• 제목/요약/키워드: Inhibiting Factors

검색결과 244건 처리시간 0.036초

Triptolide improves myocardial fibrosis in rats through inhibition of nuclear factor kappa B and NLR family pyrin domain containing 3 inflammasome pathway

  • Shen, Jianyao;Ma, Hailiang;Wang, Chaoquan
    • The Korean Journal of Physiology and Pharmacology
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    • 제25권6호
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    • pp.533-543
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    • 2021
  • Myocardial fibrosis (MF) is the result of persistent and repeated aggravation of myocardial ischemia and hypoxia, leading to the gradual development of heart failure of chronic ischemic heart disease. Triptolide (TPL) is identified to be involved in the treatment for MF. This study aims to explore the mechanism of TPL in the treatment of MF. The MF rat model was established, subcutaneously injected with isoproterenol and treated by subcutaneous injection of TPL. The cardiac function of each group was evaluated, including LVEF, LVFS, LVES, and LVED. The expressions of ANP, BNP, inflammatory related factors (IL-1β, IL-18, TNF-α, MCP-1, VCAM1), NLRP3 inflammasome factors (NLRP3, ASC) and fibrosis related factors (TGF-β1, COL1, and COL3) in rats were dete cted. H&E staining and Masson staining were used to observe myocardial cell inflammation and fibrosis of rats. Western blot was used to detect the p-P65 and t-P65 levels in nucleoprotein of rat myocardial tissues. LVED and LVES of MF group were significantly upregulated, LVEF and LVFS were significantly downregulated, while TPL treatment reversed these trends; TPL treatment downregulated the tissue injury and improved the pathological damage of MF rats. TPL treatment downregulated the levels of inflammatory factors and fibrosis factors, and inhibited the activation of NLRP3 inflammasome. Activation of NLRP3 inflammasome or NF-κB pathway reversed the effect of TPL on MF. Collectively, TPL inhibited the activation of NLRP3 inflammasome by inhibiting NF-κB pathway, and improved MF in MF rats.

상심자와 건조상심자 추출물의 항산화 효과 및 전지방세포 분화억제 효과에 관한 연구 (Study of Mori Fructus and Dried Mori Fructus Extracts on the Antioxidant Effect and the Inhibitory Effect on Adipocyte Differentiation)

  • 김형구;왕경화;임동우;채희성;진영원;최한석;김호준
    • 한방재활의학과학회지
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    • 제24권4호
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    • pp.1-13
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    • 2014
  • Objectives This study was to investigate the antioxidative capacity, antiobesity effect and anti-diabetes effects of Mori Fructus and dried Mori Fructus in Raw 264.7 cells and 3T3-L1 cells. Methods 3 different types of Mori Fructus extracts (water 100%, ethanol 30%, ethanol 100%) were used in this study. And 3 different types of dried Mori Fructus extracts (water 100%, ethanol 30%, ethanol 100%) were used in this study. Total polyphenol compund, total favonoid compound, DPPH radical scavenging, ROS activity, NO, cell proliferation were measured in the experiment. Expressions of adipogenic transcription factors including $C/EBP-{\alpha}$, $C/EBP-{\beta}$, $PPAR-{\alpha}$, $PPAR-{\gamma}$, $AMPK-{\alpha}$ were analyzed by Real time PCR. Results Mori Fructus extracts measurements are higher than dried Mori Fructus extracts measurements at Total flavonoid compound and total flavonoid compound. Mori Fructus extracts measurements are lower than dried Mori Fructus extracts measurements at DPPH radical scavenging, ROS activity, NO. In RT-PCR analysis, there is a tendency that dried Mori Fructus extracts inhibit the expression of $C/EBP-{\alpha}$, $C/EBP-{\beta}$ genes. In RT-PCR analysis, there is a tendency that dried Mori Fructus extracts promote the expression of $PPAR-{\alpha}$, $PPAR-{\gamma}$, $AMPK-{\alpha}$ genes. Conclusions Mori Fructus is effective on inhibiting the oxidation and dried Mori Fructus is effective on inhibiting the obesity and diabetes.

수확 전 염화칼슘 및 알카리환원수 처리가 느타리버섯 저장에 미치는 영향 (Effect of Preharvest Treatment of $CaCl_2$ and Alkaline-Reduced Water on the Quality of Oyster Mushroom during Storage)

  • 최윤수;이경민;서건식;김민경;황용수
    • 농업과학연구
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    • 제37권3호
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    • pp.355-360
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    • 2010
  • This experiment was focused to determine the effect of preharvest treatment of alkaine-reduced water (ARW) and $CaCl_2$ on the storage of oyster mushroom. ARW was prepared through electrolysis of water with $CaCl_2$ (0.1%) as salts and $CaCl_2$ (0.1%) was dissolved in deionized water. Mushrooms were harvested after two sprays of each solutions and quality factors including firmness and browning was determined during storage. The severity of browning was more greater when stored 20 days. Unlike $CaCl_2$, ARW containing 139 ug/L calcium was positive on maintaining freshness in terms of delay of firmness loss and respiration drop, keeping soluble carbohydrate content such as trehalose, and inhibiting the occurrence of browning. Browning, however, seemed to be more influenced by the developmental stage of mushroom at harvest. Even no significant difference was found, the level of ${\beta}$-glucan was low in ARW treatment compared to that of control. Further research including application and preparation methods of ARW is required to clarify the potential of ARW on keeping freshness of oyster mushroom through inhibiting tissue browning.

표면강화형흡수방지재 적용 콘크리트의 기공률 및 내마모성 특성 (Porosity and Abrasion Resistance of Concrete Coated by Surface enhanced type Water Repellent)

  • 박명주;노재호;이병재
    • 한국구조물진단유지관리공학회 논문집
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    • 제23권4호
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    • pp.31-36
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    • 2019
  • 콘크리트는 일반적으로 구조물에 활용되는 재료로써 다양한 환경조건에 노출된다. 특히 물과 같은 매체를 통해 콘크리트에 유해한 인자가 유입되므로 많은 피해를 야기 시킨다. 이에 콘크리트 내구성을 높이기 위해 많은 재료가 개발되고 있는 실정이다. 그중에 실란과 실록산 화합물은 흡수방지제로 활용도가 높은 재료로 알려져 있다. 그러나 노후화되거나 열화된 콘크리트에 처리할 경우 기재 자체가 약해 쉽게 박리되어 그 기능을 상실하는 문제점이 있다. 그래서 본 연구에서는 실록산 화합물로 표면 처리된 멜라민-포름알데히드 수지를 활용해 콘크리트에 흡수방지제 효과와 동시에 표면강화 성능을 부여하기 위한 실험을 진행하였고, 이를 확인하기 위해 콘크리트의 기공률 및 표면경도 특성을 연구하였다.

인간 피부각질세포 HaCaT Cell에서 TNF-α/IFN-γ로 유도된 염증 반응에 대한 펄스형 전자기장(PEMF) 자극의 염증 인자 완화 효과 (Effect of Pulsed Electromagnetic Field Stimulation on TNF-α/IFN-γ induced inflammatory response in human skin keratinocytes HaCaT Cell to reduce inflammatory factors)

  • 김준영;박찬호;박창순;이용흠
    • 대한의용생체공학회:의공학회지
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    • 제44권6호
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    • pp.443-449
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    • 2023
  • The purpose of this study was to observe cell death in human keratinocytes stimulated against the infectious cytokines TNF-α and IFN-γ, and to observe the expression of Phospho-NF-κB due to phosphorylation of IkB to confirm the mechanism of inhibiting the expression of inflammatory cytokines. As a result of cell viability analysis, differences in PEMF stimulation time were observed little by little after 1 hour, 3 hours, 6 hours, 12 hours, 24 hours, and 48 hours, but there was no statistical significance according to PEMF stimulation time for each time (p>0.05). No significant difference was observed in the total amount of NF-κB present in the cytoplasm and nucleus, but a significant decrease in the expression of phosphorylated NF-κB was observed in the group exposed to PEMF stimulation for 24 hours (*p<0.05). The expression of IL-1β was observed in all inflammation-induced groups, and the concentration of IL-1β compared to α-Tubulin expression was reduced by about 54% in the PEMF-stimulated group for 24 hours compared to the control group (***p<0.001). As a result of the study, it is shown that PEMF stimulation does not negatively affect HaCaT cells from 0 to 48 hours and can inhibit the expression of inflammatory cytokines by inhibiting the pathway of NF-κB.

Aurantio-obtusin exerts an anti-inflammatory effect on acute kidney injury by inhibiting NF-κB pathway

  • Haiyan Xiang;Yun Zhang;Yan Wu;Yaling Xu;Yuanhao Hong
    • The Korean Journal of Physiology and Pharmacology
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    • 제28권1호
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    • pp.11-19
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    • 2024
  • Acute kidney injury (AKI) is one of the major complications of sepsis. Aurantio-obtusin (AO) is an anthraquinone compound with antioxidant and anti-inflammatory activities. This study was developed to concentrate on the role and mechanism of AO in sepsis-induced AKI. Lipopolysaccharide (LPS)-stimulated human renal proximal tubular epithelial cells (HK-2) and BALB/c mice receiving cecal ligation and puncture (CLP) surgery were used to establish in vitro cell model and in vivo mouse model. HK-2 cell viability was measured using MTT assays. Histological alterations of mouse renal tissues were analyzed via hematoxylin and eosin staining. Renal function of mice was assessed by measuring the levels of serum creatinine (SCr) and blood urea nitrogen (BUN). The concentrations of pro-inflammatory cytokines in HK-2 cells and serum samples of mice were detected using corresponding ELISA kits. Protein levels of factors associated with nuclear factor kappa-B (NF-κB) pathway were measured in HK-2 cells and renal tissues by Western blotting. AO exerted no cytotoxic effect on HK-2 cells and AO dose-dependently rescued LPS-induced decrease in HK-2 cell viability. The concentrations of pro-inflammatory cytokines were increased in response to LPS or CLP treatment, and the alterations were reversed by AO treatment. For in vivo experiments, AO markedly ameliorated renal injury and reduced high levels of SCr and BUN in mice underwent CLP operation. In addition, AO administration inhibited the activation of NF-κB signaling pathway in vitro and in vivo. In conclusion, AO alleviates septic AKI by suppressing inflammatory responses through inhibiting the NF-κB pathway.

Repression of $PPAR{\gamma}$ Activity on Adipogenesis by $17{\beta}$-estradiol in Differentiated 3T3-L1 Cell

  • Yoon, Mi-Chung;Jeong, Sun-Hyo
    • 대한의생명과학회지
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    • 제15권3호
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    • pp.179-185
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    • 2009
  • In our previous report, we showed that $PPAR{\gamma}$ does not influence adipogenesis in females with functioning ovaries, indicating that $PPAR{\gamma}$ activity on adipogenesis is associated with sex-related factors. Among the sex-related factors, estrogen has been recognized as a major factor in inhibiting adiposgenesis in females. Thus, we hypothensized that $17{\beta}$-estradiol (E) inhibits 3T3-L1 cell adipogenesis by preventing $PPAR{\gamma}$ activity. E decreased triglyceirde accumulation in differentiated 3T3-L1 cells compared with control group. E also decreased the expression of $PPAR{\gamma}$ mRNA as well as $PPAR{\gamma}$ dependent adipocyte-specific genes, such as adipocyte fatty acid binding protein and tumor necrosis factor $\alpha$. In addition, E not only decreased luciferase reporter activity by $PPAR{\gamma}$, but also transfection of estrogen receptor $\alpha$ ($ER{\alpha}$) or $ER{\beta}$ led to decreases in $PPAR{\gamma}$ reporter gene activation. Moreover, E-activated ERs significantly decreased the luciferase reporter gene activation induced by $PPAR{\gamma}$ transfection, suggesting that estrogen-activated ERs inhibit $PPAR{\gamma}$-dependent transactivation. Accordingly, our results demonstrate that E inhibits the action of $PPAR{\gamma}$ on adipogenesis through E activated ER, providing evidence that lack of estrogen may potentiate $PPAR{\gamma}$ action on adipogenesis.

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Metformin Suppresses MHC-Restricted Antigen Presentation by Inhibiting Co-Stimulatory Factors and MHC Molecules in APCs

  • Shin, Seulmee;Hyun, Bobae;Lee, Aeri;Kong, Hyunseok;Han, Shinha;Lee, Chong-Kil;Ha, Nam-Joo;Kim, Kyungjae
    • Biomolecules & Therapeutics
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    • 제21권1호
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    • pp.35-41
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    • 2013
  • Metformin is widely used for T2D therapy but its cellular mechanism of action is undefined. Recent studies on the mechanism of metformin in T2D have demonstrated involvement of the immune system. Current immunotherapies focus on the potential of immunomodulatory strategies for the treatment of T2D. In this study, we examined the effects of metformin on the antigen-presenting function of antigen-presenting cells (APCs). Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of metformin was also confirmed using mice that had been injected with metformin followed by soluble OVA. These results provide an understanding of the mechanisms of the T cell response-regulating activity of metformin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.

The Molecular Mechanism of Baicalin on RANKL-induced Osteoclastogenesis in RAW264.7 Cells

  • Ko, Seon-Yle
    • International Journal of Oral Biology
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    • 제38권2호
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    • pp.67-72
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    • 2013
  • This study examined the anti-osteoclastogenic effects of baicalin on receptor activator of NF-${\kappa}$B ligand (RANKL)-induced RAW264.7 cells. Baicalin is a flavonoid that is produced by Scutellaria baicalensis and is known to have multiple biological properties, including antibacterial, anti-inflammatory and analgesic effects. The effects of baicalin on osteoclasts were examined by measuring 1) cell viability; 2) the formation of tartrate-resistant acid phosphatase (TRAP) (+) multinucleated cells; 3) RANK/RANKL signaling pathways and 4) mRNA levels of osteoclast-associated genes. Baicalin inhibited the formation of RANKL-stimulated TRAP (+) multinucleated cells and also suppressed the RANKL-stimulated activation of p-38, ERK, cSrc and AKT signaling. Baicalin also inhibited the RANKL-stimulated degradation of $I{\kappa}B$ in RAW264.7 cells. In addition, the RANKL-stimulated induction of NFATc1 transcription factors was found to be abrogated by this flavonoid. Baicalin was further found to decrease the mRNA expression of osteoclast-associated genes, including carbonic anhydrase II, TRAP and cathepsin K in the RAW264.7 cells. Our data thus demonstrate that baicalin inhibits osteoclastogenesis by inhibiting the RANKL-induced activation of signaling molecules and transcription factors in osteoclast precursors.

Structural and Thermodynamic Characteristics of cHLH Peptide and cHLH/HDM2 Complex

  • Im, Haeri;Cho, Sunhee;Ham, Sihyun
    • EDISON SW 활용 경진대회 논문집
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    • 제5회(2016년)
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    • pp.62-66
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    • 2016
  • Tumor suppressor protein p53 loses its function upon binding with the HDM2 protein, and inhibiting the p53-HDM2 interaction is critical to suppress tumor cell growth. Recently, the cyclized helix-loop-helix peptide (cHLH) mimicking the ${\alpha}-helix$ part of the p53 protein has been designed and found to exhibit high binding affinity with HDM2. Here, we report the structural and thermodynamic characteristics of the bound complex of the cHLH peptide with the HDM2 protein. We performed molecular dynamics simulations to investigate the structural features of the cHLH peptide as well as its complex with the HDM2. The binding free energy calculation based on the integral equation theory was also executed to quantify the binding affinity for the cHLH/HDM2 complex and to understand the factors contributing to the binding affinity. We found a variety of factors for the helix stability of the cHLH peptide as well as in the complexation with the HDM2, which may provide an insight into the development of anti-cancer drug designs.

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