• Archives of Pharmacal Research
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• v.25 no.6
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• pp.923-931
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• 2002

Sopungsungi-won (SP) is a known for\mula for senile constipation and diabetes mellitus, based on traditional Korean medicine. The preventive effect of SP on the development of overt diabetes in Zucker diabetic fatty (ZDF) rats was evaluated. When administered orally through a diet for 8 weeks, diabetic conditions such as hyperglycemia, polydipsia and hypertriglyceridemia were all ameliorated in SP-treated rats. In parallel with the onset and progression of hyperglycemia in the ZDF control rats; there was a marked decline in plasma insulin concentrations from 26.1 $\mu$U/ml, at age 7 weeks, to 14.8 $\mu$U/ml at age 15 weeks. In the SP-treated rats, however, the plasma insulin concentrations did not decline, and SP at a dose of 5 g/kg significantly increased the insulin levels to 31.9 $\mu$U/ml. Early normalization of plasma insulin and a retained ability to subsequently increase plasma insulin were indicative of a pancreatic $\beta$ cell protective action by the SP for\mula. In addition, expressions of an insulin-responsive gene and corresponding protein, glucose transporter 4 (GLUT4), in skeletal \muscle, were also determined in SP- and rosiglitazone-treated ZDF rats. mRNA and protein levels of GLUT4 in SP-treated rats were upregulated in a dose dependent manner. Furthermore, when ZDF rats were treated with 2 g/kg of the SP for\mula, the activity of glucose-6-phosphatase was decreased by 49%, whereas the activity of glucokinase was increased by 196%, compared to the ZDF control rats. Taken together, these data provide evidence that the SP for\mula markedly lowered the plasma glucose levels, probably through an effect not only on improvement of insulin action, but through a combined sti\mulation of glycolysis and an inhibition of gluconeogenesis in the liver, and also suggest the validity of SP's clinical use in the treatment of type 2 diabetes mellitus following further toxicological investigation.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.3
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• pp.149-155
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• 2003

The aim of the present study was to examine the effects of platycodin D and $D_3$, which are active components derived from the roots of Platycodon grandiflorum A. DC., on the contractile force of the i3olated rat aorta and blood pressure of the anesthetized rat, and also to elucidate its mechanism of action. Both phenylephrine (an adrenergic ${\alpha}1$-receptor agonist) and high potassium (a membranedepolarizing agent) caused great contractile responses in the isolated aortic strips. Platycodin D at high concentration $(24{\mu}g/ml)$ inhibited contractile responses induced by phenylephrine $(10^{-5}\;M)$ and high potassium $(5.6{\times}10^{-2}\;M)$, while low concentrations of platycodin D $(4{\sim}8{\mu}g/ml$) did not affect those responses. However, platycodin $D_3\;(8{\sim}32{\mu}g/ml)$ did not alter the contractile responses evoked by phenylephrine and high $K^+$. Interestingly, the infusion of platycodin $D_3$ (1.0 mg/kg/30 min) significantly reduced the pressor responses induced by intravenous norepinephrine. However, platycodin $D_3$ (1.0 mg/kg/30 min) did not affect them. Taken together, these results show that intravenously administered platycodin D depresses norepinephrine-induced pressor responses in the anesthetized rat, at least partly through the blockade of adrenergic ${\alpha}1$-receptors. Platycodin D also caused vascular relaxation in the isolated aortic strips of the rat via the blockade of adrenergic ${\alpha}1$-receptors, in addition to an unknown direct mechanism. However, platycodin $D_3$ did not affect both norepinephrine-induced pressor responses and the isolated rat aortic contractile responses evoked by phenylephrine and high potassium. Based on these results, there seems to be much difference in the mode of action between platycodin D and platycodin $D_3$.

• Journal of Life Science
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• v.16 no.3 s.76
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• pp.400-408
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• 2006

Nutritional components of 4 kinds of red seaweeds, Meristotheca papulosa, Chondrus ocellatus, Gracilaria verrucosa, Gigartina tenella, were investigated to elucidate their functionality. Antioxidant activity and nitrite scavenging activity were analyzed from 70% ethanol extracted from these red seaweeds. Large difference in ash contents was found to exhibit among all samples analyzed in this study; $9.8{\pm}0.2g/100g$ for Gracilaria verrucosa and Gigartina tenella for $17.8{\pm}0.6g/100g$. While its crude fiber content was almost the same as those in other sample within a range between $2.0{\pm}0.4g/100g$ and $6.0{\pm}0.7g/100g$. Phenolic compounds content of Gracilaria verrucosa was also the highest as $78.4{\pm}1.0mg/g$, while the total flavonoids contents of Chondrus ocellatus and Gracilaria verrucosa were $14.9{\pm}0.5mg/g$ and $13.9{\pm}0.8mg/g$, respectively. These amounts were two folds higher than Meristotheca papulosa and Gigartina tenella. The total content of minerals was the highest in Meristotheca papulosa(12,107.7 mg/kg). The amount of glutamic acid was relatively high despite of small variation in measured levels of composition amino acid ($49.1{\sim}125.6mg/g$) for most samples investigated. SOD-like ability was significantly increased with increasing sample concentration, but its activity was lower. Gigartina tenella with highest electron donation ability exhibited increases in activity as $53.96{\pm}0.98%$ in concentration of 250 ${\mu}g/ml$ and $70.52{\pm}1.09%$ in 1000 ${\mu}g/ml$, respectively. In case of concentration of 100 ${\mu}g/ml$, particularly, the level of hydroxy radical scavenging activity were $57.87{\pm}1.70{\sim}62.07{\pm}0.87%$ which was significantly higher activity than ascorbic acid and BHT. Nitrite scavenging activity was the highest in Gracilaria verrucosa. Its activity was also increased from $24.04{\pm}1.9{\sim}27.52{\pm}0.82%$ in $100{\sim}500{\mu}g/ml$ concentration tp $34.81{\pm}1.36%$ in concentration of 1000 ${\mu}g/ml$.

• Korean Journal of Clinical Pharmacy
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• v.7 no.2
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• pp.51-63
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• 1997

The effect of cimetidine administration on the pharmacokinetic parameters of cyclosporine were determined in healthy voluteers. This study was performed in 10 volunteers of age ranged 22-48 years and body weight 48-62 kg. This study was performed with cross-over design. Mono cyclosporine and cyclosporine metabolites was extracted from whole blood analysed by fluororescence polarization immune assay (TDX-FLX, Abbott). After coadministration of cimetidine (300 mg) with cyclosporine (300 mg) orally, maximum concentration of mono cyclosporine was significantly increased $1221{\pm}143\;ng/ml\;to\;1562{\pm}184\;ng/ml$ (P<0.05), area under the time curve of cyclosporine (12 hr) also was significantly increased $7478{\pm}829\;ng/ml{\cdot}hr\;to\;9721{\pm}879\;ng/ml{\cdot}hr$ (P<0.05) and absolute baioavailability of cyclosporine was increased $50\pm5.6\%\;to\;57.6\pm6.1\%\;(P<0.05)$ compared to control group. The blood concentrations of cyclopsorine metabolites were significantly decrased (P<0.05) after coadministration of cimetidine. In cimetidine pretreated group, blood mono cyclosporine concentrations were increased significan시y $1220.0\pm203.00\;ng/ml\;to\;1510.0\pm204.00\;ng/ml$ compared with control group (P<0.05). In the mono cyclosporine pharmacokinetic parameter after oral administration absorption rate and maximum concentration were significantly higher in cimetidine coadministered and pretreated group than control group (P<0.05). The ratio of metabolites and mono cyclosporine concentrations was decreased significantly from $70.8\%\;in\;control\;to\;34.8\%$ in coadministration of cimetidine orally. As matter of facts these reults are considered to inhibition of cyclosporine hepatic metabolism and increasing of cyclosporine absorption rate in gastrointestinal tract because of maintaining cyclosporine stability in elevated gastric pH by cimetidine. We considered, it appeares that cimetidine increase bioavailability of cyclosporine by increasing oral absorption and by decreasing hepatic clearance. But the absorption and clearance of cyclosporine was highly variable individually, and therefore we consider that cyclosporine blood level monitoring would be essential in patients with cimetidine co-administration.

• The Korean Journal of Pharmacology
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• v.1 no.1 s.1
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• pp.17-36
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• 1965

Besides it's all important analgesic action, morphine has, among others, hyperglycemic effect, though not important clinically, which is believed to be resulted from augmented glycogenolysis in the liver and muscles due to the increased liberation of epinephrine from the adrenal medulla upon the stimulation of the posterior part of hypothalamus. It is known that adrenergic blocking agents are acting inhibitory to this sort of hyperglycemia. Much, however, should as yet be studied for the drugs which affect central nervous system and release of endogenous catecholamine as far as their effects on hyperglycemia are concerned. Much is still not known about the effect of ginseng, which has been highly regarded in the Herb Medicine, as far as it's influence on the blood sugar is concerned. Author investigated the effects of chlorpromazine, reserpine and ginseng on epinephrine induced, and morphine-induced hyperglycemiae. Animals used in this experiment were healthy albino rabbits weighing approximately 2.0 kg of body weight and were all fasted for 24 hours, before the experiment undertaken. Blood sugar determination was carried out by Nelson-Somogy method. Results obtained are summarized as follows; 1. The groups of rabbits administered intravenously with epinephrine 0.02 mg/kg, and 0.05 mg/kg, showed marked and transient hyperglycemia within 15 minutes after injection. The maximal rate of elevation in blood sugar to the control level, were 28% and 57% respectively. The blood sugar returned to the control level within 3 hours. Thus, the hyperglycemic responses were paralleled with epinephrine doses. 2. The hyperglycemic responses by morphine were different according to the doses. The groups of rabbits in which 4 mg/kg of morphine was administered, did not show any hyperglycemic effect, but, in which 10 mg/kg of morphine administered, showed severe hyperglycemic effect, resulting in the maximal level within 2 hours after injection. The maximal rate of increasing in blood sugar ,level was 88%. Compared .with epinephrine-injected groups, morphjne-injected groups showed more persistent hyperglycemic effect, but returned to control blood sugar .level in 6 hours after injection. 3. The intravenous injection of chlorpromazine 2 mg/kg and 8 mg/kg evoked a slight, and persistent hyperglycemia. The maximal rate of increasing in blood sugar level were 15% and 23% respectively. These hyperglycemia gradually returned to the normal level in 5 or 6 hours after injection. Thus, the intensity of response was paralleled with the dose of chlorpromazine. 4. The intravenous injection of reserpine 0.2 mg/kg and 0.5mg/kg, showed the most persistent but steady elevation of blood sugar level in this experiments, resulting in the maximal level in 5 hours after injection. The maximal rate of increasing of blood sugar level were 18% and 39% respectively. 5. The blood sugar level from 24 hours to 30 hours after intraperitoneal administration of reserpine 1.0mg/kg, did not show statistically significant difference, compared with control groups. 6. The oral administration of ginseng extract 15 ml/kg did not. show any :change in blood sugar level. 7. The intravenous administration of epinephrine 0.05 mg/kg or morphine 4 mg/kg to the group pretreated with ginseng extract 15 ml/kg $20{\sim}30$ minutes before the experiment, evoked more marked hyperglycemic effect than the non-pretreated group. 8. The intravenous administration of epinephrine 0.02 mg/kg, morphine 4 mg/kg, or morphine 10 mg/kg to the groups pretreated with reserpine 0.2 mg/kg or 0.5 mg/kg $20{\sim}30$ minutes before experiment, produced more marked and persistent hyperglycemic effects than the groups injected with single epinephrine or morphine injection. 9. When epinephrine 0.05 mg/kg or morphine 10 mg/kg administered intravenously to the groups pretreated with the intraperitoneal administration of reserpine 1 mg/kg 24 hours before experiment morphine-induced hyperglycemia was inbibited, but epinephrine-induced hyperglycemia was augmented. 10. When epinephrine 0.05mg/kg or morphine 10 mg/kg administered intravenously to the groups pretreated with chlorpromazine, 2 mg/kg, 4 mg/kg, and 8 mg/kg $20{\sim}30$ minutes before the experiment, morphine-induced hyperglycemia was inbibited, but epinephrine-induced hyperglycemia was more persistent.

• Journal of Microbiology and Biotechnology
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• v.29 no.8
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• pp.1230-1239
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• 2019

Scutellaria baicalensis Georgi has been widely used in China for treatment of various diseases. This study investigated the effect of Scutellaria baicalensis Georgi extracts (SBE) against Coxsackievirus B3 (CVB3)-induced myocarditis in vitro and in vivo. In vitro, Hela cells and primary myocardial cells were infected with CVB3 and treated with SBE ($50-800{\mu}g/ml$) and ribavirin ($200{\mu}M$) for 48 h and then determined by CCK8 assay. Real-time PCR and western blotting assays were performed. In vivo, a myocarditis model was induced in male BALB/c mice by injecting CVB3 suspension intraperitoneally for three times, followed by treatment with SBE (400 and 200 mg/kg) and ribavirin (100 mg/kg) for 28 days. SBE ameliorated the cytotoxicity of CVB3 in Hela cells, especially at $400{\mu}g/ml$ (39.93% vs 65.67%, p < 0.05) without influencing cell growth and also significantly reduced CVB3 replication in primary myocardial cells. The levels of AKT, ERK, and p38 were increased after CVB3 infection. SBE could downregulate the expressions of AKT and p38. In vivo, the mortality rate from CVB3 reached to 66.67%, while 10.00% and 23.33% of this came after 400 and 200 mg/kg SBE treatment, respectively (p < 0.05). The CVB3 replication was obviously reduced after SBE administration from day 5. Similarly, the levels of AKT, ERK, and p38 mRNAs and proteins were increased, and SBE suppressed the expression of AKT and p38. Our study indicates that SBE is a promising potent antiviral agent against CVB3-induced myocarditis by inhibition of virus replication via depressing AKT and p38 expressions.

• Journal of Environmental Health Sciences
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• v.20 no.1
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• pp.83-95
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• 1994

This study was performed to investigate the preventive effect of KDD against lead toxicity. KDD of 133, 266, 532 and 1,064 mg/kg were administered twice to the rats of Sprague-Dawley strain and then 300 mg/kg lead acetate was given to times, respectively. 1. The $\delta$-ALAD concentration in the urine showed 10.6 ~16.4 mg/kg in the control group indicated statistical significance for the experimental group II, III, IV, V (p<0.05). Also, the Coproporphyrin concentration had 0.119 ~ 0.226 $\mu$g/ml in the control group indicated statiscial significance for the experimental group V of 10 weeks (p<0.05). 2. The $\delta$-ALAD concentration in the blood showed 13.28 ~ 16.08 ALAD unit in the control group indicated statistical significance for the experimental group I (Pb 300 mg/kg) of 6 and 8 weeks, for the experimental group III, IV of 8 and 10 weeks, and for the experimental group V of 4 weeks (p<0.05). The $\delta$-ALAD concentration of experimental group I (Pb 300 mg/kg) group was inclined to decrease during the experiment period. The $\delta$-ALAD concentration of experimental group I (Pb 300 mg/kg) showed statistical significance for the experimental group II, III, IV, V of 6, 8 and 10 weeks. But, there was no statistical significance in the concentration change of hemoglobin, RBC, WBC, hematocrit, Ca, protein among the experimental groups. In conclusion, this study revealed the preventive effect of KDD against lead toxicity and its mechnism inferred to facilitate lead excretion in urinary following hinderance of lead absorption in the gastric-intestine and organs.

• Journal of Veterinary Clinics
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• v.20 no.1
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• pp.115-120
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• 2003

This study was conducted to investigate the hematological changes of the dogs when administrated excessive amount of the Artemisia capillaris extract for a short period. In this experiment, clinically healthy dogs(n = 20, average weight = 7.68 kg) were divided into 2 groups : Artemisia capillaris rude juice extract group(CR) and concentrated extract group(CE). They were inserted stomach tube and administrated the extracts (5 ml/kg) for 8 days. The followings are the results of this experiment.: 1). The number of red blood cell(RBC) was significantly (p<0.05) decreased in CE group on day 4, 5, 6, whereas CJE group showed significantly (p<0.05) difference on day 5. 2). The packed cell volume(PCV) and hemoglobin concentration were significantly (p<0.05) decreased in both groups during experimental periods. 3). The met hemoglobin was significantly (p < 0.05) increased from 12 hrs after administration to day 8 in CJE group wheres, it was significantly (p<0.05) increased on day 6,7 in CE group.

• Journal of Aquaculture
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• v.7 no.3
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• pp.151-158
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• 1994

To evaluate the reproductive ability of gynogenetic diploid male. Paralichthys olivaceus. histological analysis of testis. cytological analysis of spermatozoa and fertilization test with normal aggs were studied and the results are as follow; The gonads of gynogenetic diploid male were histologically normal. and many spermatozoa were observed in their testis. Number of spermatozoa from the control and gynogenetic diploid male were $2.58\times10^9$ and $2.42\times10^9$ cells per 1 ml of milt. respectively (P> 0.05). Amount of milt per kg body weight from the gynogenetic diploid male was significantly higher (P< 0.01) than that from the control male (8.3ml). Size and morphology from the two experimental groups were not different (P>0.05). More than $80\%$ of fertilization rates and hatching rates were observed when the eggs from the control were fertilized with the gynogenetic diploid male sperms.

• YAKHAK HOEJI
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• v.41 no.2
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• pp.255-259
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• 1997

Effects of the aqueous extract of Aquilariae Lignum (Thymelaeaceae) on the allergic reactions were investigated. Oral administration of this extract (50, 250, and 500mg/kg) exhi bited a dose-dependent inhibition on passive cutaneous anaphylactic reactions in rats. Administrations of this extract (500mg/kg, i.p.) at 60 min before and 5, 10 min after the compound 48/80 treatment (8mg/kg, i.p.) decreased the mortality rates to 0, 0, and 14.2%, respectively. The aqueous extract of Aquilariae Lignum (0.05 ~ 1.6mg/ml) showed a dose-related inhibition on histamine release from rat peritoneal mast cells. The morphological examination also clearly showed that the aqueous extract of Aquilariae Lignum prevented the degranulation of mast cells in rats.