• The Korean Journal of Physiology and Pharmacology
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• v.1 no.3
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• pp.325-335
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• 1997

Evidence for the existance of at least two subclasses of renal adenosine receptors has been presented. N-6-cyclohexyladenosine (CHA) is a relatively selective $A_1$ adenosine agonists, whereas 5'-N-ethylcarboxamidoadenosine (NECA) acts as a preferential agonist of $A_2$ adenoisne receptor. N6-(L-2-phenylisoproryl)-adenosine (PIA) almost unselectively activates both $A_1\;and\;A_2$ adenosine receptors at micromolar concentrations. During the characterization of adenosine receptor in the kidney, we have discovered a novel phenomenon, that is, an intramuscular administration of CHA for 3 days caused a diuresis and a suppression of urinary concentrating ability. To further characterize this novel phenomenon, an intramuscular administration of adenosine and other adenosine angonists, PIA and NECA, and prior treatment of adenosine antagonists, caffeine, theophylline and 1,3-diethyl-8-phenyl-xanthine (DPX) were performed. Systemic administration of CHA, PIA, and NECA for 3 days caused a suppression in heart rate, blood pressure and general motor activity without change in rectal temperature. Systemic administration of CHA, 0.5, 1 and 2 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and decrease in urinary osmolarity and free water reabsorption. This phenomenon was reversible and repeatable. Administration of adenosine (40 mg/kg/day) produced no apparent effect on the renal function, whereas PIA (2 mg/kg/day) produced an similar effect to CHA on the renal function. Systemic adminstration of NECA, 0.025, 0.05 and 0.25 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and dose-dependent increases in excreted amount of creatinine, urinary osmolarity and free water reabsorption. These renal effects of adenosine agonist were maximum at second day during the drug administration. In terms of increase in urine volume and the suppression of urinary concentrating ability, NECA was potent than CHA. Prior treatment of caffeine (50 mg/kg/day) or theophylline (50 mg/kg/day) abolished the diuretic effect of CHA, whereas DPX (50 mg/kg/day) did not affect the CHA effect. CHA, 0.5 mg/kg/day, produced no change in plasma renin activity and plasma levels of aldosterone, epinephrine, and norepinephrine. These results suggest that this novel phenomenon produced by an activation of renal adenosine receptors plays an important role in urinary concentrating mechanism.

• The Korean Journal of Pharmacology
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• v.22 no.2
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• pp.105-114
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• 1986

This study was undertaken to search for a new antiarrhythmic agent in natural plants. Extracts of Buxus microphylla var. koreana Nakai have been used as folk remedies of several diseases, including malaria and venereal disease, but any study on the pharmacological actions of this plant has not yet been carried out and its active ingredients have not been identified. In our laboratory, we isolated buxuletin (nonalkaloid) and cyclobuxine D (steroidal alkaloid) from Buxus microphylla var. koreana Nakai and reported their pharmacological actions: diuretic effects of buxuletin in rabbits and hypotensive effect of cyclobuxine D in rats. In the present study, we investigated the effect of cyclobuxine D on isolated frog heart and heart rate in urethane anesthetized rats. In order to clarify the mechanism of bradycardic effect of cyclobuxine D, we examined the changes of the ECG parameters (PR, QRS and R ${\alpha}$ T interval) produced by intravenous injection of cyclobuxine D in anesthetized rats. Cyclobuxine D depressed the contractile force in isolated frog heart and exerted a dose-dependent bradycardic effect in anesthetized rats. Intracerebroventricular injection of cyclobuxine D caused a fall in blood pressure and an increase in heart rate, but those effects were not significant. Cyclobuxine D prolonged the PR interval and RaT interval (${\alpha}$ Tindicates the apex of T), but was without significant effects on the duration of the QRS complex and PRc in urethane anesthetized rats.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.37 no.4
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• pp.351-356
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• 2011

Citrus unshiu (C. unshiu) Markovich were dried peel of mandarin orange, of which fresh fruit was one of the famous foods in Korea and Eastern Asia. In the oriental medicine, C. unshiu peel was known to have a diuretic effect and to strengthen spleen function. Recently, natural flavonoids of C. unshiu peel have been investigated. In this study, C. unshiu peel extract containing flavonoid-glycosides was cultured with Schizophyllum commune (S. commune) mycelia producing ${\beta}$-glu- cosidase and its biological activities were investigated. ${\beta}$-glucosidase of S. commune mycelia converted the flavonoid-glycosides (rutin and hesperidin) into aglycones (naringenin and hesperetin). Fermented C. unshiu peel extract compounds were analyzed by HPLC system. The photoprotective potential of fermented C. unshiu peel extract was tested in human dermal fibroblasts (HDFs) exposed to UVA. Fermented C. unshiu peel extract extract also showed notable in vitro anti-inflammatory effect on cellular systems generating cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) metabolites. Also, UVB-induced production of interleukin-$1{\alpha}$ in human HaCaT cells was reduced in a dose-dependent manner by treatment with fermented C. unshiu peel extract. These results suggest that fermented C. unshiu peel extract may mitigate the effects of photoaging in skin by reducing UV-induced adverse skin reaction.

• The Korean Journal of Pharmacology
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• v.21 no.1
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• pp.49-61
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• 1985

In view of the facts that dopamine (DA) when given directly into a lateral ventricle (i.c.v.) of the rabbit brain induces antidiuresis and that haloperidol, a non-specific antagonist of DA receptors, produces anti-diuresis in smaller doses and diuresis and natriuresis in larger doses, the present study was undertaken to delineate the roles of various DA receptors involved in the center-mediated regulation of renal function. Bromocriptine (BRC), a relatively specific agonist of D-2 receptors and at the same time a D-,1 antagonist, elicited natriuresis and diuresis when given i.c.v. in doses ranging from 20 to 600 {\mu}g/kg$, roughly in dose-related fashion, while the renal perfusion and glomerular filtration progressively decreased with doses, indicating that the diuretic, natriuretic action resides in the tubules, not related to the hemodynamic effects. These diuresis and natriuresis were most marked with 200 ${\mu}g/kg$, with the fractional sodium excretion reaching about 10%. With 600 ${\mu}g/kg$, however, the diuretic, natriuretic action was preceded by a transient oliguria resulting from severe reduction of renal perfusion, concomitant with marked but transient hypertension. When given intravenously, however, BRC produced antidiuresis and antinatriuresis along with decreases in renal hemodynamics associated with systemic hypotension, thus indicating that the renal effects produced by i.c.v. BRC is not caused by a direct renal effects of the agent which might have reached the systemic circulation. In experiments in which DA was given i.c.v. prior to BRC, 150 ${\mu}g/kg$ DA did not affect the effects of BRC (200 ${\mu}g/kg$), while 500 ${\mu}g/kg$ DA abolished the BRC effect. In rabbits treated with reserpine, 1 mg/kg i.v.,24 h prior to the experiment, i.c.v. BRC could unfold its renal effects not only undiminished but rather exaggerated and more promptly. In preparations in which one kidney is deprived of nervous connection, the denervated kidney responded with marked diuresis and natriuresis, whereas the innervated, control kidney exhibited antidiuresis. These observations suggest that i.c.v. BRC influences the renal function through release of some humoral natriuretic factor as well as by increasing sympathetic tone, and that various DA receptors might be involved with differential roles in the center-mediated regulation of the renal function.

• Journal of Veterinary Clinics
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• v.24 no.4
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• pp.597-602
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• 2007

Furosemide is a potent diuretic used in the horse for the prophylaxis of exercise-induced pulmonary hemorrhage(EIPH), and in a variety of clinical condition. The purpose of this study was to set up the effect of furosemide in Thoroughbred horses, and to examine the time of maximal effect of furosemide to prevent the EIPH. The animals of the experiment were 4 Thoroughbred racing horses(female, average 6 yrs, BW $507{\pm}80.2kg$) in Jeju stud farm and the experiment was cross-over design between furosemide(1 mg/kg IV) and normal saline(0.1 ml/kg, IV) administration. We investigated the changes of clinical signs(body weight, skin turgor, capillary refilling time, jugular distensibility), CBC(PCV RBC), serum chemistry(TP, AST, GGT, glucose, LDH, BUN and creatinine) and electrolytes ($Na^+,\;K^+,\;Cl^-,\;Ca^{2+}$) on 0, 30 mins, 1, 2, 4, 8 and 24 hrs in furosemide and saline administration roup, respectively. The weight decreased significantly(P<0.05) in 4 hrs after furosemide treatment, but skin turgor, CRT, jugular distensibility remained unchanged throughout the experimental period. RBC and PCV decreased after furosemide administration but soon recovered. TP increased to the highest level in 30 mins after furosemide administration and recovered in 8 hrs. Furosemide administration resulted in increases in glucose, AST, GGT, LDH, BUN, creatinine(P<0.05) and decreases in $Ca^{2+},\;Na^+,\;K^+,\;Cl^-$ (P<0.05). All of values were within normal range throughout the experimental period. There was the alteration of blood and serum chemistry after furosemide administration, all of values were within normal range. And the best time of furosemide administration will be 30 minutes before the racing in order to preventing EIPH.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.1-10
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• 1982

In an attempt to delineate the role of beta-adrenoceptors found to be existing in the brain tissue in the central regulation of renal function, isoproterenol, a ${\beta}-adrenergic$ agonist, was administered directly into a lateral ventricle of the rabbit brain and the changes of renal function were observed. Also, the effects of propranolol, a specific ${\beta}-adrenergic$ blocking agent, and its influence upon the isoproterenol action were studied. Isoproterenol, in doses ranging from 5 to $50\;{\mu}g/kg\;i.c.v.$, elicited antidiuresis which seemed to be related to the decreased renal hemodynamics brought about by the systemic hypotension. With moderate doaes of $15\;{\mu}g/kg$ the antidiuresis was less prominent and there was a tendency toward natriuresis, but with higher doses the natriuretic effect became less evident, overrun by the systemic hypotension. Propranolol, $500\;{\mu}g/kg\;i.c.v.$, produced little effect on the renal function, but it eliminated the antidiuretic action of $50\;{\mu}g/kg$ isoproterenol i.c.v. and reversed it to a diuretic and natriuretic one, along with increases in renal plasma flow and glomerular filtration rate. The systemic hypotension also was markedly attenuated by propranolol pretreatment. Thus, it was evident that the renal action of i.c.v. isoproterenol was not blocked by propranolol and became explicit only when the hypotensive action of isoproterenol which seems to he propranolol-sensitive is removed. Various possibilities to account for this disparity in sensitivity were discussed. It is suggested from these observations that the central ${\beta}-adrenoceptors$ might also be involved in the regulation of renal function along with ${\alpha}-adrenoceptors$, though less significant than the latter.

• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.245-252
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• 1993

Amiloride is a potassium sparing duretic which specifically inhibits $Na{^+}$ channels. In the present study, we investigated the possible interaction of amiloride with $A_1$ adenosine receptors-adenylyl cyclase system in crude adipocytic plasma membrane fractions prepared from Sprague-Dawley rats. When the function of $G_i$ protein (inhibitory guanine nucleotide binding protein) was assessed by determining the effects of GTP on isoproterenol-stimulated adenylyl cyclase activity, the inhibitory effect of high concentrations of GTP was not observed in the presence of amiloride. In contrast, the adenosine receptor-mediated inhibition of the enzyme activity, as determined empolying 2-chloroadenosine, was either unchanged or even more enhanced by amiloride depending on the concentrations of 2-chloroadenosine. Thus, it appears that GTP- and receptor-mediated inhibitory function of $G_{i}$ proteins can be separated from one another. Receptor-mediated function of $G_{s}$ protein did not appear to be significantly affected by amiloride, since the inhibition of isoproterenol-stimulated adenylyl cyclase activity by propranolol under the same conditions was not significantly altered by amiloride. The enhancement of 2-chloroadenosine-mediated inhibition of adenylyl cyclase by amiloride was maintained in the presence of 150 mM NaCl. In summary, these results suggest that amiloride interacts both with $A_{l}$ adenosine receptors and with $G_i$ proteins in adipocytic membranes. Its binding to the $A_1$ adenosine receptors appears to facilitate the coupling of the receptors with $G_i$ proteins thereby enhancing the inhibition of isoproterenol-stimulated adenylyl cyclase activity by $A_1$ adenosine agonist, and the direct interaction with $G_i$ proteins appears to remove the GTP-dependent inhibitory effect on adenylyl cyclase activity.

• Journal of Life Science
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• v.30 no.6
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• pp.501-512
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• 2020

Sasa quelpaertensis Nakai leaf has been used as a folk medicine for the treatment of gastric ulcer, dipsosis, and hematemesis based on its anti-inflammatory, antipyretic, and diuretic characteristics. We have previously reported the procedure for deriving a phytochemical-rich extract (PRE) from S. quelpaertensis and how PRE and its ethyl acetate fraction (EPRE) exhibits an anticancer effect by inducing apoptosis in various gastric cancer cells. To explore the molecular targets involved in this apoptosis, we investigated the mRNA and microRNA profiles of EPRE-treated SNU-16 human gastric cancer cells. In total, 2,875 differentially expressed genes were identified by RNA sequencing, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the EPRE-modulated genes are associated with apoptosis, mitogen-activated protein kinase, inflammatory response, tumor necrosis factor signaling, and cancer pathways. Subsequently, protein-protein interaction network analysis confirmed interactions among genes associated with cell death and apoptosis, and 27 differentially expressed microRNAs were identified by further sequencing. Here, GO and KEGG pathway analysis revealed that EPRE modified the expression of microRNAs associated with the cell cycle and cell death, as well as signaling of tropomyosin-receptor-kinase receptor, transforming growth factor-b, nuclear factor kB, and cancer pathways. Taken together, these results provide insight into the mechanisms underlying the anticancer effect of EPRE.

• Korean Journal of Medicinal Crop Science
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• v.21 no.6
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• pp.474-485
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• 2013

Pharmacological studies and clinical practices have indicated that Radix Astragali, a dried root of Astragalus membranaceus possesses a lot of biological activities, including antioxidant, hepatoprotective, anti-diabetic, tonic, diuretic, antimicrobial, antiviral, and immunological activities. These biological activities approved by the modern pharmacological studies are mainly due to the constituents of Astragalus membranaceus including polysaccharides, saponins, flavonoids, amino acids, and trace elements. In resent, the main constituents in the root part showing a lot of biological activities has been isolated also from the aboveground parts such as leaves and sprouts in our laboratory. However, the safety evaluation for the aboveground parts of Astragalus membranaceus should be checked before expanding their application as one of food. In the study, a 90-day rat oral gavage study has been conducted with the extracts from Astragalus membranaceus-above-ground parts at doses of 1000, 3000, and 5000mg/kg/day. The following endpoints were evaluated: clinical observations, body weight, gross and microscopic pathology, clinical chemistry, and hematology. Based on the analysis of these endpoints, it was estimated that NOEL (no observed effect level) for male rats and NOAEL (no observed adverse effect level) for female rats are 5000mg/kg/day of the water-extracts from Astragalus membranaceus-aboveground parts.

• The Korea Journal of Herbology
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• v.33 no.2
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• pp.59-67
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• 2018

Objective : Plantago asiatica L. has been used for many years in Korea, China, and Japan for the treatment of many diseases such as anti-inflammatory, anti-asthma and diuretic. But the anti-obesity effect of Plantaginis asiaticae Folium has not been studied yet. Thus, this study aimed to demonstrate the anti-obesity efficacy of Plantaginis asiaticae Folium water extract (PAF) in high fat diet-induced obesity animal model. Method : Male, five-weeks old C57BL/6 mice were divided into 5 groups; ND (normal diet + 0.9% saline), HFD (high-fat diet + 0.9% saline), PC (high-fat diet + Garcinia cambogia 500 mg/kg), PAF 100, 300 (high-fat diet + PAF 100, 300 mg/kg. Treatments were performed daily for 6 weeks per os. We evaluated the changes of body weight, white adipose tissues weight, hepatic and fecal lipids level, pancreatic lipase activity and lipid profiles in plasma. Result : Body weights, adipose tissue weights and FER were significantly lower in mice fed the high-fat diet with PAF treatment than in mice fed the high-fat diet alone. In plasma, TG, TC, LDL-C, ATS and ALT levels significantly decreased in PAF groups compared with HFD group. Also, hepatic triglyceride (TG) levels decreased and fecal TG increased in PAF groups compared to HFD group. In addition, the activity of pancreatic lipase was decreased in the PAF groups compared to that of HFD group. Conclusion: These results suggest PAF extract is effective in preventing and improvement obesity, so it might be a potential and safe material for anti-obesity agent of weight control or functional supplements.