• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.12
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• pp.1663-1670
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• 2012

The inhibitory effects of rose hip (Rosa canina L.) water extracts from two different manufactures on osteoarthritis was comparatively investigated in primary cultures of rat cartilage cells. To identify the effects of rose hip extracts against $H_2O_2$ (300 ${\mu}M$, 2 hr) treatment, cell survival was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell survival increased by rose hip extracts in the range of 100 to 600 ${\mu}g/mL$ of $H_2O_2$ treatment. To determine the anti-inflammatory effects of rose hip extracts, tumor necrosis factor alpha (TNF-${\alpha}$), nitric oxide (NO), and Cox-2 expression were measured after lipopolysaccharide (LPS) activation. TNF-${\alpha}$ level with rose hip extract treatment was decreased by 27.4% and 31.9% at 600 ${\mu}g/mL$ of $H_2O_2$ treatment. Nitric oxide was inhibited by rose hip extract at 100~600 ${\mu}g/mL$ of $H_2O_2$ treatment in a dose-dependent manner. In addition, Cox-2 protein expression was dose-dependently decreased while Cox-1 had no change in expression level. The severity of osteoarthritis is controlled by a balance between anabolic and catobolic factors in an articulation, therefore the expression of these factors plays a critical role in preventing osteoarthritis. In measuring anabolic factors, the genetic expression of collagen type I increased with rose hip treatment, while the genetic expression of collagen II did not change. In addition, the genetic expression of aggrecan (proteoglycan core protein) was significantly increased. while the genetic expression of matrix metalloproteinase (MMP) 3, 7 and 13, known catabolic factors, was significantly inhibited by treatment with rose hip extract. The expression of MMP13 was especially highly influenced. In conclusion, rose hip water extracts show inhibitory effects on cell death by $H_2O_2$ mediated oxidative stress, which is related to inhibitory effects on inflammation due to TNF-${\alpha}$, NO, and Cox-2. The ability of rose hip extracts to ameliorate inflammation in primary cultures of cartilage cells seems to associate with an increased genetic expression of specific anabolic factors, collagen type I and aggrecan, and a decreased expression of catabolic factors, MMPs (3, 7, and 13). However, there were no significant differences between rose hip extracts from the two manufacturers.

• Journal of Life Science
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• v.26 no.1
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• pp.34-41
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• 2016

Black chokeberries (scientific name Aronia melanocarpa) have been reported to have major effects due to anti-oxidant, anti-inflammatory, and anti-cancer capabilities. In this study, we investigated the anti- wrinkle effects of A. melanocarpa, including collagenase inhibition effects and their molecular biological mechanisms, such as oxidative stress-induced matrix metalloproteinase (MMP), mitogen-activated protein (MAP) kinase, and activator protein (AP)-1 expression and/or phosphorylation. In collagenase inhibition activity, the ethyl acetate fraction of black chokeberry (AE) was 77.2% at a concentration of 500 μg/ml, which was a significant result compared to that of Epigallocatechin gallate (positive control, 83.9% in 500 μg/ml). In the reactive oxygen species (ROS) assay, the AE produced 78% of ROS in 10 μg/ml and 70% of ROS in 75 μg/ml, which was a much lower percentage than the ROS production of H₂O₂-induced CCRF S-180II cells. In the MTT assay, cell viability was increased dose-dependently with AE in H₂O₂-induced cells. In protein expression by western blot assay, the AE suppressed the expression and phosphorylation of MMPs (MMP-1, -3, -9), MAPK (ERK, JNK, and p38), and AP-1 (c-Fos and c-Jun), and expressed the pro-collagen type I in H₂O₂-induced cells. These results suggest that black chokeberries have anti-wrinkle and collagen-production effects, and they may be used in applications for material development in the functional food and cosmetic industries.

• Journal of Life Science
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• v.27 no.10
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• pp.1207-1214
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• 2017

Schisandrae Fructus (SF), the fruit of Schisandra chinensis (Turcz.) Baill., is widely used in traditional medicine for the treatment of a number of chronic diseases. SF extracts have been recently reported to attenuate the inflammatory responses in SW1353 human chondrocyte cells in in vitro and monosodium iodoacetate (MIA)-induced cartilage degradation in in vivo osteoarthritis (OA) models. However, their protective and therapeutic potentials against OA in primary culture chondrocytes and animal models remain unclear. Therefore, we investigated the effects of the ethanol extract of SF on the activity of matrix metalloproteinases (MMPs), biomarkers for diagnosis of OA, on interleukin $(IL)-1{\beta}-induced$ primary cultured rat cartilage chondrocytes and MIA-induced osteoarthritis in a rat model. Our data indicated that SF treatment significantly reduced the mRNA expression and enzyme activity of MMP-1, -3 and -13 in $IL-1{\beta}-induced$ primary cultured rat cartilage chondrocytes. The chondro-protective effects of SF were then analyzed in a rat OA model using a single intra-articular injection of MIA in the right knee joint. According to our results, the elevated levels of MMP-1 and -3 were markedly ameliorated by SF administration. Collectively, these findings indicate that SF could be a candidate for the treatment of OA.

• 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.20 no.4
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• pp.528-534
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• 2010

Garlic (Allium sativum) has been well-known as a folk remedy for a variety of ailments since ancient times, and it is well documented that enhanced garlic consumption leads to a decrease in incidences of cancer. Tight junctions (TJs) are critical structures for the maintenance of cellular polarity, acting as paracellular permeability barriers and playing an essential role in regulating the diffusion of fluid, electrolytes and macromolecules through the paracellular pathway. Matrix metalloproteinases (MMPs) have been implicated as possible mediators of invasiveness and metastasis in some cancers. In this study, we investigated the potential effects of water extract of aged black garlic (ABG) on the correlation between tightening of TJs and anti-invasive activity in human gastric carcinoma AGS cells. The inhibitory effects of ABG on cell motility and invasiveness were found to be associated with increased tightness of TJs, which was demonstrated by an increase in transepithelial electrical resistance. Additionally, the activities of MMP-2 and -9 in AGS cells were inhibited by treatment with ABG, and this was also correlated with a decrease in the expression of their mRNA and proteins. Furthermore, RT-PCR and immunoblotting results indicated that ABG repressed the levels of the claudin proteins, major components of TJs that play a key role in the control and selectivity of paracellular transport. In conclusion, these results suggest that ABG treatment may inhibit tumor metastasis and invasion, and therefore may act as a dietary source to decrease the risk of developing cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2269-2272
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• 2013

Matrix metalloproteinases (MMPs) degrade various components of the extracellular matrix and functional polymorphisms in encoding genes may contribute to genetic susceptibility to many cancers. Up to now, associations between MMP-7 (-181A>G) and digestive system cancer risk have remained inconclusive. To better understand the role of the MMP-7 (-181A>G) genotype in digestive cancer development, we conducted this comprehensive meta-analysis encompassing 3,518 cases and 4,596 controls. Overall, the MMP-7 (-181A>G) polymorphism was associated with higher digestive system cancer risk on homozygote comparison (GG vs. AA, OR=1.21, 95% CI = 1.12-1.60) and in a dominant model (GG/GA vs. AA, OR=1.16, 95% CI =1.03-1.46). On subgroup analysis, this polymorphism was significantly linked to higher risks for gastric cancer (GG vs. AA, OR=1.22, 95% CI = 1.02-1.46; GA vs. AA, OR=1.82, 95% CI =1.16-2.87; GG/GA vs. AA, OR=1.13, 95% CI =1.01-1.27; GG vs. GA/AA, OR= 1.25, 95% CI = 1.06-2.39. We also observed increased susceptibility to colorectal cancer and esophageal SCC in both homozygote (OR = 1.13, 95% CI = 1.06-1.26) and heterozygote comparisons (OR = 1.45, 95% CI = 1.11-1.91). In the stratified analysis by controls, significant effects were only observed in population-based studies (GA vs. AA, OR=1.16, 95% CI=1.08-1.50; GA/AA vs. GG, OR=1.10, 95% CI=1.01-1.72). According to the source of ethnicity, a significantly increased risk was found among Asian populations in the homozygote model (GG vs. AA, OR=1.40, 95% CI=1.12-1.69), heterozygote model (GA vs. AA, OR=1.26, 95% CI=1.02-1.51), and dominant model (GG/GA vs. AA, OR=1.18, 95% CI=1.08-1.55). Our findings suggest that the MMP-7 (-181A>G) polymorphism may be a risk factor for digestive system cancer, especially among Asian populations.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6813-6823
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• 2015

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor ${\beta}$ ($TGF{\beta}$) superfamily is a large group of structurally related proteins including $TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The $TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$, ${\alpha}5{\beta}1$) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the $TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial.

• Molecules and Cells
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• v.39 no.11
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• pp.790-796
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• 2016

Dental pulp is a highly vascularized tissue requiring adequate blood supply for successful regeneration. In this study, we investigated the functional role of stem cells from human exfoliated deciduous teeth (SHEDs) as a perivascular source for in vivo formation of vessel-like structures. Primarily isolated SHEDs showed mesenchymal stem cell (MSC)-like characteristics including the expression of surface antigens and in vitro osteogenic and adipogenic differentiation potentials. Moreover, SHEDs were positive for NG2, ${\alpha}$-smooth muscle actin (SMA), platelet-derived growth factor receptor beta ($PDGFR{\beta}$), and CD146 as pericyte markers. To prove feasibility of SHEDs as perivascular source, SHEDs were transplanted into immunodeficient mouse using Matrigel with or without human umbilical vein endothelial cells (HUVECs). Transplantation of SHEDs alone or HUVECs alone resulted in no formation of vessel-like structures with enough red blood cells. However, when SHEDs and HUVECs were transplanted together, extensive vessel-like structures were formed. The presence of murine erythrocytes within lumens suggested the formation of anastomoses between newly formed vessel-like structures in Matrigel plug and the host circulatory system. To understand underlying mechanisms of in vivo angiogenesis, the expression of angiogenic cytokine and chemokine, their receptors, and MMPs was compared between SHEDs and HUVECs. SHEDs showed higher expression of1VEGF, SDF-$1{\alpha}$, and $PDGFR{\beta}$ than HUVECs. On the contrary, HUVECs showed higher expression of VEGF receptors, CXCR4, and PDGF-BB than SHEDs. This differential expression pattern suggested reciprocal interactions between SHEDs and HUVECs and their involvement during in vivo angiogenesis. In conclusion, SHEDs could be a feasible source of perivascular cells for in vivo angiogenesis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.11
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• pp.1695-1700
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• 2014

Oriental herbal liquor (Yakju) is a type of Korean traditional alcoholic beverage that uses Nuruk and oriental herbs for fermentation. The purpose of this study was to develop cosmetic ingredients using Jubak, which is a by-product of alcoholic fermentation of oriental herbal liquor. To investigate antioxidant, whitening, and anti-aging effects of Jubak, we prepared extract of Jubak and its solvent fractions. Ethyl acetate fraction (KSD E4-3) showed the most prominent free radical [1,1-diphenyl-2-picrylhydrazyl (DPPH)] scavenging activity ($SC_{50}$: 0.75 mg/mL). KSD E4-3 significantly inhibited in vitro mushroom tyrosinase activity ($IC_{50}$: 0.82 mg/mL) and reduced the melanin contents in mouse melanoma melanocyte, B16F10 cells. KSD E4-3 down-regulated protein expression of tyrosinase related proteins (TRP)-1, -2, which play key roles in melanogenesis. For anti-aging effects, inhibition of matrix metalloproteinase (MMPs) expression was evaluated using human keratinocyte, HaCaT cells. Treatment of HaCaT cells with KSD E4-3 reduced expression of MMP-1, -2, -9 and inhibited proteolytic activities of MMP-2, -9. These results suggest that KSD E4-3 induces down-regulation of cellular melanogenesis and protects against photoaging induced by UVB-induced damage. Thus KSD E4-3 could potentially be a valuable cosmetic ingredient.

• Development and Reproduction
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• v.4 no.1
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• pp.45-52
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• 2000

Membrane type matrix metalloproteinases(MT-MMPs) have been suggested to play an important role during structural remodeling of various tissue. Expression patterns of MT1-MMP and MT2-MMP mRNAs were investigated in oocytes, embryos, ovary and oviduct of mouse during their differentiation or periovulatory period using RT-PCR technique. Both cDNA products of MT1- and MT2-MMP of immature oocytes were barely discernable with a minimum amount but the expressions were distinct in mature oocytes regardless that they were matured in vivo or in vitro. MT2-MMP was not expressed by 2-cell embryos but was expressed by 4-cell stage embryos. From the morula stage untill hatched blastocyst stage, embyos showed intesnse expression of MT2-MMP with a sudden increase at blastocyst stage. While mouse ovarian tissues showed both expression of MT1- and MT2-MMP, there was no stage-specific difference throughout the estrous cycle. Mouse oviducts also exhibit constant amount of both MT1- and MT2-MMP expressions throughout periovulatory period, i.e., before or after ovulation. These observations lead to suggest that the differential expressions of maternal MT1- and MT2-MMP during meiotic resumption of mouse oocytes and embryonic expression of MT2-MMP particularly at blastocyst stage might play a role in the differentiation of mouse oocytes and／or embryos. The precise function of MT1- and MT2-MMP with regards to their participation in the remodeling of ovarian and oviductal tissues remains in a question.