• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.147-162
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• 1992

The objectives of the present experiments were to characterize the effects of the peptides belonging to the pancreatic polypeptide family on the contractility of cerebral arteries and to observe the interactions of these peptides with the cyclic nucleotide activators and the potassium channel openers. Dogs of either sex, $20{\sim}30\;Kg$ in weight, were sacrificed. Basilar and middle cerebral arteries from brain were isolated and prepared for myography in the PSS equilibrated with 95% $O_2$ and 5% $CO_2$ at $37^{\circ}C$. The endothelial cells of the spiral strips were removed by CHAPS solution (0.3% w/v, 15 seconds). 1. PP, PYY and NPY contracted the arterial strips concentration-dependently with a rank order of potency of PYY>NPY>PP. These peptides were 20 to 200 times more potent than norepinephrine, and only PYY showed a greater potency than 5-HT. 2. Cyclic nucleotide activators, forskolin (for cAMP) and sodium nitroprusside (for cGMP) reduced the basal tone and inhibited the PP-, PYY- and NPY- induced contractions by concentration-dependent manners. Forskolin was more potent in reducing basal tone than sodium nitroprusside. 3. Potassium channel openers, RP 49356, P 1060 and BRL 38227 reduced the basal tone concentration-dependently and tended to inhibit the PP-, PYY- and NPY- induced contractions. Notably, BRL 38227 with low concentration $(0.1\;{\mu}M)$ enhanced the contractions induced by those peptides while P 1060 inhibited the contractions concentration-dependently. 4. The combinations of the cyclic nucleotide activators and the potassium channel openers were slightly additive in reducing the basal tone. P 1060 and BRL 38227 enhanced the relaxant effect of sodium nitroprusside significantly. On the PYY-induced contration $(0.1\;{\mu}M)$, $K^+$ channel openers tended to inhibit the inhibitory actions of forskolin and sodium nitroprusside. P 1060 and BRL 38227 antagonized the inhibitory action of sodium nitroprusside significantly. The results of the present study may be summarized that in canine cerebral arteries, not only NPY but also PYY may play a role in a cerebrovascular spasm, and intracellular concentration of either cAMP or cGMP may be involved in the mechanism of vasoconstrictive actions of these peptides, which may be affected either positively or negatively by a $K^+$ channel opener.

• Journal of the korean academy of Pediatric Dentistry
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• v.27 no.1
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• pp.15-23
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• 2000

Streptococcus salivarius is a normal inhabitant in the human oral cavity. Streptococcus salivarius 119 in this study was isolated from the oral cavity of child and identified, and its action mechanism on the formation of denal plaque by Streptococcus matans was studied. 1. The optical density of absorbance at 550 nm was 0.327 in the culture of Streptococcus mutans in disposable cuvette, whereas being 0.119 in the combined culture of Streptococcus mutans and Streptococcus salivarius 119. 2. The mean weight of produced artificial plaque on the wires in the beaker was 84.7mg in culture of Streptococcus mutans only, whereas being reduced to 12.3mg in the combined culture of Streptococcus mutans and Streptococcus salivarius 119. 3. When Streptococcus mutans was cultured in the media containing culture supernatant of Streptococcus salivarius 119 in BHI broth, the mean weight of produced artificial plaque was 100.5mg on the wires, whereas being reduced to 20.4mg in the media containing culture supernatant of Streptococcus salivarius 119 in BHIS broth. 4. The viable cells of Streptococcus oralis and Streptococcus salivarius 119 were $4.8\times10^7\;and\;7.5\times10^8$ per ml respectively after each culture, wheras being $4.2\times10^7\;and\;5.8\times10^7$ per ml in the combined culture of Streptococcus oralis and Streptococcus salivarius 119. 5. The polymer produced by Streptococcus salivarius 119 was glucan on the thin layer chromatography. 6. The glucan produced by Streptococcus salivarius 119 was water-soluble glucan containing $1\rightarrow6$ linkages as the main linkage on the thin layer chromatography. These results suggested that isolated Streptococcus salivarius 119 inhibited the formation of artificial plaque by the production of water-soluble glucan.

• Journal of Oral Medicine and Pain
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• v.32 no.2
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• pp.137-150
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• 2007

Trees emit phytoncide into atmosphere to protect them from predation. Phytoncide from different trees has its own unique fragrance that is referred to as forest bath. Phytoncide, which is essential oil of trees, has microbicidal, insecticidal, acaricidal, and deodorizing effect. The present study was performed to examine the effect of phytoncide on Porphyromonas gingivalis, which is one of the most important causative agents of periodontitis and halitosis. P. gingivalis 2561 was incubated with or without phytoncide extracted from Hinoki (Chamaecyparis obtusa Sieb. et Zucc.; Japanese cypress) and then changes were observed in its cell viability, antibiotic sensitivity, morphology, and biochemical/molecular biological pattern. The results were as follows: 1. The phytoncide appeared to have a strong antibacterial effect on P. gingivalis. MIC of phytoncide for the bacterium was determined to be 0.008%. The antibacterial effect was attributed to bactericidal activity against P. gingivalis. It almost completely suppressed the bacterial cell viability (>99.9%) at the concentration of 0.01%, which is the MBC for the bacterium. 2. The phytoncide failed to enhance the bacterial susceptibility to ampicillin, cefotaxime, penicillin, and tetracycline but did increase the susceptibility to amoxicillin. 3. Numbers of electron dense granules, ghost cell, and vesicles increased with increasing concentration of the phytoncide, 4. RT-PCR analysis revealed that expression of superoxide dismutase was increased in the bacterium incubated with the phytoncide. 5. No distinct difference in protein profile between the bacterium incubated with or without the phytoncide was observed as determined by SDS-PAGE and immunoblot. Overall results suggest that the phytoncide is a strong antibacterial agent that has a bactericidal action against P. gingivalis. The phytoncide does not seem to affect much the profile of the major outer membrane proteins but interferes with antioxidant activity of the bacterium. Along with this, yet unknown mechanism may cause changes in cell morphology and eventually cell death.

• Journal of Life Science
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• v.28 no.8
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• pp.945-954
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• 2018

Omega-3 polyunsaturated fatty acids (${\omega}3$-fatty acid) have been found to possess anticancer properties in a variety of cancer cell lines and animal models, but their effects in human tongue squamous cell carcinomas (SCCs) remain unclear. This study was designed to examine the effect of ${\omega}3$-fatty acid desaturase (fat-1) gene expression on invasion and tumorigenicity in human tongue SCC cells and the molecular mechanism of its action. Docosahexaenoic acid (DHA) treatment inhibited in vitro invasion in a dose-dependent manner. In zymography, matrix metalloproteinase-9 (MMP-9) and Matrix metallopeptidase-2 (MMP-2) activities were reduced, and MMP-9 and MMP-2 promoter activities were inhibited by the DHA treatment. In addition, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) promoter reporter activities were inhibited in SCC-4 and SCC-9 cells after the DHA treatment. To investigate the effect of a high level of endogenous ${\omega}3$ fatty acids, a stable SCC-9 cell line expressing the ${\omega}3$-desaturase gene (fSCC-9sc) was generated. The growth rate and colony-forming capacity of fSCC-9sc were remarkably decreased as compared with those of fSCC-9cc. Likewise, the tumor size and volume of fSCC-9sc implanted into nude mice were significantly inhibited, with increases in the cell death index. Furthermore, a transwell chamber invasion assay showed a reduction in cell invasion of the fSCC-9sc lines when compared with that of the fSCC-9cc line. These findings suggested that fat-1 gene expression inhibited tumorigenicity, as well as invasion in human tongue SCC cells. Thus, utilization of ${\omega}3$ fatty acids may represent a promising therapeutic approach for chemoprevention and the treatment of human tongue SCCs.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.484-491
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• 2016

The present study investigated the effect of Sinetrol-XPur (polyphenolic Citrus spp. and Paullinia cupana Kunth dry extract) and defined the action mode for cyclic adenosine monophosphate (cAMP)-dependent uncoupling protein (UCP)-2 activation. Leptin-deficient obese mice were treated with two different doses, 100 mg/kg body weight (BW) and 300 mg/kg BW of each AIN93G supplement, for 7 weeks. Treatment of obese mice with both low and high doses of Sinetrol-XPur significantly reduced body weight gain compared to control obese mice. White adipose tissue weight of mice was reduced by 30.96% in high dose-supplemented groups. Serum total cholesterol and triglyceride were reduced by a high dose of Sinetrol-XPur by 20.02% and 30.96%, respectively. Serum level of high density lipoprotein (HDL) was significantly increased by treatment with both doses, as the ratio of HDL to low density lipoprotein increased by 138.78% and 171.49%, respectively. Regarding expression of biochemical factors related to lipid metabolism, fatty acid synthase significantly decreased and UCP-2 increased upon treatment with a high dose of Sinetrol-XPur, but there was no significant difference in lipoprotein lipase and hormone-sensitive lipase. To define cellular mechanism, intracellular cAMP levels in 3T3-L1 adipocytes significantly increased in a dose-dependent manner over the range of $50{\sim}250{\mu}m/mL$. The phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine clearly blocked cAMP, suggesting that Sinetrol-XPur promotes lipolysis of adipocytes through inhibition of cAMP-dependent PDE, resulting in induction of cAMP response element binding protein and UCP-2. These results suggest that Sinetrol-XPur supplementation is a viable option for reducing body weight and fat by improving serum lipid profiles and genetic expression of lipid metabolic factors, especially activation of cAMP-dependent UCP-2.

• The Journal of the Korean bone and joint tumor society
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• v.11 no.1
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• pp.46-53
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• 2005

Purpose: Bisphosphonates (BPs) are the analogues of endogenous pyrophosphates: they have been used in the treatment of skeletal diseases such as Paget's disease, osteoporosis, and tumorinducing ostelysis, and are used in treatment of osteolytic metastasis of breast cancer recently. They are also used as one of the therapeutic agents for metastasis of prostatic cancer of which metastasis makes the mixed nature of osteolysis and ostegenesis. Although the action mechanism of BPs are well known for diseases with excessive osteoclastic bone resorption, the direct effect of BPs has not been known yet. This study was intended to see the tumor suppression capability of Zoledronic acid(ZOL) using nude mouse with osteosarcoma. Materials and Methods: MG-63 and HOS osteosarcoma cell lines were used and the transforemed MG-63-GFP and HOS-GFP cells, which were made for detection under fluorescent light, were subcutaneously injected to make osteosarcoma. The five 6-week male mice were used for the experiment at each group. After the injection, mice were cultivated until tumor pieces grow up to $3{\times}3{\times}3$ $mm^3$ and ZOL of 120 ug/kg was subcutaneously injected twice a week. Sizes of tumor were measured twice a week and photographed under fluorescent light. Results: In in vivo test with HOS osteosarcoma cell lines, mean size of tumors was 2,520 $mm^3$ in control group and was 131 $mm^3$ in ZOL group, which showed 94% of reduction comparing with the control ; with MG-63 osteosarcoma cell lines, mean size of tumors was 2,866 $mm^3$ in control group and was 209 $mm^3$ in test group with 72% of reduction (p<0.05). Conclusion: In in vivo tests with nude mice, we suggest that ZOL has direct effect on osteosarcoma cells and it would be used as one of the therapeutic agents for osteosarcoma, especially to ZOL-sensitive osteosarcoma cells.

• The Korean Journal of Pharmacology
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• v.20 no.1 s.34
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• pp.55-65
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• 1984

Comparative effects of $PGF_{2{\alpha}}$ and ouabain on the isolated rat(Sprague-Dowley) atria were studied. The isolated rat atria were prepared for isometric myography in the isolated organ bath containing Feigen's solution perfused with 95% $O_2$ and 5% $CO_2$, and the pH of the medium was maintained at 7.4. The cumulative concentration-response relationship revealed the positive inotropic effects of both drugs with the higher potency of $PGF_{2{\alpha}}$ and the higher efficacy of ouabain. $PGF_{2{\alpha}}$ showed a positive chronotropic effect, but ouabain showed a tendency of increasing the contraction rate. In low-Ca(1.4 mM) medium, the positive inotropic and chronotropic effect of $PGF_{2{\alpha}}$(by $3{\times}10^{-8}M$) were preponderant $(p<0.05{\sim}p<0.005)$ over those of ouabain(by $3{\times}10^{-3}M$). $Ca^{++}$-addition(cumulative, to 2.8, 4.2, 5.6, and 7.0 mM) into the medium evoked the more sensitive response in the $PGF_{2{\alpha}}$ group than in the ouabain group. In low-K(2.8 mM) medium, the $PGF_{2{\alpha}}a(3{\times}10^{-8}M)$ group and the ouabain$(3{\times}10^{-3}M)$ group showed similar tensions(DT and RT) and contraction rates. And both group showed significantly(p<0.05p<0.01) higher tensions and contraction rates than those of the control group. By the cumulative addition of the $K^+$(to 4.2, 5.6, 7.0 and 8.4 mM), only the DT of the $PGF_{2{\alpha}}$ group was sustained at signifcantly$(p<0.05{\sim}p<0.01)$ higher level than the DT of the control group. The $K^+$-addition inhibited the positive inotropic effect of ouabain significantly (p<0.05). The cumulative addition of lidocaine in high concentrations $(1{\times}10^{-5}\;to\;1{\times}10^{-3}M)$ evoked no significant influence on the intropic activities of $PGF_{2{\alpha}}$ and ouabain, but significant ${\beta}$-blockade with propranolol could not inhibit the positive intropic and chronotropic effect of $PGF_{2{\alpha}}$. In conclusion, it is presumed that $PGF_{2{\alpha}}$ may have some more active mechanism of accelerating the influx of $Ca^{++}$ across the cell membrane of the isolated rat atria as compared with ouabain, and the action site may be located at the cell membrane. As a supposition which needs further investigations, it is presumed that $PGF_{2{\alpha}}$ may have its specific membrane receptors on the atrial muscle or sinus node cells.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.87-100
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• 1994

It has been known for some time that dopamine-containing cells are existed in sympathetic ganglia, i.e., small, intensely fluorescent cells. However, its role and mechanism of action as a peripheral neurotransmitter are poorly understood so far. In the present study, an attempt was made to examine the effect of apomorphine, which is known to be a selective agonist of dopaminergic $D_2$. receptor on secretion of catecholamines (CA) from the isolated perfused rat adrenal gland. The perfusion of a low concentration of 10uM apomorphine into an adrenal vein for 20 min produced significant reduction in CA secretion induced by 5.32 mM ACh, 56 mM KCl, 100 uM DMPP and 100 uM McN-A-343. Increasing apomorphine concentration to 30 uM led to more markedly decreased CA secretion as compared to the case of 10 uM apomorphine and also did inhibit clearly CA release by $10^{-5}M$ Bay-K-8644. Furthermore, in adrenal glands preloaded with a higher dose of 100 uM apomorphine, CA releases evoked by ACh, excess $K^+$, DMPP and McN-A-343 were almost abolished by the drug. The perfusion of $3.3{\pm}10^{-5}M$ metoclopramide, which is well-known as a selective dopaminergic $D_2$ antagonist, produced significantly inhibitory effect of CA release by ACh, DMPP and McN-A-343 but did not affect that by excess $K^+$. However, preloading of 30uM apomorphine in the presence of metoclopramide did not modify the CA secretory effect of excess $K+$ and DMPP. These experimental results demonstrate that apomorphine causes dose-dependent inhibition of CA secretion by cholinergic receptor stimulation and also by membrane depolarization from the isolated perfused rat adrenal gland, suggesting that these effects appear to be exerted by inhibiting influx of extracellular calcium into the rat adrenal medullary chromaffin cells through activation of inhibitory dopaminergic receptors.

• Journal of Life Science
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• v.31 no.2
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• pp.209-218
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• 2021

This study aimed to evaluate the anti-obesity effects of Cudrania tricuspidata leaf extract in the order of leaf development on the shoot (L0, L1, L2, L3, L4, and L5). The leaves at the apex of a Cudrania tricuspidata shoot were classified as L0; the next leaves of the apex were classified as L1, L2, L3, and L4 from highest to lowest; and the lowest leaf was classified as L5. A series of 70% ethyl alcohol leaf extracts were screened for the inhibitory effects of adipogenesis in 3T3-L1 preadipocytes. We found that the apical leaf extract of Cudrania tricuspidata (CTL0) was the most effective. Next, a study was conducted on the inhibitory action mechanism of CTL0. Treatment with CTL0 significantly suppressed the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner, as confirmed by the decrease in lipid droplet content observed with Oil Red O staining. Treatment with 12.5 ㎍/ml, 25 ㎍/ml, and 50 ㎍/ml of CTL0 significantly reduced the lipid droplet content. Glucose and cellular triglyceride concentrations were reduced in the 3T3-L1 cells on the CTL0-treated medium compared to the differentiation medium (DM control, DMEM + insulin + dexamethasone + rosiglitazone). Compared with DM, CTL0 significantly inhibited the expression of key pro-adipogenic transcription factors, including peroxisome proliferator-activated receptor γ (PPARγ), LPL, A-FABP, and Glut4. These findings show that CTL0 extract has potent anti-obesity effects.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.11
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• pp.1648-1657
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• 2014

In this study, the hepatic lipid-lowering effects and related mechanism of action of sujeonggwa were examined in hypercholesterolemia-induced apoprotein E knockout (apo E ko) mice. Sujeonggwa drink was prepared with cinnamon, ginger, and sugar by modifying the traditional recipe of sujeonggwa. Sugar was partially substituted with either stevia or short chain fructooligosaccharide (scFOS) in order to reduce the calorie content of sujeonggwa, which was measured by descriptive analysis. Apo E ko mice (n=42) were induced to have hypercholesterolemia (plasma total cholesterol concentration >1,000 mg/dL) by administration of a high cholesterol diet for 4 weeks, followed by division into six groups. Experimental groups were orally administered water as a vehicle (normal group), sugar solution (control group), commercially available 'V' sujeonggwa drink (positive control group), or three different types of sujeonggwa drinks (S-sugar, S-stevia, and S-scFOS group) for 6 weeks while high cholesterol diet was provided to all animals. Compared to the control group, concentrations of hepatic triglycerides, total cholesterol, thiobarbituric acid reactive substances, and reactive oxygen species in S-sugar, S-stevia, S-scFOS were significantly reduced (P<0.05), indicating that sujeonggwa had inhibitory effects on hepatic lipid accumulation. Protein expression levels of fatty acid synthase (FAS) and its transcription factor, sterol regulatory element-binding protein (SREBP)-1 responsible for triglyceride synthesis, as well as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and its transcription factor, SREBP-2 responsible for cholesterol synthesis, were also reduced in S-sugar, S-stevia, and S-scFOS groups (P<0.05). These benefits of sujeonggwa were even greater in S-stevia and S-scFOS compared to S-sugar. The beneficial effects of S-stevia on regulation of hepatic lipid metabolism were slightly greater than those of S-scFOS although the differences were not significant. In conclusion, sujeonggwa drinks, especially functional sujeonggwa drinks in which sugar was partially substituted with stevia or scFOS, inhibited hepatic lipid accumulation via suppressing FAS and HMGCR protein expression through down-regulation of SREBP-1 and 2.