• 제목/요약/키워드: suppressive effects

검색결과 413건 처리시간 0.038초

Amelioration of Cognitive Dysfunction in APP/PS1 Double Transgenic Mice by Long-Term Treatment of 4-O-Methylhonokiol

  • Jung, Yu-Yeon;Lee, Young-Jung;Choi, Dong-Young;Hong, Jin Tae
    • Biomolecules & Therapeutics
    • /
    • 제22권3호
    • /
    • pp.232-238
    • /
    • 2014
  • Alzheimer's disease (AD) is the most common neurodegenerative disease without known ways to cure. A key neuropathologic manifestation of the disease is extracellular deposition of beta-amyloid peptide (Ab). Specific mechanisms underlying the development of the disease have not yet been fully understood. In this study, we investigated effects of 4-O-methylhonokiol on memory dysfunction in APP/PS1 double transgenic mice. 4-O-methylhonokiol (1 mg/kg for 3 month) significantly reduced deficit in learning and memory of the transgenic mice, as determined by the Morris water maze test and step-through passive avoidance test. Our biochemical analysis suggested that 4-O-methylhonokiol ameliorated $A{\beta}$ accumulation in the cortex and hippocampus via reduction in beta-site APP-cleaving enzyme 1 expression. In addition, 4-O-methylhonokiol attenuated lipid peroxidation and elevated glutathione peroxidase activity in the double transgenic mice brains. Thus, suppressive effects of 4-O-methylhonokiol on $A{\beta}$ generation and oxidative stress in the brains of transgenic mice may be responsible for the enhancement in cognitive function. These results suggest that the natural compound has potential to intervene memory deficit and progressive neurodegeneration in AD patients.

Fe-17wt%Mn 합금의 진동감쇠능에 미치는 탄소와 티타늄 첨가의 영향 (Effects of carbon content and Titanium Addition on Damping Capacity in Fe-17wt%Mn Alloy)

  • 백승한;김정철;지광구;신명철;최종술
    • 열처리공학회지
    • /
    • 제9권1호
    • /
    • pp.53-61
    • /
    • 1996
  • Effects of carbon and Ti on damping capacity are investigated in an Fe-17%Mn alloy. The suppressive force of carbon against ${\gamma}{\rightarrow}{\varepsilon}$ transformation increases linearly with an increase in its content, lowering Ms temperature and volume fraction of ${\varepsilon}$ martensite. Carbon deteriorates damping capacity by reducing the interfacial area of damping sources and mobility of the boundaries contributing to anelastic deformation. The reduction in damping capacity is accelerated when carbon-containing alloy is aged at higher temperatures above room temperature. The effect of Ti on damping capacity is found to be benificial in carbon-containing alloy, which is attributed to the depletion of carbon solute due to the formation of TiC.

  • PDF

PPARγ Physiology and Pathology in Gastrointestinal Epithelial Cells

  • Thompson, E. Aubrey
    • Molecules and Cells
    • /
    • 제24권2호
    • /
    • pp.167-176
    • /
    • 2007
  • Peroxisome proliferator-activated receptor-gamma ($PPAR{\gamma}$) is expressed at very high levels in the gastrointestinal epithelium. Many of the functions of $PPAR{\gamma}$ in gastrointestinal epithelial cells have been elucidated in recent years, and a pattern is emerging which suggests that this receptor plays an important role in gastrointestinal physiology. There is also strong evidence that $PPAR{\gamma}$ is a colon cancer suppressor in pre-clinical rodent models of sporadic colon cancer, and there is considerable interest in exploitation of $PPAR{\gamma}$ agonists as prophylactic or chemopreventive agents in colon cancer. Studies in mice and in human colon cancer cell lines suggest several mechanisms that might account for the tumor suppressive effects of $PPAR{\gamma}$ agonists, although it is not in all cases clear whether these effects are altogether mediated by $PPAR{\gamma}$. Conversely, several reports suggest that $PPAR{\gamma}$ agonists may promote colon cancer under certain circumstances. This possibility warrants considerable attention since several million individuals with type II diabetes are currently taking $PPAR{\gamma}$ agonists. This review will focus on recent data related to four critical questions: what is the physiological function of $PPAR{\gamma}$ in gastrointestinal epithelial cells; how does $PPAR{\gamma}$ suppress colon carcinogenesis; is $PPAR{\gamma}$ a tumor promoter; and what is the future of $PPAR{\gamma}$ in colon cancer prevention?

Modulation of LPS-Stimulated Astroglial Activation by Ginseng Total Saponins

  • Kim, Sok-Ho;Shim, Se-Hwan;Choi, Dea-Seung;Kim, Jong-Hoon;Kwon, Young-Bae;Kwon, Jung-Kee
    • Journal of Ginseng Research
    • /
    • 제35권1호
    • /
    • pp.80-85
    • /
    • 2011
  • Ginseng, a traditional medicine in Asian countries, is known to prevent various neuropathologic diseases such as Alzheimer's. Ginseng total saponins (GTS) in particular are one of the most effective ginseng extract compounds for neuroprotection. However, their protective effects on astrocytes are rarely reported. In pathological circumstances, astroglial activation plays a pivotal role in neuroinflammation. Subsequently, neuroinflammation induced by activated astrocytes causes brain damage. The purpose of the present study was to determine the suppressive effects of GTS on astroglial activation in lipopolysaccharide (LPS)-stimulated rat primary astrocytes. Astrocytes treated for 24 h with LPS demonstrated suppressed glialfibrillary acidic protein expression in a dose-dependent manner in the presence of GTS. GTS reduced production of proinflammatory cytokines such as tumor necrosis factor-${\alpha}$ and interleukin-1${\beta}$ and inhibited the level of inducible nitric oxide synthase, and cyclooxygenase-2 in LPS-stimulated astrocytes. Furthermore, GTS suppressed intracellular reactive oxygen species production. These modulations due to GTS may indicate neuroprotective antiinfl ammatory properties which may in turn be related to improvements in neurological performance.

CP-690550 Treatment Ameliorates Established Disease and Provides Long-Term Therapeutic Effects in an SKG Arthritis Model

  • Oh, Keunhee;Seo, Myung Won;Kim, In Gyu;Hwang, Young-Il;Lee, Hee-Yoon;Lee, Dong-Sup
    • IMMUNE NETWORK
    • /
    • 제13권6호
    • /
    • pp.257-263
    • /
    • 2013
  • Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signaling mediators have been shown to play critical roles. An increasing numbers of therapeutic options have been added for the effective control of RA. Nevertheless, there is still a category of patients that fails treatment and suffers from progressive disease. The recently developed immunosuppressant CP-690550, a small molecule JAK kinase inhibitor, has been implicated as an important candidate treatment modality for autoimmune arthritis. In this study, we evaluated the therapeutic effect of CP-690550 on established arthritis using an SKG arthritis model, a pathophysiologically relevant animal model for human RA. CP-690550 treatment revealed remarkable long-term suppressive effects on SKG arthritis when administered to the well-advanced disease (clinical score 3.5~4.0). The treatment effect lasted at least 3 more weeks after cessation of drug infusion, and suppression of disease was correlated with the reduced pro-inflammatory cytokines, including IL-17, IFN-${\gamma}$, and IL-6 and increased level of immunoregulatory IL-10.

The Inhibitory Effect of Prunioside A Acyl Derivatives on NO Production in RAW 264.7 Cell

  • Lee, Woo-Yiel;Kim, Byung-Hee;Lee, Young-Hang;Choi, Han-Gil;Jeon, Byung-Hun;Jang, Seon-Il;Kim, Young-Jun;Chung, Hun-Taeg;Kim, Young-Soon;Chai, Kyu-Yun
    • Bulletin of the Korean Chemical Society
    • /
    • 제25권10호
    • /
    • pp.1555-1558
    • /
    • 2004
  • Prunioside A is a unique, highly oxidized monoterpene glycoside isolated from the methanol extract of Spiraea prunifolia var. Simpliciflora's root. The ester derivatives were synthesized from the hydrolyzed compounds of prunioside A by ${\beta}$-glucosidase. The derivatives showed suppressive effects on the generation of nitric oxide in murine machrophage-like RAW 264.7 cells stimulated by lipopolysaccharide and interferon- ${\gamma}$.

The Biologic Effect of Millimeter Wave Irradiation Followed to Photodynamic Therapy on the Tumor

  • Ahn, Jin-Chul;Lee, Chang-Sook;Chang, So-Young;Yoon, Sung-Chul
    • 대한의생명과학회지
    • /
    • 제17권1호
    • /
    • pp.79-84
    • /
    • 2011
  • Photodynamic therapy consists of a photosensitizer, suitable light source and oxygen. The excitation of the photosensitizer at a cancer mass results in oxidation which would ultimately reduce the mass via apoptosis. Millimeter wave (MMW) therapy has also been known to be effective on cancer cell mass reduction, human cell regeneration and immunity enhancement among the Russian clinicians and scientists. In the present study, the two modalities were combined to achieve synergistic effects while reducing the administration dosage of the photosensitizer, photogem, thus minimizing the side effects. The CT-26 adenocarcinoma cell mass was implanted on mice and the tumors were exposed to a simple MMW irradiation or a combined treatment of MMW and PDT. The treatments continued for 4 weeks and the size of the tumor was measured continuously. The significant therapeutic result of MMW was not found during 4 weeks, preferably more cancer recurrence possibility after MMW irradiation was observed. The results of this study suggest that the combination of MMW irradiation and photodynamic treatment should not be recommended. The result of the MMW treatment alone, however, displayed suppressive effect on cancer cell proliferation for both in vitro and in vivo. The results of the present study suggest that the millimeter wave therapy deserves a further study.

Novel Suppressive Effects of Ketotifen on Migration and Invasion of MDA-MB-231 and HT-1080 Cancer Cells

  • Kim, Hyun Ji;Park, Mi Kyung;Kim, Soo Youl;Lee, Chang Hoon
    • Biomolecules & Therapeutics
    • /
    • 제22권6호
    • /
    • pp.540-546
    • /
    • 2014
  • The high mortality rates associated with cancer reflect the metastatic spread of tumor cells from the site of their origin. Metastasis, in fact, is the cause of 90% of cancer deaths. Therefore, considerable effort is being made to inhibit metastasis. In the present study, we screened ketotifen for anti-migratory and anti-invasive activities against MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer cells. Cancer cell migration and invasion were measured using multi-well chambers. Additionally, western blots were used to examine the effects of ketotifen on the expressions of CDC42, Rho, Rac, and matrix metalloproteinase 9 (MMP-9). The results showed that ketotifen dose-dependently suppressed the migration and invasion of MDA-MB-231 and HT-1080 cells. Ketotifen also suppressed the expressions of CDC42, Rac, and Rho, which, significantly, are involved in MDA-MB-231 and HT-1080 cancer cell migration. Moreover, ketotifen suppressed the expression and activity of MMP-9, which is involved in degradation of the extracellular matrix leading to invasion. The overall data suggested that ketotifen suppresses the migration and invasion of MDA-MB-231 and HT-1080 cancer cells via inhibition of CDC42, Rac, Rho, and MMP-9 expression.

Citron Essential Oils Alleviate the Mediators Related to Rosacea Pathophysiology in Epidermal Keratinocytes

  • Jeon, Hyeon Woo;Na, Eui Young;Yun, Sook Jung;Lee, Seung-Chul;Lee, Jee-Bum
    • Annals of dermatology
    • /
    • 제30권6호
    • /
    • pp.653-661
    • /
    • 2018
  • Background: Citron is well known for an abundance of antioxidative and anti-inflammatory ingredients such as vitamin C, polyphenol compounds, flavonoids, and limonoids. Objective: In this study, we aimed to evaluate the effects of citron essential oils on rosacea mediators in activated keratinocytes in vitro. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated with $1{\alpha}$, 25-dihydroxyvitamin $D_3$ ($VD_3$) and interleukin 33 (IL-33) with LL-37 to induce rosacea mediators such as kallikrein 5 (KLK5), cathelicidin, vascular endothelial growth factor (VEGF), and transient receptor potential vanilloid 1 (TRPV1). These mediators were analyzed by performing reverse-transcription polymerase chain reaction (PCR), quantitative real-time PCR, immunocytofluorescence and enzyme-linked immunosorbent assay after NHEKs were treated with citron seed and unripe citron essential oils. Results: The messenger RNA (mRNA) and protein levels of KLK5 and LL-37 induced by $VD_3$ were suppressed by citron seed and unripe citron essential oils. Furthermore, the mRNA and protein levels of VEGF and TRPV1 induced by IL-33 with LL-37 were also suppressed by citron essential oils. Conclusion: These results show that citron essential oils have suppressive effects on rosacea mediators in activated epidermal keratinocytes, which indicates that the citron essential oils may be valuable adjuvant therapeutic agents for rosacea.

흑삼이 폐고혈압 유발 흰쥐에 미치는 영향 (Effects of Black Ginseng on Hypertension-induced Rats)

  • 송낙근;최학주;김동희;노성수;서영배
    • 대한본초학회지
    • /
    • 제24권4호
    • /
    • pp.69-75
    • /
    • 2009
  • Objectives : To access the safety and efficacy of Black Ginseng (BG), a traditional herbal medicine on hypertension, we examined various parameters involved in the pathogenesis of hypertension. Methods : We made deoxycorticosterone acetate (DOCA;25 mg/kg/3times/weeks for 3 weeks)-induced hypertension Sprague-Dawley (SD) rats. And experiment group was treated with extract of black ginseng (BG;200 mg/kg/day). Results : In results, the weight of experiment group treated with BG was increased compared with normal and control group. And the heart and lung weights of experiment group were decreased compared with control group. The blood pressure and pulse rate of group treated with BG were significantly decreased compared with control group. In addition, BG greatly reduced the levels of aldosterone. These results suggested that BG has suppressive effects on hypertension, and BG has potential as a safe and effective therapeutics for hypertension. Conclusions : The present data show evidences on anti-hypertension activity of BG in an experimental animal system, which can provide further insights into the development of anti-hypertension therapeutic agents.