• Biomolecules & Therapeutics
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• v.2 no.2
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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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• v.5 no.1
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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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• v.39 no.5
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• pp.386-391
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• 1992

Background: Recently, bronchial provocation of the airway of atopic asthmatic subjects with inhaled allergen has been shown to produce an initial peripheral blood eosinopenia followed by an eosinophilia occurring approximately 12 to 18 hrs after the challenge. However there are few studies about the change of peripheral eosinophil count (PEC) after bronchial provocation with nonspecific stimuli such as histamine or methacholine. Interestingly our preliminary study demonstrated a notable change of PEC during bronhial provocation with inhaled histamine in some asthmatic subjects. This study was designed to reevaluate our preliminary data and to further investigate the change of PEC during as well as after bronchial provocation with inhaled histamine in bronchial asthma tics. Methods: Sixteen asthmatic subjects participated in this study. Bronchial provocation with inhaled histamine was done between 9 AM and 12 MD. Blood samplings for PEC were done with 5 minutes intervals during the procedure, and repeated at 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, and 48 hours after the procedure. Results: The results were as follows; 1) The patients were divided into two groups characterized by each pattern in the change of PEC during the procedure. A group (11 of sixten, group I) showed an increasing pattern of PEC and another group (5 of sixteen, group II) showed a decreasing pattern of PEC during the procedure. 2) Group I demonstrated a tendency to maintain continuously higher level of PEC than the baseline value until 48 hours after the procedure. 3) Group II demonstrated a tendency to maintain continuously lower level of PEC than the baseline value until 48 hours after the procedure. 4) There were no significant differences in their clinical parameters including baseline eosinophil count, baseline $FEV_1$, $PC_{20}$ of histamine, and serum IgE level between group I and group II. Conclusion: Our results suggest that the change of PEC produced by inhaled histamine in asthmatic subjects is much different from that produced by inhaled allergen, and that each patient may have their individual characteristics in the change of PEC in response to bronchial provocation with inhaled histamine. Alternatively these findings suggest that eosinophils may be partially involved in the early asthmatic reaction.

• YAKHAK HOEJI
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• v.35 no.2
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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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• v.8 no.3
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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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• v.23 no.1
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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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.

• YAKHAK HOEJI
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• v.35 no.3
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.10
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• pp.1500-1509
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• 2014

The object of this study was to investigate the inhibitory effects of chios mastic gum (MG) on gastric acid secretion in an ethanol-induced SD rat model and primary parietal cells. Rats were randomly divided into four groups: Vehicle (normal group), Control (treated with ethanol), MG50 (treated with ethanol and mastic gum at 50 mg/kg b.w), MG100 (treated with ethanol and mastic gum at 100 mg/kg b.w). Groups treated with both MG50 and MG100 showed attenuation of gastric mucosal injury, sub-epithelial loss, hemorrhaging, and gastric juice secretion. We also examined the acidity of gastric juice during gastric injury. Oral administration of both MG50 and MG100 significantly decreased acidity of gastric juice by % and %, respectively. To examine the stimulatory factors related to gastric acid secretion, mRNA expression levels of H2r, M3r, CCK2r, and $H^+/K^+$ ATPase were measured by real-time PCR. Compared with a vehicle group, mRNA expression levels of H2r, CCK2r, and $H^+/K^+$ ATPase clearly increased in the control group. However, levels of H2r, CCK2r, and $H^+/K^+$ ATPase slightly but significantly decreased in MG-treated groups compared with control. Blood level of histamine significantly decreased in MG-treated groups, which indicates the involvement of MG on in histamine-related acid secretion. To identify the mode of action of MG in regulating histamine-related pathways, intracellular level of cAMP and mRNA levels of H2r, M3r, CCK2r, and $H^+/K^+$ ATPase were measured in primary parietal cells. While mRNA levels of M3r and CCK2r remained unchanged, levels of H2r and $H^+/K^+$ ATPase significantly decreased upon MG treatment. Subsequently, intracellular levels of cAMP decreased. These results suggest that mastic gum has the ability to inhibit gastric acid secretion by regulating a histamine-related pathway.