• Biomolecules & Therapeutics
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• 제2권2호
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• pp.173-184
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• 1994

The general and some pharmacological actions of DWP 305 were investigated in animals and the following results were obtained. In central nervous system, DWP 305 had no effects on the pentobarbital induced anaesthesia, locomotor activity, rotarod test, traction test, analgesic action in mice and body temperature in rat. DWP 305 showed no depressive action on convulsion induced by strychnine, electronic shock and pentylenetetrazole. From these results, DWP 305 was considered to have no pharmacological effect on the central nervous system. Furthermore, DWP 305 had no influences on the normal blood pressure and heart rate. In the isolated ileum of guinea pig, DWP 305 inhibited contractive effects against the acetylcholine (10$^{-6}$ g/mι), histamine (10$^{-6}$ g/mι), 5-hydroxytryptamine (10$^{-6}$ g/mι) and BaCl$_2$(10$^{-4}$ g/mι) at a concentration of 2.15$\times$10$^{-4}$ g/ml in bath. In the isolated trachea and vats deference, DWP 305 showed no effect on the contractions produced by histamine and norepinephrine, respectively. DWP 305 showed inhibitory effect on the contractions produced by acetylcholine and oxytocin at a concentration of 2.15$\times$10$^{-4}$ g/ml on the isolated nonpregnant rat uterus. DWP 305 had no effect on the isolated right atrium of guinea pig, bile excretion, urine volume, pH, gastrointestinal motility, gastric secretion and blood aggregation.

• Natural Product Sciences
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• 제5권1호
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• pp.25-32
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• 1999

The pharmacological actions of ambrein were investigated alone or in combination as a pretreatment with agonists (adrenaline, noradrenaline, acetylcholine, histamine, nicotine), antagonists (atropine, atenolol) and calcium channel blocker (verapamil) in vivo in anaesthetized SWR rats using blood pressure, heart rate and myocardial contractility as parameters. Ambrein in the dose range of 50-200 mg/kg to the normotensive anaesthetized rats demonstrated negative chronotropic effect and increased the myocardial contractility significantly. At the mid dose (100 mg/kg) this increase in contractile force was 36% and 44% above the normal at 30 min and 60 min intervals post-treatment, respectively. Both of the lower and high doses (50 mg/kg and 200 mg/kg) had similar effects. Furthermore, this contractile response was dose related. Also, this compound produced a considerable increase in myocardial contractility when used as a pretreatment with some agonists and antagonists. The results on blood pressure did not show a considerable change when ambrein was used alone. However, ambrein pretreatment at the dose of 100 mg/kg did not block the effects of adrenaline, noradrenaline, isoprenaline and acetylcholine on heart rate and blood pressure. On the other hand, this pretreatment attenuated the sympathoadrenal effects of nicotine significantly. Chronotropic and blood pressure changes produced by histamine were also inhibited by ambrein pretreatment. This pretreatment significantly reversed the effects of atenolol but failed to demonstrate any change in the negative chronotropic, inotropic and hypotensive responses induced by verapamil. It is concluded that ambrein induced nonselective dose dependent antagonism of the effects of some agonists and antagonists require contribution of some neuromediators. However, the positive isotropic effects of ambrein possibly involve the enhancement of slow Ca channels and/or activation of ${\beta}-adrenergic$ receptors in the heart. At this moment it is difficult to explain the exact mode of action of ambrein and the studies dealing with Ca channel blocker and adrenergic blocker followed by ambrein may help to define the factors which contribute to its positive inotropic effects.

• Tuberculosis and Respiratory Diseases
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• 제39권5호
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• pp.386-391
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• 1992

연구배경 : 최근 알레르겐 흡입을 이용한 기관지유발 검사시 말초혈액 호산구수의 변화가 있음이 알려져 있고, 이는 기도 조직내로의 호산구 유입과 관련이 있음이 밝혀졌다. 그러나 히스타민나 에타콜린 흡입과 같은 비특이적 자극에 의한 기관지유발시 말초혈액 호산구수의 변화에 대한 연구는 아직 불충분하다. 이에 대해 저자들은 예비적으로 몇몇 천식 환자들을 대상으로 히스타민 기관지유발검사후 기도수축이 일어날때까지 말초혈액 호산구수를 단계적으로 측정해본 결과, 호산구수가 점차로 증가하는 환자군과 반대로 감소하는 환자군이 있음을 관찰하였다. 따라서 본연구에서는 저자들의 이러한 예비연구 결과를 재검토하고, 히스타민 기관지유발 검사중에 나타난 말초혈액 호산구수의 변화가 검사후에는 어떤 경과를 밟게 되는지를 관찰하고자 하였다. 방법 : 16명의 천식 환자를 대상으로 히스타민 기관지 유발검사를 시행함과 동시에, 검사전 및 검사후 노력성 1초 호기량($FEV_1$)이 기저치의 20% 이상 감소할때까지는 5분간격으로, 그다음에는 1시간, 2시간, 4시간, 8시간 및 48시간후에 각각 말초혈액 호산구수홀 측정하여 그 변화 경과를 관찰하였다. 결과 : 1) 히스타민 기관지유발검사중의 말초혈액 호산구수 변화를 기준으로 관찰하였을때, 11명(group I)은 기도수축 직전에 기저치보다 증가하는 양상을 보였고, 나머지 5명(group II)은 기도수축 직전에 기저치보다 감소하는 양상을 보였다. 2) Group I에 속한 환자들은 모두 기도수축 후에도 계속 호산구수가 기저치보다 증가된 상태로 유지되는 양상을 보였다. 3) Group II에 속한 환자들은 대부분 기도수축 후에도 계속 호산구수가 기저치보다 감소된 상태로 유지되는 양상을 보였다. 4) Group I과 group II간의 말초혈액 호산구수 기저치, $FEV_1$ 기저치, 히스타민 유발농도 및 혈청 IgE 양에는 의미 있는 차이가 없었다. 결론 : 히스타민 기관지유발검사후 나타나는 말초혈액 호산구수의 변화는 알레르겐 기관지유발검사시와는 다른 양상을 나타내며, 환자에 따라 계속 증가 혹은 감소되는 나름대로의 특징적인 양상을 보이는 것으로 나타났다. 아울러 조기 천식반응에도 호산구가 어느정도 관여할 것으로 추측된다.

• 약학회지
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• 제35권2호
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• pp.135-141
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• 1991

The general pharmacological tests with rhGM-CSF indicated that it had no influences on rotarod and locomotor activity tests, but shortened hexobarbital-sleeping time at the large dose of 3 mg/kg s.c. in mice. It elicited no hypothermic, analgesic and antiepileptic action. No influences on blood pressure and respiration in rabbits were observed at the dose of 1 mg/kg, i.v. and it did neither affect the receptors of adrenaline, acetylcholine, serotonin, histamine, kinin and oxytocin, nor antagonize the actions of histamine, serotonin and oxytocin at its concentrations of 1$\times$$10^{-6}$g/ml. However, this substance was demonstrated to stimulate the formation of leucocytes in rats.

• Journal of Pharmaceutical Investigation
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• 제8권3호
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• pp.16-23
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• 1978

This study was carried out for the purpose of observing the effect of Korean Acanthopanax Radicis Cortex on renal hypertension and to clarify the mechanism of this effect, making use of its ethanol extract. Adult male or female rats, weighing 180-250g, were divided into 3 groups; the first for normotensive control, the second for hypertensive control and the third for hypertensive Acantopanax-treatment. Rats in the normotensive and hypertensive control group were administered 0.9% saline subcutaneously only, whereas those in the Acanthopanax-treated hypertensive group were administered 50mg/kg Acanthopanax ethanol extract subcutanously once a day. Changes of original blood pressure, and responses of blood pressure to various 4gents(norepinephrine, angiotensin, acetylcholine, serotonin and histamine) were recorded for each group on the initial, 18th, 32nd and 46th days of the experiment. The results obtained in this experiment are as follows: 1) The initial blood pressure was $102.6{\pm}7.6mmHg$ on the average. The blood pressures of the normotensive control group were not observed to alter significantly at any period in the course of the experiment. 2) The mean blood pressures in the hypertensive control group were recorded at $120.3{\pm}10.4mmHg$ on the 18th day, at $134.5{\pm}9.2$ on the 32nd day and at $138.8{\pm}8.3$ on the 46th day, thus revealing significant elevation in comparison with the corresponding normotensive control group blood pressures. On the other hand, the mean blood pressures in Acanthopanax-treated hypertensive group on the 18th, 32nd and 46th days were $118.3{\pm}9.7,\;129.9{\pm}8.3\;and\;120.2{\pm}8.3mmHg$ respectively. The blood pressures of the hypertensive-Acanthopanax group recorded. on the 46th day revealed a significant difference as compared with those of the corresponding hypertensive control group. 3) On the 46th day of this experiment, the responses of blood pressure to acetylcholine in the hypertensive-Acanthopanax group were suppressed significantly as compared with those of the hypertensive control group, and in the latter group, angiotensin was decreased markedly as compared with the corresponding normotensive control group. In contrast, pressor action of norepinephrine and depressor action of serotonin and histamine did not differ significantly among the three groups. These results suggest that Acanthopanax ethanol extract suppresses the induction of renal hypertension by means of a cholinergic action such as that caused by acetylcholine.

• The Korean Journal of Physiology
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• 제23권1호
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• pp.119-127
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• 1989

This study was undertaken to investigate the effect of medial amygdala on the gastric acid secretion and plasma gastrin concentration in the rats with chronic gastric fistula. After the medial nucleus of amygdala was damaged bilaterally by radiofrequency a. c. through stereotaxically inserted electrodes, the gastric juice was collected in the basal and histamine-stimulated states for 1 hour. The gastric juice was also collected while the medial nucleus of amygdala was stimulated with biphasic square wave in the both states. After the collection of the gastric juice, blood samples were drawn from the abdominal aorta for the radioimmunoassay of plasma gastrin. The results were as follows: 1) The damage of the medial amygdala significantly decreased the gastric juice volume and the acid output in the histamine-stimulated state. 2) The electrical stimulation of the medial amygdala significantly increased the gastric juice volume and the acid output in the histamine-stimulated state, and the acid output in the basal state. 3) The damage of the medial amygdala significantly decreased the plasma gastrin concentration but the electrical stimulation of the medial amygdala did not affect the plasma gastrin concentration. It is therefore suggested that the medial amygdala has a facilitatory influence on the histamine-stimulated gastric acid secretion in rats, and the influence may not be attributed to gastrin release.

• 동의생리병리학회지
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• 제21권3호
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• pp.617-625
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• 2007

Samul-Tang (SMT) has been used for nourishing of the blood, hematopoiesis as a herbal medicine history. The purpose of this study is to find out anti-allergic inflammatory reaction of SMT. To clarify the mechanism, the effect of SMT on vascular permeability of rat cutaneous tissue and histamine and cytokines (IL-6, IL-8, TNF-${\alpha}$) release from mast cells were observed. The results are the pretreatment with SMT significantly decreased the compound 48/80-induced degranulation and histamine release from RPMC, SMT also inhibited the anti-DNP lgE-induced increment of vascular permeability of rat cutaneous tissue. SMT significantly reduced the PMA plus A23187-induced increment of expression of IL-6, IL-8, and TNF-${\alpha}$ in HMC-1 Cell. The Present study provide evidence that SMT inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression, and suggest the mechanisms of action. Furthermore, in vivo and in vitro anti-allergic effect of SMT suggests a possible therapeutic application of this agent in inflammatory allergic diseases.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.242-242
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• 1994

Cortex mori (Morus alba L.), the root bark of mulberry tree, has been used as an antiphlogistic, diuretic, and expectorant in herbal medicine. The purpose of this study was to determine whether Cortex mori could inhibit the ovalbumin (OA) -induced late asthmatic reaction in guinea pigs. Guinea pigs were sensitized by two exposures to an aerosol of OA(1.0%) and then challenged with aerosolized antigen(2.0%), The animals were pretreated by three inhalations of the aerosoled Cortex mori either before antigen sensitization or cahllenge. Bronchoalveolar lavage fluid(BALF) and peripheral blood were collected at 17 hours after OA challenge. The cell populations in BALF and peripheral blood were examined to determine the changes of the relative proportions of eosinophils,neutrophils and mononuclear cells etc. Beta-glucuronidase activity in BALF was measured to evaluate the alveolar macrophage activation. OA-induced histamine release from guinea pig peritoneal fluid cells was measured by radioisotope enzymatic asssay. Results were as follows. The number of eosinophils, neutriphils and lymphocytes recovered in BALF were significantly increased in the 17h following aerosol challenge with OA. Among them, eosinophil and neutriphils were decreased remarkably in group that had been preinhalated with Cortex mori. The number of lymphocytes in BALF were not decreased in group pretreated with CM before sensitization but decreased in Group pretreated with CM before challenge. After OA challenge, the number of eosinophils in peripheral blood were markedly increased, but Cortex mori inhibited significantly the OA-induced eosinophilia. Beta-glucuronidase activity in the supernatants of BALF were significantly increased in the 17h following aerosol challenge with OA, however, pretreatment of Cortex mori had no influence on Beta-glucuronidase activity, suggesting that Cortex mori had no inhibitory effect on OA-induced alveolar macrophage activation. Cortex mori inhibited the OA-induced histamine release from guinea pig peritoneal fluid cells. From the above results, it is suggested that Cortex mori contains some substances with an activity to inhibit the the OA-induced late phase reaction of the bronchial asthma in guinea pigs.

• 약학회지
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• 제35권3호
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• pp.174-181
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• 1991

These experiments were conducted to investigate the effects of glycyrrhizin(GL) and glycyrrhetinic acid(GA) on histamine synthesis, lymphocyte blastogenesis in C57BL/6J mice splenocytes, IL-1 production, $Ca^{2+}$ uptake by macrophage-like P388D$_{1}$ cells and plaque forming cell assay against SRBC. Histamine contents, lymphocyte blastogenesis, IL-1 activity, $Ca^{2+}$ uptake and plaque forming cell were determined by enzyme isotope method, [sup 3/H]-thymidine incorporation, C3H/HeJ mouse thymocytes proliferation, the addition of 5 $\mu$Ci/ml $^{45}$Ca$^{2+}$ to P388D$_{1}$, cell suspension and assay to sheep red blood cell, respectively. Cytotoxicity, which was expressed as 50% mortality, was occurred by the addition of GL(10$^{-3}$M) and GA(10$^{-4}$M). Histamine production in mouse spleen cell culture was significantly increased by the addition of 0.25 $\mu\textrm{g}$/ml of Con A, after 48 hour incubation. Con A dependent T-lymphocyte proliferation was also enhanced by the addition of 0.25 .mu.g/ml of Con A. The effects of GL on histamine contents and T-lymphocyte proliferation were significantly decreased at high dose (10$^{-5}$M), while IL-1 activity was remarkably suppressed by 10$^{-8}$~10$^{-4}$M of GL. $Ca^{2+}$ uptake was not changed, but antibody production was increased by GL(10 mg/kg). GA inhibited histamine contents at 10$^{-9}$~10$^{-7}$ and depressed Con A (0.25 $\mu\textrm{g}$/ml) dependent T-lymphocyte proliferation at 10$^{-7}$~10$^{-5}$M of GA, but increased suboptimal dose (Con A 0.1 $\mu\textrm{g}$/ml) at 10$^{-9}$~10$^{-7}$M of GA. IL-1 activity was suppressed by 10$^{-8}$~10$^{-4}$M of GA and $Ca^{2+}$ uptake was enhanced by 10$^{-9}$~10$^{-6}$ of GA, but antibody production was not changed by GA. From the above results, it is suggested that GL and GA have immuno-regulatory action. GL decreased cell-mediated immune response, and increased humoral immune response at high dose. On the other hand, low dose of GA enhanced cell-mediated immune response, while high doses of GA decreased humoral immune reaction.

• 한국식품영양과학회지
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• 제43권10호
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• pp.1500-1509
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• 2014

본 연구는 위 벽세포 in vitro 실험모델과 알코올로 위를 자극한 in vivo 실험모델을 이용하여 매스틱 검의 위산 분비 억제 및 위장 점막 보호 효과를 확인하고자 하였다. 위 조직의 병리학적인 관찰을 통하여 효과를 관찰한 결과 알코올로 위를 자극한 군에서 위 점막 조직의 손상과 표면 상피세포의 손실을 관찰할 수 있었으나, 매스틱 검 50 및 100 mg/kg 투여한 군에서 모두 control 그룹과 비교했을 때 손상이 회복되었음을 확인할 수 있었다. 위액 분비량 및 위액 산도를 비교한 결과에서도 알코올의 자극으로 인하여 증가한 위액 분비량과 위액 산도를 매스틱 검이 유의적으로 감소시켰음을 확인할 수 있었다. 혈장 histamine 농도와 그로 인해 영향을 받은 H2r 발현량 변화로 위산 분비 관련 인자를 확인한 결과에서도 매스틱 검을 투여한 그룹에서 유의적으로 그 농도가 감소한 것을 확인하였다. 또한 위 벽세포에서 위산 분비 증가와 관련된 수용체인 CCK2r과 $H^+/K^+$ APTase 발현 변화도 역시 매스틱 검의 투여가 효과적으로 발현을 억제한 것으로 나타났다. 이러한 동물실험 결과를 바탕으로 세포 수준에서의 기전 규명을 위한 연구를 추가적으로 진행하였으며, 세포 내 cAMP 농도, $H^+/K^+$ APTase 및 H2r의 발현 변화를 관찰한 결과 매스틱 검의 처리가 효과적으로 이들의 발현을 감소시켰음을 확인하였다. 따라서 매스틱 검의 위산 분비 억제 및 점막 보호 활성 효과는 형태학적 및 병리학적 관찰, histamine 분비 억제, 수용체 발현 억제효과 등으로 확인한 결과, histamine을 통한 위산 분비 경로를 조절함으로써 위산 분비 및 위장 점막 손상에 대해 보호 효과를 나타내었으며 이는 이전 실험 결과들과 동일한 농도에서 효과가 나타났음을 확인하였다.