• The Korean Journal of Physiology
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• 제11권1호
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• pp.27-32
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• 1977

Diospyros Kaki Thunberg is the species of persimmon tree that grows in Korea. Although its fresh or dried fruits are often served as a desert, it has little been known if persimmon tree has any specific pharmacological action. The leaves and branches of persimmon tree has long been used as folk remedies for palsy and frostbite in the southern part of Korea and it is also in use for the treatment of hiccup and nocturnal enuresis in chinese herbal medicine. Recently it was reported that an intravenous administration of Diospyros Kaki Thunberg ethanol extract (KTEE) into the animals lowered arterial blood pressure. Lee concluded from his study on the mechanism of depressor action of KTEE that at least a part of depressor response he observed was caused by acetylcholine-like action of KTEE. On the other hand little study has been made on the effect of KTEE on the motility of isolated animal intestines. Therefore the present study was undertaken to investigate effect of KTEE and the mechanism of its action on the motility of isolated rabbit duodenum. Ethanol extract of Diospyros Kaki Thunberg was prepared by boiling 1 kg of dried branches of persimmon tree in 1 liter of ethanol and the motility of isolated rabbit duodenum was recorded on physiograph by means of force transducer connected with Magnus apparatus. Doses of KTEE used were $5{\times}10^{-4}gm/ml,\;1{\times}10^{-3}gm/ml,\;and\;2{\times}10^{-3}gm/ml$. And the isolated duodenum was separately pretreated with acetylcholine $(5{\times}10^{-7}gm/ml)$, pilocarpine $(2.5{\times}10^{-6}gm/ml)$, histamine $(5{\times}10^{-6}gm/ml)$ and barium chloride $(2.5{\times}10^{-5}gm/ml)$ in order to find out interactions of these drugs with KTEE. The results obtained are as follows: 1. At doses of $5{\times}10^{-4}gm/ml,\;1{\times}10^{-3}gm/ml$ KTEE reduced contractions of isolated duodenum, while tonus as well as contaction of duodenum were depressed with $2{\times}10^{-3}gm/ml$ of KTEE. 2. Since the inhibitory effect of KTEE on the intestinal motility was not blocked by pretreatment with acetylcholine, pilocarpine, and barium chloride, it was strongly suggested that the inhibitory action of KTEE on intestinal motility is mainly Caused by its antihistamine effect. 3. It is also concluded that the principal substance of KTEE responsible for inhibition of intestinal motility may also have a vasodilating activity and would not be an acetylcholine-like substance in case it is same substance as that cause depressor responses.

• 대한약리학회지
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• 제22권2호
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• pp.96-104
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• 1986

최근에 미나라아제비과 (Ranunculaceae)에 속하는 부자(Aconiti tuber)로부터 강심작용을 나타내는 성분을 분리하여 Higenamine이라 명명하였고 그 작용기전을 밝히려는 시도가 활발히 진행되고 있다. 그러나 생약제로 부터 얻을 수 있는 Higenamine은 극히 미량이고 그 과정 또한 복잡하다. 따라서 본 연구에서는 유효성분을 대량 얻기 위한 방법으로서 전합성(total Synthesis)을 시도하였으며 IR, UV, NMR 및 elemental 분석등을 통하여 합성된 물질을 확인하였으며 가토에 대하여 in vivo에서 혈압, 심박동수, 호흡 및 말초저항에 미치는 영향과 아울러 in vitro에서 심근수축 증강작용(positive inotropic action) 및 심박속도 증강작용(positivechronotropic action)을 관찰 분석하여 다음과 같은 결론을 얻었다. 1) Higenamine은 $1-10\;{\mu}g/kg/min$ 정맥주사시 수축기 및 이완기혈압 모두를 용량 의존적으로 하강시켰고 후자가 전자보다 더욱 현저하였으며 호흡은 촉진되었고 말초 혈류량은 증가되었으나 심박동수는 영향이 없었다. 2) 혈압에 대한 Higenamine의 작용은 propranolol 전처치에 의하여 억제되었다. 3) Higenamine의 catechol핵과 커다란 아미노기는 베타 수용체기 대하여 전자는 활성을 후자는 친화력과 관계있을 것으로 추정하였다. 이상의 결과 Higenamine은 adrenergic ${\beta}$-수용체에 작용하여 그 작용을 발휘하는 것으로 사료 되었다.

• The Korean Journal of Physiology and Pharmacology
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• 제4권6호
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• pp.445-453
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• 2000

The present investigation tested the hypothesis that the activation of protein kinase G (PKG) leads to a phosphorylation of $Ca^{2+}-activated$ potassium channel $(K_{Ca}\;channel)$ and is involved in the activation of $K_{Ca}$ channel activity in cerebral arterial smooth muscle cells of the rabbit. Single-channel currents were recorded in cell-attached and inside-out patch configurations of patch-clamp techniques. Both molsidomine derivative 3-morpholinosydnonimine-N-ethylcarbamide $(SIN-1,\;50\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate $(8-pCPT-cGMP,\;100\;{\mu}M),$ a membrane-permeable analogue of cGMP, increased the $K_{Ca}$ channel activity in the cell-attached patch configuration, and the effect was removed upon washout of the drugs. In inside-out patches, single-channel current amplitude was not changed by SIN-1 and 8-pCPT-cGMP. Application of ATP $(100\;{\mu}M),$ cGMP $(100\;{\mu}M),$ ATP+cGMP $(100\;{\mu}M\;each),$ PKG $(5\;U/{\mu}l),$ ATP $(100\;{\mu}M)+PKG\;(5\;U/{\mu}l),$ or cGMP $(100\;{\mu}M)+PKG\;(5\;U/{\mu}l)$ did not increase the channel activity. ATP $(100\;{\mu}M)+cGMP\;(100\;{\mu}M)+PKG\;(5\;U/{\mu}l)$ added directly to the intracellular phase of inside-out patches increased the channel activity with no changes in the conductance. The heat-inactivated PKG had no effect on the channel activity, and the effect of PKG was inhibited by 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer $(Rp-pCPT-cGMP,\;100\;{\mu}M),$ a potent inhibitor of PKG or protein phosphatase 2A (PP2A, 1 U/ml). In the presence of okadaic acid (OA, 5 nM), PP2A had no effect on the channel activity. The $K_{Ca}$ channel activity spontaneously decayed to the control level upon washout of ATP, cGMP and PKG, and this was prevented by OA (5 nM) in the medium. These results suggest that the PKG-mediated phosphorylations of $K_{Ca}$ channels, or some associated proteins in the membrane patch increase the activity of the $K_{Ca}$ channel, and the activation may be associated with the vasodilating action.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2007년도 추계 학술대회
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• pp.57-58
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• 2007

Purpose: Ginseng is a well-known medical plant used in traditional Oriental medicine. Korean red ginseng (KRG) has been known to have potent biological activities such as radical scavenging, vasodilating, anti-tumor and anti-diabetic activities. However, the mechanism of the beneficial effects of KRG on diabetes is yet to be elucidated. The present study was designed to investigate the anti-diabetic effect and mechanism of KRG extract in C57BL/KsJ db/db mice. Methods: The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. During the experiment, body weight and blood glucose levels were measured once every week. At the end of treatment, we measured Hemoglobin A1c (HbA1c), blood glucose, insulin, triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). Morphological analyses of liver, pancreas and white adipose tissue were done by histological observation through hematoxylin-eosin staining. Pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. To elucidate an action of mechanism of KRG, DNA microarray analyses were performed, and western blot and RT-PCR were conducted for validation. Results: Compared to the DC group mice, body weight gain of PIO treated group mice showed 15.2% increase, but the other group mice did not showed significant differences. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in RGL, 18.3% in RGH, 67.7% in MET, 52.3% in GPZ, 56.9% in PIO-treated group. With decreased plasma glucose levels, the insulin resistance index of the RGL-treated group was reduced by 27.7% compared to the DC group. Insulin resistance values for positive drugs were all markedly decreased by 80.8%, 41.1% and 68.9%, compared to that of DC group. HbA1c levels in RGL, RGH, MET, GPZ and PIO-treated groups were also decreased by 11.0%, 6.4%, 18.9%, 16.1% and 27.9% compared to that of DC group, and these figure revealed a similar trend shown in plasma glucose levels. Plasma TG and NEFA levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the RGL-treated group compared to those in DC group. Histological analysis of the liver of mice treated with KRG revealed a significantly decreased number of lipid droplets compared to the DC group. The control mice exhibited definitive loss and degeneration of islet, whereas mice treated with KRG preserved islet architecture. Compared to the DC group mice, KRG resulted in significant reduction of adipocytes. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin production, but decreased glucagon production. KRG treatment resulted in stimulation of AMP-activated protein kinase (AMPK) phosphorylation in the db/db mice liver. To elucidate mechanism of action of KRG extract, microarray analysis was conducted in the liver tissue of mice treated with KRG extract, and results suggest that red ginseng affects on hepatic expression of genes responsible for glycolysis, gluconeogenesis and fatty acid oxidation. In summary, multiple administration of KRG showed the hypoglycemic activity and improved glucose tolerance. In addition, KRG increased glucose utilization and improved insulin sensitivity through inhibition of lipogenesis and activation of fatty acid $\beta$-oxidation in the liver tissue. In view of our present data, we may suggest that KRG could provide a solid basis for the development of new anti-diabetic drug.