• Journal of Chest Surgery
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• v.40 no.4 s.273
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• pp.264-272
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• 2007

Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCS' migration under high glucose conditions. Material and Method: The balloon-injury method was employed to induce neointima formation by VEGF. For f4 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). Result: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, ($0.15{\pm}0.04 mm^2$ and $ 36.03{\pm}3.78%$ compared to $0.24{\pm}0.03mm^2\;and\;61.85{\pm}5.11%$, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from $52.82{\pm}4.20%\;to\;38.11{\pm}6.89%$, by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCS. Conclusion: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition. Therefore, these results suggest that specific blockade of VEGFR-1 by anti-Flt-1 peptide may have therapeutic potential against the arterial stenosis of diabetes mellitus patients or that occurring under a high glucose condition.

• Journal of Life Science
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• v.28 no.5
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• pp.524-531
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• 2018

The essential oil from Abies koreana E.H. Wilson had been developed, however, its efficacy has not yet been studied especially in terms of skin care research. The aim of this study is to investigate the effects of Abies koreana extracts (AKE) on melanogenesis and wrinkle formation in B16F10 melanoma cells (B16F10) and human dermal fibroblast cell line (HDF). The essential oil was extracted by hydrodistillation method and purified by anhydrous sodium sulfate. At a concentration of $10^{-5}$-fold, viability in these cells had been defined by cytotoxicity assays. Anti-melanogenic effects on B16F10 were evaluated using tyrosinase inhibition assay, and real-time PCR for verifying gene expression of tyrosinase, tyrosinase related protein-1 and -2 (TRP-1 and -2). AKEs reduced about 5-fold of tyrosinase inhibitory activity compared to ${\alpha}$-melanocyte-stimulating hormone (${\alpha}$-MSH)-induced group and about 30% reduction compared to Arbutin induced group. The mRNA levels of three melanin-related factors were increased, separately. To investigate the effects of anti-wrinkle, procollagen type I c peptide synthesis assay (PIP) and Western blot were performed. At AKE-treated group, PIP was up-regulated and the expression of collagen type 1 and matrix metalloproteinase (MMP)-1 were improved. Furthermore, AKE presented anti-wrinkle effects by increasing UVB-inhibited collagen type 1 expression, and reducing UVB-induced MMP-1 production at $60mJ/cm^2$ of UVB radiation. Therefore, Abies koreana extracts has potentials as a safe and an effective skin ingredient for whitening and anti-wrinkle.

• Journal of Life Science
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• v.17 no.8 s.88
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• pp.1090-1099
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• 2007

Myristicin, l-allyl-3,4-methylenedioxy-5-methoxybenzene, was one of the major essential oils of nutmeg. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood. Recently, it was shown that T-bet and GATA-3 was master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether myristicin regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in ovalbumin (OVA)-induced asthma model mice. Myristicin reduced levels of IL-4, Th2 cytokine production in OVA-sensitized and challenged mice. In the other side, it increased $IFN-{\gamma}$, Th1 cytokine production in myristicin administrated mice. We also examined to ascertain whether myristicin could influence eosinophil peroxidase (EPO) activity. After being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic reactions. These reactions included an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, and the development of airway hyper-responsiveness (AHR). The administration of myristicin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, these findings provide new insight into the immunopharmacological role of myristicin in terms of its effects in a murine model of asthma.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.2
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• pp.227-233
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• 2004

Chronic exposure to solar radiation, particularly ultraviolet (UV) light, causes a variety of adverse reactions on human skin, such as sunburn, photoaging and photocarcinogenesis. Free radicals and reactive oxygen species (ROS) caused by UV exposure or other environmental facts play critical roles in cellular damage. And, repeated-UV irradiation activated the expression of the matrix metalloproteinase (MMP) and induced skin irritation. Therefore, the development of effective and safe photoprotectants that can reduce and improve the skin damage has been required. The purpose of this study was to investigate the photo-protective effect of several chinese medical plants (Juniperus chinensis) on the UV -induced skin cell damages. We tested free radical and superoxide scavenging effect in vitro. Fluorometric assays of the proteolytic activities of MMP-1 (collagenase) were performed using fluorescent collagen substrates. UVA induced MMP-1 synthesis and activity were analyzed by enzyme-linked immunosorbent assay (ELISA) and gelatin-based zymography in skin fibroblasts. We also examined anti-inflammatory effects by the determination test of proinflammatory cytokine, interleukin 6 in HaCaT keratinocytes. Expression of prostaglandin E$_2$ (PGE$_2$) after UVB irradiation was measured by competitive enzyme immunoassay(EIA) using PGE$_2$ monoclonal antibody. In the human skin we tested anti-irritation effect on the SLS-induced damage skin after appling the extract containing emulsion. We found that Juniperus chinensis extract had potent radical scavenging effect by 98% at 100$\mu\textrm{g}$/mL. The extract of Juniperus chinensis showed strong inhibitory effect on MMP-1 activities by 97% at 100 $\mu\textrm{g}$/mL and suppressed the UVA induced expression of MMP-1 by 79% at 25$\mu\textrm{g}$/mL. This extract also showed strong inhibition on MMP-2 activity in UVA irradiated fibroblast by zymography. In the test of proinflammatory cytokines of human keratinocytes Juniperus chinensis extract decreased expression of interleukin 6 about 30%. The amount of PGE$_2$ by HaCaT keratinocytes was significantly increased at the doses of above 10 mJ/$\textrm{cm}^2$ of UVB (p < 0.05). At the concentrations of 3.2-25$\mu\textrm{g}$/mL of this extract, the production of PGE$_2$ by HaCaT keratinocytes (24 h after 10mJ/$\textrm{cm}^2$ UVB irradiation) was significantly inhibited in culture supernatants (p < 0.05). In SLS-induced skin irritation model in vivo, we found to reduce skin erythema and improve barrier recovery after appling Juniperus chinensis extract containing emulsion when compared to irritated non-treated and placebo-treated skin. Our results suggest that Juniperus chinensis extract can be effectively used for the prevention of UV and SLS-induced adverse skin reactions and applied as anti-aging and anti-irritation cosmetics.

• Tuberculosis and Respiratory Diseases
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• v.56 no.1
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• pp.51-66
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• 2004

Objectives : The matrix metalloproteinases (MMPs) that participate in the extracellular matrix metabolism play a important role in the progression of pulmonary fibrosis. The effects of the MMPs are regulated by several factors including Th-1 cytokines, $interferon-{\gamma}$ ($IFN-{\gamma}$). Up to now, $IFN-{\gamma}$ is known to inhibit pulmonary fibrosis, but little is known regarding the exact effect of $IFN-{\gamma}$ on the regulation of the MMPs. This study investigated the effects of $interferon-{\gamma}$ on the pulmonary fibrosis and the expression of the lung MMP-2,-9, TIMP-1,-2, and Th-2 cytokines in aa rat model of bleomycin induced pulmonary fibrosis. Materials and methods : Male, specific pathogen-free Sprague-Dawley rats were subjected to an intratracheal bleomycin instillation. The rats were randomized to a saline control, a bleomycin treated, and a bleomycin+$IFN-{\gamma}$ treated group. The bleomycin+$IFN-{\gamma}$ treated group was subjected to an intramuscular injection of $IFN-{\gamma}$ for 14 days. At 3, 7, 14, and 28 days after the bleomycin instillation, the rats were sacrificed and the lungs were harvested. In order to evaluate the effects of the $IFN-{\gamma}$ on lung fibrosis and inflammation, the lung hydroxyproline content, inflammation and fibrosis score were measured. Western blotting, zymography and reverse zymography were performed at 3, 7, 14, 28 days after bleomycin instillation in order to evaluate the MMP-2,-9, and TIMP-1,-2 expression level. ELISA was performed to determine the IL-4 and IL-13 level in a lung homogenate. Results : 1. 7 days after bleomycin instillation, inflammatory changes were more severe in the bleomycin+$IFN-{\gamma}$ group than the bleomycin group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$2.08{\pm}0.15:2.74{\pm}0.29$, P<0.05), but 28 days after bleomycin instillation, lung fibrosis was significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$3.94{\pm}0.43:2.64{\pm}0.13$, P<0.05). 2. 28 days after bleomycin instillation, the lung hydroxyproline content was significantly reduced as a result of $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$294.04{\pm}31.73{\mu}g/g:194.92{\pm}15.51{\mu}g/g$, P<0.05). 3. Western blotting showed that the MMP-2 level was increased as a result of the bleomycin instillation and highest in the 14 days after bleomycin instillation. 4. In zymography, the active forms of MMP-2 were significantly increased as a result of the $IFN-{\gamma}$ treatment 3 days after the bleomycin instillation, bleomycin+$IFN-{\gamma}$ group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$209.63{\pm}7.60%:407.66{\pm}85.34%$, P<0.05), but 14 days after the bleomycin instillation, the active forms of MMP-2 were significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$159.36{\pm}20.93%:97.23{\pm}12.50%$, P<0.05). 5. The IL-4 levels were lower in the bleomycin and bleomycin+$IFN-{\gamma}$ groups but this was not significant, and the IL-13 levels showed no difference between the experiment groups. Conclusion : The author found that lung inflammation was increased in the early period but the pulmonary fibrosis was inhibited in the late stage as a result of $IFN-{\gamma}$. The inhibition of pulmonary fibrosis by $IFN-{\gamma}$ appeared to be associated with the inhibition of MMP-2 activation by $IFN-{\gamma}$. Further studies on the mechanism of the regulation of MMP-2 activation and the effects of MMP-2 activation on pulmonary fibrosis is warranted in the future.

• Journal of Life Science
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• v.19 no.6
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• pp.735-743
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• 2009

The common word flavonoids is often used to classify a family of natural compounds, highly abundant in all higher plants, that have received significant therapeutic interest in recent years. Naringin is associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases; however the molecular basis of this effect remains to be elucidated. Thus we attempted to elucidate the anti-allergic effect of Naringin in ovalbumin (OVA)-induced asthma model mice. The OVA-induced mice showed allergic reactions in the airways. These included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of Naringin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Naringin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Naringin in terms of its effects on asthma in mice.