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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules & Therapeutics
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Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 4, Issue 4 - Dec 1996
Volume 4, Issue 3 - Sep 1996
Volume 4, Issue 2 - Jun 1996
Volume 4, Issue 1 - Mar 1996
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Studies on Antiulcer Effects of DA-9601, an Artemisia herba Extract against Experimental Gastric Ulcers and Its Mechanism
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 111~121
Antiulcer effects of Artemisia herba extract (DA-9601) were evaluated in various types of experimental gastric ulcer induced in rats. And the effects of DA-9601 on mucus, basal and stimulated gastric acid secretion were also investigated in rats. DA-9601 (12.5∼400 mg/kg, p.o.) prevented the formation of gastric ulcers induced by 60% EtOH in 150 mM HC1, restraint water immersion stress, platelet activating factor (PAF), aspirin in 150 mM HCI with Pylorus-ligation and indomethacin. DA-9601 (4∼400 mg/kg, p.o.) significantly accelerated the healing rate of acetic acid-induced gastric ulcer and significantly stimulated mucus secretion in a dose-dependent manner. DA-9601 (20∼200 mg/kg, i.d.), however, did not inhibit basal gastric acid secretion in pylorus ligated rats and DA-9601 (200 mg/kg, i.d.) failed to influence histamine-, pentagastrin- and carbachol- stimulated gastric acid secretion. These results suggest that DA-9601 has inhibitory action on gastric lesion and ulceration through increasing mucus secretion in the stomach of rats without influencing basal and stimulated gastric acid secretion.
In Vitro Effect of Aspalatone on Platelet Aggregation and Thromboxane Production in Human Platelet Rich Plasma
Suh, Dae-Yeon ; Han, Byung-Hoon ;
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 122~126
In vitro inhibitory effect of aspalatone ((3-(2-methyl-4-pyronyl)]-2-acetyloxybenzoate) on collagen-, ADP-, and epinephrine-induced platelet aggregation in human platelet rich plasma (PRP) was compared with the effects of reference drugs (acetylsalicylic acid, cilostazol and ticlopidine). Aspalatone inhibited time and dose dependently human platelet aggregation induced by collagen; relative potency was in the order of cilostazol>acetylsalicylic acid>aspalatone>ticlopidine. Aspalatone, like acetylsalicylic acid, potently inhibited only the secondary phase of ADP-and epinephrine-induced aggregation. Thromboxane
production evoked by collagen in human PRP was inhibited significantly and concentration-dependently by aspalatone and acetylsalicylic acid. These results were in agreement with the earlier studies in which the antiplatelet action of aspalatone was indicated to be due to the inhibition of platelet cyclooxygenase activity (Han et al., Arzneim. Forsch./Drug Res. 44(II), 1122, 1994; Suh and Han, Yakhak Hoeji 39, 565, 1995). In addition, the inhibitory activity of aspalatone on the platelet aggregation appears to be inversely related to the rate of nonspecific deacetylation of the drug in plasma.
Toxicity Studies of DA-l25, an Anthracycline Antitumor Antibiotic : Intravenous Repeated Doses for 26 Weeks in Beagle Dogs
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 127~137
This study was performed to investigate the toxicity of DA-125 in beagle dogs, an anthracycline antitumor antibiotic. The dogs were administered DA-125 i.v. at 0.0023, 0.0375, 0.15 and 0.6 mg/kg/day, 6 days/week for 26 weeks. At 0.6 mg/kg, all male and female dogs were either sacrificed moribundly or dead during the 26-week treatment. The dogs revealed inactivity, salivation, dark bloody discharge, swelling of the subcutaneous injection site, abscess, and ulceration in the abdominal wall and legs. At 0.15 mg/kg, anorexia, salivation, and swelling of the injection site were observed. The food consumption was decreased with a statistical significance at 6 and 12 weeks treatment in males of 7.6 mg/kg. At 0.0375, 0.15 and 0.6 mg/kg, body weights were decreased significantly in a dose-related fashion after 17 weeks treatment. Total white blood cell counts for male dogs at 0.6 mg/kg were lower than those of control dogs after 13 weeks treatment, which appeared mainly due to decreased neutrophils. At 0.15 mg/kg, testicular atrophy was found in all males by gross pathology and the testicular weights were significantly decreased when compared to those of control males. Microscopically, the testis showed moderate atrophy of the seminiferous tubules and marked decrease in number of spermatozoa in the epididymal tubules. At 0.6 mg/kg, petechia or echymotic hemorrhage was observed in gastrointestinal tract, heart, lungs, and other organs at the necropsy, Marked atrophy of thymus were observed in both males and females. In addition, severe testicular atrophy was noted in all males. Microscopically, gastrointestinal tract showed hemorrhage, epithelial denudation, hypermucus secretion, and atrophy of intestinal villi. Seminiferous tubules of the atrophic testis were lined with Sertoli cells only and devoid of germ cells. Severe oligospermia or aspermia was present in the epididymal tubules. Bone marrow showed marked depletion of hemopoietic cells. In addition, marked atrophy was found in the lymphoid tissue of gastrointestinal tract, various Iymph nodes, and thymus. Injection sites showed marked inflammatory response with necrosis, necrotizing vasculitis, thrombus formation, and ulceration in the skin. According to the present results, no observed effect level appeared to be 0.0375 mg/kg. At 0.15 mg/kg, testis was a target organ, while at 0.6 mg/kg hemopoietic tissue, gastrointestinal tract, and testis were considered to be target organs. At 0.6 mg/kg the test compound seems to inflict a damage on the blood vessels causing hemorrhage in the various organs and tissues.
A 13 Week Subcutaneous Toxicity Study of Recombinant Human Epidermal Growth Factor (DWP401) in Mice
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 138~147
DWP401, a recombinant human epidermal growth factor, was subcutaneously administered to ICR mice at the dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day (15rats/sex/group) in order to evaluate the subchronic toxicity. General observations, examinations for food and water consumption, ophthalmoscopy and urinalysis were carried out during the study. For the complete gross and microscopic examinations, 10 mice/ sex/group were sacrificed at the ends of the dosing period, and the remaining animals were sacrificed with a 5 week recovery period. Examinations for hematology and blood biochemistry were also carried out at the time of recovery period. Based on the results, it was thought that the target tissue or organs were mesothelial cell, injection site, spleen, adrenal gland, ovary and transitional epithelial cell of urinary tract, and no observed toxic level of DWP401 was 0.04 mg/kg while definite toxic dose level might be 0.2 mg/kg.
Screening of the Extracts of Herbal Medicines which Stimulate the Hydrolysis of Phosphoinositides in Jurkat T-lymphocyte Cells
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 148~153
Activation of the T lymphocytes results in a variety of early biochemical events ultimately leading to cell proliferation and lymphokine production. Stimulation of the signal transduction cascade in T cells through the T cell receptor coincides with activation of the phosphatidylinositol-phospholipase C (PI-PLC) pathway. Therefore, we have established a model system to screen immune-simulator that can increase the hydrolysis of phosphoinositides in human T cell leukemia Jurkat cells. As a result of screening from herbal medicine extract, 4 extracts (O1ibanum, Ephedrae Herba, Real Gar, Saussureae Radix) were found 14 increase the production of inositol phosphates. All the active fraction from the four kinds of extract were fluted in a different retention time on C-18 HPLC and these active fraction also showed difference in cell specificity. And all the active fractions increased DNA synthesis in T cell. Therefore, it is suggested that the active fraction among 4 extracts might contain a compound having different properties one another.
General Pharmacology of Recombinant Erythropoietin (LB-00014)
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 154~161
General pharmacological properties of LB-00014, an erythropoietin which was produced by recombinant DNA technique in Biotech Research Institute, LG Chemical Ltd. were examined. The administration of LB-00014 (60, 600, 6000 IU/kg, iv) in mice had no effect in general behavior and central nervous system, and no influences on normal body temperature, writhing syndromes induced by 0.7% acetic acid solution and chemoshock produced by strychnine and pentetrazole solution. LB-00014 (60, 600, 6000 IU/kg, iv) given to anesthetized rabbits showed no effect on blood pressure of carotid artery and respiration rates, and it did not influence the responses produced by injection of acetylcholine or epinephme. The administration of LB-00014 (601, 600, 6000 IU/kg, iv) in rats had no effect on the plasma prothrombin time, activated partial thromboplastin time and hemolytic action. The platelet aggregation induced by collagen in human plasma was not influenced by LB-00014 (10, 100, 1000 lU/kg, iv). It showed no direct effect at 100 and 1000IU/m1 in isolated stomach fundus and uterus of rats and ileum of guinea-pig, and it also had no inhibition of contraction produced by acetylcholine, oxytocin, serotonin and histamine in the above-mentioned preparations. It did not influence gastric secretion, pH and acid output at 6000 IU/kg, iv in rats, but showed a significant increase in intestinal propulsion of mice at 6000 IU/kg, iv. Its administration (60, 600, 6000 lU/kg, iv) caused no effect on urine and electrolyte excretion in rats. These results indicate that LB-00014 does not exsert any of serious pharmacological effects.
Anti-stress Effect of Cholic acid Derivatives in Restraint Stress Induced Rats
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 162~166
This study was done to investigate whether cholic acid derivatives have anti-stress activity and what is a cause of this anti-stress effect. Seven cholic acid derivatives (cholic acid, taurocholic acid, ursodeoxycholic acid, tauroursodeoxychoic acid, chenodeoxy cholic acid, dehydrocholic acid, hyodeoxycholic acid) were used, silymarin and valproic acid were used as positive controls. Stress was induced by restraint immobilization technique plus water immersion (24hrs) and adrenal weight, spleen weight, adrenal ascorbic acid, serum cholesterol, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), adrenal cholesterol, glucose and corticosterone levels were measured as stress indicators. Most cholic acid derivatives markedly decreased the adrenal weight, and TUDCA and DHCA increased the spleen weight. The restraint stress induced increments in serum LDH, ALP and cholesterol were attenuated by most cholic acid derivatives. Cholic acid, taurocholic acid and tauroursodeoxycholic acid only increased the content of adrenal ascorbate. While valproic acid showed an inhibitory effect against stress, silymarin did not. Our findings suggest that most cholic acid derivatives have anti-stress effect and that their anti-stress effect is, in part, related to choleretic activity.
Effects of Pilocarpine and Kainic Acid on EEG and Behavior Activity in Freely Behaving Rats
Choi, Byung-Ju ; Cho, Jin-Hwa ; Lee, Maangee-G. ;
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 167~173
This study was undertaken to evaluate a behavior-electroencephalogram (EEG) pattern relationship in pilocarpine- and kainic acid-induced convulsions of rats. Also we intended to examine the effect of a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, and diazepam on the pilocarpine-induced behavioral and electrical seizures in rats. The electrical activities at frontal and hippocampal areas and behavior activities were measured in freely moving rats. At the beginning of the experiments, the rats displayed an exploratory behavior. This awake and moving phase with a low amplitude, irregular, 4-10 Hz wave was followed by a still phase. Pilocarpine (400 mg/kg, i.p.) and kainic acid (0.5 mg/kg, i.c.v.) induced tonic and clonic seizures. The pilocarpine-induced change in electrical activities exhibited a weak correlation with behavioral convulsion at all stages. The amplitude and duration of the electrical response were not linear with the degree of behavioral score. An application of MK-801 (dizocilpine, 7.5 mg/kg) did not affect the amplitudes of the convulsant-induced electrical activities, though the same dose of this drug caused the deformation of the electrical pattern. There was no effect of MK-801 on the behavioral and electrical activities as expected. Diazepam (1 mg/kg) did not affect the amplitude of the electrical activities induced by pilocarpine but changed the pattern of these activities. Our study shows that there is no linear relationship between degree of behavior and amplitude of electrical activities of convulsants. This may indicate that the NMDA receptor stimulation can be processed by the neocortical or hippocampal network in a different way between behavioral and electrical activities.
General Pharmacology of Artemisia Extract Powder, DA-9601
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 174~183
The general pharmacological properties of Artemisia extract powder (DA-9601) produced from Artemisia asiatica leaves were investigated in mice, rats, guinea pigs and rabbits. DA-9601 at the dose of 800 mg/kg po had no influences on general behaviour, barbital sleeping time and motor coordination of mice. The material at the oral dose of 800 mg/kg did exhibit neither analgesic action nor hypothermic effect. Anticonvulsant action, muscle relaxant action and the effect on intestinal propulsion were not identified at 800 mg/kg po. In the isolated ileum and trachea of guinea pig, the material did not show direct erect and inhibitory action of chemically or electrically stimulated contraction at the concentration of
g/ml. The sinus rates of atria and contractility of papillary muscle of guinea pig were not influenced by DA-9601 at a dose of
g/ml. No influences on blood pressure and respiration were observed at 40 mg/kg iv, in rabbits. However, transient decreases in blood pressure of rabbits were observed as given 120 mg/kg in iv route with slight respiratory depression, and slight diuretic effect could be found without any changes in
General Pharmacology of LB20304a, a New Quinolone Antibiotic
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 184~189
General pharmacological studies of LB20304a (a mesylate salt form of a new quinolone antibiotic LB20304 following oral administration of 300 mg/kg and 1000 mg/kg, almost maximum tolerance dose in mice and rat, respectively, were performed in terms of effects on general behaviour, central nervous system, gastrointestinal system, and blood coagulation system in mice and rats. With regards to general behaviour of mice, at oral dose of 300 mg/kg, LB20304a reduced muscle tone and locomotor activity. In terms of CNS, at oral treatment of 300 mg/kg, LB20304a showed some analgesic effects in mice, and oral dose of 1000 mg/kg caused drop in normal body temperature of rat, while it enhanced the pentylenetetrazole-induced clonic convulsion to tonic convulsion and/or death in mice at the doses of unto 300 mg/kg. In addition, LB20304a increased hexobarbital-induced sleeping time two and three times in mice at oral doses of 20 mg/kg and 300 mg/kg, respectively. Rota-rod and traction test in mice were not influenced by the dose of 300 mg/kg and 200 mg/kg, respectively. LB20304a reduced gastric secretion of rat at dose of 1000 mg/kg, and increased intestinal motility of mice at dose of 300 mg/kg. In rats, blood coagulation index, such as PT (prothrombin time) and aPTT (activated partial thromboplastin time) were not affected by the treatment of upto 1000 mg/kg of LB 20304a.
Immunosuppressive Effect of Aflatoxin B1
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 190~195
Aflatoxin B1 (AFB1) has been reported to directly suppress the immune responses. In the present study, the effect of AFB1 on immune functions was investigated. Splenic lymphocytes were treated with various doses of the mitogens (lipopolysaccharide, concanavalin A) in the presence of AFB1. AFB1 pretretment decreased the number of plaque forming cells (PFC) in a dose-dependent manner. Antibody production of IgM and IgG class was significantly decreased in AFB1-treated splenic cells. In addition, when animals were exposed to AFB1, the susceptibility of bacterial infection as well as the growth of tumor cells was increased. These data suggest that AFB1 affected the immune function and humoral immunity impaired by AFB1 treatment contributed to pathological process.
MK-801 Binding Profiles with the Agonist, Partial Agonist, and Antagonist Acting at the Glycine Binding Site of the N-Methyl-D-Aspartate Receptor
Cho, Jung-sook ; Park, No-Sang ; Kong, Jae-Yang ;
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 196~201
The N-methyl-D-aspartate (NMDA) receptor-ion channel complex is activated by the simultaneous presence of L-glutamate and glycine, allowing the binding of MK-801 to the phencyclidine (PCP) site of the receptor. The
MK-801 binding assay system was established for determination of pharmacological functions of test compounds acting at the glycine site of the receptor. The binding in the presence of 0.1
M L-glutamate was increased by an agonist (glycine) in a dose-dependent fashion, while decreased by either partial agonist (R-(+)-HA-966) or antagonist (5,7-dichlorokynurenic acid: 5,7-DCKA). To distinguish partial agonism from antagonism, various concentrations of 7-chlorokynurenic acid (7-CKA) were added in the assay to eliminate the interference of the endogenous glycine present in the membrane preparations. The bindings in the presence of L-glutamate (0.1
) and 7-CKA (1, 5, or 10
) were increased by R-(+)-HA-966. Being a weak partial agonist, the extent of potentiation was much less than that by the agonist. These binding profiles were clearly distinguishable from those by the antagonist, 5,7-DCKA, which exhibited no intrinsic activity. The binding assays established in the present study are a useful system to classify ligands acting at the glycine site of the NMDA receptor by their pharmacological functions.
Skin Irritation Test of Clonidine Patch
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 202~204
Clonidine, an antihypertensive drug, stimulates postsynaptic
adrenergic receptors in the CNS and lowers arterial pressure by erects on both cardiac output and peripheral resistance. However, many patients experience that sedation and xerostomia occured upon oral administration of clonidine. These side effects are due to high plasma peak concentration and can be avoided when clonidine is given transdermally. In this study, we performed the skin irritation test for transdermal administration of clonidine patch on New Zealand white rabbits. Twelve New Zealand white rabbits were divided into two groups according to the dose levels, respectively. After transdermal administration of clonidine patch with two doses, clinical manifestations, body weight loss and postmortem findings were observed. We could not find any significant evidence of skin irritation by transdermal administration of clonidine patch.
Antihypertensive Action of Clonidine Patch
Biomolecules & Therapeutics, volume 4, issue 2, 1996, Pages 205~207
Clonidine, an antihypertensive drug, stimulates postsynaptic alpha-2 adrenergic receptors in the central nervous system and lowers arterial pressure through the effects on both cardiac output and peripheral resistance. However, many patients experience that sedation and xerostomia occur upon oral administration of clonidine. These side effects are due to high plasma peak concentration and can be avoided when clonidine is given transdermally. In this study, we tested the antihypertensive effects of trandermal administration of clonidine patch on spontaneously hypertensive rat (SHR) which is a model animal for human essential hypertension. Forty eight SHR (male) were divided into six groups according to the dose levels, respectively. After transdermal administration of clonidine patch of each dose, systolic blood pressure and heart rate were measured. Clonidine patch produced maximal antihypertensive and bradycardiac effects 48 hrs after administration and antihypertensive effects showed dose-dependency. We suggest that antihypertensive effects of clonidine patch are similar to those of orally given clonidine and clonidine patch can be used instead of clonidine tablet.