• Title/Summary/Keyword: potential induced degradation

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Reconsideration of Classical Antibiotic Lincomycin: Anti-inflammatory Effect in LPS-stimulated RAW 264.7 Cells

  • Yang, Eun-Jin;Lee, Nari;Hyun, Chang-Gu
    • Microbiology and Biotechnology Letters
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    • v.48 no.3
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    • pp.366-372
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    • 2020
  • Since, side effects of antibiotics are frequently emphasized these days, their use is gradually diminishing, and alternative drugs are being developed. We have sought to reintroduce them as raw materials for human health as conventional 'weapons' that have been retired after their historical duties. In this study, we investigated the anti-inflammatory effects of lincomycin (LIN), on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our findings show that LIN potently inhibited production of LPS-induced proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), without cytotoxicity. Consistent with these findings, LIN strongly decreased protein expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX-2). Furthermore, LIN reduced pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. To further elucidate the mechanisms of these inhibitory effects of LIN, we studied LPS-induced IκB-α degradation, and mitogen-activated protein kinase (MAPK) phosphorylation. LIN suppressed downregulation of inhibitory κB (IκB-α) degradation, and the phosphorylation of the c-Jun N-terminal kinase (JNK) pathway. Based on these results, we suggest that LIN may be considered a potential candidate as an anti-inflammatory cosmetic or a medicine for human health.

Antimelanogenic Effect of Taurine in Murine Melanoma B16F10 Cells (B16F10 Murine Melanoma 세포에서 멜라닌생성억제에 대한 타우린의 효과)

  • Joung, Hyo-Sook;Song, Kyung-Hee;Kim, An-Keun
    • YAKHAK HOEJI
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    • v.51 no.5
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    • pp.350-354
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    • 2007
  • Taurine has been shown to be tissue-protective against oxidant-induced injury and is a powerful regulator of the immune system. However, there is no study on the antimelanogenic effect of taurine. In this study, we investigated the whitening effect of taurine in B16F10 mouse melanoma cells. Cell viability was measured by MTT assay. We examined melanin contents and tyrosinase activity according to time and concentration. Extracellular signal regulated kinase (ERK) is an important regulator of melanogenesis. It has been reported that activated ERK induced microphthalmia associated transcription factor (MITF) phosphorylation and its subsequent degradation and thus reduced melanin synthesis. In our B16F10 cell culture system, taurine led to decrease melanin contents by 21% at 48 hr. We then observed taurine effects on ERK-P, MITF and tyrosinase by Western blot. ERK was activated at 18 hr and 24 hr, whereas MITF reduced. We could not observe any differences in the levels of tyrosinase. These results suggested that taurine inhibited melanogenesis by ERK signal pathway via MITF degradation. We expect that taurine has potential skin whitening agents in cosmetics.

Autophagy and Longevity

  • Nakamura, Shuhei;Yoshimori, Tamotsu
    • Molecules and Cells
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    • v.41 no.1
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    • pp.65-72
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    • 2018
  • Autophagy is an evolutionally conserved cytoplasmic degradation system in which varieties of materials are sequestered by a double membrane structure, autophagosome, and delivered to the lysosomes for the degradation. Due to the wide varieties of targets, autophagic activity is essential for cellular homeostasis. Recent genetic evidence indicates that autophagy has a crucial role in the regulation of animal lifespan. Basal level of autophagic activity is elevated in many longevity paradigms and the activity is required for lifespan extension. In most cases, genes involved in autophagy and lysosomal function are induced by several transcription factors including HLH-30/TFEB, PHA-4/FOXA and MML-1/Mondo in long-lived animals. Pharmacological treatments have been shown to extend lifespan through activation of autophagy, indicating autophagy could be a potential and promising target to modulate animal lifespan. Here we summarize recent progress regarding the role of autophagy in lifespan regulation.

Effects of Gwibitang on Glutamate-induced Apoptosis in C6 Glial Cells (귀비탕이 Glutamate에 의한 C6 Glial Cell의 Apoptosis에 미치는 영향)

  • 강익현;이인;한상혁;문병순
    • The Journal of Korean Medicine
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    • v.22 no.4
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    • pp.45-57
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    • 2001
  • Objectives : The water extract of Gwibitang (GBT) has been traditionally used for treatment of psychologic disease and brain damage in Oriental Medicine, This study was designed to investigate the effect of GBT on the glutamate-induced toxicity of rat C6 glial cells. Methods : The cultured cells were pretreated with GBT and exposed to glutamate, The cell damage was assessed by using MTT assay and Hoechst, IC-l staining, Results : GBT had protective effects in glutamate-induced cytotoxicity, which was revealed as apoptosis characterized by chromatic condensation and the loss of mitochondrial membrane potential in C6 glial cells. However, GBT and glutamate had no effect in the activation of caspase family cysteine proteases including caspase-3, -8 and -9 proteasesin C6 glial ce]]s, GBT significantly recovered the depletion of GSH and inhibited the generation of $H_2O_2$ by glutamate in C6 glial cells. In addition, both GBT and antioxidants such as GSH and NAC protected the glutamate-induced cytotoxicity in C6 glial cells, indicating that GBT possibly has antioxidative effect. Moreover, GBT also inhibited the glutamate-induced degradation of $IkB{\alpha}$ in C6 glial cells, This result suggest that GBT has some inhibitory effects on the transcriptional activation of $NF-_{k}B$. Conclusions : GBT has protective effects in glutamate-induced cytotoxicity via an antioxidative mechanism.

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Quercitrin Gallate Down-regulates Interleukin-6 Expression by Inhibiting Nuclear Factor-kB Activation in Lipopolysaccharide-stimulated Macrophages

  • Min, Kyung-Rak;Kim, Byung-Hak;Chang, Yoon-Sook;Kim, Young-Soo
    • Natural Product Sciences
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    • v.12 no.2
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    • pp.113-117
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    • 2006
  • Quercitrin gallate was previously isolated from Persicaria lapathifolia (Polygonaceae) as an inhibitor of superoxide production. In the present study, quercitrin gallate was found to inhibit interleukin (IL)-6 production in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 with an $IC_{50}$ value of $63\;{\mu}M$. Furthermore, quercitrin gallate attenuated LPS-induced synthesis of IL-6 transcript but also inhibited LPS-induced IL-6 promoter activity, indicating that the compound could down-regulate IL-6 expression at the transcription level. Since nuclear factor (NF)-kB has been shown to play a key role in LPS-inducible IL-6 expression, an effect of quercitrin gallate on LPS-induced NF-kB activation was further analyzed. Quercitrin gallate exhibited a dosedependent inhibitory effect on LPS-induced nuclear translocation of NF-kB without affecting inhibitory kB (IkB) degradation, and subsequently inhibited LPS-induced NF-kB transcriptional activity in macrophages RAW 264.7. Taken together, quercitrin gallate down-regulated LPS-induced IL-6 expression by inhibiting NF-kB activation, which could provide a pharmacological potential of the compound in IL-6-related immune and inflammatory diseases.

Rodgersia podophylla Leaves Suppress Inflammatory mediators through activation of Nrf2/HO-1 signaling, and inhibition of LPS-induced NF-κB and MAPKs signaling in RAW264.7 cells

  • Kim, Ha Na;Kim, Jeong Dong;Park, Su Bin;Jeong, Jin Boo
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.04a
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    • pp.94-94
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    • 2019
  • In this study, we elucidated the anti-inflammatory mechanisms of leaves extracts from Rodgersia podophylla (RPL) in RAW264.7 cells. RP-L significantly inhibited the production of the proinflammatory mediators such as NO, iNOS, IL-$1{\beta}$ and IL-6 in LPS-stimulated RAW264.7 cells. RPL increased HO-1 expression in RAW264.7 cells, and the inhibition of HO-1 by ZnPP reduced the inhibitory effect of RPL against LPS-induced NO production in RAW264.7 cells. Inhibition of p38, ROS and $GSK3{\beta}$ attenuated RPL-mediated HO-1 expression. Inhibition of ROS inhibited p38 phosphorylation and $GSK3{\beta}$ expression induced by RPL. In addition, inhibition of $GSK3{\beta}$ blocked RPL-mediated p38 phosphorylation. RPL induced nuclear accumulation of Nrf2, and Inhibition of p38, ROS and $GSK3{\beta}$ abolished RPL-mediated nuclear accumulation of Nrf2. Furthermore, RPL blocked LPS-induced degradation of $I{\kappa}B-{\alpha}$ and nuclear accumulation of p65. RP-L also attenuated LPS-induced phosphorylation of ERK1/2 and p38. Our results suggest that RPL exerts potential antiinflammatory activity by activating ROS/$GSK3{\beta}$/p38/Nrf2/HO-1 signaling and inhibiting NF-${\kappa}B$ and MAPK signaling in RAW264.7 cells. These findings suggest that RPL may have great potential for the development of anti-inflammatory drug.

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The effect of Sagunja-tang on TNBS-induced Inflammatory Bowel Disease in Mouse (사군자탕(四君子湯)이 TNBS로 유발(誘發)된 생쥐의 염증성(炎症性) 장질환(腸疾患)에 미치는 영향(影響))

  • Hong, Sang-Sun;Ryu, Bong-Ha;Yoon, Seong-Woo;Kim, Jin-Sung
    • The Journal of Internal Korean Medicine
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    • v.31 no.4
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    • pp.731-751
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    • 2010
  • Objectives : The present study aimed to find out the effect of Sagunja-tang on the prevention and treatment of inflammatory bowel disease using mice with TNBS-induced inflammatory bowel disease. Methods : Mice with TNBS-induced inflammatory bowel disease were medicated with Sagunja-tang, and the weight changes, colon length, lipid peroxidation, and myeloperoxidase activity were observed. Levels of the inflammatory markers interleukin (IL)-$1{\beta}$ and cyclooxygenase-2 (COX-2), its transcription factor activation, phospho-NF-${\kappa}$B (pp65), in the colon by enzyme-linked immunosorbent assay and immunoblot analysis were also measured. Finally, the activation of fecal bacterial enzyme, ${\beta}$-glucuronidase and degradation activation of fecal glycosaminoglycan (GAG) and hyaluronic acid were observed. Results : We found that oral administration of Sagunja-tang inhibited TNBS-induced colon shortening and also inhibited myeloperoxidase activity in the colon of mice as well as IL-$1{\beta}$ and COX-2 expression. Sagunja-tang also inhibited TNBSinduced lipid peroxidation and pp65 activation in the colon of mice. In addition, Sagunja-tang inhibited ${\beta}$-glucuronidase activation and fecal hyaluronic acid degradation activation. Conclusions : It is supposed that Sagunja-tang has a potential therapeutic effect on inflammatory bowel disease through the inhibition of both NF-${\kappa}$B activation and lipid peroxidation, and the improvement of intestinal conditions.

Protective Effect of Gryllus Bimaculatus Methanol Extract on UVB-induced Photoaging in Human Skin Fibroblasts (UVB로 손상된 피부 섬유아세포에서 쌍별귀뚜라미 메탄올 추출물의 보호효과)

  • Jeong, Taekyoung;Yu, Myeongnam;Heo, Huijin;Yang, Jinwoo;Jeong, Heonsang;Lee, Junsoo
    • Journal of the Korean Society of Food Culture
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    • v.35 no.5
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    • pp.478-482
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    • 2020
  • We evaluated the protective effects of cricket methanol extract (CME) on ultra-violet B (UVB)-induced photoaging in human skin fibroblasts. The fibroblast cells were treated with 10, 50, and 100 ㎍/mL of CME for 24 h, and then exposed to UVB (30 mJ/㎠). CME showed a dose-dependent cytoprotective effect without any observable cytotoxicity. CME reduced UVB-induced production of reactive oxygen species (ROS) by 34.4, 34.9, 40.6% at concentrations of 10, 50, 100 ㎍/mL respectively. CME inhibited the release of matrix metalloproteinase (MMP) 1 and 3. Furthermore, CME also reduced UVB-induced collagen degradation in the fibroblast cells. Taken together, our data suggests that CME has a significant protective effect on UVB-induced photoaging of the skin. This benefit occurs through multiple mechanisms. The results also suggest a potential role for CME as an ingredient in anti-photoaging cosmetic products in the future.

Lycorine induces apoptosis by enhancing protein degradation of survivin in human oral cancer cell lines (Lycorine의 사람 구강 암 세포주에서 survivin 단백질 분해 증진으로 세포자멸사 유도)

  • Jeong, Joseph H.;Cho, Nam-Pyo;Jang, Boonsil
    • The Korean Journal of Oral and Maxillofacial Pathology
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    • v.41 no.1
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    • pp.1-7
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    • 2017
  • Lycorine, a natural alkaloid extracted from the Amaryllidaceae plant family, was reported to various physiological and pharmacological effects including anti-cancer activity. Nevertheless, there is no report of the anticancer effect of lycorine in oral cancer cells. The effects of lycorine on cell proliferation and apoptosis were examined through trypan blue exclusion assay, 4'-6-diamidino-2-phenylindole (DAPI) stain, Live/Dead assay, Western blot analysis and RT-PCR. Lycorine suppressed cell viability and induced apoptosis in MC3 and HSC-3 cell lines. Lycorine decreased survivin protein but did not affect its mRNA. It regulated survivin through accelerating protein degradation in a time-dependent manner although neither proteasome nor lysosome was not associated with lycorine-mediated protein degradation. Collectively, our results suggest that lycorine may be a potential therapeutic anti-cancer drug candidate for the treatment of human oral cancer.

Long-Term Performance of Amorphous Silicon Solar Cells with Stretched Exponential Defect Kinetics and AMPS-1D Simulation (비정질실리콘 태양전지에 대한 장시간 성능예측: 확장지수함수 모형 및 컴퓨터 모의실험)

  • Park, S.H.;Lyou, Jong-H.
    • Journal of the Korean Vacuum Society
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    • v.21 no.4
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    • pp.219-224
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    • 2012
  • We study for long-term performance of amorphous silicon solar cells under light exposure. The performance is predicted with a kinetic model in which the carrier lifetimes are determined by the defect density. In particular, the kinetic model is described by the stretched-exponential relaxation of defects to reach equilibrium. In this report, we simulate the light-induced degradation of the amorphous silicon solar cells with the kinetic model and AMPS-1D computer program. And data measured for outdoor performances of various solar cells are compared with the simulated results. This study focuses on examining the light-induced degradation for the following amorphous silicon pin solar cells: thickness${\approx}$300 nm, built-in potential${\approx}$1.05 V, defect density (at t=0)${\approx}5{\times}10^{15}cm^{-3}$, short-circuit current density (at t=0)${\approx}15.8mA/cm^2$, fill factor (at t=0)${\approx}0.691$, open-circuit voltage (at t=0)${\approx}0.865V$, conversion efficiency (at t=0)${\approx}9.50%$.