• 제목/요약/키워드: CrebA

검색결과 173건 처리시간 0.023초

홍화씨와 흰민들레 복합물의 Scopolamine 유도 기억력 손상에 대한 보호 효과 (Protective Effects of Combination of Carthamus tinctorius L. Seed and Taraxacum coreanum on Scopolamine-induced Memory Impairment in Mice)

  • 김지현;;김민조;박찬흠;이재양;신유수;조은주
    • 한국약용작물학회지
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    • 제28권2호
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    • pp.85-94
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    • 2020
  • Background: Alzheimer's disease (AD) is caused by various factors, such as cholinergic dysfunction, regulation of neurotrophic factor expression, and accumulation of amyloid-beta. We investigated whether or not a combination of Carthamus tinctorius L. seed and Taraxacum coreanum (CT) has a protective effect on scopolamine-induced memory impairment in a mouse model. Methods and Results: Mice were orally pretreated with CT (50, 100 and 200 mg/kg/day) for 14 days, and scopolamine (1 mg/kg/day) was injected intraperitoneally before subjecting them to behavior tests. CT-administered mice showed better novel object recognition and working memory ability than scopolamine-treated control mice. In T-maze and Morris water maze tests, CT (100 and 200 mg/kg/day) significantly increased space perceptive ability and occupancy to the target quadrant, respectively. In addition, 100 and 200 mg/kg/day of CT attenuated cholinergic dysfunction through inhibition of butyryl cholinesterase in brain tissue. Furthermore, CT-administered mice showed higher cyclic adenosine monophosphate-response element-binding protein (CREB) levels and lower amyloid precursor protein (APP) levels compared to scopolamine-treated control mice. Conclusions: CT improved scopolamine-induced memory impairment through inhibition of cholinergic dysfunction, up-regulation of CREB, and down-regulation of APP. Therefore, CT could be a useful therapeutic agent for AD with protective effects on cognitive impairment.

Papaverine Exerts Neuroprotective Effect by Inhibiting NLRP3 Inflammasome Activation in an MPTP-Induced Microglial Priming Mouse Model Challenged with LPS

  • Leem, Yea-Hyun;Park, Jin-Sun;Park, Jung-Eun;Kim, Do-Yeon;Kim, Hee-Sun
    • Biomolecules & Therapeutics
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    • 제29권3호
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    • pp.295-302
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    • 2021
  • Microglial priming is the process of microglial proliferation and activation in response to neurodegeneration and abnormal protein accumulation. Priming makes microglia susceptible to secondary inflammatory stimuli and causes exaggerated inflammatory responses. In the present study, we established a microglial priming model in mice by administering a single injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg). MPTP induced microglial activation without dopaminergic degeneration; however, subsequent treatment with a sub-toxic dose of lipopolysaccharides (LPS) induced an amplified inflammatory response and caused nigrostriatal dopaminergic degeneration. These pathological and inflammatory changes, including microglial activation and dopaminergic cell loss in the substantia nigra (SN) area were reversed by papaverine (PAP) administration. In addition, MPTP/LPS enhanced interleukin-1β (IL-1β) expression and processing via nod-like receptor protein 3 (NLRP3) inflammasome activation in the SN region of mice. However, PAP treatment suppressed inflammasome activation and subsequent IL-1β maturation. Moreover, PAP inhibited nuclear factor-κB (NF-κB) and enhanced cAMP-response element binding protein (CREB) activity in the SN of MPTP/LPS mice. These results suggest that PAP inhibits the activation of NLRP3 inflammasome by modulating NF-κB and CREB signaling pathways, which results in reduced microglial activation and neuronal cell death. Thus, PAP may be a potential candidate for the treatment of Parkinsons's disease, which is aggravated by systemic inflammation.

Enhancement of skin barrier and hydration-related molecules by protopanaxatriol in human keratinocytes

  • Lee, Jeong-Oog;Hwang, So-Hyeon;Shen, Ting;Kim, Ji Hye;You, Long;Hu, Weicheng;Cho, Jae Youl
    • Journal of Ginseng Research
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    • 제45권2호
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    • pp.354-360
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    • 2021
  • Background: Protopanaxatriol (PPT) is a secondary intestinal metabolite of ginsenoside in ginseng. Although the effects of PPT have been reported in various diseases including cancer, diabetes and inflammatory diseases, the skin protective effects of PPT are poorly understood. Methods: HaCaT cells were treated with PPT in a dose-dependent manner. mRNA and protein levels which related to skin barrier and hydration were detected compared with retinol. Luciferase assay was performed to explore the relative signaling pathway. Western blot was conducted to confirm these pathways and excavated further signals. Results: PPT enhanced the expression of filaggrin (FLG), transglutaminase (TGM)-1, claudin, occludin and hyaluronic acid synthase (HAS) -1, -2 and -3. The mRNA expression levels of FLG, TGM-1, HAS-1 and HAS-2 were suppressed under NF-κB inhibition. PPT significantly augmented NF-κB-luc activity and upregulated Src/AKT/NF-κB signaling. In addition, PPT also increased phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK, JNK and p38 and upstream MAPK activators (MEK and MKK). Furthermore, transcriptional activity of AP-1 and CREB, which are downstream signaling targets of MAPK, was enhanced by PPT. Conclusion: PPT improves skin barrier function and hydration through Src/AKT/NF-κB and MAPK signaling. Therefore, PPT may be a valuable component for cosmetics or treating skin disorders.

황칠(黃漆)이 만성 스트레스 유발 백서의 스트레스 및 수면 호르몬에 미치는 영향 (Effect of Resina Dendropanacis Morbiferus on Stress and Sleep Hormone in Chronic Mild Stress-Induced Rats)

  • 송영길;김경옥
    • 동의신경정신과학회지
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    • 제28권3호
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    • pp.287-302
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    • 2017
  • Objectives: To evaluate effects of Resina Dendropanacis Morbiferus (RDM) on stress and sleep hormones when administered to Chronic Mild Stressed (CMS) rats. Methods: Twenty-five healthy rats were randomly divided into 5 groups; Normal, CMS (Control), Resina Dendropanacis Mobiferus 50 mg/kg (RDM 50), 100 mg/kg (RDM 100), and 200 mg/kg (RDM 200). All rats except the normal group were exposed to unpredicted stress conditions such as water deprivation, empty bottles, forced thread mill, etc. according to timetable of CMS for 3 weeks. After a week starting experiments, rats in RDM 50, RDM 100, and RDM 200 groups were fed orally once a day for 2 weeks. Afterward, blood samples were taken from rats to analyze complete blood count, AST, ALT, and glucose. Noradrenalin, GABA and Melatonin were measured by ELISA kit. BDNF, CREB and TrkB were measured by RT-PCT. Results: 1. In Noradrenalin content, RDM 100 and RDM 200 groups revealed significant decrease compared to the control group. 2. In GABA content, RDM 50 and RDM 100 groups revealed significant decrease compared to the control group. 3. In Melatonin content, RDM 100 and 200 groups revealed significant decrease compared to the control group. 4. In Activity of BDNF, RDM 100 and 200 groups revealed significant increase compared to the control group. 5. In Activity of CREB and TrkB, RDM 100 group revealed significant increase compared to the control group. 6. In Erythrocyte and Thrombocyte changes, red blood cells and hematocrit significantly increased in RDM 50 and RDM 200 groups than the control group. Hemoglobin and platelet significantly increased in all experimental groups and the control group. 7. In Weight gain content, all RDM groups revealed insignificant increase compared to the control group. 8. In Glucose content, RDM 50, RDM 100, and RDM 200 groups revealed significant decrease compared to the control group. Conclusions: Results suggest that RDM have effects on stress and sleep hormones when administered to Chronic Mild Stressed (CMS) rats.

Imipramine Ameliorates Depressive Symptoms by Blocking Differential Alteration of Dendritic Spine Structure in Amygdala and Prefrontal Cortex of Chronic Stress-Induced Mice

  • Leem, Yea-Hyun;Yoon, Sang-Sun;Jo, Sangmee Ahn
    • Biomolecules & Therapeutics
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    • 제28권3호
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    • pp.230-239
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    • 2020
  • Previous studies have shown disrupted synaptic plasticity and neural activity in depression. Such alteration is strongly associated with disrupted synaptic structures. Chronic stress has been known to induce changes in dendritic structure in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC), but antidepressant effect on structure of these brain areas has been unclear. Here, the effects of imipramine on dendritic spine density and morphology in BLA and mPFC subregions of stressed mice were examined. Chronic restraint stress caused depressive-like behaviors such as enhanced social avoidance and despair level coincident with differential changes in dendritic spine structure. Chronic stress enhanced dendritic spine density in the lateral nucleus of BLA with no significant change in the basal nucleus of BLA, and altered the proportion of stubby or mushroom spines in both subregions. Conversely, in the apical and basal mPFC, chronic stress caused a significant reduction in spine density. The proportion of stubby or mushroom spines in these subregions overall reduced while the proportion of thin spines increased after repeated stress. Interestingly, most of these structural alterations by chronic stress were reversed by imipramine. In addition, structural changes caused by stress and blocking the changes by imipramine were corelated well with altered activation and expression of synaptic plasticity-promoting molecules such as phospho-CREB, phospho-CAMKII, and PSD-95. Collectively, our data suggest that imipramine modulates stress-induced changes in synaptic structure and synaptic plasticity-promoting molecules in a coordinated manner although structural and molecular alterations induced by stress are distinct in the BLA and mPFC.

형방도적산(荊防導赤散)이 급성코카인 투여로 인해 유도된 흰쥐의 행동량과 c-Fos 발현에 미치는 영향 (Effect of Hyeongbangdojeok-san on Acute Cocaine-induced Behavioral Effect and Immediate Early Gene Expression in Rats.)

  • 서지용;최애련;구덕모
    • 사상체질의학회지
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    • 제22권4호
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    • pp.65-76
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    • 2010
  • 1. Objectives The present study was designed to investigate the effect of Soyangin Hyeongbangdojeok-san(HBDJS) on acute cocaine-induced behavior effect and gene expression in the rat brain. 2. Methods Experimental animals were composed of saline(SAL), cocaine(COC), HBDJS + COC, HBDJS + SAL group. Rats received HBDJS(100, 200 mg/kg, p.o.) 1 h prior to cocaine hydrochloride(20 mg/kg, i.p.) treatment respectively. After cocaine injection, locomotor activity and rearing were measured in a rectangular container equipped with a video camera above the center of the floor for 60 min. In addiction, c-Fos expression in the rat brain was detected using immunohistochemistry 2 h after cocaine injection. And the effect of HBDJS on acute cocaine-induced pERK, pElk, pCREB upstream of c-Fos expression was detected using western blotting and immunohistochemistry 15 min after cocaine challenge. 3. Results The present results show that HBDJS at dose of 200 mg/kg attenuated cocaine-induced both locomotor activity and rearing. Also HBDJS at dose of 200 mg/kg significantly decreased c-Fos expression in the rat brain(nucleus accumebns and striatum). However HBDJS at dose of 200 mg/kg have no effect on cocaine-induced pERK, pCREB, pElK-1 expression. HBDJS is c-Fos expression through ERK-independent pathway. 4. Conclusions. These results suggest that HBDJS may be effective in suppressing the reinforcing effects of cocaine.

산딸기 잎 추출물이 멜라닌 생성에 미치는 영향 (Effect of Rubus crataefifolius Leaf Extract on Melanin Synthesis)

  • 김미경;김대용
    • 한국응용과학기술학회지
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    • 제38권3호
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    • pp.883-890
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    • 2021
  • 본 연구는 B16F10 melanoma 세포에서 산딸기 잎 추출물(Rubus crataefifolius Leaf Extract, RCLE)의 멜라닌 생성 억제 효과를 확인하고자 수행되었다. α-MSH로 자극한 B16F10 melanoma 세포에서 멜라닌 함량과 tyrosinase 활성, 멜라닌 생성관련 효소들인 TRP-1, TRP-2 및 MITF의 단백질 발현 수준을 조사하였고 이에 대한 RCLE의 효과를 검증하였다. RCLE는 tyrosinase 활성과 멜라닌 생성을 효과적으로 억제하였고 멜라닌 생성 경로에 관여하는 PKA와 CREB의 인산화와 MITF의 발현을 억제하였으며 멜라닌 생성 관련 단백질의 발현을 하향 조절하였다. 이러한 결과는 RCLE가 MITF 발현을 억제하여 α-MSH로 자극된 멜라닌 합성을 억제한다는 것을 보여준다. 따라서 이러한 연구결과는 RCLE가 과도한 멜라닌 생성으로 인한 색소 침착을 완화시킬 수 있는 기능성 화장품 소재로 활용될 수 있음을 시사한다.

초밀집 이종 이동 통신망을 위한 적응형 셀 선택 기법 (An Adaptive Cell Selection Scheme for Ultra Dense Heterogeneous Mobile Communication Networks)

  • 조정연;반태원;정방철
    • 한국정보통신학회논문지
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    • 제19권6호
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    • pp.1307-1312
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    • 2015
  • 스마트폰의 대중화에 따라 무선 데이터 트래픽이 기하급수적으로 증가하고 있으며, 이러한 데이터 트래픽을 원활히 수용하기 위하여 차세대 이동통신 네트워크에 대한 연구가 활발히 진행 중이다. 특히, 매크로 셀과 소형 셀을 활용하여 공간 재활용성을 높임으로써 네트워크 용량을 획기적으로 개선할 수 있는 이종 이동 통신망이 많은 관심을 끌고 있다. 이종 이동 통신망에서는 매크로 기지국과 소형 기지국 간의 송신전력의 차이로 인하여 부하 불균형과 간섭등의 문제가 발생하며, 이를 해결하기 위하여 cell range expansion (CRE) 기술을 활용한다. 본 논문에서는, 초밀집 이종 이동 통신망 에서 CRE bias (CREB)를 적응적으로 적용하는 새로운 셀 선택 방식을 제안하고 시스템 레벨 시뮬레이션을 통하여 셀 평균 전송률을 분석하고, 기존의 셀 선택 방식과 비교 한다.

Effect of Beta-Asarone on Impairment of Spatial Working Memory and Apoptosis in the Hippocampus of Rats Exposed to Chronic Corticosterone Administration

  • Lee, Bombi;Sur, Bongjun;Cho, Seong-Guk;Yeom, Mijung;Shim, Insop;Lee, Hyejung;Hahm, Dae-Hyun
    • Biomolecules & Therapeutics
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    • 제23권6호
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    • pp.571-581
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    • 2015
  • ${\beta}$-asarone (BAS) is an active component of Acori graminei rhizoma, a traditional medicine used clinically in treating dementia and chronic stress in Korea. However, the cognitive effects of BAS and its mechanism of action have remained elusive. The purpose of this study was to examine whether BAS improved spatial cognitive impairment induced in rats following chronic corticosterone (CORT) administration. CORT administration (40 mg/kg, i.p., 21 days) resulted in cognitive impairment in the avoidance conditioning test (AAT) and the Morris water maze (MWM) test that was reversed by BAS (200 mg/kg, i.p). Additionally, as assessed by immunohistochemistry and RT-PCR analysis, the administration of BAS significantly alleviated memory-associated decreases in the expression levels of brain-derived neurotrophic factor (BDNF) and cAMP-response element-binding protein (CREB) proteins and mRNAs in the hippocampus. Also, BAS administration significantly restored the expression of Bax and Bcl-2 mRNAs in the hippocampus. Thus, BAS may be an effective therapeutic for learning and memory disturbances, and its neuroprotective effect was mediated, in part, by normalizing the CORT response, resulting in regulation of BDNF and CREB functions and anti-apoptosis in rats.

매괴화(玫瑰花) 에탄올추출물이 α-MSH로 유도된 과색소 형성 억제와 작용기전 연구 (Inhibitory Effect of the Ethanol Extract of Rosae rugosae Flos on the Hyperpigmentation and its Action Mechanism Induced by α-MSH)

  • 이진호;인명희;강석훈;문연자;우원홍;임규상
    • 한방안이비인후피부과학회지
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    • 제28권1호
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    • pp.41-52
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    • 2015
  • Objective : This study investigated the inhibitory mechanism of the hypopigmentating effects on ethanol extract of Rosae rugosae Flos (ERR) that has not yet been examined. Methods : We analyzed the anti-melanogenic effects of ethanol extracts from Rosae rugosae Flos by tyrosinase activity, melanin contents. We also examined protein expression levels of tyrosinase, TRP-1, TRP-2, MITF and ERK by western blot analysis in melanoma cells. Results : In this investigation, ERR effectively reduced ${\alpha}$-MSH-stimulated melanin synthesis by suppressing expression of tyrosinase and tyrosinase-related protein-1 (TRP-1). On the other hand, the expression of tyrosinase-related protein-2 (TRP-2) were not affected by treatment with ERR. ERR inhibited the expression of microphthalmia-associated transcription factor (MITF) as a key transcription factor for tyrosinase expression regulating melanogenesis. The upstream signaling pathway including cAMP response element-binding protein (CREB) and MAPKs were also inhibited by ERR. Pretreatment with PD98059, ERK inhibitor, attenuated the inhibitory effect of ERR on ${\alpha}$-MSH-induced tyrosinase activity. Conclusions : Our study suggested that the anti-melanogenic activity of ERR is correlated with the suppression of tyrosinase gene through CREB/MITF/ERK pathway.