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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules and Therapeutics
Journal Basic Information
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
Selecting the target year
A Study on Antigenicity of G009, a Polysaccharide Isolated from Gandoderma lucidum IY009 in Mice and Guinea pigs
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 1~6
In the present study, the antigenic potential of G009, a polysaccharide isolated from Ganoderma lucidum IY009, was determined in BALB/C mice and Hartley guinea pigs. Antigenicity tests, including passive cutaneous anaphylaxis (PCA), active systemic anaphylaxis (ASA) and indirect hemagglutination test (IHA) were performed according to the established guidelines of National Institute of Safety Research. The results were as follows: 1. Mice showed no production of antibodies against G009 sensitized with an adjuvant, aluminum hydroxide gel (alum), when judged by the heterologous PCA test in rats. Meanwhile, antibodies against ovalbumin (OVA) sensitized with alum were clearly detected. 2. In the studies with guinea pigs, both the sensitization of G009 alone and of G009 with complete Freund's adjutant (CFA) did not produce positive reactions in homologous PCA. In the case of ASA, however, G009 alone and G009 with CFA produced positive reactions. 3. No G009 specific reaction was observed in an IHA assay using sera isolated from G009 sensitized mice. These findings suggest that G009 have no antigenicity potential in mice but may have weak antigenicity in guinea pjgs.
Effect of 5-Hydroxytryptamine(5-HT) on Renal Function in Dog
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 7~18
5-Hydroxytryptamine(5-HT, serotonin), when given into the vein, produced antidiuretic action accompanied with reduction of glomerular filtration(GFR), renal plasma flow(RPF), osmolar clearance(Cosm) and amounts of sodium or potassium excreted in urine(
), with the augmented reabsorption rates of sodium and potassium in renal tubules. 5-HT, when infused into a renal artery, exhibited diuretic action accompanied with the augmented RPF and increased
in only infused kidney. Antidiuretic action of 5-HT infused into the vein was not influenced by ketanserin, 5-H
receptor blockade, given into a renal artery, vein or carotid artery, by methysergide, 5-H
receptor blockade, given into a renal artery, whereas above antidiuretic action was inhibited by methysergide given into vein or carotid artery. Diuretic action of 5-HT infused into a renal artery in only experimental kidney was blocked by ketanserin injected into a renal artery, was not influenced by methysergide administered into a renal artery. Above results suggest that 5-hydroxytryptamine(5-HT) produced the antidiuretic action through central 5-H
receptor and the diuretic action through 5-H
receptor located in renal tubules of kidney.ney.
Subacute Toxicity of SKI306X, an Antiinflammatory Herbal Extracts, in Rats
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 19~31
This study was performed to determine the subacute toxicities of SKI306X, an antiinflammatory herbal extract, in rats. SKI306X was administered orally to rats once a day for 4 weeks at doses of 0.3, 1.0, and 3.0 g/kg/ day. Each group consisted of 20 male and 20 female rats, including 5 male and 5 female rats per group for an interim study at the end of 2-week administration and for a 2-week recovery study, respectively. Throughout the study, all rats survived and no adverse clinical signs were observed. Although male rats treated with high dose (3.0 g/kg/day) of SKI306X showed slight loss of body weight (approximately 5%) in comparison with control animals during the administration period, their body weight loss was normally restored during the recovery period. No significant change was found in all hematological parameters of SKI306X-treated groups except for the decreased number of red blood cells in all female groups at the interim study. Statistically significant changes were observed in several blood enzyme levels of SKI306X-treated groups; however, most of these significant changes were within normal range and statistically significant values did not show dose-related responses. In SKI306X-treated groups, the absolute and relative weights of liver, heart, and stomach were statistically different from those of control group, but these differences disappeared at the end of recovery period and also drug-related gross and histopathological findings in these organs were not found. No other drug-related gross and histopathological findings were observed. It is concluded from the results of this study that non-toxic dose of SKI306X was estimated to be between 0.3 and 1.0 g/kg/day and the maximum tolerated dose of SKI306X was assumed to be higher than 3.0 g/kg/day.
Acute Toxicity of SKI306X, an Antiinflammatory Herbal Extract, in Rats
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 32~35
SKI306X is a herbal extract prepared from three herbs Clematis mandshurica, Trichosanthes kirilowii and Prunella vulgaris. It showed strong antiinflammatory actions on carrageenan-induced edema, acetic acid-induced pain, adjuvant-induced arthritis, and oxygen radical-generated reactions. In this study, the acute toxicity of SKI306X was evaluated in rats by a single oral administration. Thirty male and thirty female rats were divided into 6 groups according to the dose levels, respectively. After oral administration of SKI306X with several doses (5.0 g/kg, 3.3 g/kg, 2.2 g/kg, 1.5 g/kg, 1.0 g/kg), mortality, clinical signs, body weight, and gross findings in organs were examined. No toxic effect was shown in terms of mortality, clinical signs, body weight changes and gross findings. It is suggested the LD
of SKI306X would be more than 5.0 g/kg in rats.s.
Antihistaminic Action of the Several Medicinal Plant Extracts
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 36~45
The antihistaminic action of eighteen herbal medicines was investigated by the radioligand binding and functional assays. The hexane fractions of Trichosanthis radix, Mori cortex radicis and Evodiae fructus dosedependently inhibited [
H] mepyramine binding to H
, receptor in guinea-pig brain homogenates and histamine-induced contraction of isolated guinea-pig ileum. Antihistaminic action of the hexane and ethyl acetate fractions of Mori cortex radicis and the hexane fraction of Evodiae fructus was more potent than their antimuscarinic action evaluated from the inhibition of [
H]QNB binding and carbachol response. The ethyl acetate and chloroform fractions from Scutellariae radix also inhibited histamine-induced contraction, but antihistaminic potencies of these fractions were almost identical with their antimuscarinic potencies. The hexane fractions of Mori cortex radicis and Evodiae fructus inhibited selectively the increase of histamine-induced cutaneous vascular Permeability in the rat dorsal skins. However, the ethyl acetate fraction from Scutellariae radix inhibited eqipotently the effects of histamine and serotonin on the vascular permeability. These results demonstrate that the hexane and ethyl acetate fractions of Mori cortex radicis and the hexane fraction of Evodiae fructus have the selective histamine H
receptor blocking activity.
A Study on Growth-inhibiting Protein of Human Cancer Cells Secreted from 373-L1 Cell-line
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 46~50
Inhibition of the growth of human cancer cells by proteins secreted from 373-L1 cells was investigated in the present study. The growth of human cancer cells was inhibited by co-culture with 373-L1 cells under 10% FBS and DME, DME, GIT and serumless medium, respectively. The conditioned medium of cultured 373-L1 cells under serumless medium was concentrated 100-fold through an ultrafiltration cell with a 10,000 molecular weight cutoff at 4
under positive pressure using nitrogen(373-L1 EM). 373-L1 EM inhibited the growth of HeLa, Hep G 2, KHOS-Np, A43l and MCF-7 cells. 3T3-L1 EM was purified with FPLC, DEAE-ion exchange chromatography and phenyl-sepharose chromatography. The major protein of 373-L1 EM has a molecular weight of 66,000-68,000 in SDS-PAGE analysis. The results suggest that the inhibitory activity of 373-L1 EM appears to be due to some protein(m.w.66,000-68,000) secreted by 373-L1 cells.
Reproductive Toxicity Study of SM-101(sulbactam.metampicillin): Fertility Study in Rats
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 51~58
A new composite antibiotic, SM-101(sulbactam.metampicillin), was at dose levels of 0, 250, 500 and 1000 mg/kg/day administered intravenously to Sprague-Dawley male rats from predating to mating period and to females from premating to early gestation period. Effects of test agent on general findings and reproductive performance of parent animals and embryonic development were examined. In male parents, two deaths occurred at 1000 mg/kg. The increase in kidney weight of the 1000 mg/kg group were also observed. The decrease in body weight and food consumption were found at 500 and 1000 mg/kg. The decrease in spleen weight were seen at 250, 500 and 1000 mg/kg. In female parents, three deaths were found at 1000 mg/kg. Mating performance and fertility of parent animals were not adversely affected by all doses tested. F1 fetuses showed no changes related to treatment of SM-101. The results show that the no effect dose level(NOEL) for general toxicity of parent animals is under 250 mg/kg/day and NOELS for reproductive capability and fatal development are over 1000 mg/kg/day.
Reproductive Toxicity Study of SM-101(sulbactam.metampicillin): Teratogenicity Study in Rats
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 59~67
A new composite antibiotic, SM-101(sulbactam·metampicillin), was at dose levels of 0, 375, 750 and 1500 mg/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. Two-third of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development of F1 fetuses, as well as growth, behaviour and mating performance of F1 offspring were examined. In dams, two deaths occurred at 375 and 1500 mg/kg, respectively. The decrease in the weight of adrenal glands of the 1500 mg/kg group was observed. The prolongation of pregnancy period was found at 1500 mg/kg. F1 fetuses showed no changes related to the treatment of SM-101. In F1 offspring, the increase in spleen weight was seen at all doses treated. No treatment-related abnormalities were observed in each treated group in terms of development, behaviour and reproductive performance. In F2 fetuses, no drug-induced abnormalities occurred at all doses. The results show that the no-effect dose levels (NOELS) for dams and Fl offspring are under 375 mg/kg/day and NOELs for F1/F2 fetuses are over 1500 mg/kg/day.
Efficacy and General Pharmacology of Recombinant Human Erythropoietin(DA-3285)
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 68~77
Efficacy and general pharmacology of recombinant human erythropoietin (rHu-EPO), were investigated. Efficacy studies were conducted in normal, cisplatin- and acute hemorrhage-induced anemic rats. Normal and anemic animals were treated intravenously with rHu-EPO for 5 days and the changes in the numbers of red blood cells (RBC), hemoglobin (Hb), hematocrit (Hct) and reticulocytes (Ret) were examined. In normal rats, rHu-EPO significantly increased RBC, Hb, Hct and Ret at doses of 50∼ 1250 IU/kg/day. Cisplatin-induced anemic rats showed significant increase of RBC, Hb, Hct and Ret in a dose-dependent manner after administration of rHu-EPO (50∼200 lU/kg/day). And in acute hemorrhage-induced anemic rats, rHu-EPO(4∼100 Iu/kg/day) accelerated recovery of anemia with significant increase in Ret. These changes disappeared gradually after cessation of the treatment. The general pharmacological effects of rHu-EPO were investigated in mice, rats, guinea-pigs, rabbits and cats. rHu-EPO had no influences on central nervous, cardiovascular, gastrointestinal and blood coagulation system. It also had no influence on the contraction of phrenic nerve-diaphragm preparation. rHu-EPO produced significant increase of urine volume at a dose of 7000 IU/kg. These results suggest that rHu-EPO might be useful for the therapy of anemia without serious side effect.
Pharmacokinetics and Tissue Distribution of Recombinant Human Erythropoietin (DA-3285) in the Laboratory Animals
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 78~83
The pharmacokinetics and tissue distribution of DA-3285 (recombinant human erythropoietin, recently manufactured by Research Laboratories of Dong-A Pharmaceutical Company) were studied in the laboratory animals. The plasma, urine, and tissue concentration of DA-3285 were measured by a double-antibody sandwich enzyme immunoassay. After intravenous administration of DA-3285, 20, 100, 500 and 2500 units/kg to rats, the plasma concentrations declined polyexponentially with the terminal half-lives of 2.15, 2.10, 2.31, and 2.35 hr, respectively. Total body clearance (20.7∼26.6 mι/hr/kg) and apparent volume of distribution at steady state (57.2∼70.1 mι/kg) were independent of the dose and AUC increased proportionally with the dose. The renal clearance was much lower than total body clearance, suggesting that extrarenal clearance, presumably metabolism , plays a significant role in elimination of DA-3285. In all rat tissues, the tissue to plasma ratios were smaller than unity, indicating less affinity of DA-3285 to rat tissues and was proved by considerably less value of Vdss. After 3 times a week for consecutive 3 weeks i.v. administration of DA-3285, 100 units/kg to rats, the plasma concentrations and pharmacokinetic parameters of DA-3285 were not significantly different from those in a single administration. After s.c. administration to the rat, plasma concentrations of DA-3285 peaked at 6 hr and the extent of bioavailability was 26.7%. In mice, rabbits and dogs, at DA-3285 dose of 100 units/kg, the mean terminal haw-lives were 2.78, 3.05, and 4.01 hr, respectively. Compared with reported data in the literatures, DA-3285 has similar properties to rh-EPO manufactured by other companies in view of pharmacokinetics.
The Effect of Alnus japonica Cortex Extract on Gastric Lesion and Ulcer of Rats
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 84~88
Alnus japonica cortex has been used as antidiarrhea, antihemorrhage and the remedy of indigestion. This study was performed to investigate the effectiveness of the methanol extracts of the Alnus japonica cortex on the gastric lesion and ulcer. The methanol extract was fractionated with hexane, chloroform and butanol, followed by bioassay on antigastritic and antiulcer activity. The methanol extract showed low acute toxicity with minimum lethal dose of more than 5000 mg/kg, p.o. in mice. The chloroform and the butanol fraction reduced gastric lesion in HCI. ethanol induced gastritic model. On gastric secretion in pylorus ligated rat, the hexane and chloroform fraction decreased the volume and acidity. The butanol fraction had significant inhibitory effects on aspirin and Shay's ulcer. The butanol fraction showed a tendency to inhibit the decrease of mucin secretion due to ingestion of absolute ethanol.
The Effect of Cimicifuga heracleifolia on Carben Tetrachloride-induced Hepatotoxicity in Rats
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 89~96
The effect of Cimicifuga heracleifolia on CC1
-induced hepatotoxicity was investigated. Cimicifuga heracleifolia has been used to diaphoresis, antipyretics and detoxification in oriental remedy. We examined the effect of Cimicifuga heracleifolia methanol extract by blood chemical analysis and histopathologic examination. ALT and AST were decreased by 38% and 67% in pretreatment group of Cimicifuga heracleifolia compared to CC1
control group respectively. There were significant changes neither in total protein, albumin, triglyceride and cholesterol nor in BUN and creatinine. In histopathologic examination, there were severe necrosis and hemorrhage with infiltration of inflammatory cells around the central vein, zone 3 in the liver of CC1
treated rat. Ballooning degeneration of hepatocytes were frequently noted in the periphery of the hemorrhagic necrosis. In Cimicifuga heracleifolia pretreatment group, we observed mild degree of ballooning degeneration and inflammatory cell infiltration. No gross necrosis was observed. We measured malondialdehyde (MDA) formation by TBA method. It showed that the formation of MDA in Cimicifuga heracleifolia pretreatment group was decreased compared to the
control group. We got the result of the effect of Cimicifuga heracleifolia on CC1
-induced hepatotoxicity by decreasing serum ALT and AST. It seems that the decrease of lipid peroxidation is related to the recovery effect.
C-terminal Truncation Mutant of the Human
-adrenergic Receptor Expressed in E. coli as a Fusion Protein Retains Ligand Binding Affinity
Shin, Jin-Chul ; Lee, Sang-Derk ; Shin, Chan-Young ; Lee, Sang-Bong ; Ko, Kwang-Ho ;
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 97~102
To investigate whether human
-adrenergic receptor devoid of the C-terminal two transmembrane helices retain its ligand binding activity and specificity, 5'780-bp DNA fragment of the receptor gene which encodes amino acid 1-260 of human
-adrenergic receptor was subcloned into the bacterial fusion protein expression vector and expressed as a form of glutathione-S-transferase (GST) fusion protein in E. coli DH5
. The receptor fusion protein was expressed as a membrane bound form which was verified by SDS-PAGE and Western blot. The fusion protein expressed in this study specifically bound
-adrenergic receptor ligand [
H] Dihydroalprenolol. In saturation ligand binding assay, the
value was 7.6 nM which was similar to that of intact
-adrenergic receptor in normal animal tissue (
=1~2 nM) and the
value was 266 fmol/mg membrane protein. In competition binding assay, the order of binding affinity of various adrenergic receptor agonists to the fusion protein was isoproterenol》epinephrine norepinephrine, which was similar to that of intact receptor in normal animal tissue. These results suggest that N-terminal five transmembrane helices of the
-adrenergic receptor be sufficient to determine the ligand binding activity and specificity, irrespective of the presence or absence of the C-terminal two transmembrane helices.s.s.s.
The Third Intracellular Loop of truman
-adrenergic Receptor Expressed in E. coli Decreased Binding Affinity of Isoproterenol to
Shin, Jin-Chul ; Shin, Chan-Young ; Lee, Mi-Ok ; Lee, Sang-Bong ; Ko, Kwang-Ho ;
Biomolecules and Therapeutics, volume 4, issue 1, 1996, Pages 103~109
To investigate the effect of the third intracellular loop (i3 loop) peptide of human
-adrenergic receptor on receptor agonist binding, we expressed third intracellular loop region of human
-adrenergic receptor as glutathione S-transferase fusion protein in E. coli. DNA fragment of the receptor gene which encodes amino acid 221-274 of human
-adrenergic receptor was amplified by polymerase chain reaction and subcloned into the bacterial fusion protein expression vector pGEX-CS and expressed as a form of glutathione-S-transferase (GST) fusion protein in E. coli DH5
. The receptor fusion protein was identified by SDS-PAGE and Western blot using monoclonal anti-GST antibody. The fusion protein expressed in this study was purified to an apparent homogeneity by glutathione Sepharose CL-4B affinity chromatography. The purified i3 loop fusion proteins at a concentration of 10
/ι caused right shift of the isoproterenol competition curve of [
H]Dihydroalprenolol binding to hamster lung
-adrenergic receptor indicating lowered affinity of isoproterenol to
-adrenergic receptor possibly due to the uncoupling of receptor and G protein in the presence of the fusion protein. The uncoupling of receptor and G protein suggests that i3 loop region plays a critical role on
-adrenergic receptor G protein coupling.