• Archives of Pharmacal Research
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• 제26권3호
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• pp.244-251
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• 2003

Plant nutrients are believed to provide protection against various diseases including inflammation. Since interactions of the cell adhesion molecules are known to play important roles in mediating inflammation, inhibiting adhesion protein upregulation is a possible therapeutic target. In this study, the interacellular adhesion molecule-1 (ICAM-1) was induced in human umbilical endothelial cells (HUVECs) after stimulation with $TNF-{\alpha}$. In addition, alginate, ascorbic acid and allicin were demonstrated to inhibit the $TNF-{\alpha}$ induced expression of ICAM-1 on the HUVECs in a dose-dependent manner. These compounds also inhibited the production of NO and $H_2O_2$ induced by $TNF-{\alpha}$, which suggests that the inhibition of ICAM-1 expression by the three compounds may be due to the modulated production of the reactive oxygen/nitrogen components. Overall, these results indicate that these dietary components have a therapeutic potential in the treatment of various inflammatory disorders associated with an increase in endothelial leukocyte adhesion molecules.

• 대한의생명과학회지
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• 제20권1호
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• pp.32-38
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• 2014

Potassium cyanate (KOCN) that is known as an inducer of the protein carbamylation is an inorganic compound and is the conjugate based of cyanic acid (HOCN). Based on these studies, we confirmed that KOCN induces the apoptosis of the human colorectal cancer cell line, HCT 116 cells, by various mitochondrial pathways. To investigate other mechanisms of KOCN-mediated apoptosis, in the present study, we examined KOCN-induced cytokines production in HCT 116 cells and identified the intracellular signaling pathway in these processes. We first demonstrated that KOCN considerably increased the cell apoptosis via intracellular $Ca^{2+}$ signaling, mitochondrial dysfunction and ROS production. And then we examined TNF-${\alpha}$ and IL-$1{\beta}$ levels mediated by KOCN in HCT 116 cells. Although IL-$1{\beta}$ was not involved in KOCN-mediated HCT 116 cell apoptosis, the release of TNF-${\alpha}$ was mediated by KOCN in HCT 116 cells via NF-${\kappa}B$ activation. Apoptosis was also enhanced by incubation with supernatants from HCT 116 cells after KOCN treatment and this effect was partially reduced by BAY 11-7085 pre-treated supernatant. Taken together, our results indicate that KOCN-induced apoptosis in HCT 116 cells is dependent on the releases of TNF-${\alpha}$ and the increased factors and that the mechanism involves the activation of NF-${\kappa}B$.

• Natural Product Sciences
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• 제18권4호
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• pp.254-260
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• 2012

Adipose inflammation is linked to the development of insulin resistance and type 2 diabetes. Hesperidin (HES) is a flavonoid with antioxidant, anti-inflammatory and anti-diabetic properties. However, whether HES improves inflammation-mediated insulin resistance in adipose tissues remains unclear. The purpose of this study was to investigate whether HES attenuates inflammation-mediated insulin resistance in adipose tissue. Herein, RAW 264.7 cells and differentiated 3T3-L1 adipocytes were pretreated with various concentrations of HES in complete media for 1 h and then cultured in the presence or absence of LPS or TNF-${\alpha}$. Our results demonstrated that HES remarkably inhibited LPS-induced production of IL-6, TNF-${\alpha}$, and NO by RAW 264.7 cells in a dose-dependent manner. Also, HES inhibited TNF-${\alpha}$-induced production of IL-6 and $PGE_2$ in differentiated 3T3-L1 cells, while upregulated TNF-${\alpha}$-suppressed expression of adiponectin and PPAR-${\gamma}$ mRNA. These findings suggest that HES may ameliorate inflammation-mediated insulin resistance in adipose tissue.

• Natural Product Sciences
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• 제19권4호
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• pp.316-323
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• 2013

Adipose tissue-derived chronic inflammation contributes to development of insulin resistance in obesity, leading to type 2 diabetes and cardiovascular disease. Baicalin, a flavonoid, has antioxidant, anti-inflammatory, antihyperglycemic, anti-adipogenic, and antiobesity effects. However, whether baicalin attenuates adipose tissue-derived development of insulin resistance remains still unclear. This study was to investigate effect of baicalin on the inflammatory changes involved in the development of insulin resistance in adipose tissue. RAW 264.7 cells and differentiated 3T3-L1 adipocytes were pretreated with various concentrations of baicalin in complete media for 1 h and then cultured in the presence or absence of LPS or TNF-${\alpha}$. Our results demonstrated that baicalin remarkably inhibited LPS-induced production of TNF-${\alpha}$, IL-6, and NO by RAW 264.7 cells in a dose-dependent manner. Baicalin also inhibited TNF-${\alpha}$-induced production of IL-6 and $PGE_2$ in differentiated 3T3-L1 cells in a dose-dependent manner, while upregulated TNF-${\alpha}$-suppressed expression of adiponectin and PPAR-${\gamma}$ mRNA and IRS-1 protein. These findings suggest that baicalin may prevent the adipose tissue-derived development of insulin resistance in obesity.

• 대한수의학회지
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• 제51권3호
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• pp.239-241
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• 2011

In this study, we investigated the kinetics of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6 and high mobility group box 1 (HMGB1) concentrations in a 48-h model of canine endotoxemia by lipopolysaccharide (LPS) injection. Four healthy beagles were slowly administered 1 mg/kg of LPS diluted in normal saline, while two others were administered normal saline as controls. Blood collection was performed at 0 h (baseline), 1 h and 3 h (for TNF-${\alpha}$), 6 h, 12 h, 24 h and 48 h of the experiment, and cytokine levels were determined using the sandwich ELISA method. Early increments of TNF-${\alpha}$ and IL-6 were observed (< 3 h), but HMGB1 levels increased the most at 12 h of the experiment and gradually decreased until 48 h. During the whole experiment, IL-6 and HMGB1 were sustained over 12 h of LPS injection, whereas TNF-${\alpha}$ decreased within 6 h of LPS injection. Taken together, canine HMGB1 levels increase relatively late (< 12 h) and sustained longer than TNF-${\alpha}$ and IL-6 in response to endotoxin. This is the first study to evaluate canine HMGB1 cytokine from endotoxemia in dogs.

• BMB Reports
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• 제42권5호
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• pp.265-270
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• 2009

Due to their multiple biological activities, flavonoids have gained attention as potentially useful therapeutics for a variety of diseases including cancer, cardiovascular diseases, and autoimmune diseases. In this study, we demonstrated that several flavonoids, including kaempferol, quercetin, fisetin, and chrysin block TNF-$\alpha$ induced IL-8 promoter activation and gene expression in HEK 293 cells. In addition, phosphorylation and degradation of $I{\kappa}B{\alpha}$ and translocation of NF-${\kappa}B$ p65 were inhibited by these flavonoids in TNF-$\alpha$-stimulated HEK 293 cells. Furthermore, generation of reactive oxygen species (ROS) in response to TNF-$\alpha$ was reduced by the flavonoids. Moreover, although pretreatment with fisetin, quercetin, or chrysin decreased cell viability, kaempferol did not. Taken together, these findings suggest that kaempferol would be useful for the treatment of TNF-$\alpha$-induced inflammatory diseases.

• Korean Journal of Acupuncture
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• 제25권1호
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• pp.131-138
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• 2008

목적 : 본 연구의 목적은 폐열해수, 장열번갈, 습열사리, 황달, 옹종정창등의 치료효능이 있는 연교약침액이 사람 기관지 상피세포주인 A549에 TNF-${\alpha}$ 및 IL-4를 투여하여 나타나는 케모카인의 발현에 미치는 영향을 관찰하고자 하는 것이다. 방법 : A549 세포주에 연교약침액을 농도별로 (0, 0.5, 1, 5, 10, 50 ${\mu}g/ml$) 전처치한 후, TNF-${\alpha}$ 및 IL-4를 투여하여 RANTES, eotaxin 및 TARC의 분비를 유도하고, 케모카인 분비량을 ELISA법을 이용하여 측정하였다. 실험에 사용한 연교약침액의 농도에 따른 세포 독성 유무를 관찰하고자 MTT assay를 수행하여 세포생존율을 측정하였다.결과 : 연교약침액의 농도가 세포내에서 독성을 일으키는지 MTT assay로 측정한 결과 세포독성은 관찰되지 않았으며, 연교약침액은 TNF-${\alpha}$ 및 IL-4투여로 인하여 증가된 RANTES, eotaxin 및 TARC의 분비를 통계학적으로 유의하게 감소시킴을 관찰하였다. 결론 : 연교약침액은 천식과 알레르기 질환에 관련이 있는 케모카인의 효과적인 감소를 이끌어 냄을 확인하였으며, 이러한 결과는 연교약침액이 천식 및 알레르기 환자에 대해 효과적인 임상 활용이 가능할 것으로 사료된다.

• IMMUNE NETWORK
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• 제11권1호
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• pp.42-49
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• 2011

Background: In this study, we have investigated the effect of Korean red ginseng (KRG) extracts on the production of TNF-${\alpha}$ and IL-8 in human keratinocytes. Also, to examine the antioxidative effect of red ginseng extracts, free radical scavenging activity and superoxide dismutase (SOD) activity in human dermal fibroblasts was measured. Methods: To investigate the effect of KRG in atopic dermatitis, we measured the level of TNF-${\alpha}$ and IL-8 secretion in LPS-stimulated human keratinocytes after the treatment of KRG extracts using enzyme-linked immunosorbent assay. Anti-oxidative activity was investigated by measuring 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and SOD activity. Results: The stimulation of human keratinocytes with KRG extracts shifted the LPS-induced cytokine secretion toward a more immunosuppressive response. KRG dose-dependently decreased TNF-${\alpha}$ and IL-8 production in HaCaT cells and a significant inhibition of TNF-${\alpha}$ was shown when cells were treated with 500 and $1,000{\mu}g/ml$ of KRG extracts. Additionally, KRG extracts showed DPPH radical scavenging and SOD activity in a dose-dependent manner. Particularly, SOD activities of concentrations higher than $60{\mu}g/ml$ of KRG extracts were significantly different in human dermal fibroblast cells. Conclusion: Based on this study, KRG extracts may be a useful immunosuppressive agent in the treatment of atopic dermatitis.

• Advances in Traditional Medicine
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• 제9권2호
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• pp.149-156
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• 2009

Equisetum hyemale Linne. (EH) (Equisetaceae) has been used for the treatment of eye and skin disease, chronic eczema, pneumoconiosis and asthma in Korea and China. Human leukemic mast cells are widely distributed in the connective tissues of mammals and other vertebrates. Phorbol 12-myristrate 13-acetate (PMA) and calcium ionophore A23187 stimulated Human leukaemic mast cell line-1 (HMC-1) can produce a variety of inflammatory mediators and several pro-inflammatory and chemotactic cytokines such as TNF-$\alpha$, IL-6 and IL-8. Since TNF-$\alpha$, IL-6 and IL-8 are major factors during the inflammatory process, we studied the effects of EH on TNF-$\alpha$, IL-6 and IL-8 release in HMC-1 stimulated with PMA and A23187. The result of this study indicate that EH inhibits TNF-$\alpha$, IL-6 and IL-8 in activated HMC-1 cells via $I{\kappa}B$/Nuclear factor-${\kappa}B$ pathway. Therefore, EH might contribute significantly to the prevention or treatment of mast-cell mediated inflammatory diseases and EH has potential use in the therapy of chronic allergic inflammation.

• Archives of Pharmacal Research
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• 제22권3호
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• pp.267-273
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• 1999

In this study we examined the potential for the synergistic augmentation of the antitumor activity of inflammatory mouse peritoneal macrophages by stimulation with protein A combined with $IFN-\gamma$. The moderate augmentative effect induced by preincubation with protein A was demonstrated to be concentration-dependent, whereas IFN-, had a very low activating effect. Following preincubation with both protein A and $IFN-\gamma$, a marked enhancement of macrophage activity was noted. In addition, based on the utilization of neutralizing antibody to TNF-$\alpha$ or the inhibition of NO Production, TNF-$\alpha$ and NO were proven to be involved as mediators during the activation of tumoricidal macrophages by protein A in combination with $IFN-\gamma$. We also demonstrated that supernatants from macrophages treated with protein A plus $IFN-\gamma$ contained both TNF-$\alpha$ and NO at markedly increased levels. Thus, tumor cell lysis in the combined system was mediated via TNF-$\alpha$ or NO. These results demonstrate the synergistic effects on mouse pertioneal macrophage function of protein A in combination with $IFN-\gamma$ and suggest that combinations of such agents may serve as the basis for future in vivo immunotherapy.