• 동의생리병리학회지
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• 제17권6호
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• pp.1393-1403
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• 2003

The genetic effects of restraint stress challenge on HPA axis and the therapeutic effect of Boshimgeonbi-Tang on the stress were studied with cDNA microarray analyses on hypothalamus using an immobilization-stress mouse as stress model. Male CD-1 mice were restrained in a tightly fitted and ventilated vinyl holder for 2hours once a day, and this challenge was repeated for seven consecutive days. The body weights of the immobilization-stress mice were diminished about 25 percent degree as compared to normal ones. Seven days later, total RNA was extracted from the organs of the mouse, body-labeled with CyDye/sup TM/ fluorescence dyes (Amersham Bioscience Co., NJ), and then hybridized to cDNA microarray chip. Scanning and analyzing the array slides were carried out using GenePix 4000 series scanner and GenePix Pro/sup TM/ analyzing program, respectively. The expression profiles of 109 genes out of 6000 genes on the chip were significantly modulated in hypothalamus by the immobilization stress. Energy metabolism-, lipid metabolism-, apoptosis- and signal transduction-related genes were transcriptionally activated whereas DNA repair-, protein biosynthesis-, and structure integrity-related genes were down-regulated in hypothalamus. The 58 genes were up-regulated by the mRNA expression folds of 1.5 to 7.9. and the 51 genes were down-regulated by 1.5 - 3.5 fold. The 20 genes among them were selected to confirm the expression profiles by RT-PCR. The mRNA expression levels of Tnfrsf1a (apoptosis), Calm2 (cell cycle), Bag3 (apoptosis), Hspe1 (protein folding), Aatk (apoptosis), Dffa (apoptosis), Itgb1 (cell adhesion), Vcam1 (cell adhesion), Fkbp5 (protein folding), BDNF (neuron survival) were restored to the normal one by the treatment of Boshimgeonbi-Tang.

• 한국균학회지
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• 제30권1호
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• pp.37-43
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• 2002

버들송이버섯(A. cylindracea)와 말똥진흙버섯(P. igniarius)의 균사체 추출액과 배양액을 용매별 분획 후 각 분획별로 항산화 효과를 검색하였다. 전자공여능의 측정 결과, A. cylindracea 균사체 추출액의 ethyl acetate 분획과 butanol 분획, 배양액의 butanol 분획 그리고 Phellinus igniarius 균사체 추출액의 diethyl ether 분획, 배양액의 diethyl ether 분획, ethyl acetate 분획에서 모두 70% 이상의 강한 항산화 활성을 나타내었다. 과산화지질 생성 억제 실험에서는 A. cylindracea 균사체 추출액의 diethyl ether 분획과 butanol 분획, 물분획 그리고 배앙액의 물분획에서 과산화지질의 생성이 억제되었다. Xanthine oxidase의 활성 측정에서는 A. cylindracea 균사체 추출액에서 uric acid 양이 감소하는 것으로 측정되었다. 아질산염 소거능의 측정 결과에서는 A. cylindracea 균사체 추출액의 diethyl ether 분획과 배양액의 ethyl acetate 분획, 물분획 그리고 P. igniarius 균사체 추출액의 diethyl ether 분획과 배양액의 diethyl ether 분획, chloroform 분획, butanol 분획, 물분획에서 $50{\sim}60%$의 고른 활성을 나타내는 것으로 측정되었으며, melanin 생성 저해 활성에 대한 결과는 A. cylindracea 균사체 추출액의 물분획과 P. igniarius 균사체 추출액의 butanol 분획에서 무첨가구에 비해 2배 이상의 저해 활성이 있는 것으로 조사되었다. 이상의 결과 말똥진흙버섯과 버들송이버섯의 균사체추출액이 강한 항산화활성을 나타내었다.

• 대한화장품학회지
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• 제30권1호
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• pp.29-32
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• 2004

내형질 세망 조직에서 N-글리코실레이션 과정의 초기 단계를 차단하면 멜라닌 생 합성의 주 효소인 티로시나제의 활성이 저해된다. 본 연구에서는 in vitro 환경에서 N-글리코실레이션 저해제의 활성을 증가시키고자 전달체로 pH 감응성을 갖는 나노크기의 지질구조체를 제조하고 이를 평가하였다. 이 pH 감응성 지질구조체 Melexsome은 일반적인 지질성분인 포스포리피드와 콜레스테롤 기반의 지질안정 성분으로 구성되며, 통상적인 리포좀 제조법에 따라 제조되었다. 글리코실레이션 저해 성분물질을 포집시킨 Melel[some의 효과는 EndoH ＆ PNGaseF 분해와 western blotting 방법에 의해 평가하였고, 멜라닌 합성량 또한 측정 되었다. 이 결과, pH 감응성을 갖도록 제조된 Melexsome이 N-글리코실레이션 저해제의 효능을 효과적으로 증진시킴을 알 수 있었다. 또한, 공초점 주사 현미경에 의한 세포관찰 결과에 따르면 Melexsome은 여타의 전달체에 비하여 세포질 내에 보다 효과적으로 전달되는 것으로 보여지며, 따라서 이같은 양친성 지실성분 기반의 pH 감응성 나노 전달체는 N-글리코실레이션 저해제의 전달 시스템으로서 미백 화장료 제품이 가져야 하는 침착된 색소에 의해 어두워진 피부톤의 개선 효과를 극대화 시키는데 적합하다고 여겨진다.

• 생명과학회지
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• 제15권3호
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• pp.461-467
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• 2005

간기능 보호 작용이 있는 것으로 알려진 DDB, selenium과 glutathione의 혼합제제인 DWP-04의 간보호 작용을 검토할 목적으로 DWP-04를 실험동물에 경구로 투여하고서 D-galactosamine으로 간독성을 유발하여 혈액의 변동 및 간 조직에서의 활성산소 생성계 및 해독계의 활성에 미치는 영향을 관찰한 결과 GaIN의 단독투여는 대조군에 비하여 혈중 간 기능 지표효소 및 간 조직에서의 지질과산화의 함량이 현저히 증가하였으나, DWP-04의 전처리로 현저히 감소되었다. CaIN의 단독 투여로 활성산소의 생성계인 phase 1계의 효소가 현저히 증가하던 것이 DWP-04의 처리로 억제되었으며 해독계인 phase II계의 효소는 GaIN의 투여로 대조군에 비하여 억제되던 것이 DWP-04의 전처리로 정상군에는 미치지 않으나 유의성 있게 증가되었다. 간 조직중 glutathine의 함량은 CaIN의 투여로 현저히 억제되었으며 DWP-04의 투여로 증가하였는데 이러한 결과는 DWP-04의 투여로 glutathione peroxidase의 활성보다는 $\gamma-glutamylcysteine$ synthetase의 활성을 조절한 결과로 생각된다. 이상의 결과를 종합하여 볼 때 DWP-04의 투여는 활성산소의 생성 및 해독계를 조절하므로서 GaIN으로 인한 간손상을 보호하는 효과가 있는 것으로 사료된다.

• 한국임상약학회지
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• 제8권2호
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• pp.107-112
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• 1998

Lovastatin is a lipid lowering agent for the treatment of hypercholesterolemia and belongs to a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, lovastatin disrupts the biosynthesis of cholesterol in hepatic and peripheral cells and increases the synthesis of high-density-lipoprotein HDL) receptors. Following oral administration, the lactone ring of lovastatin is hydrolysed to the active inhibitor of HMG CoA reductase, lovastatin acid. Lovastatin is known to have poor oral absorption and wide individual variation. In this study, bioequivalence test of two lovastatin formulations, the test drug ($Lovaload^{TM}$, Chong Kun Dang Pharmaceutical Co.) and the reference drug ($Mevacor^{TM}$, Chung Wae Pharmaceutical Co.) were conducted according to the guidelines of Korea Food and Drug Administration (KFDA). A total of 18 healthy male volunteers, $31.90\pm3.60$ years old and $72.17\;7.88$ kg of body weight in average, were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of lovastatin acid in plasma were measured upto 12 hours following a single oral administration of eight tablets (20 mg of lovastatin per tablet) by high-performance liquid chromatography with UV detection at 238 nm. The area under the concentration-vs-time curve from 0 to 12 hours $(AUC_{0-12h})$ was calculated by the trapezoidal summation method. The statistical analysis showed that there are no significant differences in $AUC_{0-12h),\;C_{max}\;and\;T_{max}$ between the two formulations ($6.72\%,\;1.52\%,\;and\;0.88\$, respectively). The least significant differences between the formulations at $\alpha$=0.05 were less than $20\%\;(11.65\%,\;19.73\%,\;and\;14.81\%\;for\;AUC_{0-12h},\;C_{max}\;and\;T_{max}$, respectively). The $90\%$ confidence intervals for these parameters were also within $\pm20\%\;(-1.50{\leq}{\delta}{\leq}15.00$, $-12.50{\leq}{\delta}{\leq}15.50,\;and\;-9.64{\leq}{\delta]{\leq}11.40{\leq}\;for\;\;AUC_{0-12h}$ ,$C_{max}\;and\;T_{max}$, respectively). In conclusion, the new generic product $Lovaload^{TM}$ was proven to be bioequivalent with the reference drug.

• 한국응용곤충학회지
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• 제46권2호
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• pp.261-267
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• 2007

몇 가지 환경 친화적 살충제를 사용하여 지하집모기 유충에 대한 생물활성을 조사하였다. 본 실험에 사용한 약제로는 키틴합성저해제인 Novaluron, 탈피촉진제인 Methoxyfenozide, 탈피억제제인 Pyriproxyfen 그리고 지질생합성저해제인 Spiromesifen을 사용하였다. 지하집모기의 유충에 대한 약제별 반수치사농도는 각각 0.00039, 0.07193, 0.65006 그리고 0.04839 ppm으로 키틴합성저해제인 Novaluron 가 가장 낮은 농도를 보였다. 모기 유충방제에 필요한 효과적인 약제 처리시기를 결정하기 위하여 모기 유충의 령기에 따른 약제 감수성 실험을 실시한 결과, Novaluron 은 부화 후 2 일차, 4 일차, 7 일차 및 10 일차에서 각각 100%, 84.5%, 71% 그리고 48.5% 의 방제가로 IGR 약제의 특정이 나타났다. 또한, Methoxyfenozide, Pyriproxyfen 그리고 Spiromesifen은 부화 후 2 일차에서 80% 이하의 살충효과로 Novaluron 과 비교하여 낮은 방제가를 나타냈었다. 한편 모기유충에 대한 효과적인 약제 노출시간을 알아본 결과 Novaluron은 100% 살충효과를 나타내는데 3시간이 필요하였고, 나머지 약제들은 12 시간 이상의 노출시간에서도 100% 방제효과를 나타내지 못하였다.

• 한국식품과학회지
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• 제21권5호
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• pp.624-632
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• 1989

등줄숭어알 지질조성은 왁스에스테르(56.6-62.2%), 인지질 (19.2-18.5%), 트리글리세리드 (17.8-14.4%)의 순이었다. 왁스에스테르의 주요지방산은 C16 : 1 (25.9-27.3%)>C18 : 1(14.7-18.5%)>$C20 : 5{\omega}3$(16.3-9.6%)의 순이었으며, 알콜은 C16 : 0(57.3-53.3%)>C18 : 0(9.3-11.7%)>C18 : 1(18.9-12.7%)의 순이었다. 이중결합 2개 이상의 고도불포화 알콜은 전혀 검출되지 않았다. 홀수지방산(6.4-8.5%)과 알콜(7.4-7.5%)도 상당량 존재하였다. 수소첨가한 왁스에스테르는 탄소수별로 분리되었으나, 같은 탄소수를 가진 이성체는 분리되지 않았다. 왁스에스테르 분자종의 조성을 보면 시료 A의 경우는 C32(45.0%)>C34(19.2%)>C30(12.2%)순이었고, 시료 B의 경우는 C34(36.3%)>C32(31.4%)C36(18.1%)의 순이었다. 왁스에스테르는 구성지방산과 알콜이 nonrandom combination으로 에스테르화 되었으며, 이를 $360^{\circ}C$에서 40분간 가열하면 완전히 random화 됨을 알 수 있었다. 등줄숭어에 존재하는 왁스에스테르의 생합성에 관여하는 효소는 기질인 지방산과 알콜 탄소수에 강한 특이성을 가지고 있음을 추측할 수 있었다.

• Journal of Animal Science and Technology
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• 제63권4호
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• pp.934-953
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• 2021

Ciglitazone is a member of the thiazolidinedione family, and specifically binds to peroxisome proliferator-activated receptor-γ (PPARγ), thereby promoting adipocyte differentiation. We hypothesized that ciglitazone as a PPARγ ligand in the absence of an adipocyte differentiation cocktail would increase adiponectin and adipogenic gene expression in bovine satellite cells (BSC). Muscle-derived BSCs were isolated from six, 18-month-old Yanbian Yellow Cattle. The BSC were cultured for 96 h in differentiation medium containing 5 µM ciglitazone (CL), 10 µM ciglitazone (CM), or 20 µM ciglitazone (CH). Control (CON) BSC were cultured only in a differentiation medium (containing 2% horse serum). The presence of myogenin, desmin, and paired box 7 (Pax7) proteins was confirmed in the BSC by immunofluorescence staining. The CL, CM, and CH treatments produced higher concentrations of triacylglycerol and lipid droplet accumulation in myotubes than those of the CON treatment. Ciglitazone treatments significantly increased the relative expression of PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα), C/EBPβ, fatty acid synthase, stearoyl-CoA desaturase, and perilipin 2. Ciglitazone treatments increased gene expression of Pax3 and Pax7 and decreased expression of myogenic differentiation-1, myogenin, myogenic regulatory factor-5, and myogenin-4 (p < 0.01). Adiponectin concentration caused by ciglitazone treatments was significantly greater than CON (p < 0.01). RNA sequencing showed that 281 differentially expressed genes (DEGs) were found in the treatments of ciglitazone. DEGs gene ontology (GO) analysis showed that the top 10 GO enrichment significantly changed the biological processes such as protein trimerization, negative regulation of cell proliferation, adipocytes differentiation, and cellular response to external stimulus. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that DEGs were involved in the p53 signaling pathway, PPAR signaling pathway, biosynthesis of amino acids, tumor necrosis factor signaling pathway, non-alcoholic fatty liver disease, PI3K-Akt signaling pathway, and Wnt signaling pathway. These results indicate that ciglitazone acts as PPARγ agonist, effectively increases the adiponectin concentration and adipogenic gene expression, and stimulates the conversion of BSC to adipocyte-like cells in the absence of adipocyte differentiation cocktail.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2001년도 춘계학술발표대회
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• pp.51-51
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• 2001

Cocaine and amphetamine-regulated transcript (CART) is a satiety factor that is regulated by leptin. It was reported that the mice intracerebroventricularly injected with CART showed behavioral changes resembled with the typical behavioral alterations found in the mice carrying disorders in the brain serotonergic (5-HT) system. Hence, this study was conducted to find out the relationships between CART and 5-HT. We first examined the mRNA levels of CART after the injections of para-chlorophenylalanine (pCPA, 300 mg/kg i.p., single injection or daily for three consecutive days) in the rat brains by in situ hybridization using the mouse CART cDNA probe cloned in our laboratory. Systemic administrations of pCPA, a potent inhibitor of tryptophan hydroxylase, the rate limiting enzyme of 5-HT biosynthesis, acutely depletes the brain 5-HT transporter (5-HTT) in the dorsal raphe nucleus (DRN), which reuptakes terminal 5-HT. Results indicated that the mRNA level of CART significantly decreased in the arcuate nucleus, paraventricular nucleus, and lateral hypothalamic nucleus by three days of daily injection with pCPA with no noticeable change detected 24 hrs after the single injection. The message levels of 5-HTT in DRN decreased in both single and three days of injections. Secondly, to investigate whether CART affect to 5-HT, mouse genomic CART gene, which is consist of 3 exons and 2 introns and mouse neurofilament light (NF-L) chain promoter were cloned. Then, we constructed neuron specific expression vector, which was transfected into HeLa cell using lipid-mediated transfection system. Expression of GFP and CART linked to NF-L-chain promoter in the transfected HeLa cell were detected by using fluorescent microscope and RT-PCR. These results confirmed normal expression of DNA constructs in vitro. Then, to increase brain specific expression of CART in vivo transgenic mice carrying CART gene controlled the deleted NF-L-chain promoter were generated by the DNA microinjection into pronuclei of fertilized embryos. Transgenic mice were detected by Southern blot. Further study is necessary to examine CART expression and 5-HTT in these transgenic mice. Therefore, these results suggest that there maybe a positive molecular correlation between CART and 5-HT in responding to the stimuli.

• Biomolecules & Therapeutics
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• 제32권1호
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• pp.84-93
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• 2024

Rosmarinic acid (RA) is a phenolic ester that protects human keratinocytes against oxidative damage induced by ultraviolet B (UVB) exposure, however, the mechanisms underlying its effects remain unclear. This study aimed to elucidate the cell signaling mechanisms that regulate the antioxidant activity of RA and confirm its cyto-protective role. To explore the signaling mechanisms, we used the human keratinocyte cell line HaCaT and SKH1 hairless mouse skin. RA enhanced glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS) expression in HaCaT cells in a dose- and time-dependent manner. Moreover, RA induced nuclear factor erythroid-2-related factor 2 (NRF2) nuclear translocation and activated the signaling kinases protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the ERK inhibitor U0126, and small interfering RNA (siRNA) gene silencing suppressed RA-enhanced GCLC, GSS, and NRF2 expression, respectively. Cell viability tests showed that RA significantly prevented UVB-induced cell viability decrease, whereas the glutathione (GSH) inhibitors buthionine sulfoximine, LY294002, and U0126 significantly reduced this effect. Moreover, RA protected against DNA damage and protein carbonylation, lipid peroxidation, and apoptosis caused by UVB-induced oxidative stress in a concentration-dependent manner in SKH1 hairless mouse skin tissues. These results suggest that RA protects against UVB-induced oxidative damage by activating AKT and ERK signaling to regulate NRF2 signaling and enhance GSH biosynthesis. Thus, RA treatment may be a promising approach to protect the skin from UVB-induced oxidative damage.