• Title/Summary/Keyword: MMP-1 inhibition

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Anti-wrinkle effect of berberine by inhibition of MMP-2 and MMP-9 activity in fibroblasts (섬유아세포에서의 MMP-2 및 MMP-9 활성 억제에 의한 베르베린의 항주름 효과)

  • Jang, Young-Ah;Lee, Jin-Tae
    • Journal of Applied Biological Chemistry
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    • v.61 no.1
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    • pp.9-15
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    • 2018
  • We analyzed the antioxidant and anti-wrinkle activities of berberine, isolated from dried rhizome of Coptis japonica Makino, to determine its cosmetic potential. We performed the 3-[4,5-dimethylthiazol]-2-yl]-2,5-diphenyl-tetrazoliumbromide (MTT) assay to evaluate the toxicity of the berberine. We also measured the ROS and hyaluronic acid production, and expression of MMP-2, MMP-9, TIMP-1, TIMP-2, and tumor necrosis factor-alpha ($TNF-{\alpha}$) to evaluate the antioxidant and anti-wrinkle activities of berberine, respectively. The cytotoxicity of ultraviolet light, in presence of berberine, was measured by the MTT assay using CCD-986sk fibroblasts, and no cytotoxicity was observed at concentrations less than $25{\mu}g/mL$. We also found that berberine decreased ROS production in a concentration-dependent manner and promoted the synthesis of hyaluronic acid. Further, berberine reduced the protein levels and mRNA expression of MMP-2 and MMP-9, which are associated with wrinkle formation, and increased the expression of TIMP-1 and TIMP-2. In addition, the inhibitory effect of berberine on $TNF-{\alpha}$, known as pro-inflammatory cytokine, was inhibited by $TNF-{\alpha}$ gene in a concentration-dependent manner. These results suggest that berberine holds cosmetic value owing to its antioxidant activity, by inhibiting ROS production and anti-wrinkle activity by reducing MMP-2 and MMP-9 and increasing TIMP-1 and TIMP-2 expression.

Whitening and anti-wrinkle effect of Spirodela polyrhiza extracts (부평초 추출물의 미백 및 항주름 효과)

  • Kim, Dong Hee;Park, Tae Soon;Kim, Se Gie
    • Journal of Applied Biological Chemistry
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    • v.62 no.4
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    • pp.391-398
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    • 2019
  • The antioxidant, whitening, and anti-wrinkle activity of Spirodela polyrhiza extracts and fractions were evaluated to determine its efficacy as a functional cosmetic material. 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging activities were 44.2 and 74.3%, respectively, at 100 ㎍/mL of SE-E (the ethyl acetate fraction of 70% ethanol extract). To measure anti-wrinkle effects, procollagen biosynthesis and matrix metalloproteinase-1 (MMP-1) inhibition activity were determined. At 25 ㎍/mL of SE (70% ethanol extract), the biosynthesis activity was 48.5%, and SE-E showed the best activity (57.8%) at the same concentration. MMP-1 inhibition activity of SE and SE-E was 13.4 and 28.5%, respectively, at 25 ig/mL. Finally, the inhibition of cellular melanin synthesis and cellular tyrosinase were measured to determine the whitening effect; at 25 ㎍/mL, the inhibition activities of SE were 9.6 and 13.8%, respectively, and those for SE-E were 15.4 and 22.0%, respectively. Our results confirmed the possibility of SE and SE-E as effective functional materials. Further research investigating the antimicrobial, anti-inflammatory, and anticancer activities of S. polyrhiza is necessary to confirm its potential use in the food, cosmetics, and drug industries.

Vitamin D Inhibits Expression and Activity of Matrix Metalloproteinase in Human Lung Fibroblasts (HFL-1) Cells

  • Kim, Seo Hwa;Baek, Moon Seong;Yoon, Dong Sik;Park, Jong Seol;Yoon, Byoung Wook;Oh, Byoung Su;Park, Jinkyeong;Kim, Hui Jung
    • Tuberculosis and Respiratory Diseases
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    • v.77 no.2
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    • pp.73-80
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    • 2014
  • Background: Low levels of serum vitamin D is associated with several lung diseases. The production and activation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of emphysema. The aim of the current study therefore is to investigate if vitamin D modulates the expression and activation of MMP-2 and MMP-9 in human lung fibroblasts (HFL-1) cells. Methods: HFL-1 cells were cast into three-dimensional collagen gels and stimulated with or without interleukin-$1{\beta}$ (IL-$1{\beta}$) in the presence or absence of 100 nM 25-hydroxyvitamin D (25(OH)D) or 1,25-dihydroxyvitamin D ($1,25(OH)_2D$) for 48 hours. Trypsin was then added into the culture medium in order to activate MMPs. To investigate the activity of MMP-2 and MMP-9, gelatin zymography was performed. The expression of the tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) was measured by enzyme-linked immunosorbent assay. Expression of MMP-9 mRNA and TIMP-1, TIMP-2 mRNA was quantified by real time reverse transcription polymerase chain reaction. Results: IL-$1{\beta}$ significantly stimulated MMP-9 production and mRNA expression. Trypsin converted latent MMP-2 and MMP-9 into their active forms of MMP-2 (66 kDa) and MMP-9 (82 kDa) within 24 hours. This conversion was significantly inhibited by 25(OH)D (100 nM) and $1,25(OH)_2D$ (100 nM). The expression of MMP-9 mRNA was also significantly inhibited by 25(OH)D and $1,25(OH)_2D$. Conclusion: Vitamin D, 25(OH)D, and $1,25(OH)_2D$ play a role in regulating human lung fibroblast functions in wound repair and tissue remodeling through not only inhibiting IL-$1{\beta}$ stimulated MMP-9 production and conversion to its active form but also inhibiting IL-$1{\beta}$ inhibition on TIMP-1 and TIMP-2 production.

Inhibitory Effect of Ginkgolide B on Platelet Aggregation in a cAMP- and cGMP-dependent Manner by Activated MMP-9

  • Cho, Hyun-Jeong;Nam, Kyung-Soo
    • BMB Reports
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    • v.40 no.5
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    • pp.678-683
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    • 2007
  • Extracts from the leaves of the Ginkgo biloba are becoming increasingly popular as a treatment that is claimed to reduce atherosclerosis, coronary artery disease, and thrombosis. In this study, the effect of ginkgolide B (GB) from Ginkgo biloba leaves in collagen (10 ${\mu}g/ml$)-stimulated platelet aggregation was investigated. It has been known that human platelets release matrix metallo-proteinase-9 (MMP-9), and that it significantly inhibited platelet aggregation stimulated by collagen. Zymographic analysis confirmed that pro-MMP-9 (92-kDa) was activated by GB to form an MMP-9 (86-kDa) on gelatinolytic activities. And then, activated MMP-9 by GB dose-dependently inhibited platelet aggregation, intracellular $Ca^{2+}$ mobilization, and thromboxane $A_2$ ($TXA_2$) formation in collagen-stimulated platelets. Activated MMP-9 by GB directly affects down-regulations of cyclooxygenase-1 (COX-1) or $TXA_2$ synthase in a cell free system. In addition, activated MMP-9 significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which have the anti-platelet function in resting and collagen-stimulated platelets. Therefore, we suggest that activated MMP-9 by GB may increase the intracellular cAMP and cGMP production, inhibit the intracellular $Ca^{2+}$ mobilization and $TXA_2$ production, thereby leading to inhibition of platelet aggregation. These results strongly indicate that activated MMP-9 is a potent inhibitor of collagen-stimulated platelet aggregation. It may act a crucial role as a negative regulator during platelet activation.

Effects of Sabaek-san on the Metrix Metalloproteinase-9 in the Bronchial Asthma Mouse Model (사백산이 천식유발 백서에서 metrix metalloproteinase-9(MMP-9)에 미치는 영향)

  • Lee Hai Ja
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1694-1698
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    • 2004
  • We hope to evaluate the effects of Sabaek-san for the bronchial asthma using assesment on the metrix metalloproteinase-9(MMP-9) after Sabaek-san was intravenously administered OVA-sensitized and -challenged mice. Seventy-two female mice, 8-10 weeks of age and free of murine specific pathogens, were used. Of the seventy-two mice, twenty-four mice were not sensitized and forty-eight mice were sensitized by intraperitoneal injection of OVA. Of the sensitized mice, twenty-four mice didn't administrate Sabaek-san and twenty-four administrated Sabaek-san. Mice were sensitized on days 1 and 14 by intraperitoneal injection of 20 fig OVA. On days 21, 22 and 23 after the initial sensitization, the mice were challenged for 30 minutes with an aerosol of 1% OVA in saline. Sabaek-san administered 200㎎/㎏ in the tail of the mouse, one time per day, for 7 days, beginning 14 days after first sensitization. Bronchoalveolar lavage was performed 72 hours after the last challenge, and total cell numbers in the BAL fluid were count. Also, level of MMP-9 in the BAL fluid were measured by Enzyme immunoassays and Western blot analysis. Enzyme immunoassay revealed that MMP-9 levels in the BAL fluids significantly increased 72 h after OVA inhalation compared with levels in the control group. After administration of the Sabaek-san, the levels of the MMP-9 in BAL fluids 72 h after OVA inhalation reduced dramatically. Western blot analysis revealed that MMP-9 levels increased in the all mice which were challenge with OVA without administered Sabaek-san compared the normal mouse. However, in the groups of the administered Sabaek-san, the MMP-9 level markedly decreased. Sabaek-san might be effect the treatment of the bronchial asthma as a inhibition of the MMP-9.

Met inactivation by S-allylcysteine suppresses the migration and invasion of nasopharyngeal cancer cells induced by hepatocyte growth factor

  • Cho, Oyeon;Hwang, Hye-Sook;Lee, Bok-Soon;Oh, Young-Taek;Kim, Chul-Ho;Chun, Mison
    • Radiation Oncology Journal
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    • v.33 no.4
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    • pp.328-336
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    • 2015
  • Purpose: Past studies have reported that S-allylcysteine (SAC) inhibits the migration and invasion of cancer cells through the restoration of E-cadherin, the reduction of matrix metalloproteinase (MMP) and Slug protein expression, and inhibition of the production of reactive oxygen species (ROS). Furthermore, evidence is emerging that shows that ROS induced by radiation could increase Met activation. Following on these reports of SAC and Met, we investigated whether SAC could suppress Met activation. Materials and Methods: Wound healing, invasion, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT), soft agar colony forming, western blotting, and gelatin zymography assays were performed in the human nasopharyngeal cancer cell lines HNE1 and HONE1 treated with SAC (0, 10, 20, or 40 mM) and hepatocyte growth factor (HGF). Results: This study showed that SAC could suppress the migration and invasion of HNE1 and HONE1 cell lines by inhibiting p-Met. An increase of migration and invasion induced by HGF and its decrease in a dose dependent manner by SAC in wound healing and invasion assays was observed. The reduction of p-Met by SAC was positively correlated with p-focal adhesion kinase (p-FAK) and p-extracellular related kinase (p-ERK in both cell lines). SAC reduced Slug, MMP2, and MMP9 involved in migration and invasion with the inhibition of Met-FAK signaling. Conclusion: These results suggest that SAC inhibited not only Met activation but also the downstream FAK, Slug, and MMP expression. Finally, SAC may be a potent anticancer compound for nasopharyngeal cancer treated with radiotherapy.

MiR-886-5p Inhibition Inhibits Growth and Induces Apoptosis of MCF7 Cells

  • Zhang, Lei-Lei;Wu, Jiang;Liu, Qiang;Zhang, Yan;Sun, Zhu-Lei;Jing, Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1511-1515
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    • 2014
  • Background and Aims: To explore the molecular mechanisms of miR-886-5p in breast cancer., we examined roles in inhibiting growth and migration of MCF-7 cells. Methods: MiR-886-5p mimics and inhibitors were used to express or inhibit MiR-886-5p, respectively, and MTT and clone formation assays were used to determine the survival and proliferation. Hoechst 33342/ PI double staining was applied to detect apoptosis. The expression of caspase-3, caspase-8, caspase-9, MT1-MMP, VEGF-C and VEGF-D was detected by Western blotting, and the levels of MMP2 and MMP9 secreted from MCF-7 cells were assessed by ELISA. MCF-7 cell migration was determined by wound healing and Transwell assays. Results: We found that the growth of MCF-7 cells was inhibited upon decreasing miR-886-5p levels. Inhibiting miR-866-5p also significantly induced apoptosis and decreased the migratory capacity of these cells. The expression of VEGF-C, VEGF-D, MT1-MMP, MMP2, and MMP9 was also found to be decreased as compared to controls. Conclusions: Our data show that downregulation of miR-886-5p expression in MCF-7 cells could significantly inhibit cell growth and migration. This might imply that inhibiting miR-886-5p could be a therapeutic strategy in breast cancer.

Antioxidant Activity and Inhibition of MMP-1 Expression of Schizandrae fructus (Schizandra chinensis) Extract (오미자 추출물의 항산화 활성 및 MMP-1 발현저해)

  • Park, Sung-Min;Kim, Jin-Jun;Jeong, Kwan-Young;Han, Sang-Keun;Jeong, Tae-Hwa;Yun, Mi-Young
    • Korean Journal of Pharmacognosy
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    • v.44 no.1
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    • pp.47-52
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    • 2013
  • We invesitagat the effects of antioxidant and suppression of MMP-1 in UV-irradiated human dermal fibroblasts (HDF) by schizandrin isolated from Schisandra chinensis. Ultrasonic technique was used to extract schizandrin from S. chinensis. The higher contents of schizandrin (6.34 mg/ml) in 70% EtOH extract obtained by ultrasonic treatment at 20 MHz for 2 h during 10 days. Schizandrin had antioxidant activities. Schizandrin (1-10 ${\mu}g/ml$) induced a significant dose-dependent decrease in the expression fo MMP-1 protein. These results suggest that schizandrin is a potential candidate for the prevention and treatment of skin aging.

Anti-wrinkle Activities Verification of Buplerum falcatum Extracts on CCD-986sk (CCD-986sk세포내 시호 추출물의 항주름 활성 검증)

  • Kim, Dong-Hee;Park, Tae-Soon;Son, Jun-Ho
    • Journal of Applied Biological Chemistry
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    • v.58 no.2
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    • pp.183-187
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    • 2015
  • The electron donating ability, elastase inhibitory, procollagen synthesis and Matrix metalloprotease-1 (MMP-1) activities were measured in order to verify the anti-wrinkle properties of extracts from Buplerum falcatum as a functional ingredient for cosmetic products. Electron donating ability and elastase inhibition activities were 80 and 52% at a dose of $1,000{\mu}g/mL$ of B. falcatum 70% ethanol extract. Pro-collagen synthesis was increased with the increase concentration of B. falcatum extract on CCD-986sk in addition to decrease the amount of protein of MMP-1. The results suggested that B. falcatum extract can be used to reduced electron donating ability, elastase, pro-collagen synthesis and MMP-1 activity and is a potential candidate for cosmedical materials.

The Effect of Cosmetic on Anti-Wrinkle of Acer mono Sap (우산고로쇠의 향장효과)

  • Sohn, Sang Hyun;Lee, Sang Won;Shin, Yu Su;Kim, Hyung Don;Yang, Seung Ok;Kim, Seung Yu;Kim, Young Ock
    • Korean Journal of Medicinal Crop Science
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    • v.21 no.4
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    • pp.262-267
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    • 2013
  • The purpose of this study was to research for anti-oxidation and anti-wrinkle effects of Acar mono Sap (AM). To cosmetic effect of AM, safety effect (MTT assay), anti-wrinkle effect (elastase, MMP-1 inhibition assay) and anti-oxidant effect (DPPH assay) were measured. When water extract of AM was used for cell viability, it was over 100% at 6% (6 ml/100 ml in phosphate buffer) concentration. AM showed 45.7% elastase inhibition and 23.7% MMP-1 inhibition at 50% (50 ml/100 ml in phosphate buffer) concentration so that it had good anti-wrinkle characteristic. And AM showed 68.9% antioxidation capacity at 50% concentration by using a DPPH assay. Consequently, AM can be used as natural materials or additives for human skin owing to their beneficial biologic functions, including the anti-wrinkle effect, for cosmetic compositions.