• Title/Summary/Keyword: 억제인자

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Inhibitory Activity of Wild-Simulated Ginseng against Non-Alcoholic Fatty Liver Disease in HepG-2 Cells (산양삼(Wild-Simulated Ginseng)의 비알코올성 지방간 억제활성)

  • So Jung Park;Yurry Um;Min Yeong Choi;Jin Boo Jeong
    • Korean Journal of Plant Resources
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    • v.36 no.1
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    • pp.26-31
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    • 2023
  • In this study, we investigated in vitro inhibitory activity of wild-simulated ginseng (WSG) against non-alcoholic fatty liver disease using HepG-2 cells. T0901317 treatment increased the lipid accumulation in HepG-2 cells, but WSG treatment inhibited T0901317-mediated lipid accumulation. In addition, WSG downregulated T0901317-mediated expression of SREBP-1c, ACC, FAS and SCD-1 protein. In addition, WSG increased the phosphorylation level of LKB1 and AMPK. Compound C treatment blocked WSG-mediated downregulation of SREBP-1c protein. In conclusion, WSG is considered to inhibit the accumulation of lipids and triglycerides in HepG-2 cells by inducing the activation of LKB1 and AMPK successively, thereby reducing the expression of FAS, ACC, and SCD-1 through suppression of SREBP-1c expression.

Anti-inflammatory effect of beluga lentil extract in RAW 264.7 macrophages (RAW 264.7 대식세포에서 벨루가 렌틸 추출물의 항염증 효과)

  • Hyeon-Ji Song;Syng-Ook Lee
    • Food Science and Preservation
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    • v.31 no.3
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    • pp.462-473
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    • 2024
  • The anti-inflammatory effect of beluga lentil extract (BLE) and its underlying mechanisms were investigated in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Treatment with BLE significantly decreased nitric oxide (NO) production and protein and mRNA expressions of inducible NO synthase (iNOS) in LPS-treated RAW 264.7 cells. Down-regulation of this inflammatory gene expression was not associated with NF-κB/MAPK signaling pathways, and further mechanistic studies demonstrated that BLE decreased LPS-induced iNOS expression through upregulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated heme oxygenase-1 (HO-1) expression. These results suggest that beluga lentil represent a potential source of natural anti-inflammatory agents, and further studies will be necessary to determine its anti-inflammatory effects in vivo.

Short-Term Efficacy of Steroid and Immunosuppressive Drugs in Patients with Idiopathic Pulmonary Fibrosis and Pre-treatment Factors Associated with Favorable Response (특발성폐섬유화증에서 스테로이드와 면역억제제의 단기 치료효과 및 치료반응 예측인자)

  • Kang, Kyeong-Woo;Park, Sang-Joon;Koh, Young-Min;Lee, Sang-Pyo;Suh, Gee-Young;Chung, Man-Pyo;Han, Jung-Ho;Kim, Ho-Joong;Kwon, O-Jung;Lee, Kyung-Soo;Rhee, Chong-H.
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.5
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    • pp.685-696
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    • 1999
  • Background : Idiopathic pulmonary fibrosis (IPF) is a diffuse inflammatory and fibrosing process that occurs within the interstitium and alveolus of the lung with invariably poor prognosis. The major problem in management of IPF results from the variable rate of disease progression and the difficulties in predicting the response to therapy. The purpose of this retrospective study was to evaluate the short-term efficacy of steroid and immunosuppressive therapy for IPF and to identify the pre-treatment determinants of favorable response. Method : Twenty patients of IPF were included. Diagnosis of IPF was proven by thoracoscopic lung biopsy and they were presumed to have active progressive disease. The baseline evaluation in these patients included clinical history, pulmonary function test, bronchoalveolar lavage (BAL), and chest high resolution computed tomography (HRCT). Fourteen patients received oral prednisolone treatment with initial dose of 1mg/kg/day for 8 to 12 weeks and then tapering to low-dose prednisolone (0.25mg/kg/day). Six patients who previously had experienced significant side effects to steroid received 2mg/kg/day of oral cyclophosphamide with or without low-dose prednisolone. Follow-up evaluation was performed after 6 months of therapy. If patients met more than one of followings, they were considered to be responders : (1) improvement of more than one grade in dyspnea index, (2) improvement in FVC or TLC more than 10% or improvement in DLco more than 20% (3) decreased extent of disease in chest HRCT findings. Result : One patient died of extrapulmonary cause after 3 month of therapy, and another patient gave up any further medical therapy due to side effect of steroid. Eventually medical records of 18 patients were analyzed. Nine of 18 patients were classified into responders and the other nine patients into nonresponders. The histopathologic diagnosis of the responders were all nonspecific interstitial pneumonia (NSIP) and that of nonresponders were all usual interstitial pneumonia (UIP) (p<0.001). The other significant differences between the two groups were female predominance (p<0.01), smoking history (p<0.001), severe grade of dyspnea (p<0.05), lymphocytosis in BAL fluid ($23.8{\pm}16.3%$ vs $7.8{\pm}3.6%$, p<0.05), and less honeycombing in chest HRCT findings (0% vs $9.2{\pm}2.3%$, p<0.001). Conclusion : Our results suggest that patients with histopathologic diagnosis of NSIP or lymphocytosis in BAL fluid are more likely to respond to steroid or immunosuppressive therapy. Clinical results in large numbers of IPF patients will be required to identify the independent variables.

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Bidirectional Cross-talk Between Estrogen Receptor and Growth Factor Receptors in Breast Cancer Cell (유방암세포에서 에스트로겐 수용체와 성장인자 수용체 사이의 양방향 상호작용)

  • Min, Gyesik
    • Journal of Life Science
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    • v.28 no.2
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    • pp.265-273
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    • 2018
  • Estrogen (E2) is involved in the development and progression of breast cancer and is mediated by estrogen receptor (ER). ER plays important roles in cellular proliferation, migration, invasion and causing drug resistance through diverse cross-talks with epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathways in breast cancer cells. Breast cancer is caused mainly by break-down of homeostasis of endocrine signaling pathways especially by the uncontrolled expression and increased activities of E2/IGF-1/EGF, ER/G-protein estrogen receptor (GPER)/IGF-1R/EGFR and their intracellular signaling mediators. These changes influence the complex cross-talk between E2 and growth factors' signaling, eventually resulting in the progression of cancer and resistance against endocrine regulators. Thus, elucidation of the molecular mechanisms in stepwise of the cross-talk between E2 and growth factors will contribute to the customized treatment according to the diverse types of breast cancer. In particular, as strategies for the treatment of breast cancer with diverse genotypes and phenotypes, there can be use of aromatase inhibitors and blockers of E2 action for the ER+ hormone-dependent breast cancer cells and use of IGF-1R/EGFR activity blockers for suppression of cancer cell proliferation from the cross-talk between E2 and growth factors. Furthermore, changes in the expression of the ECM molecules regulated by the cross-talk between ER and EGFR/IGF-1R can be used for the targeted therapeutics against the migration of breast cancer cells. Therefore, it is required for the cross-talk among the signaling pathways of ER, GPER, IGF-1R and EGFR concerning cancer progression to be elucidated in more detail at the molecular level.

Role of Reactive Oxygen Species in Transforming Growth Factor-β1-inuduced Fibronectin Secretion and α-Smooth Muscle Actin Expression in Human Lung Fibroblasts (사람 폐 섬유아세포의 전환성장인자-β1에 의한 fibronectin 분비와 α-smooth muscle actin 표현에 있어서 활성산소족의 역할)

  • Ha, Hunjoo;Yu, Mi-Ra;Uh, Soo-taek;Park, Choon Sik;Lee, Hi Bahl
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.3
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    • pp.267-276
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    • 2005
  • Background : The transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) plays a key role in lung fibrosis. However, the molecular mechanisms involved in $TGF-{\beta}1$-induced lung fibrosis are unclear. $TGF-{\beta}1$ is the key inducer of myofibroblast transdifferentiation via de novo synthesis of ${\alpha}-smooth$ muscle actin (${\alpha}-SMA$). Since $TGF-{\beta}1$ signals through reactive oxygen species (ROS) and ROS have been shown to induce accumulation of extracellular matrix (ECM) in various tissues, this study examined if ROS play a role in $TGF-{\beta}1$-induced fibronectin secretion and ${\alpha}-SMA$ expression in human lung fibroblasts, MRC-5 cells. Methods : Growth arrested and synchronized MRC-5 cells were stimulated with $TGF-{\beta}1$ (0.2-10 ng/ml) in the presence or absence of N-acetylcysteine (NAC) or diphenyleneiodonium (DPI) for up to 96 hours. Dichlorofluorescein (DCF)-sensitive cellular ROS were measured by FACScan and secreted fibronectin and cellular ${\alpha}-SMA$ by Western blot analysis. Results : $TGF-{\beta}1$ increased the level of fibronectin secretion and ${\alpha}-SMA$ expression in MRC-5 cells in a dosedependent manner. Both NAC (20 and 30 mM) and DPI (1 and $5{\mu}M$) significantly inhibited $TGF-{\beta}1$-induced fibronectin and ${\alpha}-SMA$ upregulation. The $TGF-{\beta}1$-induced cellular ROS level was also significantly reduced by NAC and DPI. Conclusions : The results suggest that NADPH oxidase-dependent ROS play an important role in $TGF-{\beta}1$-induced fibronectin secretion and ${\alpha}-SMA$ expression in MRC-5 cells, which leads to myofibroblast transdifferentiation and progressive lung fibrosis.

Effects of Schisandrae Fructus and Corni Fructus Extracts on the Proliferation and Expression of Prostatic Hyperplasia-inducing Factors in Dihydrotestosterone-stimulated LNCaP Human Prostate Carcinoma Cells (오미자와 산수유 추출물이 dihydrotestosterone가 처리된 LNCaP 인간 전립선 암세포의 증식 및 전립선 비대 유발 인자 발현에 미치는 영향)

  • Kim, Min Yeung;Ji, Seon Yeong;Hwangbo, Hyun;Lee, Hyesook;Kim, Tae Hee;Yoon, Seonhye;Kim, Hyun Jin;Kim, Sung Yeon;Kim, Tae Jung;Kim, Min Ji;Jung, Ha Eun;Choi, Yung Hyun
    • Journal of Life Science
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    • v.31 no.10
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    • pp.885-897
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    • 2021
  • Schisandrae Fructus (SF) and Corni Fructus (CF) have been used for a long time for the prevention and treatment of various diseases. Although reports have highlighted the possibility of inhibiting the onset and progression of benign prostatic hyperplasia (BPH), studies on related mechanisms are still lacking. In this study, we investigated the potential of SF and CF in improving BPH by using a dihydrotestosterone (DHT)-induced in vitro BPH model using LNCaP prostate carcinoma cells. According to our results, water and ethanol extracts of SF and CF significantly inhibited the proliferation of LNCaP cells by DHT treatment and markedly downregulated the expression of DHT-induced BPH biomarkers and growth factors. They also regulated the expression of apoptosis regulatory factors and significantly reduced DHT-mediated oxidative stress. In addition, the protective effect on major factors involved in the pathogenesis of BPH was more effective in the ethanol extract treatment group than in the water extract group. Furthermore, the improvement effect on BPH was higher in the 1:1 combined treatment group than in the ethanol extract alone treatment group of SF and CF, and 60% ethanol extracts showed a better effect than 40% ethanol extracts. Therefore, our findings demonstrate that SF and CF can protect against BPH by preventing the hyperproliferation of prostate cells through the inhibition of the androgen signaling pathway, which was correlated with their antioxidant activities. Therefore, SF and CF extracts may be useful in the clinical treatment of BPH, and the combination of these two extracts can be synergistic.

Regulation of Compaction by Synthesis and Phosphorylation of Protein in Preimplantation Mouse Embryo (생쥐 배아에서 단백질 합성과 인산화에 의한 밀집현상의 조절)

  • 이동률;이정은;윤현수;노성일;김문규
    • Development and Reproduction
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    • v.3 no.1
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    • pp.75-85
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    • 1999
  • To investigate the origin and action mechanism of cytoplasmic factors as regulators of morphogenesis, the embryonic development, RNA synthesis and protein phosphorylation were examined in reconstituted embryos. A half of 1-cell mouse embryo with both pronuclei was electrofused with the enucleated cytoplasm of 1- or 2-cell embryos which were cultured for 24 hrs from post 20 hrs hCG in CZB with or without cycloheximide (CHX, an inhibitor of protein synthesis; P+P-CHX group), genistein (Gen, an inhibitor of tyrosine protein kinase; P+2-Gen group) and 6-dimethylaminopurine (6-DMAP, an inhibitor of serine-threonine protein kinase; P+2-DMAP group), and co-cultured with Vero cells for 5 days. And their development, cell numbers at compaction, [5, 6-$^3$H]-uridine incorporation into RNA and the pattern of protein phosphorylation after labeling of [$^{32}$ P] orthophosphate were compared with that of the reconstituted embryos such as P+2 or P+P (control group). Embryonic development and the time of RNA synthesis in P+P-CHX were similar to those in P+P. But the time and the cell stages of embryonic compaction in P+P-CHX were similar to those in P+2. The compaction was initiated at 4-cell in P+2 and P+2-Gen, but at 8-cell in P+P and P+2-DMAP. On a two-dimensional gel electrophoresis, phosphorylation of 80KD and 110KD proteins were inhibited after 3 hrs of reconstruction in the embryo of P+2-DMAP when compared with that of P+2 and P+2-Gen. These results suggest that protein synthesis between 1- and 2-cell stage affects the timing of embryonic genome activation, and that cytoplasmic factors derived from oocyte or their modification regulates the time schedule of embryonic compaction in mouse. Also, serine-threonine protein kinase has an important role on the regulation of compaction.

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Comparison of Anti-inflammatory Activities among Ethanol Extracts of Sophora flavescens, Glycyrrhiza uralensis and Dictamnus dasycarpus, and their Mixtures in RAW 246.7 Murine Macrophages (RAW 246.7 대식세포 모델에서 고삼, 감초, 백선피 에탄올 추출물 및 추출복합물의 항염증 효능 비교)

  • Han, Min Ho;Lee, Moon Hee;Hong, Su Hyun;Choi, Yung Hyun;Moon, Ju Sung;Song, Myung Kyu;Kim, Min Ju;Shin, Su Jin;Hwang, Hye Jin
    • Journal of Life Science
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    • v.24 no.3
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    • pp.329-335
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    • 2014
  • Sophora flavescens, Glycyrrhiza uralensis and Dictamnus dasycarpus have been widely used in folk medicine for several inflammatory disorders in Korea and China. In this study, we compared the anti-inflammatory effects of the ethanol extracts of S. flavescens (EESF), G. uralensis (EEGU) and D. dasycarpus (EEDS), and their mixtures (medicinal herber mixtures, MHMIXs) on production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Our data indicated that treatment with EESF, EEGU and EEDD significantly inhibited the excessive production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) in LPS-stimulated RAW 264.7 cells. The ethanol extracts and MHMIXs also attenuated the production of pro-inflammatory cytokines, including interleukin-$1{\beta}$ ($IL-1{\beta}$) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) by suppressing their protein expression, respectively. Interestingly, MHMIX-1, which basic ingredients are EESF, EEGU and EEDS in the proportion 3:1:1, more safely and effectively inhibits the LPS-induced inflammatory status in LPS-stimulated RAW 264.7 macrophages compared to ethanol extracts of each medicinal herb and other MHMIXs without causing any cytotoxic effects. Our study provides scientific evidence to support that a berbal mixture, MHMIX-1 may be useful in the treatment of inflammatory diseases by inhibiting inflammatory regulator responses in activated macrophages.

Antioxidant and Anti-inflammatory Effects of Ficus erecta var. sieboldii Leaf Extract in Murine Macrophage RAW 264.7 Cells (좁은잎천선과나무(Ficus erecta var. sieboldii) 잎 추출물이 대식세포 RAW 264.7 세포에서 미치는 항산화 및 항염증 효과)

  • Jung, Yong-Hwan;Ham, Young-Min;Yoon, Seon-A;Oh, Dae-Ju;Kim, Chang-Suk;Yoon, Weon-Jong
    • Korean Journal of Plant Resources
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    • v.31 no.4
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    • pp.303-311
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    • 2018
  • In this study, a preliminary evaluation of the antioxidant and anti-inflammatory activity of the Ficus erecta var. sieboldii (Miq.) King (FES) leaf extract has been performed to assess its potential as a natural resource for food and medicinal materials. FES was extracted using 70% EtOH and then fractionated sequentially using n-hexane, $CH_2Cl_2$, EtOAc, and n-BuOH. To screen for antioxidant and anti-inflammatory agents effectively, the inhibitory effect of the FES extracts on the production of oxidant stresses (DPPH, xanthine oxidase, and superoxide) and pro-inflammatory factors (NO, iNOS, COX-2, $PGE_2$, IL-6, and $IL-1{\beta}$) in the murine macrophage cell line RAW 264.7 activated with lipopolysaccharide (LPS) was examined. Among the sequential solvent fractions of FES, the $CH_2Cl_2$ and EtOAc fractions showed decreased production of oxidant stresses (DPPH, xanthine oxidase and superoxide), and the hexane and $CH_2Cl_2$ fractions of FES inhibited the production of pro-inflammatory factors (NO, iNOS, COX-2, and $PGE_2$). The $CH_2Cl_2$ fraction also inhibited the production of pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$). These results suggest that FES has a significant effects on the production of oxidant stresses and pro-inflammatory factors and may be used a natural resource for antioxidant and anti-inflammatory agents.

A Study of Anti-wrinkle Activities as a Functional Cosmetic Ingredient of Rhododendron brachycarpum Extracts (만병초(Rhododendron brachycarpum) 추출물의 기능성 화장품 소재로써의 주름개선 활성에 관한 연구)

  • Yeom, Hyeon-Ji;Oh, Min-Jeong;Chae, Jung-Woo;Lee, Jin-Young
    • Journal of Life Science
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    • v.32 no.8
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    • pp.622-632
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    • 2022
  • The purpose of this study was to investigate activities as functional cosmetic materials, focusing on Rhododendron brachycarpum (RB) and Rhododendron fortunei (RF). The tyrosinase inhibitory effect, related to skin-whitening, was 32.6% and 39.3% respectively at the concentration of 1,000 ㎍/ml. The elastase inhibitory effect, related to skin anti-wrinkling activity, was 30% and 36.2% at 1,000 ㎍/ml concentration. Collagenase inhibitory activity showed 77.7%, and 80.2% respectively at 1,000 ㎍/ml concentration, which demonstrated excellent inhibitory activity. For a cell viability test, that measured on fibroblast cells by RB and RF extracts. Furthermore, the cell viability test showed 100.9% and 98.9% with cell viability at 100 ㎍/ml concentration in CCD-986Sk. The protein expression inhibitory effect of RB and RF extracts was measured by western blot at 25, 50, and 100 ㎍/ml concentrations, and the β-actin was used as a positive control. As a result, western blot of RB and RF extracts was measured by the expression inhibition rate of the MMP-1, MMP-2, MMP-3 protein, and was decreased by 67.2%, 65.5%, 13.6%, and 89.1%, 85.0%, and 62.7% at 100 ㎍/ml concentration. The mRNA expression inhibitory effect of RB and RF extracts was measured by RT-PCR at 25, 50, and 100 ㎍/ml concentrations, and the GAPDH was used as a positive control. According to the results of RT-PCR of RB and RF extracts, the expression inhibition rate of the MMP-1, MMP-2, and MMP-3 mRNA was decreased by 70.1%, 9.1%, 37.9%, and 38.2%, 8.3%, 57.3% at 100 ㎍/ml concentrations. So, RB and RF extracts showed the anti-wrinkle effectiveness as a functional cosmetic material.