• The Korean Journal of Physiology and Pharmacology
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• v.11 no.3
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• pp.85-88
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• 2007

Matrix metalloproteinases (MMPs) can degrade a wide range of extracellular matrix components. It has been reported that MMP-9 are activated after focal ischemia in experimental animals. (-)-Epigallocatechin-3-gallate (EGCG), a major constituent of green tea polyphenols, is a potent free radical scavenger and reduces the neuronal damage caused by oxygen free radicals. And it has been known that EGCG could reduce the infarction volume in focal brain ischemia and inhibit MMP-9 activity. To delineate the relationship between the anti-ischemic action and the MMP-9-inhibiting action of EGCG, we investigated the effect of EGCG on brain infarction and the activity of matrix metalloproteinase-9 induced by permanent middle cerebral artery occlusion (pMCAO) in ICR mice. EGCG (40 mg/kg, i.p. $15{\sim}30min$ prior to MCAO) significantly decreased infarction volume at 24 hr after MCAO. GM 6001 (50 mg/kg, i.p. $15{\sim}30min$ prior to MCAO), a MMP inhibitor, also significantly reduced infarction volume. In zymogram, MMP-9 activities began to increase at ipsilateral cortex at 2 hr after MCAO, and the increments of MMP-9 activities were attenuated by EGCG treatment. Western blot for MMP-9 also showed patterns similar to that of zymogram. These findings demonstrate that the anti-ischemic action of EGCG ire mouse focal cerebral ischemia involves its inhibitory effect on MMP-9.

• Korean Journal of Clinical Pharmacy
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• v.28 no.2
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• pp.131-137
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• 2018

Background: In South Korea, 22.3% of women ${\geq}50years$ of age and 37% of women ${\geq}70years$ of age visit the doctor to obtain treatment for osteoporosis. According to the analysis of the National Health Insurance Services claim data between 2008 and 2012, the number and incidence of hip and vertebral fractures increased during the same period. Denosumab, a newly marketed medicine in Korea, is the first RANK inhibitor. Methods: A cost-utility analysis was conducted from a societal perspective to prove the superiority of denosumab to alendronate. A Markov cohort model was used to investigate the cost-effectiveness of denosumab. A 6-month cycle length was used in the model, and all patients were individually followed up through the model, from their age at treatment initiation to their time of death or until 100 years of age. The model consisted of eight health states: well; hip fracture; vertebral fracture; wrist fracture; other osteoporotic fracture; post-hip fracture; post-vertebral fracture; and dead. All patients began in the well-health state. In this model, 5% discounted rate, two-year maximum offset time, and persistence were adopted. Results: The total lifetime costs for alendronate and denosumab were USD 5,587 and USD 6,534, respectively. The incremental cost-effectiveness ratio (ICER) for denosumab versus alendronate was USD 20,600/QALY. Given the ICER threshold in Korea, the results indicated that denosumab was remarkably superior to alendronate. Conclusion: Denosumab is a cost-effective alternative to the oral anti-osteoporotic treatment, alendronate, in South Korea.

• Bulletin of the Korean Chemical Society
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• v.29 no.9
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• pp.1717-1722
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• 2008

The 70 kDa heat-shock protein (Hsp70) involved in various cellular functions, such as protein folding, translocation and degradation, regulates apoptosis in cancer cells. Recently, it has been reported that the green tea flavonoid (−)-epigallocatechin 3-gallate (EGCG) induces apoptosis in numerous cancer cell lines and could inhibit the anti-apoptotic effect of human Hsp70 ATPase domain (hATPase). In the present study, docking model between EGCG and hATPase was determined using automated docking study. Epi-gallo moiety in EGCG participated in hydrogen bonds with side chain of K71 and T204, and has metal chelating interaction with hATPase. Hydroxyl group of catechin moiety also participated in metal chelating hydrogen bond. Gallate moiety had two hydrogen bondings with side chains of E268 and K271, and hydrophobic interaction with Y15. Based on this docking model, we determined two pharmacophore maps consisted of six or seven features, including three or four hydrogen bonding acceptors, two hydrogen bonding donors, and one lipophilic. We searched a flavonoid database including 23 naturally occurring flavonoids and 10 polyphenolic flavonoids with two maps, and myricetin and GC were hit by map I. Three hydroxyl groups of B-ring in myricetin and gallo moiety of GC formed important hydrogen bonds with hATPase. 7-OH of A-ring in myricetin and OH group of catechin moiety in GC are hydrogen bond donors similar to gallate moiety in EGCG. From these results, it can be proposed that myricetin and GC can be potent inhibitors of hATPase. This study will be helpful to understand the mechanism of inhibition of hATPase by EGCG and give insights to develop potent inhibitors of hATPase.

• Journal of Ginseng Research
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• v.14 no.1
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• pp.57-62
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• 1990

In order to Investigate the mechanism of the leaf-burning disease of ginseng (Panax ginseng C.A. Meyer), studies on the generation of singlet oxygen (1O2) and the photooxidation of the pigments were carried out in comparison with the ones of soybean (G1ycine max L). The studies were mainly focalized on the effects of light intensity, light intensity, inhibitor and electron donor/acceptor of the Photosynthetic electron transport system. When we measured the amounts of 1O2 generated in the thylakoids of ginseng and soybean by the irradiation of light (300 w/m2) as a function its time. It was identified that a higher amount of 1O2 was formed in the ginseng thylakoid than the case of soybean. A generation ratio of lO2 between ginseng and soybean sltbstantially identical in the range of light intensities 50∼150w/m2 However much higher amount of 1O2 was generated in ginseng by irradiation of strong intensity of light (200 500w/m2). Wave length dependency on the generation of 1O2 and the pigment photooxidation was observed on ginseng thylakoids; red light (600-700 nm) gave a maximum effect in the contrast with blur green light (400-60 nm). When the ginseng thylalioid was treated with the electron donor (Mn2+) and acceptors (DCPIP, FeCy) of the photosynthetic electron transport system. a drastic inhibition of 1O2 generation was observed. However, treatment with its inhibitors (DCMU, KCW) activated 1O2 generation. An interesting fact that an electron donor or acceptor of the photosystem II(P680) Inhibited 1O2 generation, suggests an intimate relationship between 1O2 generation and photosystem II.

• Corrosion Science and Technology
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• v.9 no.1
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• pp.20-28
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• 2010

According to the bipolar model, ion selectivity of some species in the passive film is important factor to control the passivation. An increase of cation selectivity of outer layer of the passive film can stabilize the film and improves the corrosion resistance. Therefore, the formation and roles of ionic species in the passive film should be elucidated. In this work, two types of solution (hydrochloric or sulfuric acid) were used to test high N and Mo-bearing stainless steels. The objective of this work was to investigate the formation of oxyanions in the passive film and the roles of oxyanions in passivation of stainless steel. Nitrogen exists as atomic nitrogen, nitric oxide, nitro-oxyanions (${NO_x}^-$), and N-H species, not nitride in the passive film. Because of its high mobility, the enriched atomic nitrogen can act as a reservoir. The formation of N-H species buffers the film pH and facilitates the formation of oxyanions in the film. ${NO_x}^-$ species improve the cation selectivity of the film, increasing the oxide content and film density. ${NO_x}^-$ acts similar to a strong inhibitor both in the passive film and at active sites. This facilitates the formation of chromium oxide. Also, ${NO_x}^-$ can make more molybdate and nitric oxide by reacting with Mo. The role of Mo addition on the passivation characteristics of stainless steel may differ with the test environment. Mo exists as metallic molybdenum, molybdenum oxide, and molybdate and the latter facilitates the oxide formation. When nitrogen and molybdenum coexist in stainless steel, corrosion resistance in chloride solutions is drastically increased. This synergistic effect of N and Mo in a chloride solution is mainly due to the formation of nitro-oxyanions and molybdate ion. Oxyanions can be formed by a 'solid state reaction' in the passive film, resulting in the formation of more molybdate and nitric oxide. These oxyanions improve the cation selectivity of the outer layer and form more oxide and increase the amount of chromium oxide and the ratio of $Cr_2O_3/Cr(OH)_3$ and make the film stable and dense.

• Journal of Life Science
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• v.13 no.6
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• pp.924-932
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• 2003

Epigallocatechin-3 Gallate (EGCG), a major constituent of green tea, has attracted increasing interest because of its many reported health benefits. Here we demonstrate for the first time that EGCG stimulates phospholipase D (PLD) activity in U87 human astroglioma cells. EGCG-induced PLD activation was abolished by the phospholipase C (PLC) inhibitor and a lipase inactive PLC-\gama1$ mutant, and was dependent on intracellular $Ca^{ 2+}$, and possibly involved $Ca^{ 2+}$ calmodulin-dependent protein kinase II (CaM kinase II). Interestingly, EGCG induced translocation of PLC-\gama1$ from the cytosol to the membrane and PLC-\gama1$interaction with PLD1. Taken together, these results demonstrate for the first time that in human astroglioma cells, EGCG regulates PLD activity via a signaling pathway involving a PLC-\gama1$ (inositol 1,4,5-trisphosphate-$Ca^{ 2+}$)-CaM kinase II-PLD pathway.

• Preventive Nutrition and Food Science
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• v.15 no.3
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• pp.189-195
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• 2010

Water extracts from 20 medicinal plants, traditionally used for postmenopausal symptoms in Korea, were examined for their vasorelaxant activity in isolated rat thoracic aorta rings precontracted with norepinephrine (NE). Among the 20 medicinal plants, Cornus officinalis (CoEx, 0.3 mg/mL), Schisandra chinensis (ScEx, 0.3 mg/mL), Erythrina variegate (EvEx, 0.3 mg/mL), and Epimedium koreanum (EkEx, 0.3 mg/mL) showed rapid relaxation of endothelium-intact aorta ($69\pm4%$, $40\pm3%$, $25\pm2%$, and $23\pm3%$ of active tone induced by NE, respectively). In contrast, the extracts of Erythrina variegata (EvEx), Angelica gigas (AgEx), Pueraria thunbergiana (PtEx), and EkEx lead to gradual (i.e., long-term) relaxation to baseline in endothelium-intact vessels. The time to complete relaxation was 20～40 min. These 6 plant extracts were selected for the investigation of possible underlying mechanisms. The CoEx-, ScEx-, or EkEx-induced rapid relaxations were virtually abolished by endothelium denudation, and were significantly inhibited by pretreatment with nitric oxide (NO) synthase inhibitor $N^G$-nitro-L-arginine (L-NNA, 10 ${\mu}M$), indicating that increased formation of NO might contribute to the endothelium-mediated relaxation. In long-term responses, the endothelium denudation did not affect PtEx-induced relaxation, whereas it delayed responses by EvEx and AgEx, and significantly inhibited the effect of EkEx. Among EvEx, AgEx, and PtEx, EvEx attenuated the $CaCl_2$-induced vasoconstriction in high-potassium depolarized medium, implying that EvEx is involved in inhibition of the extracellular calcium influx to smooth muscle through voltage dependent calcium channels. These results provide the scientific rationale for the interrelationships between the use of 20 medicinal plants and their effects on cardiovascular health in estrogen deficient conditions.

• Nutrition Research and Practice
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• v.12 no.3
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• pp.183-190
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• 2018

BACKGROUND/OBJECTIVE: This study was designed to investigate how a Portulaca oleracea L. extract (POE) stimulates insulin secretion in INS-1 pancreatic ${\beta}-cells$. MATERIALS/METHOD: INS-1 pancreatic ${\beta}-cells$ were incubated in the presence of various glucose concentrations: 1.1 or 5.6, 16.7 mM glucose. The cells were treated with insulin secretagogues or insulin secretion inhibitor for insulin secretion assay using an insulin ELISA kit. In order to quantify intracellular influx of $Ca^{2+}$ caused by POE treatment, the effect of POE on intracellular $Ca^{2+}$ in INS-1 pancreatic ${\beta}-cells$ was examined using Fluo-2 AM dye. RESULTS: POE at 10 to $200{\mu}g/mL$ significantly increased insulin secretion dose-dependently as compared to the control. Experiments at three glucose concentrations (1.1, 5.6, and 16.7 mM) confirmed that POE significantly stimulated insulin secretion on its own as well as in a glucose-dependent manner. POE also exerted synergistic effects on insulin secretion with secretagogues, such as L-alanine, 3-isobutyl-1-methylxanthine, and especially tolbutamide, and at a depolarizing concentration of KCl. The insulin secretion caused by POE was significantly attenuated by treatment with diazoxide, an opener of the $K{^+}_{ATP}$ channel (blocking insulin secretion) and by verapamil (a $Ca^{2+}$ channel blocker). The insulinotropic effect of POE was not observed under $Ca^{2+}$-free conditions in INS-1 pancreatic ${\beta}-cells$. When the cells were preincubated with a $Ca^{2+}$ fluorescent dye, Fluo-2 (acetoxymethyl ester), the cells treated with POE showed changes in fluorescence in red, green, and blue tones, indicating a significant increase in intracellular $Ca^{2+}$, which closely correlated with increases in the levels of insulin secretion. CONCLUSIONS: These findings indicate that POE stimulates insulin secretion via a $K{^+}_{ATP}$ channel-dependent pathway in INS-1 pancreatic ${\beta}-cells$.

• Journal of Life Science
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• v.22 no.3
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• pp.298-305
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• 2012

The general term flavonoids is often used to categorize a family of natural compounds that are highly abundant in all higher plants, and which in recent years have attracted scientific interest as therapeutics. Lutein is a xanthophyll and one of 600 known naturally occurring carotenoids. It is found in green vegetables such as spinach and kale, and has been demonstrated to exert anti-inflammatory activities. However, its anti-allergic effect in the Th1/Th2 immune response is poorly understood. In this study, we attempt to determine whether lutein regulates inflammatory mediators in an ovalbumin (OVA)-induced murine asthma model. To address this, mice were sensitized and challenged with OVA, and then treated with lutein before the last OVA challenge. Administration of lutein significantly suppressed the OVA-induced airway hyper-responsiveness. It also resulted in a significant alleviation of the infiltration of inflammatory cells into the bronchoalveolar lavage. Additionally, lutein attenuated the increased expression of Th2 responses in OVA-challenged mice. These results demonstrate that lutein is a potent inhibitor that reduces Th2 immune responses. Furthermore, they show that the immunopharmacological function is mediated by a pathway that involves and is regulated by Th2 immune response.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.444-453
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• 2022

Background: Compound K (CK) is among the protopanaxadiol (PPD)-type ginsenoside group, which produces multiple pharmacological effects. Herein, we examined the effects of CK on muscle atrophy under hyperlipidemic conditions along with its pro-myogenic effects. Further, the molecular pathways underlying the effects of CK on skeletal muscle have been justified. Methods: C2C12 myotubes were treated with palmitate and CK. C2C12 myoblasts were differentiated using CK for 4-5 days. For the in vivo experiments, CK was administered to mice fed on a high-fat diet for 8 weeks. The protein expression levels were analyzed using western blotting analysis. Target protein suppression was performed using small interfering (si) RNA transfection. Histological examination was performed using Jenner-Giemsa and H&E staining techniques. Results: CK treatment attenuated ER stress markers, such as eIF2a phosphorylation and CHOP expression and impaired myotube formation in palmitate-treated C2C12 myotubes and skeletal muscle of mice fed on HFD. CK treatment augmented AMPK along with autophagy markers in skeletal muscle cells in vitro and in vivo experiments. AMPK siRNA or 3-MA, an autophagy inhibitor, abrogated the impacts of CK in C2C12 myotubes. CK treatment augmented p38 and Akt phosphorylation, leading to an enhancement of C2C12 myogenesis. However, AMPK siRNA abolished the effects of CK in C2C12 myoblasts. Conclusion: These findings denote that CK prevents lipid-induced skeletal muscle apoptosis via AMPK/autophagy-mediated attenuation of ER stress and induction of myoblast differentiation. Therefore, we may suggest the use of CK as a potential therapeutic approach for treating muscle-wasting conditions associated with obesity.