• The Journal of Pediatrics of Korean Medicine
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• v.12 no.1
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• pp.183-210
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• 1998

Cheonggisan(CGS) is well known for its effect on such allergic disease as urticaria and atopic dermatitis. Gagamcheonggisan(GCGS) was formulated by subtracting several herbs from CGS and adding several herbs to CGS. Even though it is being used frequently in the clinicai medicine for the treatment of above hypersensitivity diseases, basic study to make sure the mechanism of its action is rare. In this study the author tried to know the effect of CGS and GCGS on the vascular permeability, contact dermatitis, granular secretion from mast cells and function of macrophages. The results obtained in this study are as follows : 1. Administration of CGS and GCGS decreased the vascular permeability induced by serotonin and histamine. The decrease by serotonin is more typical and dose-dependent. 2. Administration of CGS and GCGS inhibited foot-pad and ear swelling responses induced by sheep red blood cells and picryl chloride respectively, the inhibition of foot-pad swelling responses is bigger than that of ear swelling responses and both of them are not dependent on the dose3. Treatment of peritoneal mast cells with CGS and GCGS water extract decreased the histamine release triggered by compound 48／80 in a dose dependent fashion 4. Administration of CGS and GCGS increased the phagocvtic activity of peritoneal macrophages and treatment of peritoneal macrophages with CGS activated phagocytic function in a dose dependent fashion. 5. Administration of CGS and GCGS enhanced such reactive oxygen intermediates(ROIs) as superoxide and hydrogen peroxide production from peritoneal macrophages. 6. Treatment of CGS and GCGS activated peritoneal macrophages for the production of ROIs. The above results show that CGS and GCGS decreased the hypersensitivity reactions by inhibiting non-specific inflammatory mediator release and vascular permeability without affecting general immune responsiveness.

• Korean Journal of Pharmacognosy
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• v.51 no.3
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• pp.151-157
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• 2020

When blood vessels are damaged, a rapid hemostatic reaction occurs to minimize blood loss and maintain normal circulation. Platelet activation and aggregation is essential in this process. However, excessive platelet aggregation or abnormal platelet aggregation may be the cause of cardiovascular disease, such as thrombosis, stroke and atherosclerosis. Therefore, it is important to prevent and treat cardiovascular disease by finding substances that can regulate platelet activation and suppress aggregation reactions. Isoscopoletin, which is mainly found in the roots of plants Artemisia or Scopolia, has been reported to have potential pharmacological effects on anticancer and Alzheimer's disease, but its role and mechanisms for platelet aggregation and thrombus formation are unknown. This study confirmed the effect of isoscopoletin on major regulation of collageninduced human platelet aggregation, TXA₂ production and intracellular granular secretion (ATP and serotonin release). In addition, the effects of isoscopoletin on phosphorylation of phosphorylated proteins PI3K/Akt and MAPK involved in signal transduction in platelet aggregation was studied. As a result, isoscopoletin significantly inhibited the phosphorylation of PI3K/Akt and MAPK, significantly inhibiting platelet aggregation through TXA₂ production and intracellular granular secretion (ATP and serotonin release). Therefore, we suggest that isoscopoletin is an anti-platelet substance that regulates phosphorylation of phosphorus proteins such as PI3K/Akt and MAPK and is valuable as a preventive and therapeutic agent for platelet-derived cardiovascular disease.

• Toxicological Research
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• v.6 no.1
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• pp.109-119
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• 1990

Ro09-0198, a cyclic peptide isolated from culture filtrates of Streptoverticillium griseoverticillatum, induced lysis of erythrocytes. Ro-09-0198-induced hemolysis was temperature-dependent and the sensitivity of hemolysis differed greatly among animal species. Preincubation of the peptide with phosphatidylethanolamine reduced the hemolytic activity, whereas other phospholipids present in erythrocytes in nature had no effect. A study of the structural requirements on phosphatidylethanolamine necessary for interaction with the peptide indicates that Ro09-0198 recognizes strictly a particular chemical structure of phosphatidylethanolamine: dialkylphosphoethanolamine as well as 1-acylglycerophosphoethanolamine showed the same inhibitory effct on hemolysis induced by Ro09-0198 as diacylphosphatidyl-ethanolamine, whereas phosphoethanolamine gave no inhibitory effect. Neither phosphatidyl-N-monomethylethanolamine nor alkylphosphopropanolamine had an inhibitory effect. Proton resonances of the peptide were observed in dimethyl sulfoxide solution in the presence of 1-dodecanoyl-sn-glycerophosphoethanolamine. This peptide caused permeability increase and aggregation of liposomes containing phosphatidylethanolamine. A glycerol backbone and a primary amino group of phosphatidylethanolamine are necessary for interaction with Ro09-0198 to cause membrane damage. Ro09-0198 induced a selective permeability change on liposomes. Glucose and umbelliferyl phosphate were effluxed significantly, but sucrose was only slightly permeable and inulin could not be released. Platelet aggregation and serotonin release simultaneously induced by Ro09-0198. Addition of peptide to rat platelet, loaded with the fluorescent $Ca^{++}$ chelator quin-2, caused immediate rise in cytosolic free $Ca^{++}$ to liposomal membrane containing phosphatidylethanolamine was observed dose dependently.

• Biomedical Science Letters
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• v.22 no.4
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• pp.127-139
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• 2016

A species of the fungal genus Cordyceps has been used as an ingredient of traditional Chinese medicine. In this study, we prepared cordycepin-enriched WIB-801CE, an ethanol extract from culture solution of Cordyceps militaris-hypha, and evaluated its antiplatelet effects on human platelet aggregation. WIB-801CE dose-dependently inhibited ADP-, collagen-, and thrombin-induced platelet aggregation. These antiplatelet effects by WIB-801CE were associated with the attenuation of thromboxane $A_2$ ($TXA_2$) production and serotonin release by ADP, collagen, and thrombin. The inhibition of $TXA_2$ production by WIB-801CE was due to the inhibition of cyclooxygenase-1, $TXA_2$ synthase, and cytosolic phospholipase $A_2$ activity. Therefore, these data suggest that WIB-801CE may be a beneficial component against protection from platelet aggregation-mediated thrombotic disease.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.5
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• pp.307-312
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• 2011

It has been rereported that axons which display 5-hydroxytryptamine (5-HT) immunoreactivity are abundant in the pancreas and the majority of serotonergic axons terminate within intrapancreatic ganglia, islet and acini. This histological result strongly suggests that intrapancreatic serotonergic nerves could affect to the pancreatic endocrine and exocrine secretion. Thus, this study was aimed to investigate whether intrapancreatic serotonergic nerves could affect pancreatic exocrine secretion and an action mechanism of the intrapancreatic serotonergic nerves. The rats were anesthetized with a single injection of urethane. The median line and the abdominal aorta was carefully dissected and cannulated with PE-50 tubing just above the celiac artery, and then tightly ligated just below the superior mesenteric artery. The pancreatic duct was also cannulated with Tygon microbore tubing. With the addition of serotonin, pancreatic volume flow and amylase output were significantly inhibited electrical field stimulation (EFS). On the other hand, pancreatic volume flow and amylase output were significantly elevated in EFS with the addition of spiperone. EFS application, however, pancreatic volume flow and amylase output had no significant change in cholecystokinin (CCK) alone when serotonin was applied under a 5.6 mM glucose background. Pancreatic volume flow and amylase output under 18 mM glucose background were significantly elevated in CCK plus serotonin than in CCK alone. These data suggest that intrapancreatic serotonergic nerves play an inhibitory role in pancreatic exocrine secretion and an important role in the insulin action or release.

• The Korean Journal of Physiology
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• v.24 no.1
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• pp.161-170
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• 1990

The effects of $H^{+}$ on the arterial contraction and their mechanisms were investigated in the renal artery of a rabbit. The helical strips of isolated renal artery were immersed in the HEPES-buffered or $CO_{2}/HCO_{3}^{-}$-buffered Tyrode's solution. The contractions induced by agonists (norepinephrine, histamine, serotonin and angiotensin II) or high $K^{+}$ were observed with change of extracellular or intracellular $H^{+}$ concentration. The contractions induced by norepinephrine, histamine, serotonin, angiotensin II or high $K^{+}$ in HEPES-buffered Tyrode's solution were inhibited by increase in extracellular $H^{+}$ concentration and potentiated by decrease in extracellular $H^{+}$ concentration. The degrees of these effects were most evident in the contraction induced by serotonin and angiotensin II, moderate in those by histamine and high $K^{+}$, and least in those by norepinephrine. Maximal contraction by norepinephrine, histamine and high $K^{+}$ were not influenced by change in extracellular $H^{+}$ concentration, but influenced in those contration by serotonin and angiotensin II. The attenuated contractions by an acidic pH were not returned to the level of contraction at normal pH (7.4) by elevation of extracellular $Ca{2+}$ concentration. The agonists (norepinephrine, histamine and serotonin)-induced contractions in $Ca{2+}$-free Tyrode's solution were also attenuated by increase in extracellular $H^{+}$ concentration and potentiated by decrease in extracellular $H^{+}$ concentration. Elevation of $Pco_{2}$ in the $CO_{2}/HCO_{3}^{-}$-buffered Tyrode's solution, which increase the intracellular $H^{+}$ concentration, at constant extracellular pH (7.4), increased the contraction by 30 mM $K^{+}$. From the above results, it is suggested that the decrease in contractions by increase in extracellular $H^{+}$ concentration may be resulted from that $H^{+}$ make the receptors less sensitive to agonists and cell membrane hyperpolarize and then inhibit the $Ca{2+}$ influx as well as $Ca{2+}$ release from intracellular $Ca{2+}$ storage site.

• Journal of Oriental Neuropsychiatry
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• v.30 no.3
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• pp.209-220
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• 2019

Objectives: As a general emotion, everyone can temporarily experience depression, but depressive disorder is a disease that excessively affects daily life. Among the various causes of depression, the deficiency of monoamine-based neurotransmitters such as serotonin and epinephrine are considered significant. Thus, antidepressants that target monoamines are used frequently. However, side effects such as nausea, vomiting, insomnia, anxiety, and sexual dysfunction are observed. Thus, it is necessary to develop a new therapeutic agent with fewer side effects. In this study, we investigated the antidepressant effect of JG02, used to treat depression by normalizing the flow of qi (氣) in Korean medicine. Methods: C57BL/6 mice were selected and randomly divided into six groups: normal, control, amitriptyline, and JG02 (50, 125, 250 mg/kg), respectively. Except for normal, depression was induced by applying restraint stress at the same time for six hours daily for 14 consecutive days. Saline, amitriptyline or JG02 samples were orally administered two hours before applying the stress. After that, a forced swimming test and an open field test were performed. Additionally, serum corticosterone, serotonin mRNA, BDNF mRNA, and protein in the hippocampal region were measured and compared. Results: JG02 decreased immobility time rate in the FST and increased the zone transition number and travel distance in the OFT. Also, JG02 inhibited the release of serum corticosterone, and increased serotonin, BDNF gene expression, and BDNF protein in the hippocampus. Conclusions: In this study, JG02 showed significant antidepressant effects on the chronic restraint stress mice model. When further research is performed based on JG02, the development of a new antidepressant is considered highly possible.

• Bulletin of the Korean Chemical Society
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• v.33 no.12
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• pp.4035-4040
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• 2012

Presented study describes the synthesis of photo cross-linkable and water soluble hydroxyethyl starch hydroxyethyl methacrylate (HESHEMA) samples with different degree of substitution (DS) by functionalization of hydroxyethyl starch (HES) with hydroxyethyl methacrylate (HEMA) or hydroxyethyl methacrylate carbonylimidazole (HEMACI) in DMSO using two different routes. It was revealed that the reaction time for HESHEMA synthesis can be reduced from 5 days to 24 h by conducting the reaction at $80^{\circ}C$ instead of at room temperature. Solubility of HESHEMA was found to be dependent on DS which in turn was dependent on ratio between HES and HEMA or HEMACI. HESHEMA samples with DS > 0.24 depicted insoluble in water, whereas the samples with DS < 0.05 did not form appreciable gel. HESHEMA samples with appropriate DS were converted into hydrogels by cross-linking polymer chains under UV radiations and resulting HESHEMA hydrogels showed swelling up to 1200%. Application of HESHEMA in controlled drug delivery was investigated by diffusion based encapsulation of Ondansetron, a serotonin 5-$HT_3$ receptor antagonist drug, mainly used for nausea and vomiting treatment.

• Archives of Pharmacal Research
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• v.22 no.3
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• pp.320-323
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• 1999

The anti-allergic actions of the leaves of Castanea crenata (Fagaceae) were studied. The water extract demonstrated potent anti-allergic actions in in vivo and in vitro experiments. The oral or intraperitoneal administration of the extract (100 or 200 mg/kg) caused a significant inhibition of the 48 hr-PCA (up to 90%) and the vascular permeability induced by histamine or serotonin in rats (about 80%). The anaphylactic release of ${\beta}$-hexosaminidase for RBL-2H3 cells was also significantly inhibited by the extract in as dose-dependent manner with an IC50 value of 230 $\mu\textrm{g}$/ml. The activity-guided fractionation of the extract, based on the determination of inhibitor effect upon the release of ${\beta}$-hexosaminidase, led to the isolation of quercetin as an active principle responsible for the inhibition of degranulation.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.11-15
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• 1995

Serotonergic neurons in medulla oblongata play an important role in the endogenous descending pain inhibitory system. To illucidate the factors involved in the regulation of medullary serotonergic neurons, we studied the effects of cholecystokinin (CCK) and agents acting on various second messenger systems on 5-hydroxytryptamine (5-HT) release from cultured neurons of rat fetal (gestational age 14th day) medulla oblongata. Cultured cells maintained for 10 days in vitro were stimulated for 48 hours with CCK or other neuropeptides at 10 micromolar concentration. CCK ($10{\mu}M$) and substance P ($10{\mu}M$) significantly increased. 5-HT release. However, somatostatin, proctolin, thyrotropin releasing hormone, and interleukin-6 did not have any effects on 5-HT release. Nimodipine ($1{\mu}M$), a calcium channel blocker, almost completely, and calmidazolium ($1{\mu}M$), a calmodulin antagonist, significantly inhibited the CCK-induced 5-HT release. The total 5-HT content (intracellular 5-HT plus released 5-HT) was significantly increased by CCK. However, the intracellular 5-HT content was not significantly changed by CCK. Forskolin ($5{\mu}M$), an adenylate cyclase activiator, but not $2{\mu}M$ phorbol myristate acetate (PMA), a protein kinase C activator, significantly enhanced 5-HT release. The total 5-HT content (intracellular 5-HT plus released 5-HT) was significantly increased by forskolin. However, the intracellular 5-HT content was not significantly changed by forskolin. PMA had no effect on intracellular 5-HT levels. These results suggest that CCK regulates serotonergic neurons in the medulla oblongata by enhancing 5-HT secretion through calcium influx and caimodulin, and that cyclic AMP system but not protein kinase C system is involved in 5-HT release.