ca2+ channel blocking action. When provoked intracellular stored Ca2+ release by carbachol in Ca2+-free conditions, initial phasic contraction due to Ca2+ release was significantly inhibited by the extracts. As taken together, we conclude that water extracts of Coptidis Rhizoma may be beneficial in bronchospasm or other broncheal tube narrowing conditions such as asthma.

우피소근의 알칼로이드 분획이 과산화지질 생성에 미치는 영향

이동웅(Dong Ung Lee),신억섭(Uk Seob Shin),이수진(Su Jin Yi),허근(Keung Huh) 대한약학회 1994 약학회지 Vol.38 No.6

The crude alkaloidal fraction of the root of Cynanchum caudatum Max.(Asclepiadaceae) was tested for the effects on the activities of free radical generating enzymes and the formation of lipid peroxide. Aldehyde oxidase was strongly inhibited to about 90% of the activity by treating 1.0mg/ml of alkaloidal fraction, corresponding to competitive inhibition. Moreover, the formation of lipid peroxide which causes damage of cell membrane was reduced in proportion to the increasing alkaloid concentration. However, xanthine oxidase of which structure and function are similar to those of aldehyde oxidase was not inhibited by the alkaloidal fraction.

牛皮消根의 polyoxypregnane 화합물의 Aldehyde Oxidase 및 지질과산화 억제효과

이동웅(Dong Ung Lee),이남재(Nam Jae Lee) 대한약학회 2000 약학회지 Vol.44 No.3

The roots of Cynanchum caudatum (Asclepiadaceae) have been used in folk medicine in Japan and China for the prevention and treatment of various geriatric diseases and also as a cardiotonic agent. Constituents of this plant have mainly been examined for glycosides: besides two steroidal alkaloids, gagaminine and gagamine which was firstly isolated by us, more than 35 polyoxypregnane glycosides and aglycones have also been identified. Gagaminine inhibits potently the hepatic aldehyde oxidase activity and lipid peroxidation in vitro. The present work deals with the comparison of antioxidative activities of gagamine, a new pregnane alkaloid, three isolated polyoxypregnanes containing a keto group at C-20 with those of gagaminine, a potent antioxidant, in order to explain the structure-activity relationships. The results of this study further prove that the cinnamoyl group of gagaminine is very important for the inhibition on the aldehyde oxidase activity while the nicotinoyl group is necessary for anti-lipid peroxidation. Besides that, the keto compounds having no ester group at C-12 were found to be more active than the others except gagaminine.

은조롱뿌리의 5-Lipoxygenase활성 억제성분

이원철,이동웅,Lee, Won-Churl,Lee, Dong-Ung 한국생약학회 1997 생약학회지 Vol.28 No.4

The effects of the extract of the root of Cynanchum wilfordi (Asclepiadaceae), the alkaloid fraction, and the isolated main constituent (gagaminine) on 5-lipoxygenase(5-LOEC 1.13.11.34) in bovine PMNL have been studied. The effect of the crude extracts of wildand cultivated plant was also compared each other. Furthermore, the inhibitory effect of gagaminine on 5-Lo was compared with those of the standard drugs. Gagaminine inhibited 5-Lo activity with an $IC_{50}$ value of $26\;{\mu}M$, this result indicates that gagaminine may be useful for in vivo experiments as 5-LO inhibitor.

생약의 Benzodiazepine 수용체 효현활성 검색(I) -수종의 신경안정 생약 추출물에 대한 활성 검색-

하정희,박용기,강병수,이동웅,Ha, Jeoung-Hee,Park, Yong-Ki,Kang, Byung-Soo,Lee, Dong-Ung 한국생약학회 1999 생약학회지 Vol.30 No.2

This study was aimed to evaluate an agonistic activity to benzodiazepine receptor of several medicinal plants, which have been used as sedatives in oriental medicine. Methanol extracts of medicinal plants which were used in this study inhibited the binding of $[^3H]Ro15-1788$, a selective benzodiazepine receptor antagonist to benzodiazepine receptor of rat cortices. Inhibitory activity of Cyperus rotundus was observed to be the highest among the tested medicinal plants. Methanol extracts of Cyperus rotundus and Zizypus jujuba inhibited a $[^3H]flunitrazepam$, a selective benzodiazepine receptor agonist, binding to benzodiazepine receptor. GABA significantly enhanced the inhibition of $[3H]flunitrazepam$ binding by Cyperus rotundus and Zizypus jujuba, and these positive GABA shifts supported the strong possibility of agonistic activity to benzodiazepine receptor. From these results, it may be concluded that the substance or substances with neurochemical properties characteristic of a benzodiazepine receptor agonist may be important components and contribute to the sedative property of these medicinal plants.

오공(蜈蚣)의 항산화효과에 관한 연구

최용건 ( Yong Keon Choi ),이동웅 ( Dong Ung Lee ),김근우 ( Geun Woo Kim ),구병수 ( Byung Soo Koo ) 대한한방신경정신과학회 2008 동의신경정신과학회지 Vol.19 No.3

Objective : The purpose of this study was to evaluate the antioxidative effects of the extract of Scolopendra subspinipes which has been used mainly for detoxication in the oriental medicine and reported to have sedative action, antiinflammatory effect, antihypertensive property and immunity enhancing activity. Method : Inhibitory activities on oxygen radical generating enzymes (aldehyde oxidase and xanthine oxidase) and increasing activities on oxygen radical scavenging enzymes (superoxide dismutase, glutathione peroxidase, glutathione-S-transferase) were investigated. Furthermore, the content of glutathione in the mouse brain, DPPH radical scavenging activity and also anti-lipid peroxidative effects in vivo and in vitro were estimated. Results : The extract showed weak inhibitory effects on the activities of aldehyde oxidase and xanthine oxidase which are oxygen radical generating enzymes. The extract inhibited lipid peroxidation with 26.1% against control group at 500 mg/kg in vivo and with 11.2% against control group at 10 mg/kg in vitro in a dose-dependent manner, which means this drug may protect radical-induced cell damages. The extract showed dose-dependently the scavenging effect on DPPH radical with 24.8% activity at 10 mg/ml in vitro. The extract enhanced the activities of superoxide dismutase, glutathione peroxidase and glutathione-S-transferase, which are oxygen radical scavenging enzymes, with 28.9%, 22.3% and 23.1%, respectively at 500mg/kg in vivo. Finally, this extract strongly increased the glutathione content in the mouse barin. Conclusion : Above results indicated that Scolopendra subspinipes can be useful for the protection or treatment of some diseases caused by reactive oxygen species.

천궁의 GABA<SUB>A</SUB>-Benzodiazepine 수용체 복합체와의 상호작용

강지현(Gi-Hyun Kang),이동웅(Dong-Ung Lee),하정희(Jeong-Hee Ha) 대한생물치료정신의학회 1997 생물치료정신의학 Vol.3 No.2

천궁(Cnidium Officinale)는 미나리과 다년생초본식물로서 대뇌 억제 및 진정 작용이 있다는 여러 문헌 등을 참고하여 볼 때 천궁은 항불안작용을 나타낼 가능성이 시사되었다. 이에 본 연구는 천궁을 사용하여 실험 동물에서 천궁의 항불안 작용을 검색하고 그 작용기전의 일부를 밝히고자 천궁을 극성 및 비극성 용매로 추출하여 분획을 만들고 이들 분획의 GABA -benzodiazepine 수용체 복합체 결합반응에 미치는 영향을 관찰하고자 하였다. 실험 결과 천궁 표준추출물 경구투여는 생쥐의 elevated plus maze 검사에서 그 효과는 diazepam 1㎎/㎏ 투여 후 실시한 elevated plus maze 검사 결과보다 낮았으나, 개방통로에로의 진입회수 및 개방통로에서의 체류시간을 증가시킴으로써 불안해소작용을 나타내었다. 또 천궁의 표준추출물은 benzodiazepine 수용체 길항제인 [³H]Ro15-1788 결합을 억제함으로써 수용체 활성물질의 존재 가능성이 관찰되었다. 이러한 행동검사상의 불안해소작용 및 benzodiazepine 수용체 활성도를 나타내는 구성성분을 추적하고자 천궁의 표준추출물의 분획화를 실시하였는데, 이를 통하여 얻은 각 분획들을 사용하여 수용체 활성도를 검색한 결과, 모든 분획에서 활성도를 나타내었으나 그 중 chloroform 분획의 활성도가 crude한 추출물인 methanol 추출물이나 다른분획에 비하여 가장 높은 활성도를 나타냄을 관찰하였다. 천궁의 chloroform분획은 [³H]flunitrazepam의 흰쥐대뇌피질조직에 있는 benzodiazepine 수용체에 대한 결합반응을 억제시켰으며, 이러한 억제도는 GABA 및 chloride 존재에 의해 더욱 항진되는 positive GABA shift 현상이 관찰되었다. 이상의 결과를 종합해볼 때, 천궁의 chloroform분획내에는 benzodiazepine 수용체에 대해 효현제 활성을 지니는 물질이 있음을 추측할 수 있으며, 이는 천궁의 항불안 작용의 중요한 한 기전으로 생각된다. C. Officinale is a medicinal plant which has been known to have anxiolytic and sedative activity. A survey of the relevant literature has indicated that the putative anxiolytic activity of C. Officinale has not been scientifically investigated. Therefore, the present study was designed to assess anxiolytic property and interaction with benzodiazepine receptor of C. Officinale. The putative anxiolytic activity of methanol extract of C. Officinale was performed in mice using an elevated plus maze paradigm. Chronic oral administration of C. Officinale showed anxiolytic action in mice. The interaction of C. Officinale with benzodiazepine receptor was investigated using rat cortices. Methanol extract of C. Officinale inhibited the binding of [³H] Ro 15-1788, a selective benzodiazepine receptor antagonist to benzodiazepine receptor of rat cortices. Chlorform fraction of methanol extract showed higher binding activity to benzodiazepine receptor than crude extract by methanol. GABA significantly enhanced the potency of C. Officinale in inhibiting [³H] flunitrazepam, a selective benzodiazepine receptor agonist, binding to benzodiazepine receptor. From these findings, it can be concluded that substance or substances with neurochemical properties characteristic of a benzodiazepine receptor agonist may contribute to the anxiolytic property of C. Officinale.