• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.461-469
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• 1998

Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethy-lamines, and many of them, especially with 6,7-disubstitution, demonstrate relatively high affinity for catecholamines. Two -OH groups at 6 and 7 positions are supposed to be essential to exert ?${\beta}-receptor$ activities. However, it is not clear whether -OH at 6,7 substitution of THIs also shows ?${\alpha}-adrenoceptor$ activities. In the present study, we investigated whether -OH or $-OCH_3$ substitutions of 6,7 position of THIs differently affect the ?1-adrenoceptor affinity. We synthesized two 1-naphthylmethyl THI alkaloids, $1-{\beta}-naphthylmethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline$ HBr (YS 51) and $1-{\beta}-naphthylmethyl-6, 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline$ HCl (YS 55), and their pharmacological actions on ?${\alpha}_1-adrenoceptor$ were compared. YS 51 and YS 55, concentration-dependently relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 ${\mu}M$) in which $pEC_{50}$ were $5.89{\pm}0.21$ and $5.93{\pm}0.19$, respectively. Propranolol (30 nM) did not affect the relaxation-response curves to YS 51 and YS 55. Concentration-response curves to PE were shifted to right by the pretreatment with YS 51 or YS 55. The $pA_2$ values of YS 51 and YS 55 showed $6.05{\pm}0.24$ and $5.88{\pm}0.16$, respectively. Both probes relaxed KCl (65.4 mM)-contracted aorta and inhibited $CaCl_2-induced$ contraction of PE-stimulated endothelium- denuded rat thoracic aorta in $Ca^{2+}-free$ solutions. In isolated guinea pig papillary muscle, 1 and 10 ${\mu}M$ YS 51 increased contractile force about 4- and 8- fold over the control, respectively, along with the concentration-dependent increment of cytosolic $Ca^{2+}$ ions. While, 10 ${\mu}M$ YS 55 reduced the contractile force about 50 % over the control and lowered the cytosolic $Ca^{2+}$ level, in rat brain homogenates, YS 51 and YS 55 displaced $[^3H]prazosin$ binding competitively with Ki 0.15 and 0.12 ${\mu}M$, respectively. However, both probes were ineffective on $[^3H]nitrendipine$ binding. Therefore, it is concluded that two synthetic naphthylmethyl-THI alkaloids have considerable affinity to ?1-adrenenoceptors in rat aorta and brain.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.47 no.1
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• pp.65-73
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• 2021

It is very important to control the inflammation of the skin because it can develop into diseases such as atopy as well as scarring and aging. In this work, we recently identified the in vitro synthesis of specialized pro-resolving mediators (SPMs) known to control inflammation in the human body and the applicability of cosmetics. Using recombinant protein of lipoxygenase from Glycine max, we succeeded to prepare mixtures of mono- or di-hydroxy DHA named as S-SPMs and used them for in vitro efficacy test. To investigate anti-inflammatory effect of S-SPMs, mRNA level of TNF-α and IL-6 were analyzed. Under UVB exposed condition, expression of both were decreased by S-SPMs treatment. And we observed reduced production of nitric oxide (NO) by S-SPMs application under the condition with diesel particulate matter (DPM). At the same experimental condition, malondialdehyde (MDA) production was decreased by S-SPMs, indicating the inhibitory effect of S-SPMs in lipid peroxidation. In addition, S-SPMs treatment resulted in reduction of matrix metalloproteinases-1 (MMP-1) expression and elevation of procollagen type I synthesis. Together with this, mRNA level of filaggrin and loricrin were increased by S-SPMs, indicating enhancement of skin barrier function. These results demonstrate that S-SPMs is a good candidate to develop as a cosmetic ingredient for anti-inflammation, anti-wrinkle, and improvement of skin barrier function.

• Development and Reproduction
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• v.11 no.3
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• pp.187-193
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• 2007

Ethane 1,2-dimethane sulfonate(EDS), a Leydig cell specific toxicant, has been widely used to create the reversible testosterone withdrawal rat model. Though the maintenance of epididymal structure and function is highly dependent on the testosterone secreted from testis, its derivatives, dihydroxytestosterone(DHT) and estrogen, might have crucial roles. The aim of present study was to monitor the expression patterns of sex steroid receptors, cytochrome P450 aromatase(P450arom) and $5{\alpha}$-reductase in the rat epididymis up to 7 weeks after EDS injection. Adult male rats($350{\sim}400g$) were injected with a single does of EDS(75 mg/kg i.p.) and sacrificed on weeks 0, 1, 2, 3, 4, 5, 6 and 7. The transcriptional activities of the target genes were evaluated by semi-quantitative RT-PCRs. The transcript level of estrogen receptor alpha($ER{\alpha}$) in EDS group was significantly higher than control level on week 1(P<0.01). After week 2, there was no significant difference in $ER{\alpha}$ levels between EDS group and control. The transcript level of estrogen receptor beta($ER{\beta}$) in EDS group was significantly higher than control level on week 1(P<0.05), lowered on weeks 2 and 3(P<0.05 and P<0.01, respectively), fluctuated during weeks 4 and 6, and elevated on week 7(P<0.05). The androgen receptor (AR) message levels increased significantly week 2(P<0.01), then returned to control level on week 3. In contrast, expression of cytochrome P450 aromatase(P450arom) decreased sharply during weeks $1{\sim}3$(P<0.01 on weeks 1 and 2; P<0.05 on week 3), then went back to control level on week 4. The mRNA level of $5{\alpha}$-reductase type 2($5{\alpha}$-RT2) increased significantly on week 4(P<0.01), then returned to control level. The present study indicated that EDS administration could induce reversible alterations in the transcriptional activities of sex steroid hormone receptors and androgenconverting enzymes in rat epididymis. EDS injection model will be useful to clarify the regulation mechanism of mammalian epididymal physiology.

• Journal of Oral Medicine and Pain
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• v.38 no.3
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• pp.221-233
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• 2013

Bile acids are polar derivatives of cholesterol essential for the absorption of dietary lipids and regulate the transcription of genes that control cholesterol homeostasis. Recently it have been identified the synthetic chenodeoxycholic acid (CDCA) derivatives HS-1200 and cisplatin showed apoptisis-inducing activity on various cancer cells in vivo and in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with HS-1200 and cisplatin on human tongue squamous cell carcinoma cells (SCC25 cells). To investigate whether the co-treatment with HS-1200 and cisplatin compared to each single treatment efficiently reduces the viability of SCC25 cells, MTT assay was conducted. The induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining and an analysis DNA hypoploidy. Westen blot analysis and immunofluorescent staining were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following this co-treatment. Furthermore, proteasome activity and mitochondrial membrane potential (MMP) change were also assayed. In this study, co-treatment with HS-1200 and cisplatin on SCC25 cells showed several lines of apoptotic manifestation such as nuclear condensations, DNA fragmentation, reduction of MMP and proteasome activity, the increase of Bax and the decrease of Bcl-2, decrease of DNA content, the release of cytochrome c into cytosol, translocation of AIF and DFF40 (CAD) onto nuclei, and activation of caspase-9, caspase-7, caspase-3, PARP and DFF45 (ICAD) whereas each single treated SCC25 cells did not show these patterns. Although the single treatment of $25{\mu}M$ HS-1200 and $4{\mu}g/ml$ cisplatin for 24 h did not induce apoptosis, the co-treatment of these reagents prominently induced apoptosis. Therefore our data provide the possibility that the combination therapy with HS-1200 and cisplatin could be considered as a novel therapeutic strategy for human squamous cell carcinoma.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.13-13
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• 2018

The anti-inflammatory (INF) compounds (1-15) were isolated from Agrimonia pilosa Ledeb. (APL) by activity-guided isolation technique. The isolated compounds (1-15) were identified as quercetin-7-O-rhanmoside (1), apigenin-7-O-glycoside (2), kaempferol-7-O-glycoside (3), apigenin-7-O-[6"-(butyl)-glycoside] (4), querceitn (5), kaempferol (6), apigenin (7), apigenin-7-O-[6"-(pentyl)-glycoside] (8), agrimonolide (9), agrimonolide-6-O-glucoside (10), desmethylagrimonolide (11), desmethylagrimonolide-6-O-glucoside (12), luteolin (13), vitexin (14) and isovitexin (15). Flavonoids, compound 2, 3, 11, and 14-15 have been found in APL for the first time. Furthermore, two novel flavone derivatives, compound 4 and 8, have been isolated inceptively in plant. In the no cytotoxicity concentration ranges of $0-20{\mu}M$, nitric oxide (NO) production level of 1-15 was estimated in LPS-treated Raw 264.7 macrophage cells. The flavone aglycones, 7 (apigenin, $IC_{50}=3.69{\pm}0.34{\mu}M$), 13 (luteolin, $IC_{50}=4.62{\pm}0.43{\mu}M$), 6 (kaempferol, $IC_{50}=14.43{\pm}0.23{\mu}M$) and 5 (quercetin, $IC_{50}=19.50{\pm}1.71{\mu}M$), exhibited excellent NO inhibitory (NOI) activity in dose-dependent manner. In the structure activity relationship (SAR) study of apigenin-derivatives (APD), apigenin; Api, apigenin-7-O-glucoside; Api-G, apignenin-7-O-[6"-(butyl)-glycoside]; Api-BG and apignenin-7-O-[6"-(pentyl)-glycoside]; Api-P, from APL on INF activity was investigated. The INF mediators level such as NO, INF-cytokines, NF-KB proteins, iNOS and COX-2 were sharply increased in Raw 264.7 cells by LPS. When pretreatment with APD in INF induced macrophages, NOI activity of Api was most effective than other APD with $IC_{50}$ values of $3.69{\pm}0.77{\mu}M$. And the NOI activity was declined in the following order: Api-BG ($IC_{50}=8.91{\pm}1.18{\mu}M$), Api-PG ($IC_{50}=13.52{\pm}0.85{\mu}M$) and API-G ($IC_{50}=17.30{\pm}0.66{\mu}M$). The NOI activity of two novel compounds, Api-PG and Api-BG were lower than their aglycone; Api, but more effective than Api-G (NOI: Api-PG and Api-BG). And their suppression ability on INF cytokines such as $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 mRNA showed the similar tendency. Therefore, the anti-INF mechanism study of Api-PG and Api-BG on nuclear factor-kappa B ($NF-{\kappa}B$) pathway, representative INF mechanism, was investigated and Api was used as positive control. Api-BF was more effectively prevent the than phosphorylation of $pI{\kappa}B$ kinase (p-IKK) and p65 than Api-PG in Raw 264.7 cells. In contrast, Api-PG and Api-BG were not reduced the phosphorylation of inhibitor of kappa B alpha ($I{\kappa}B{\alpha}$). Moreover, pretreatment with Api-PG and Api-BG, dose-dependently inhibited LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNAs and proteins in macrophage cells, and their expression were correlated with their NOI activity. Therefore, APL can be utilized to health promote agent associated with their AIN metabolites.

• KSBB Journal
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• v.19 no.6 s.89
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• pp.471-477
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• 2004

Oldenlandia diffusa is a Chinese medicinal herb with antitumor activity capable of suppressing the growth of some cancer cell lines. Oleanolic acid and ursolic acid are triterpenoid compounds that exist in Oldenlandia diffusa. Recently, these have been noted for anti-inflammatory, anti-cancer, and hepato-protective effects. Application of both plant growth regulators, 2,4-D and kinetin, was found to be essential for the initiation of callus and suspension cells. Leaf blades of Oldenlandia diffusa was transformed into callus on Schenk and Hildebrandt medium supplemented with 0.5 mg/L 2,4-D and 0.1 mg/L kinetin, while optimum initiation condition for suspension cells of Oldenlandia diffusa was determined to be 0.75 mg/L 2,4-D and 0.1 mg/L kinetin. Chromatographic separation of oleanolic acid from its derivatives was achieved using Rexchrom S5-100-ODS column. Analytical conditions for oleanolic acid were determined as follows: flow rate at 1.0 mL/min, UV length at 200 nm and mobile phase of $80\%$ acetonitrile and $20\%$ water. Production of secondary metabolites was found to be increased by the treatment with elicitors or signal transducers. The maximum production of oleanolic acid was 99.6 mg/L in cultures with 0.5 mM salicylic acid. It is 1.74 times higher than that of control.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.5
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• pp.623-635
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• 2011

Inefficient rumen microbial fermentation is a major factor limiting intake of low quality roughage in ruminants. In this study, the effect of energy supplementation on rumen microbial fermentation, absorption of balanced digestion products and voluntary feed intake in sheep was investigated. A basal diet of a urea-treated mixture of wheaten chaff and barley straw (3:1 DM) containing 22.2 g N/kg DM was used. Four Merino-cross wethers weighing $45{\pm}4.38\;kg$ and fitted with permanent rumen and abomasal cannulae were allocated to four treatments in a $4{\times}4$ Latin square design. The dietary treatments were basal diet ($E_0$), or basal diet supplemented with sucrose (112.5 g/d) administered to the animals intra-ruminally ($E_R$), abomasally ($E_A$), or through both routes (50:50) ($E_{RA}$). Feed intake (basal and dietary) was increased (p<0.05) by sucrose supplementation through the rumen ($E_R$) or abomasum ($E_A$). However, there was no difference (p>0.05) in intake between animals on the control diet and those supplemented with sucrose through both intraruminal and abomasal routes ($E_{RA}$). The digestibility of DM and OM was highest in $E_R$ and $E_A$ supplemented animals. Although the rumen pH was reduced (p<0.001) in animals supplemented with sucrose entirely intra-ruminally ($E_R$), the in sacco degradation of barley straw in the rumen was not adversely affected (p>0.05). Intra-ruminal sucrose supplementation resulted in a higher concentration of total VFA, acetate and butyrate, while the pattern of fermentation showed a higher propionate: acetate ratio. Intra-ruminal supplementation also increased (p<0.05) the glucogenic potential (G/E) of the absorbed VFA. However, there was no difference (p>0.05) in microbial protein production between the four dietary treatments. Protozoa numbers were increased (p<0.05) by intra-ruminal supplementation of sucrose.

• Journal of the Korean Chemical Society
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• v.55 no.3
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• pp.478-485
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• 2011

Merocyanine derivatives transformed from spiropyran-containing compounds by irradiating the light of ultraviolet (UV) include zwitterion of phenolate anion and amine cation. Complexation of this phenolate anion on merocyaninemodified surface and Ni ion among metal ions led to a change of surface charge and it was measured with kelvin prove force microscopy (KFM). We found that the resultant surface potential decreased linearly as UV-exposed time increased, and finally were saturated. Also it was analyzed through XPS the immobilized amount of Ni ions was increased according to increase of UV-exposed time. It is considered that these properties could be applied for detection and a quantitative control of different metal ions. Further research is to aim construct specific scaffold/matrix which enable high selective, high sensitive and, especially, a quantitative immobilization of metal ions-binding biomaterials such as proteins and cells.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.28 no.2
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• pp.132-140
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• 2017

Objectives: Very early-onset schizophrenia (VEOS) is a type of psychosis having a low frequency, insidious onset, and devastating clinical outcome. In this study, the demographic features, information on medication, clinical outcomes, and intellectual capability of patients diagnosed with VEOS in a hospital were analyzed to provide therapeutic strategies for this type of schizophrenia. Methods: Using the electronic medical records of the National Center for Mental Health, 69 patients with VEOS were identified based on the DSM-5 criteria of schizophrenia. The data were summarized and analyzed according to the demographic characteristics, medications used, intellectual strength measured by the full intelligence quotient (FIQ) score, and current clinical status measured by the Clinical Global Impression-Severity (CGI-S) and various combinations of these parameters. Results: The screened study group contained similar numbers of males and females. The younger the onset of psychosis, the lower the frequency. The study population included a significantly higher proportion of births in the winter season than that of the general population. The 3 most frequently used antipsychotic medications were risperidone and its derivatives, clozapine and olanzapine. Valproic acid and divalproex sodium were the most commonly added drugs for outcome augmentation. 53.5% of the study population had received benzodiazepines and/or hypnotics. The average FIQ of the study population was 69.4, which is quite low compared to previous Korean studies with similar populations. There was a weak negative correlation between FIQ and CGI-S, but it was not statistically significant. The average CGI-S score was 4.2, which meant that the patients were moderately ill. Conclusion: This study demonstrated that patients with VEOS showed more frequent intellectual deficits at baseline and poorer outcomes than the control group. Risperidone, clozapine, valproic acid and their combinations were the most preferred medications for the treatment of psychosis. Benzodiazepines were quite commonly added for various reasons.

• Horticultural Science & Technology
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• v.29 no.4
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• pp.374-381
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• 2011

Stilbenes are polyphenolic natural products, which have antioxidative and antifungal activities. In some plants, including grapevine, the stilbene compounds, as resveratrol derivatives, exist in very diverse forms. Experiments to identify the individual stilbene compounds were carried out first to quantify them in UV-irradiated grapevine leaves. For this, stilbene glycosides were extracted from grapevine leaves which irradiated intensively with UV light. The glycoside samples were hydrolyzed by ${\beta}$-glucosidase, before analyzed by HPLC-mass spectrometer at each m/z corresponding to the mass of specific stilbenes. As results, in chromatograms, the enzymatic hydrolysis resulted in decrease and increase of the peaks expected for glycosides and aglycones, respectively. The samples were also exposed to sunlight in order to photo-isomerize the stilbene compounds. The light exposure resulted in disappearance and appearance of peaks expected for trans- and cis-isomers of stilbenes, respectively. Such a change of the peaks in chromatograms provided information needed for the inference to peak components. In this way, it was possible to identify 16 kinds of stilbene compounds from grapevine leaves. The identified stilbenes were quantified from grapevine leaves irradiated mildly by UV light. The UV-irradiation increased markedly in the content of stilbene compounds, especially trans-resveratrol by several hundredfold. In addition, piceatannol, which is a mere minor component of stilbenes in control leaves and a more active radical scavenger than resveratrol, was also increased by several tenfold by the treatment. The increase in stilbene contents as influenced by UV irradiation seems to be one of the stress coping responses of grapevine as a hormesis phenomenon.