This study conducted the research about the positive effects of Gynura Procumbens on preventing dermatitis and infectious diseases the contemporary people have. To do it, this study measured the concentration of NF-kB, the extract of Gynura Procumbens. In this regard, cytosol, the extract of Gynura Procumbens, and nucleus went through the separation process. The concentration of major NF-kB among various factors to control inflammation was measured with the use of HDF cell. Regarding RAW264.7 cell, the amounts of NO to play an important role in reacting the skin immune system as the media of neural transmission were analyzed. The outcome about the extracts of Gynura Procumbens injected show that it can be expected that as the NF-kB protein and mRNA band were reduced, Gynura Procumbens would have anti-inflammatory effects that could contribute to preventing dermatitis and diseases. In addition, the extracts of Gynura Procumbens have significantly reduced NO with their concentration increasing. In other words, Gynura Procumbens are considered to regulate dependently the production of NO in the concentration of extracts. Thus there is an expectation that the more intensive research would be conducted to heal dermatitis. And it is deemed that Gynura Procumbens would be used as materials for cosmetics as well as foods that the contemporary people can widely consume if a more careful research about anti-inflammatory effects would be sustained on a human bodies' clinical level.
Diabetes-related complications in human and veterinary medicine have been shown to be associated with hyperglycemia-induced inflammation. It has been recently suggested that the onset of insulin resistance may be caused by over-production of inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$ from immune cells. Conjugated linoleic acid (CLA) regulates inflammatory response through modulation of TNF-${\alpha}$ expression. The objective of this study was to examine the effect of CLA on nuclear factor kappaB (NF-${\kappa}B$) p65 binding activity, inhibitory kappaB ($I{\kappa}B$)-${\alpha}$ expression, and TNF-${\alpha}$ production from high glucose-treated RAW 264.7 cells. CLA was added to RAW cells that had been previously cultured with low or high concentration of glucose. The levels of TNF-${\alpha}$ protein in the culture supernatant of RAW cells exposed to high concentrations of glucose were higher than those of cells exposed to low concentrations of glucose. The treatment with the high concentration of glucose in RAW cells increased levels of NF-${\kappa}B$ p65 binding activity and the decreased $I{\kappa}B-{\alpha}$ expression when compared with those of low glucose. The treatments in combination with CLA and glucose (low and high) glucose in RAW cells increased TNF-${\alpha}$ production when compared with that glucose alone. These treatments with CLA increased TNF-${\alpha}$ production in high glucose-treated RAW cells than those with low glucose. These treatments of CLA also showed higher NF-${\kappa}B$ p65 binding activity and lower $I{\kappa}B-{\alpha}$ expression in high glucose than those in low glucose condition. This suggests that CLA can increase NF-${\kappa}B$ p65 binding activity and TNF-${\alpha}$ production from high glucose-treated RAW 264.7 cells and is likely to promote hyperglycemia-induced inflammation.
The chemopreventive effects of naringenin derived from citrus on tumor migration and the possible mechanisms involved in this protection were investigated in HT-1080 tumor cells. In this study, we found that naringenin reduced phorbol 12-myristate 13-acetate (PMA)-enhanced matrix metalloproteinases (MMP)-9 activation in a dose-dependant manner and further inhibited HT-1080 cell migration. In addition, naringenin suppressed PMA-enhanced expression of MMP-9 protein, mRNA and transcription activity levels through suppression of nuclear factor $\kappa$B (NF-$\kappa$B) activation and activator protein-1 (AP-1) translocation without changing tissue inhibitor of metalloproteinase (TIMP)-1 level. Therefore, our results suggested that the inhibitory effects of naringenin on MMP-9 activation, relation of tumor migration in vitro possibly involve mechanisms related to its ability to suppress PMA-enhanced MMP-9 gene and protein expression through NF-$\kappa$B activation and AP-1 translocation. Overall, naringenin may be a valuable anti-invasive drug candidate for cancer therapy.
Journal of the Korean Society of Food Science and Nutrition
/
v.33
no.10
/
pp.1594-1600
/
2004
Effects of mistletoe (Viscum album) extract and pueraria (Pueraria radix) extract on cellular NF-$textsc{k}$B activity were evaluated in human malignant keratinocytes (SCC-13) to elucidate the possible correlation of NF-$textsc{k}$B with antioxidant activity. The antioxidant activities of these natural extracts were examined in four different evaluation methods, i.e., lipid peroxidation value (POV) evaluation test, I,l-diphenyl-2-picrylhydrazyl radical (DPPH), nitric oxide (NO) scavenging test, and reducing power assay. Pueraria extract (0.5 mg) and mistletoe extract (5 mg) downregulated the cellular NF-$textsc{k}$B activation up to 35% and 10% compared to the control, respectively, although their effects were lower than the known NF-$textsc{k}$B downregulator, vitamin C (8.8 mg, 53%) in a cell-based NF-$textsc{k}$B activity assay system. In the POV test, relative antioxidant activities of mistletoe extract (86%) and pueraria extract (75%) were significantly higher than the known antioxidant, vitamin C (48%) at the same concentration (10 mg) and the degree of activity increased in a dose-dependent manner. Pueraria extract showed more potential radical scavenging activities than those of mistletoe extract evaluated in both DPPH and NO test. Especially, the NO radical scavenging activity of pueraria extract ($SC_{50}$/, 88 $\mu$g) was comparable to that of vitamin C ($SC_{50}$/, 77 $\mu$g). Even pueraria extract possessed a much less reducing power compared to vitamin C, it also revealed higher reducing power than that of mistletoe extract. These results indicate that mistletoe extract and pueraria extract may serve as an useful natural antioxidant agents, and led to suggest the hypothesis that compounds having an antioxidant activity, i.e., radical scavenging activity or reducing power may be correlated with the downregulation of NF-$textsc{k}$B activation in human keratinocytes.
Astaxanthin (ATX) is a red-orange carotenoid pigment that occurs naturally in a wide variety of living organisms. In this study we investigated the inhibitory effects of ATX on the induction of inducible nitric oxide synthase (iNOS), nitric oxide (NO), proinflammatory cytokines, nuclear factor-kappa B(NF-${\kappa}B$) and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In addition, we tested the superoxide radical scavenging activity of ATX by scavenging assay. iNOS and NF-${\kappa}B$ expressions were determined by immunoblot analysis. Interleukin (IL)-6 and tumour necrosis factor-${\alpha}$ (TNF-${\alpha}$) were assayed by ELISA. NO production was monitored by measuring the amount of nitrite. ROS was examined by using the 2', 7'-Dichlorodihydrofluorescin diacetate (DCFH-DA) method. At a concentration of 100 ${\mu}M$, ATX inhibited the expression level of LPS-induced NF-${\kappa}B$, as well as the production of LPS-induced NO and proinflammatory cytokines (IL-6 and TNF-${\alpha}$), by suppressing iNOS expression. In particular, the maximal inhibition rate of IL-6 and TNF-${\alpha}$ production by ATX (100 ${\mu}M$) was 65.2----- and 21.2-----, respectively. In addition, ATX inhibited the LPS-induced transcriptional activity of NF-${\kappa}B$, and this was associated with suppressing the translocations of NF-${\kappa}B$ from the cytosol to the nucleus. Moreover, at various concentrations (25-100 ${\mu}M$), ATX inhibited the intracellular level of ROS. At a concentration of 5 mg/ml, the superoxide radical scavenging activity of ATX was 1.33 times higher than ${\alpha}$-tocopherol of the same concentration. These results showed that ATX inhibited the expression of iNOS and the production of NO and proinflammatory cytokines resulting from ROS production and NF-${\kappa}B$ activation in macrophages. Furthermore, ATX was found to be more effective in superoxide radical scavenging activities compared to ${\alpha}$-tocopherol. These findings are expected to strengthen the position of ATX as anti-inflammatory medicine and antioxidant.
Journal of the Society of Cosmetic Scientists of Korea
/
v.32
no.3
s.58
/
pp.135-140
/
2006
Nuclear factor-kappaB (NF-kappaB) is a critical transcription factor for maximal expression of many of the cytokines that are involved in the pathogenesis of inflammatory diseases. In this study, we found that 12 plant extracts among 200 plants, namely, Forsythia koreana, Capsicum annuum L, Mentha arvenis, Duchesnea chrysantha, Morus alba, Saururus Chinenis (Lour) Baill, Pine needle, Zingiber mioga (Thunb.), Roscoe, Houttuynia, Prunus yedoenis, Sasa quelpaertenis, significantly inhibited LPS- induced NF-kappaB activation in a concentration-dependent manner. Additionally, 12 plant extracts were found to have antioxidant activities in DPPH assay Therefore, we have attempted to determine whether 12 herbal extracts could inhibit the expression of cytokines possessing NF-kappaB promoter in their promoter regions. Consistently 12 herbal extracts inhibited LPS-induced production of TNF alpha and interleukin-8 (IL-8). These results show that 12 herbal extracts suppresses the production of pro-inflammatory mediators through the inhibition of the NF-kappaB signaling pathway, we suggest that 12 herbal extracts can be used as a anti-inflammatory and soothing agent.
Jeon, Eun Ju;Kwak, Hee Won;Song, Ju Han;Lee, Young Woo;Chung, Jae Woo;Choi, Jae Chul;Shin, Jong Wook;Park, In Won;Choi, Byoung Whui;Kim, Jae Yeol
Tuberculosis and Respiratory Diseases
/
v.62
no.4
/
pp.299-307
/
2007
Background: High mobility group box 1 (HMGB1) is a novel, late mediator of inflammation. This study compared the pro-inflammatory effects of LPS and HMGB1. The transcriptional factors that play an important role in mediating the HMGB1-induced stimulation of IL-8 were also evaluated. Methods: RAW264.7 cells were stimulated with either LPS (100 ng/ml) or HMGB1 (500 ng/ml). The $TNF-{\alpha}$, MIP-2 and $IL-1{\beta}$ levels in the supernatant were evaluated by ELISA at 0, 2, 4, 8, 12 and 24h after stimulation. An acute lung injury was induced by an injection of LPS (5 mg/kg) or HMGB1 (2.5 mg/kg) into the peritoneum of the Balb/c mice. The lung cytokines and MPO activity were measured at 4h (for LPS) or 24h (for HMGB1) after the injection. The transcriptional factor binding sites for NF-IL6, $NF-{\kappa}B$ and AP-1 in the IL-8 promoter region were artificially mutated. Each mutant was ligated with pIL-6luc and transfected into the RAW264.7 cells. One hour after stimulation with HMGB1 (500 ng/ml), the cell lysate was analyzed for the luciferase activity. Results: The expression of MIP-2, which peaked at 8h with LPS stimulation, increased sequentially until 24h after HMGB1 stimulation. An intraperitoneal injection of HMGB1, which induced a minimal increased in $IL-1{\beta}$ expression, provoked the accumulation of neutrophils the lung. A mutation of AP-1 as well as $NF-{\kappa}B$ in the IL-8 promoter region resulted in a lower luciferase activity after HMGB1 stimulation. Conclusion: The proinflammatory effects of HMGB1, particularly on IL-8, are mediated by both $NF-{\kappa}B$ and AP-1.
Rebaudioside A is a natural sweetener isolated from Stevia rebaudiana Bertoni, one of the glycosides based on steviol. Recent studies have shown that rebaudioside A inhibits the inflammatory response by inhibiting cytokines secretion such as interleukin-$1{\alpha}/1{\beta}$ in activated RAW264.7 mouse macrophage cells by LPS. However, the inhibitory mechanism of inflammation by rebaudioside A in the presence of LPS has not been fully elucidated. Therefore, in this study, we tried to investigate the anti-inflammatory activity of rebaudioside A at the protein level when RAW264.7 cells were stimulated by LPS. The inducible nitric oxide synthase protein expression level was reduced in the group treated with $250{\mu}M$ rebaudioside A compared to the LPS-treated group. In addition, the mRNA expression level of $NF-{\kappa}B$, which is a representative nuclear transcription factor by inflammatory signal, was also decreased as compared with that of LPS-treated group. In addition, $NF-{\kappa}B$ and inhibitor-${\kappa}B$ ($I-{\kappa}B$) complexes that are known to be dissociated by $I-{\kappa}B$ phosphorylation and ubiquitination were less phosphorylated than LPS treated group in the presence rebaudioside A. Finally, we could find that rebaudioside A was involved in the $NF-{\kappa}B$ pathway through reducing extracellular signal-regulated kinase1/2 phosphorylation in a concentration-dependent manner. These results suggest that rebaudioside A might suppress inflammatory reaction through MAPK and $NF-{\kappa}B$ regulation in LPS-stimulated RAW264.7.
Song, So Hyang;Kim, Chi Hong;Kwon, Soon Seog;Kim, Young Kyoon;Kim, Kwan Hyoung;Moon, Hwa Sik;Song, Jeong Sup;Park, Sung Hak
Tuberculosis and Respiratory Diseases
/
v.58
no.2
/
pp.152-159
/
2005
Background : Exacerbations of chronic obstructive pulmonary disease (COPD) are thought to be associated with increased airway inflammation, and the $NF-{\kappa}B$ is known to be an indicator of cellular activation and of inflammatory mediator production. This study was undertaken to investigate the change of cytokine characteristics and $NF-{\kappa}B$ activity in induced sputum of COPD patients during exacerbation and recovery of the disease. Methods : Sputum induction was performed in 37 patients with COPD during exacerbation and during recovery and in 15 healthy subjects. Cell counts, levels of IL-6, IL-8 and $TNF-{\alpha}$ in induced sputum and NF-kB activity in macrophage of induced sputum were measured. Results : Patients with COPD showed significantly increased levels of IL-6, IL-8 and $TNF-{\alpha}$(p<0.01) and increased $NF-{\kappa}B$ activity in induced sputum(p<0.05) as compared with control subjects. Level of IL-8 during exacerbation of COPD decreased significantly during recovery(p<0.05). $NF-{\kappa}B$ activity and levels of IL-6 and $TNF-{\alpha}$ tended to be decreased during recovery, but not siginificantly. Conclusion : Activation of $NF-{\kappa}B$ and increased levels of IL-6, IL-8 and $TNF-{\alpha}$ were thought to be associated with pathogenesis and exacerbations of COPD.
LP-BM5 murine leukemia retrovirus induces the immune dysfunction by imbalanced secretion of Th1 and Th2 cytokines in the murine AIDS model. In the present study, it was investigated whether pycnogenol (Pyc) administration could deactivate $NF-{\kappa}B$ to regulate the gene expression of Th1 and Th2 cytokines in C57BL/6 mice with murine AIDS. Treatment with Pyc for 12 weeks significantly inhibited the loss of body weight and enlargement of spleen and lymph node usually seen with AIDS. Moreover, Pyc increased the plasma level of Th1 cytokines, IL-2 and $IFN-{\gamma}$, while reducing the plasma level of Th2 cytokines, IL-6, IL-10, and $TNF-{\alpha}$. In primary culture of splenocytes, mRNA expression of Th2 cytokines was suppressed, but that of Th1 cytokines was not affected. The LP-BM5 retrovirus infection stimulated the cytoplasmic activation of $NF-{\kappa}B$ and nuclear translocation of $I-{\kappa}B$, whereas Pyc administration significantly reduced $NF-{\kappa}B$ activation and $I-{\kappa}B$ degradation. These results suggested that the inhibitory effect of Pyc on Th2 cytokines in mice with murine AIDS was dependent on suppression of the $NF-{\kappa}B$ signaling pathway and was not dependent on $INF-{\gamma}$ level, which regulates Th2 cytokines.
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