• Title/Summary/Keyword: Matrix metalloproteinase

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Effect of Ethanol Extract from Salvia miltiorrhiza on Chemoprevention and Metastasis of Breast Cancer (단삼 에탄올추출물이 유방암 예방 및 전이에 미치는 영향)

  • Shon, Yun-Hee;Cho, Hyun-Jung;Kim, Mee-Kyung;Jung, Eun-Jung;Nam, Kyung-Soo
    • Korean Journal of Pharmacognosy
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    • v.38 no.1
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    • pp.62-66
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    • 2007
  • Ethanol extract from Salvia miltiorrhiza (SME) was tested for breast cancer chemoprevention and metastasis by measuring the activites of cytochrome P45O 1A1, aromatase, ornithine decarboxylase (ODC), and matrix metalloproteinase (MMP)-9. SME significantly inhibited cytochrome P45O 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity in a dose-dependent manner in a concentration range of 100${\sim}$l,200 ${\mu}g/ml$ (p<0.01). Microsomal aromatase (estrogen synthase) activity was suppressed 54.9%${\sim}$77.5% by the SME at concentration of 600${\sim}$l,200 ${\mu}g/ml$. ODC activity induced by 12-O-tet-radecanoylphorbol-13-acetate (TPA) was significantly reduced by the SME 900 and 1,200 ${\mu}g/ml$ (p<0.05) in MCF-7 breast cancer cells. In addition, SME (900 and 1,200 ${\mu}g/ml$) markedly inhibited MMP-9 activity, a key role in cancer metastasis. Therefore, SME is worth further investigation with respect to breast cancer chemoprevention or therapy.

Flavonoid Compounds from Viola hondoensis and Their Effect on Matrix Metalloproteinase-1 in Ultraviolet Irradiation of Cultured Human Skin Fibroblasts

  • Moon, Hyung-In;Lee, Joong-Ku;Zee, Ok-Pyo;Chung, Jin-Ho
    • Food Science and Biotechnology
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    • v.14 no.1
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    • pp.143-146
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    • 2005
  • Although many studies have been performed to elucidate the molecular consequences of ultraviolet irradiation, little is known about the effect of natural products. Ultraviolet irradiation is widely considered to be an environmental stress. Here we investigated the effect of 2',4',7-trihydroxyisoflavone on the regulation of MMP-1 and type 1 procollagen in Ultraviolet irradiation of cultured human dermal fibroblasts. Phytochemical investigation of the whole plants of Viola hondoensis led to the isolation of five flavonoids. The structures of these compounds were identified 2',4',5,7-tetrahydroxyisoflavone (1), 2',4',7-trihydroxyisoflavone (2), 4',7-dihydroxyflavone (3), isoorientin (4), and isovitexin (5) using spectroscopic analysis. Among these, 2',4',7-trihydroxyisoflavone reduced the expression of MMP-1 at the protein levels in a dose-dependent manner by ultraviolet irradiation. Taken together, our results suggest that 2',4',7-trihydroxyisoflavone an important role in the reduction of MMP-1 induction by ultraviolet irradiation.

Berberine suppresses in vitro migration of human aortic smooth muscle cells through the inhibitions of MMP-2/9, u-PA, AP-1, and NF-κB

  • Liu, Su-Jian;Yin, Cai-Xia;Ding, Ming-Chao;Xia, Shao-You;Shen, Qin-Min;Wu, Ji-Dong
    • BMB Reports
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    • v.47 no.7
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    • pp.388-392
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    • 2014
  • Berberine, a type of isoquinoline alkaloid isolated from Chinese medicinal herbs, has been reported to have various pharmacological activities. Studies have demonstrated that berberine has beneficial effects on vascular remodeling and alleviates restenosis after vascular injury. However, its mechanism of action on vascular smooth muscle cell migration is not fully understood. We therefore investigated the effect of berberine on human aortic smooth muscle cell (HASMC) migration. Boyden chamber assay was performed to show that berberine inhibited HASMC migration dose-dependently. Real-time PCR and Western blotting analyses showed that levels of matrix metalloproteinase (MMP)-2, MMP-9, and urokinase-type plasminogen activator (u-PA) were reduced by berberine at both the mRNA and protein levels. Western blotting assay further confirmed that activities of c-Fos, c-Jun, and NF-${\kappa}B$ were significantly attenuated. These results suggest that berberine effectively inhibited HASMC migration, possibly by down-regulating MMP-2, MMP-9, and u-PA; and interrupting AP-1 and NF-${\kappa}B$ mediated signaling pathways.

Processed Panax ginseng, Sun Ginseng Increases Type I Collagen by Regulating MMP-1 and TIMP-1 Expression in Human Dermal Fibroblasts

  • Song, Kyu-Choon;Chang, Tong-Shin;Lee, Hye-Jin;Kim, Jin-Hee;Park, Jeong-Hill;Hwang, Gwi-Seo
    • Journal of Ginseng Research
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    • v.36 no.1
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    • pp.61-67
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    • 2012
  • In the present study, effects of sun ginseng (SG) on the collagen synthesis and the proliferation of dermal fibroblast were investigated. Collagen synthesis was measured by assaying procollagen type I C-peptide production. In addition, the level of matrix metalloproteinase (MMP)-1 was assessed by western blot analysis. SG suppressed the MMP-1 protein level in a dose-dependent manner. In contrast, SG dose-dependently increased tissue inhibitors of MMP (TIMP)-1 production in fibroblasts. SG increased type I collagen production directly and/or indirectly by reducing MMP-1 and stimulating TIMP-1 production in human dermal fibroblasts. SG dose-dependently induced fibroblast proliferation and this, in turn, can trigger more collagen production. These results suggest that SG may be a potential pharmacological agent with anti-aging properties in cultured human skin fibroblast.

Galangin and Kaempferol Suppress Phorbol-12-Myristate-13-Acetate-Induced Matrix Metalloproteinase-9 Expression in Human Fibrosarcoma HT-1080 Cells

  • Choi, Yu Jung;Lee, Young Hun;Lee, Seung-Taek
    • Molecules and Cells
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    • v.38 no.2
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    • pp.151-155
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    • 2015
  • Matrix metalloproteinase (MMP)-9 degrades type IV collagen in the basement membrane and plays crucial roles in several pathological implications, including tumorigenesis and inflammation. In this study, we analyzed the effect of flavonols on MMP-9 expression in phorbol-12-myristate-13-acetate (PMA)-induced human fibrosarcoma HT-1080 cells. Galangin and kaempferol efficiently decreased MMP-9 secretion, whereas fisetin only weakly decreased its secretion. Galangin and kaempferol did not affect cell viability at concentrations up to $30{\mu}M$. Luciferase reporter assays showed that galangin and kaempferol decrease transcription of MMP-9 mRNA. Moreover, galangin and kaempferol strongly reduce $I{\kappa}B{\alpha}$ phosphorylation and significantly decrease JNK phosphorylation. These results indicate that galangin and kaempferol suppress PMA-induced MMP-9 expression by blocking activation of NF-${\kappa}B$ and AP-1. Therefore, these flavonols could be used as chemopreventive agents to lower the risk of diseases involving MMP-9.

Neovastat(AE-941) inhibits the airway inflammation and hyperresponsiveness in a murine model of asthma

  • Lee, Sook-Young;Paik, Soon-Young;Chung, Su-Mi
    • Journal of Microbiology
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    • v.43 no.1
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    • pp.11-16
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    • 2005
  • Matrix metalloproteinase (MMP)-9 plays an important role in the pathogenesis of bronchial asthma. Neovastat, having significant antitumor and antimetastatic properties, is classified as a naturally occurring multifunctional antiangiogenic agent. We evaluated the therapeutic effect of Neovastat on airway inflammation in a mouse model of asthma. BALB/c mice were immunized subcutaneously with ovalbumin (OVA) on days 0, 7, 14, and 21 and challenged with inhaled OVA on days 26, 29, and 31. Neovastat was administrated by gavage (5 mg/kg body weight) three times with 12 h intervals, beginning 30 min before OVA inhalation. On day 32, mice were challenged with inhaled methacholine, and enhanced pause (Penh) was measured as an index of airway hyperresponsiveness. The severity of airway inflammation was determined by differential cell count of bronchoalveolar lavage (BAL) fluid. The MMP-9 concentration in BAL fluid samples was measured by ELISA, and MMP-9 activity was measured by zymography. The untreated asthma group showed an increased inflammatory cell count in BAL fluid and Penh value compared with the normal control group. Mice treated with Neovastat had significantly reduced Penh values and inflammatory cell counts in BAL fluid compared with untreated asthmatic mice. Furthermore, mice treated with Neovastat showed significantly reduced MMP-9 concentrations and activity in BAL fluid. These results demonstrate that Neovastat might have new therapeutic potential for airway asthmatic inflammation.

Sulforaphane Inhibits Ultraviolet B-induced Matrix Metalloproteinase Expression in Human Dermal Fibroblasts

  • Lee, Sam Youn;Moon, Sun Rock
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.6
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    • pp.922-928
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    • 2012
  • Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane] is one of the most abundant isothiocyanates in some cruciferous vegetables, especially broccoli. Sulforaphaene has been shown to exhibit many pharmacological activities, including anti-oxidant, anti-inflammatory and anti-microbial activities. However, the anti-skin photoaging effects of sulforaphane have not yet been reported. In the present study, we investigated the inhibitory effects of sulforaphane on MMP-1 and -3 expressions of the human dermal fibroblasts via various in vitro experiments and elucidated the pathways of inhibition. Western blot analysis and real-time PCR revealed sulfiraphane inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB strongly activated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity, which was determined by NF-${\kappa}B$ DNA binding activity. UVB-induced NF-${\kappa}B$ activation and MMP expression were completely blocked by sulforphane. These findings suggest that sulforaphane could prevent UVB-induced MMPs expressions through inhibition of NF-${\kappa}B$ activation.

Anti-aging potential of fish collagen hydrolysates subjected to simulated gastrointestinal digestion and Caco-2 cell permeation

  • Je, Hyun Jeong;Han, Yoo Kyung;Lee, Hyeon Gyu;Bae, In Young
    • Journal of Applied Biological Chemistry
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    • v.62 no.1
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    • pp.101-107
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    • 2019
  • The objectives of this study were to evaluate the anti-aging effects and investigate the effect of simulated gastrointestinal (GI) digestion on the anti-aging properties and intestinal permeation of the potential fish collagen hydrolysates (FCH). Therefore, procollagen synthesis, matrix metalloproteinase-1 (MMP-1) production, and Caco-2 cell permeability were analyzed before and after in vitro digestion for FCHs, low-molecular weight fractions (<1 kDa), and high molecular weight fractions (>1 kDa). After being subjected to GI digestion, the level of MMP-1 inhibition was maintained, although the procollagen production was significantly (>20%) lower with all samples. Also, the digested FCHs and their <1 kDa fraction yielded 9.1 and 13.8% increased peptide transport, respectively, compared to undigested samples. Based on the effective intestinal permeation and high digestive enzyme stability, the <1 kDa fraction of FCHs is a potential bioactive material suitable for anti-aging applications in the food and cosmetics industries.

Protective effects of quercetin-3-glucosyl-(1-2)-rhamnoside from Schizophragma hydrangeoides leaves on ultraviolet A-induced photoaging in human dermal fibroblasts

  • So Yeon Oh;Sung Chun Kim;Ho Bong Hyun;Hyejin Hyeon;Boram Go;Yong-Hwan Jung;Young-Min Ham
    • Journal of Applied Biological Chemistry
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    • v.65 no.4
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    • pp.277-286
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    • 2022
  • Schizophragma hydrangeoides (S. hydrangeoides) is a vine endogenous to Jeju Island and Ulleungdo, where it grows attached to the foothills and rock surfaces. Previous research has mostly focused on the whitening effect of S. hydrangeoides leaf extract. In this study, we investigated S. hydrangeoides leaf extract further, and detected four phytochemicals in the extract: chlorogenic acid, quercetin-3-O-glucosyl-(1-2)-rhamnoside, quercetin-3-O-xylosyl-(1-2)-rhamnoside, and quercitrin. We pretreated human dermal fibroblast (HDFn) cells with previously established concentrations of the four compounds for 1 h before ultraviolet A (UVA) irradiation. Among the four compounds, quercetin-3-O-glucosyl-(1-2)-rhamnoside (Q-3-GR) best inhibited matrix metalloproteinase-1 (MMP-1) levels. Thus, we investigated the protective effects of Q-3-GR on photoaging and its underlying mechanisms. Q-3-GR significantly reduced MMP-1 production and inhibited MMP-1 protein expression in UVA-irradiated HDFn cells. Furthermore, Q-3-GR increased procollagen type I production and protein expression. Q-3-GR exerted its anti-photoaging effects by downregulating the mitogen-activated protein kinase/ activator protein-1 signaling pathway, and upregulating the transforming growth factor-β/Smad signaling pathway. Thus, S. hydrangeoides leaf-derived Q-3-GR is a potential potent cosmetic ingredient for UV-induced skin aging.

Inhibition of Matrix Metalloproteinase-2 Activity of Flavonol Glycosides from Cedreia sinensis (참죽나무에서 분리한 flavonol glycoside의 금속단백분해효소-2 억제 활성)

  • Hwang Seon-Woo;Ha Tae-Joung;Kho Yung-Hee;Chun Hyo-Kon;Lee Jun;Kwon Hyun-Sook;Park Ki-Hun;Yang Min-Suk
    • Journal of Life Science
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    • v.16 no.3 s.76
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    • pp.442-446
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    • 2006
  • Cedrela sinensis is a broadleaf tree that is widely cultivated in Korea and China. It was used for treating enteritis, dysentery, and skin itch in oriental medicine. In this study, three major flavonoids, kaempferol-3-O-rhamnoside (1), quercetin-3-O-rhamnoside (2), and quercetin-3-O-glucoside (3), were isolated from the leaf of Cedrela sinensis. The biological activities of these compounds were tested by inhibitory activity of matrix metalloproteinases-2 (Type IV collagenase) method together with a cytotoxicity and a apoptosis test against human cancer cell lines.