• Journal of Nutrition and Health
• /
• 제37권3호
• /
• pp.176-181
• /
• 2004

솔잎 BuOH획분을 하루 25, 50, 100 mg/kg BW로써 SD계 랫트에 45일 동안 투여하여 뇌조직획분의 콜레스테롤 및 LF의 침착, ACh 및 ACh의 합성효소, ChAT, 신경전달에 관여하는 효소 AChE의 활성, 카테콜라민계 신경 전달물질의 파괴효소 MAO-B의 활성에 미치는 영향을 평가하였다. 뇌조직의 mitochnodria 및 microsome 획분 중의 콜레스테롤이 BuOH-50 및 BuOH-100 투여그룹에서 14∼17% 및 23∼34%의 통계적인 억제효과가 인정되었고, 뇌조직에 대한 LF도 BuOH-50 및 BuOH-100 투여그룹에서 10∼14%의 유의적인 침착 억제효과가 인정되었다. 뇌조직중의 신경전달물질 ACh의 함량 및 ACh의 합성효소 ChAT의 활성은 BuOH획분의 거의 용량의존적으로 증가현상이 나타났지만, BuOH-50 및 BuOH-100 투여그룹에서 각각 11∼17% 및 11∼23%의 통계적인 증가효과가 인정되었을 뿐만 아니라 AChE의 활성도 BuOH-50 및 BuOH-100 투여그룹에서 14∼17%의 통계적인 증가효과가 인정되었다. 뇌조직중의 MAO-B의 활성은 BuOH 획분의 거의 용량의존적으로 억제하였지만, 그 유의성은 인정할 수 없었다. 따라서 솔잎 BuOH 획분의 투여는 뇌조직의 유동성을 축진하고 콜레스테롤의 침착을 억제하며 ACh와 그 관련효소의 활성을 촉진하여 기억ㆍ학습의 증진에 매우 효과적으로 작용할 것으로 기대된다.

• 약학회지
• /
• 제49권4호
• /
• pp.355-364
• /
• 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.

• 생약학회지
• /
• 제40권1호
• /
• pp.41-45
• /
• 2009

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzhemier's disease. Neuropathologically, PD is characterized by the selective loss of dopaminergic neurons. The neuronal toxicity of cytosolic excess dopamine (DA) has been described in many studies using several cell lines. In dopaminergic neurons, cytosolic excess DA is easily oxidized via monoamine oxidase (MAO)-B, tyrosinase or by auto-oxidation to produce neurotoxic metabolites such as DA quinone. So, in the present study, we induced cell death by treatment of DA ($600{\mu}M$) in human neuroblastoma SH-SY5Y cell which was treated samples before 24 hr, and cell viability was measured by fluorescence activated cell sorter (FACs) analysis. Of those tested, the extracts of Poria cocos (赤茯笭)(whole), Gastrodia elata (rhizomes), Eucommia ulmoides (炒)(barks), Syneilesis palmata (whole), Acorus gramineus (rhizomes), Ligustrum japonicum (leaves) showed neuroprotective effects in dose dependent manner.

• 대한약리학회지
• /
• 제26권1호
• /
• pp.67-76
• /
• 1990

웅성-마우스의 고환을 diethyl ether 마취하에서 제거하고, 수종의 steroid 홀몬을 각각 매일 1회씩 4일간 피하주사하여, 간 및 소장의 polyamine 함량과 소장의 diamine oxidase (DAO) 활성도에 미치는 그들의 영향을 검색하였다. 1. Hydrocortisone succinate 50 mg/kg (HC) 및 dehydroepiandrosterone 250 mg/kg (DHEA)에 의하여, 소장의 putrescine (PT)은 유의하게 증가되었으나, spermidine (SD) 및 spermine (SM)은 별 영향을 받지 않았고, 간의 SD은 다소 증가되고, SM은 다소 감소 되었으나, PT은 별 변동을 보이지 않았다. 2. Estradiol cypionate 5 mg/kg (E2)에 의하여, 간의 PT은 현저히 증가되었으나, 소장의 PT은 다소 증가되었고, 그외 소장 및 간의 SD와 SM의 변동은 보이지 않았다. Testosterone cypionate 5 mg/kg (TS)에 의하여는 간의 SD이 다소 감소되었을 뿐 별 변동이 없었다. 3. 소장의 DAO 활성도는 HC에 의하여 현저히 감소되었으나, E2 및 TS에 의하여는 유의하게 증가되었고, DHEA에 의하여는 별 영향을 받지않았다. 그러나 간의 monoamine oxidase 활성도는 HC, E2, DHEA, 및 TS에 의하여 영향을 받지 않았다. 4. Aminoguanidine 25 mg/kg로 소장의 DAO 활성도가 현저히 감소되었으나, 간 MAO 활성도는 영향을 받지 않았고, 소장의 PT 및 SD은 유의하게 증가되었으나, 간의 polyamine은 별 변동을 보이지 않았다. 이상의 결과로 미루어 볼때, 간 및 소장의 polyamine 대사-특히 PT 함량의 변동이 각각 E2 및 HC에 의하여 특이적으로 조절되는 바, E2에 의한 간 PT 함량의 증가는 주로 생성촉진 작용에 연유되며, HC에 의한 소장 PT 함량의 증가는 주로 polyamine의 이화성 대사를 억제함에 기인될 수 있는 것으로 사료된다.

• 사상체질의학회지
• /
• 제27권2호
• /
• pp.254-269
• /
• 2015

Objectives This study aimed to observe the effect of Taeumjowi-tang on the cisplatin-induced gastrointestinal dysfunctions in rats. Methods Four groups, each of 8 rats per group, were used in this study. Saline and distilled water treated control rats were intact vehicle control group. Delayed gastrointestinal motility was induced by intraperitoneal treatment of cisplatin 2mg/kg, once a week for 5 weeks(Cisplatin control group). Taeumjowi-tang aqueous extracts(TJ) were orally administered in a volume of 5ml/kg, once a day for 14 days from 4th cisplatin treatment(TJ group). Ondansetron 1mg/kg was subcutaneously treated, in a volume of 1ml/kg, as same as TJ(ondansetron group). We measured the body weights, intestinal charcoal transit ratio, fecal parameters, fundus MDA(malondialdehyde), GSH(glutathione) contents and SOD(superoxide dismutase), CAT(catalase) activities, TPH(tryptophanhydroxylase) and MAO(monoamine oxidase) activities, pyloric gastrin and serotonin contents with their immunoreactive cells, colonic serotonin-immunoreactive cells, the histopathology of pylorus, fundus mucosa and colon. Results 1) The body weight gains, the small intestinal charcoal transfer rates, the fecal parameters(numbers, weights and water contents) were increased in TJ, ondansetron group. 2) The inhibit of fundus antioxidant defense systems by cisplatin were decreased in TJ, ondansetron group. 3) The pyloric TPH activities were increased and the pyloric MAO activities were decreased in TJ group. 4) The pyloric gastric contents and the gastrin-immunoreactive cells were increased and the pyloric serotonin contents and the pyloric and colonic serotonin-immunoreactive cells were decreased in TJ group. 5) The pylorus atrophic changes and the gastric surface erosive damage regions by cisplatin were favorably inhibited by treatment of TJ group. Conclusions The results obtained in this study suggest that TJ favorably retarded the cisplatin related GI(gastrointestinal) dysfunctions and constipation through modulations of GI enterochromaffin cells, serotonin and gastrin-producing cells and antioxidative systems.

• Journal of Ginseng Research
• /
• 제18권1호
• /
• pp.1-9
• /
• 1994

Sprague-Dawley rats were given freely with 15% ethanol (control) and 15% ethanol containing (1) 0.1% ginseng saponin, (2) 0.02% ginsenoside $Rb_1$, and (3) $Rg_1$ (tests) instead of water for 7 days and aldehyde dehydrogenase (ALDH) and monoamine oxidase (MAO) activity in different regions of brain were examined. In control group, total ALDH activity with indoleacetaldehyde and acetaldehyde as substrate in all different regions was lower than that of normal group except in the hippocampus. The inhibitory effect on the activity was prominent in the corpus striatum and was not in the hippocampus. However, low-$K_m$ ALDH activity in all different regions was much lower than that of normal group. A considerable decrease in mitochondria ALDH activity in cerebellum and striatum was also observed in control group. In test groups total, low-$K_m$, and mitochondria AkDH activities in all different regions were higher than those in control group. Although ALDH activity in the striatum of test group was higher than control group, it was relatively depressed as compared with normal. There was not found a remarkable difference in extent of stimulating effect on the AkDH activity according to the ginseng saponin components. When biogenic aldehydes were used as substrate, ALDH activity with 3,4-dihydroxy-phenylacetaldehyde (DOPAL) in all brain regions of control group was lower than that using 5-hydroxy-indoleacetaldehyde (HIAL) and 3,4-dihydroxyphenylglycolaldehyde (NORAL) as substrate. In control group, ALDH activity with biogenic aldehydes above mentioned was markedly inhibited in the striatum contrary to other regions. The higher ALDH activity with biogenic aldehydes in test group than in control was found in the striatum, cerebrum, and cerebellum. MAO activity in the cerebellum was inhibited in control group and slightly increased in test group. The results of present study suggest that the corpus striatum is significantly affected by ethanol exposure while the hippocampus is not and that ginseng saponin fraction and ginsenosid es might have a preventive effect against depression of brain ALDH activity by chronic administration of ethanol.

• 약학회지
• /
• 제42권1호
• /
• pp.101-107
• /
• 1998

The antiparkinsonian agent l-deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, is metabolized in part to l-methamphetamine and l-amphetamine. l< /I>-Deprenyl was evaluated for amphetamine and methamphetamine-like discriminative stimulus effects in rats and its mechanism of action was investigated. Rats were trained under a 5-response, fixed ratio schedule of stimulus-shock termination or a 10-response. Fixed-ratio schedule of food-presentation which discriminate between d-amphetamine (1mg/kg, i.p.) and saline or d-methamphetamine (1mg/kg, i.p.) and saline in a two-lever, operant conditioning procedure. Full generalization was obtained to d-amphetamine (1~3mg/kg). d-methamphetamine (1~3mg/kg) and l-deprenyl (17~30mg/kg) under both the food presentation and stimulus shock termination schedule. l-Deprenyl has dose-dependent amphetamine-and methamphetamine-like discriminative stimulus properties in rats only at doses of 17 and 30mg/kg. Reversible MAO-B inhibitor, RO 16-6491 didn`t show any amphetamine-like discriminative properties. Aromatic amino acid decarboxylase inhibitor, NSD 1015 decreased % responding of l-deprenyl in the methamphetamine-trained rats under the stimulus-shock termination schedule. SKF-525A produced partial inhibition of methamphetamine-like discriminative effects of l-deprenyl under the food presentation schedule. These results suggest that l-deprenyl has no abuse liability at the therapeutic range but there needs some caution at high doses and furthermore, drug discrimination studies under the food presentation and shock termination schedule are useful for the assessment of abuse liability of psychostimulants.

• 동의신경정신과학회지
• /
• 제17권3호
• /
• pp.21-43
• /
• 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.

• Mass Spectrometry Letters
• /
• 제10권2호
• /
• pp.61-65
• /
• 2019

Korean ginseng (Panax ginseng Meyer) is a traditional herb used across the world to treat various diseases. Although, red ginseng is this herb's most famous product and has demonstrated diverse pharmacological activities, white ginseng (WG) is another ginseng product that is made fresh and individually regulated in Eastern Asia. Red and white ginseng show different characteristics due to distinct processing steps despite originating from the same plant, and the drug interactions induced by WG have not been well documented. Selegiline is a selective monoamine oxidase (MAO) inhibitor used as an antidyskinetic and antiparkinsonian agent. Here we developed a quantification method for selegiline in mouse plasma using a C8 stationary phase in triple quadrupole-mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM). The validated LC-MS/MS method was successfully applied to determine the potential interaction with WG extract (0.1 g/kg/day) pre-administered for 4 weeks. The $AUC_{0-240min}$ of selegiline was altered due to a decrease in the absorption of selegiline with repeated administration of WG extract.

• 대한약리학회지
• /
• 제26권1호
• /
• pp.1-6
• /
• 1990

본 연구에서는 흰쥐 태아 뇌간의 일차 세포배양을 이용하여 중추 serotonin(5-HT) 신경세포의 연구에 적합한 in vitro 모델을 확립하고, 여기에서 5-HT 대사의 전반적인 과정을 살펴보고자 하였다. 배양세포의 5-HT 및 5-hydroxyindoleacetic acid (5-HIAA)함량을 high performance liquid chromatography-electrochemical detection (HPLC-EC)방법 으로 측정함으로써 흰쥐태아(태령 14-15일)뇌간으로 부터 얻은 5-HT 신경세포가 배양상에서 2주까지 발달함을 추적할 수 있었고 아울러 이들 세포에서 5-HT의 합성, 저장, 대사의 각 과정을 몇가지 약물들을 이용하여 확인하였다. 배양 14일에 5-HT의 함량이 13ng/mg protein으로서 성숙한 흰쥐 뇌속에 존재하는 5-HT의 값과 유사하였다. 5-HT 합성의 속도조절효소인 tryptophan hydroxylase(TPH)의 상경적 억제제인 p-chlorophenylalanine (PCPA)처리시 aromatic L-amino acid decarboxylase (AADC)억제제인 3-hydroxybenzylhydrazine NSD 1015보다 5-HT 및 5-HIAA 함량을 더 많이 감소시켰다. TPH의 기질인 tryptophan은 5-HT의 합성을 현저히 (200%) 증가시켰으며 이 증가는 PCPA로 상당히 둔화되었다. 5-HIAA의 변화도 유사한 양상을 보였다. 5-hydroxytryptophan처리시 5-HT 및 5-HIAA 함량이 현저히 증가하였으며 이 증가는 NSD 1015로 거의 차단되었다. 5-HT 대사 경로인 monoamine oxidase (MAO)의 비특이적 억제제인 pargyline과 MAO A의 특이적 억제제인 LY-51641을 처리한 결과 5-HT 함량은 각각 대조군의 295% 및 140%로 증가하여 pargyline이 LY-51641보다 현저한 작용을 나타내었다. 그러나 5-HIAA의 함량은 반대로 현저히 감소하여 pargyline 및 LY-51641에 의해서 각각 대조군의 50% 및 40%의 함량을 나타내었다. 이상의 결과로 보아 5-HT 신경세포는 일차 세포배양상에서 활발한 5-HT대사가 이루어짐을 HPLC-EC 방법으로 확인할 수 있었으며 따라서 본 in vitro system은 중추 5-HT 신경세포에 대한 전반적인 약리 및 독성 연구에 매우 유용하게 사용될 수 있다고 사료된다.