• 약학회지
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• 제46권3호
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• pp.208-212
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• 2002

Dehydroevodiamine HCl (DHED), which is a component separated from Evodia rutaecarpa Bentham, has novel anticholinesterase and antiamnesic activities in the scopolamine-induced amnesia model. Several studies suggest that DHED might be an effective drug for the Alzheimer's disease and the vascular type of dementia. In order to evaluate the mutagenic potential of DHED, Salmonella typhimurium reversion assay, chromosomal aberration test on Chinese hamster lung cells, in vivo micronucleus assay using mouse bone marrow cells, and comet assay were performed. DHED did not increase the number of revertant in the reverse mutation test using Salmonella typhimurium TA1535, TA1537, TA98, TA100. DHED HCl, at concentration of 5 and 10 $\mu\textrm{g}$/mι, increased the number of chromosome aberrated Chinese hamster lung cells with 5 and 10％, respectively. In mouse micronucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocyte was observed in ICR mice orally administered with DHED. DHED was tested for ability to induce genotoxic effect in L5178Y cells (mouse lymphoma cells) using the single cell gel electrophoresis assay (comet assay). In comet assay, tail moment did not increase in L5178Y cells treated with 10, 100, 300 $\mu$M DHED.

• 약학회지
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• 제46권3호
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• pp.185-191
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• 2002

Alzheimer's disease (AD) involves neuronal degeneration with impaired cholinergic transmission, particularly in areas of the brain associated with learning and memory. Several cholinesterase inhibitors are widely prescribed to ameliorate the cognitive deficits in AD patients. In an attempt to examine if tacrine and donepezil, two well-known cholinesterase inhibitors, exhibit additional pharmacological actions in primary cultured rat cortical cells, we investigated the effects on neuronal injuries induced by glutamate or N-methyl-D-aspartate (NMDA), $\beta$-amyloid fragment ( $A_{{beta}25-35)}$), and various oxidative insults. Both tacrine and donepezil did not significantly inhibit the excitotoxic neuronal damage induced by glutamate. However, tacrine inhibited the toxicity induced by NMDA in a concentration-dependent fashion. In addition, tacrine significantly inhibited the $A_{{beta}25-35)}$-induced neuronal injury at the concentration of 50 $\mu$M. In contrast, donepezil did not reduce the NMDA- nor $A_{{beta}25-35)}$-induced neuronal injury. Tacrine and donepezil had no effects on oxidative neuronal injuries in cultures nor on lipid peroxidation in vitro. These results suggest that, in addition to its anticholinesterase activity, the neuroprotective effects by tacrine against the NMDA- and $A_{{beta}25-35)$-induced toxicity may be beneficial for the treatment of AD. In contrast, the potent and selective inhibition of central acetylcholinesterase appears to be the major action mechanism of donepezil.

• Biomolecules & Therapeutics
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• 제13권1호
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• pp.26-31
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• 2005

The present study examined effects of a water-soluble fraction from mulberry leaves (ML water fraction) on the circulatory and autonomic nervous systems, which were compared with those of acetylcholine (ACh) used as a reference drug in order to elucidate its mechanism of action. Intravenous administration of ACh or a ML water fraction produced temporary depressor and tachycardiac responses in a dose-dependent manner in unrestrained, conscious Sprague-Dawley rats. The systemic hemodynamic effects of ACh and a ML water fraction were almost completely blocked by pretreatment with atropine, a muscarinic antagonist. The depressor responses to ACh and a ML water fraction were slightly enhanced and prolonged by pretreatment with neostigmine, an anticholinesterase, whereas the tachycardiac responses were remarkably blocked by pretreatment with pentolinium, a ganglionic blocking agent. In vitro experiments using the ileum isolated from rats showed that ACh and a ML water fraction increased ileal contractility in a dose-dependent manner. The increases in ileal contractility were also completely abolished in the presence of atropine. Finally, the specific binding of [$^3H$]quinuclidinyl benzilate, a muscarinic antagonist, to rat cortical synaptic membranes was inhibited by a ML water fraction in a concentration-dependent manner with an IC$_{50}$ value of 9.5 mg/ml. The results suggest that the effects of a ML water fraction are mediated through direct stimulation of muscarinic cholinergic receptors by unknown cholinomimetic substance(s) contained in that fraction.

• 한국응용곤충학회지
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• 제30권1호
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• pp.18-28
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• 1991

집파리(Musca domestica L.)외 3종 곤충으로부터 0.01 M sodium phosphate buffer를 이용하여 AChE를 분리, 추출할 때 AChE의 안정성 및 buffer capacity를 고려한 적정 pH는 7.5였으며, 0.1M sidium phosphate buffer의 기질 수용액으로 AChE의 활성을 측정할 경우 효소의 활성화와 buffer capacity를 고려했을 때 pH는 7.5가 적합한 조건이었다. AChE 분리.추출을 위한 조직의 마쇄시에는 Potter Elvehjem homogenizer를 사용하였으며, 마쇄액을 원심분리하여 AChE현탁액을 조제할 때 집파리의 경우에는 성충 두부700g 상등액을, 벼멸구(Nilaparvata lugens Stal)는 5령 약충 전충체의 700g 상등액을, 배추좀나방 (Plutella xylostella L.)의 경우에는 5령 유충 전충체의 지질을 제거한 10,000g 상등액을, 그리고 담배거세미나방(Spodoptera litura F.)의 경우에는 4령 유충.두부의 700g 상등액을 AChE 0.2~0.5U 정도로 조정하여 효소원으로 사용하는 것이 대량조제, 추출수율 및 활성 측정상의 안정성등을 고려할 때 합리적인 것으로 조사되었다. 4종 곤충의 AChE현탁액을 $-18^{\circ}C$ 조건에서 냉동보관할 경우 3주까지는 90% 이상의 활성이 유지되었다. 집파리, 벼멸구 및 배추좀나방 AChE의 Km 값은 각각 0.042, 0.037 및 0.043 mM이었으며, 고농도에서 AChE 특이적 기질 저해 현상이 관찰되었으나 담배거세미나방 ChE의 경우에는 1.15 mM의 Km값을 가지며 BuChE적 특성을 보이는 듯 하나 추가실험이 요구된다. 각 곤충의 AChE를 대상으로 한 저해실험시의 적정 기질농도는 집파리, 벼멸구, 배추좀나방의 경우에는 공히 0.5 mM 그리고 담배거세미나방의 경우는 12 mM 이었다.

• Journal of Chest Surgery
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• 제20권1호
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• pp.112-127
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• 1987

Myasthenia gravis is a neuromuscular transmission function disorder characterized by fatigue and weakness of voluntary muscles. This muscular weakness is intensified by activity and stress, and improved by the use of anticholinesterase compounds. It was initially described by Erb in 1879 and later named myasthenia gravis by Jolly in 1895. Although the pathogenesis is Known to be an autoimmune related reduction in the number of available acetylcholine receptors at neuromuscular junctions, the role of thymus in myasthenia gravis is still unclear and under investigation. Thymectomy in the management of myasthenia gravis has become increasingly important since Dr. Blalock observed in 1939 that some patients with thymic tumors and myasthenia gravis improved following thymectomy. A clinical study of 102 cases of myasthenia gravis was performed at Yonsei University College of Medicine. Seoul, Korea from Jan. 1976 to Jun. 1986. In order to determine which factors are of prognostic significance, attention is focused upon pre-operative patient evaluation, problems in operative and post-operative care, and long-term follow-up observations. The results were as follows: 1. The sex distribution was 67 females and 35 males, the mean age of onset was 28.95*1.69 years, and the maximal incidence occurred between 21 and 40 years of age [56 cases: 54.9%]. 2. Clinical manifestations of ocular symptoms were seen to 70 patients [68.6%] extremities weakness in 33 [32.3%], bulbar weakness in 29 [28.4%], and dyspnea in 13 [12.7%]. 3. Study cases more than two thirds were classified as mild types [MG 1 and MG 11A] and 6 cases as grave [MG 1V] based on the modified Osserman`s classification system, 4. Thymectomy was performed in 19 cases which presented in severe myasthenia symptoms and showed no improvement with cholinergic drugs. Histologic examination of the excised thymus glands revealed no abnormalities in 4 cases, thymic hyperplasia in 5, benign thymoma in 5, and malignant thymoma in 5. 5. Immediate post-operative complications included 2 cases of pneumothorax which were treated by tube thoracostomies, there was no operative mortality. 6. The response to cholinergic drugs in 36 cases younger than 20 years old and in 27 cases older than 40 years was relatively poor, while that in 35 cases between the ages of 21 and 40 years old was good. 7. Thirty of 39 cases in groups IIB, III & IV improved markedly with medical or surgical management while only 16 of 59 cases in the mild groups [I and IIA] improved, almost all surgical cases improved in all categories. 8. There were 5 deaths. occurring between 7 months and 3 years 3 months of treatment of myasthenia gravis. The causes of death were myasthenic crisis in 2 cases, respiratory failure due to candidiasis & radiation pneumonitis in one case, cerebral hemorrhage due to high blood pressure in two case.

• Journal of Yeungnam Medical Science
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• 제13권1호
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• pp.86-96
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• 1996

1985년 8월부터 1996년 1월까지 중증 근무력증으로 진단받은 환자 52례에 대한 임상적 고찰을 통하여 다음과 같은 결론을 얻었다. 1. 전체 환자 중 남자가 19례(35.8%), 여자가 33례(64.2%)이었고 11세에서 20세 사이가 12례 (23%)로 가장 높은 빈도를 보였다. 2. 환자의 초기 증상으로는 안검하수, 복시 등의 안구증상이 37례(71.2%)로 가장 많았고 modified Osserman의 분류에 따라서도 가장 증상이 가볍고 약물치료에 잘 반응하는 I군이 36례(69.3%)로 가장 많았다. 3. 환자가 호소하는 중상의 비특이성과 회복과 재발을 거듭하는 질병의 특성으로 인해 발병 이후 진단될 때까지의 시간은 비교적 오래 걸렸고 1년이상 경과하며 진단된 경우도 16례(30.8%)나 되었다. 4. 자가면역질환이 7.6%에서 동반되었는데 갑상선기능 항진증이 2례(3.8%), 인슐린의존형 당뇨 2례(3.8%)였고 종격동 전산화 단층촬영소견에서 흉선의 비대가 의심되었던 환자는 6례(11.5%), 흉선종이 발견되었던 경우는 3례였다. 5. 환자의 치료는 대부분 항콜린에스테라제나 부선피질호르몬을 병용하는 내과적 치료를 하였으며 약물의 치료에 반응이 미비하거나 악화되는 경우 혹은 종격동 전산화 단층촬영 상에서 흉선의 이상 소견이 보인 경우에 2례(3.9%)에서는 흉선절제술이, 1례(1.9%)에서는 혈장여과요법이 추가되었고 흉선절제술과 혈장여과요법이 같이 병합 치료된 경우도 3례(5.9%) 있었다. 6. 전체 환자중 2명에서 자연치유의 경과를 보였으며 이들은 모두 I군이였다. 그리고 흉선절제술과 부신피질 호르몬 투여로 완치된 예가 1례였었다.

• Journal of Ginseng Research
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• 제38권1호
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• pp.1-7
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• 2014

Background: Although ginsenosides such as Rg1, Rb1 and Rg3 have shown promise as potential nutraceuticals for cognitive impairment, their use has been limited due to high production cost and low potency. In particular, the process of extracting pure Rg3 from ginseng is laborious and expensive. Methods: We described the methods in preparing ginseol k-g3, an Rg3-enriched fraction, and evaluated its effects on scopolamine-induced memory impairment in mice. Results: Ginseol k-g3 (25-200 mg/kg) significantly reversed scopolamine-induced cognitive impairment in the passive avoidance, but not in Y-maze testing. Ginseol k-g3 (50 and 200 mg/kg) improved escape latency in training trials and increased swimming times within the target zone of the Morris water maze. The effect of ginseol k-g3 on the water maze task was more potent than that of Rg3 or Red ginseng. Acute or subchronic (6 d) treatment of ginseol k-g3 did not alter normal locomotor activity of mice in an open field. Ginseol k-g3 did not inhibit acetylcholinesterase activity, unlike donezepil, an acetylcholinesterase inhibitor. Rg3 enrichment through the ginseol k-g3 fraction enhanced the efficacy of Rg3 in scopolamine-induced memory impairment in mice as demonstrated in the Morris water maze task. Conclusion: The effects of ginseol k-g3 in ameliorating scopolamine-induced memory impairment in the passive avoidance and Morris water maze tests indicate its specific influence on reference or long-term memory. The mechanism underlying the reversal of scopolamine-induced amnesia by ginseol k-g3 is not yet known, but is not related to anticholinesterase-like activity.