• Title/Summary/Keyword: matrix metalloproteinase (MMP) inhibition activity

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Inhibitory Effect of Siderophore Purified from Burkholderia sp. CAS-5 on the Matrix Metalloproteinase-2 (Gelatinase A) (Burkholderia sp. CAS-5 균으로 부터 생산된 시드로포어의 Matrix metalloproteinase-2(Gelatinase A) 억제 활성)

  • Kim, Kyoung-Ja
    • YAKHAK HOEJI
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    • v.50 no.4
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    • pp.228-233
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    • 2006
  • Matrix metalloproteinase-2 is known to be involved in pathological processes such as tumor invasion or rheumatoid arthritis. A soil microorganism producing siderophore under low iron stress $(up\;to\;5\;{\mu}m\;of\;iron)$ was identified as Burkholderia sp. Hydroxamate type siderophore produced by Burkholderia sp. CAS-5 was partially purified. MMP inhibitory activity of siderophore was confirmed by gelatin zymography. The $Zn^{2+}-chelating$ activity of siderophore correlated with the inhibition of MMP-2 activity.

Anti-Wrinkle Effect of Schizandra chinensis Baillon Fermented with Lactobacillus plantarum (오미자 유산균 발효물의 주름개선 효과)

  • Lee, Jung Hee;Kim, Jong Im;Choi, Hwa Jung;Lee, Jung Hyun
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.40 no.4
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    • pp.365-371
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    • 2014
  • To identify new active anti-wrinkle ingredients, this study investigated the anti-wrinkle effects of Schizandra chinensis Baillon fermented with Lactobacillus plantarum (SCF) by assessment of cytotoxicity of human dermal fibroblast, collagen biosynthesis, matrix metalloproteinase-I (MMP-1) inhibition and elastase inhibition. S. chinensis was fermented with L. rhamnosus for 1 day at $37^{\circ}C$. The cytotoxicity of SCF was evaluated by a cytopathic effect reduction method. Effects on collagen biosynthesis and matrix metalloproteinase-I (MMP-1) of SCF were evaluated by previous reported method using procollagen type-IC peptide EIA kit and Matrix Metalloproteinase-1 Biotrack activity Assay Kit, respectively. Elastase inhibition assay was conducted by reaction of enzyme and substrate using N-Suc-$(Ala)_3$-nitroanilide as the substrate. As the results, SCF didn't show cytotoxicity against human dermal fibroblast at concentration of $100{\mu}g/mL$. Also, SCF was increased collagen synthesis and showed inhibitory effect of MMP-1 (p < 0.05). In the elastase inhibition assay, the $IC_{50}$ of SCF was $36.4{\mu}g/mL$. Therefore, our results indicated that SCF possesses anti-wrinkle effects and can be used practically for anti-wrinkle care of skin.

ROLE OF NF${\kappa}B$ IN TOLL-LIKE RECEPTOR 9-MEDIATED MATRIX METALLOPROTEINASE-9 EXPRESSION (Toll-like receptor 9-매개에 의한 matrix metalloproteinase-9 발현에서 NF${\kappa}B$의 역할)

  • Lee, Sang-Hoon;Chin, Byung-Rho;Baek, Suk-Hwan
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.6
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    • pp.636-642
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    • 2007
  • Background: CpG DNA plays an important role in immune cell function. This study examined whether the temporal control of toll-like receptor (TLR)9 by CpG DNA can regulate the expression of matrix metalloproteinase-9(MMP-9). Methods and materials: Macrophages were cultured in the presence of 10% FBS. For the various MMP genes analysis, RT-PCR and real-time PCR were performed. In addition, zymography assay performed for the MMP activity. The phosphorylation assay did for the ERK1/2 and NF${\kappa}B$ activation, and luciferase promoter assay was for the NF${\kappa}B$ activity. Results: CpG DNA induced the mRNA expression of MMP-2, MMP-9, and MMP-13, but not of MMP-7, MMP-8, and MMP-12, in a time-dependent manner. Especially, the mRNA expression of MMP-9 was strongly induced by CpG DNA using real-time RT-PCR. The TLR9 inhibitor, chloroquine, suppressed CpG DNA-induced MMP-9 expression and its activity. Moreover, CpG DNA induced the phosphorylation of ERK and the inhibition of ERK by U0126 suppressed CpG DNA-induced MMP-9 expression and its activity. CpG DNA stimulated $I{\kappa}B-{\alpha}$ degradation and luciferase activity. In addition, pretreatment of SN-50, the inhibitor of NF${\kappa}B$, strongly blocked the CpG DNA-induced MMP-9 expression and activity. Conclusion: These observations suggest that CpG DNA may play important roles in the activation of macrophages by regulating the production of MMP-9 via the sequential TLR9-ERK-NF${\kappa}B$ signaling pathway.

Antioxidant and Metalloproteinase Inhibitory Activities of Ethanol Extracts from Lespedeza cuneata G. Don (야관문 에탄올 추출물의 항산화 및 Metalloproteinase 저해 활성)

  • Shin, Yong Ha;Song, Chang-Khil
    • Korean Journal of Environmental Agriculture
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    • v.36 no.4
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    • pp.263-268
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    • 2017
  • BACKGROUND: Lespedeza cuneata G. Don is a well-known medicinal plant. In this study, the biological activities of L. cuneata extracts were investigated. METHODS AND RESULTS: L. cuneata shoot was extracted with 30% ethanol and further fractionated with organic solvents. Total phenolic and flavonoid content, antioxidant activity, and matrix metalloproteinase inhibition effect of the extract and fractions were measured. Among the tested extract and fractions, the highest contents of total phenolic and flavonoids were found in ethyl acetate fraction (117.8 mg GAE/g and 35.9 mg QE/g, respectively). Ethyl acetate fraction showed the highest DPPH and ABTS radical scavenging activity, and the antioxidant activity of the other fractions followed the order n-hexane fraction>ethanol extract>methyl chloroform>n-butanol fraction. Inhibitory effect on the expression of matrix metalloproteinases (MMP1 and MMP3) was highest in the fraction of ethyl acetate, and n-butanol fraction also significantly inhibited the expression of MMP3. Antioxidant activities of L. cuneata extracts were significantly positively related to their phenolic and flavonoid content. CONCLUSION: Ethyl acetate fraction of L. cuneata ethanol extract showed potent antioxidant and matrix metalloproteinases inhibitory activities. Those activities might be related to the high total phenolic and flavonoid content of the extract.

A Study on the Anti-wrinkle Activities of Sesamum indicum L. Ethanol Extracts on CCD-986sk (CCD-986sk 세포 내 참깨 에탄올 추출물의 항주름 활성 연구)

  • Joo, Da-Hye;Yoo, Dan-Hee;Lee, Jin-Young
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.4
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    • pp.377-385
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    • 2016
  • In order to investigate the possibility of Sesamum indicum L. (S. indicum) extract as an active ingredient for wrinkle-care cosmetics, we prepared 70% ethanolic extract of S. indicum and measured its elastase inhibitory activity and collagenase inhibitory activity. We also evaluated the effect of S. indicum extract on protein and mRNA expression of MMPs in fibroblast cell (CCD-986sk). For anti-wrinkle effects, elastase inhibition activities and collagenase inhibition activities were 37.8% and 45% at a dose of $1,000{\mu}g/mL$ of S. indicum 70% ethanol extract. For a cell viability test, measured on fibroblast cell by ethanol extract of S. indicum, results showed 96% with cell viability at $100{\mu}g/mL$ concentration. According to the results of western blot of ethanol extract from S. indicum the expression of the matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-3 (MMP-3) protein was decreased by 63%, 43%, 49% at $100{\mu}g/mL$ concentration. Reverse transcription-polymerase chain reaction (PCR) of ethanol extract from S. indicum showed that the expression of MMP-1, MMP-2, MMP-3 mRNA was decreased by 82%, 79%, 82% at $100{\mu}g/mL$ concentration. The findings suggest that 70% ethanol extract from S. indicum has potential as a cosmeceutical ingredient with anti-wrinkle effects.

Baicalein Attenuates Oxidative Stress-Induced Expression of Matrix Metalloproteinase-1 by Regulating the ERK/JNK/AP-1 Pathway in Human Keratinocytes

  • Kim, Ki-Cheon;Kang, Sam-Sik;Lee, Jong-Sung;Park, Deok-Hoon;Hyun, Jin-Won
    • Biomolecules & Therapeutics
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    • v.20 no.1
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    • pp.57-61
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    • 2012
  • The matrix metalloproteinase (MMP) family is involved in the breakdown of the extracellular matrix during normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as pathological aging, arthritis, and metastasis. Oxidative conditions generate reactive oxygen species (ROS) (e.g., hydrogen peroxide [$H_2O_2$]) in cells, which subsequently induce the synthesis of matrix metalloproteinase-1 (MMP-1). MMP-1, an interstitial collagenase, in turn stimulates an aging phenomenon. In this study, baicalein (5,6,7-trihydroxyfl avone) was investigated for its in vitro activity against $H_2O_2$-induced damage using a human skin keratinocyte model. Baicalein pretreatment signifi cantly inhibited $H_2O_2$-induced up-regulation of MMP-1 mRNA, MMP-1 protein expression and MMP-1 activity in cultured HaCaT keratinocytes. In addition, baicalein decreased the transcriptional activity of activator protein-1 (AP-1) and the expression of c-Fos and c-Jun, both components of the heterodimeric AP-1 transcription factor. Furthermore, baicalein reduced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK), which are upstream of the AP-1 transcription factor. The results of this study suggest that baicalein is involved in the inhibition of oxidative stress-induced expression of MMP-1 via inactivation of the ERK/JNK/AP-1 signaling pathway.

Inhibitory Effect of Bodusan on $TNF-{\alpha}-induced$ Migration via Inhibition of Metalloproteinase Activity in Human Aortic Smooth Muscle Cells (보두산의 금속분해효소 활성 저해를 통한 사람 대동맥 평활근세포의 유주능 억제 효과)

  • Yun, Hyun-Jeong;Park, Sun-Dong
    • The Korea Journal of Herbology
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    • v.23 no.3
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    • pp.155-162
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    • 2008
  • Objectives : This study was evaluated to elucidate the inhibitory potential of Bodusan (BDS) and its components, Strychnos ignatii semen (SIS) and Glycyrrhizae Radix (GR), on human aortic smooth muscle cells (HASMC) migration and production of matrix metalloproteinase (MMP)-2 and MMP-9 by $TNF-{\alpha}$ treatment. Methods : Cytotoxic activity of BDS and its components on HASMC was using 5-(3-caroboxymeth- oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. Effect of BDS, SIS and GR on $TNF-{\alpha}-induced$ HASMC migration underside of matrigel filter was stained with hematoxylin-eosin. And total number of cells that migrated to the underside of the filter was counted. MMP-2 and MMP-9 activity was evaluated by gelatin zymography assay. Results : The matrigel migration assay showed that BDS effectively inhibited the $TNF-{\alpha}-induced$ migration of HASMC. Moreover, BDS significantly inhibited MMP-9 activity. Our present study demonstrates that BDS and its components inhibits $TNF-{\alpha}-induced$ HASMC migration and MMP-9 activity. The inhibitory effect of BDS extract is more potent than that of its component herb extracts. Conclusions : These results provide evidence that BDS has multiple effects in the inhibition of HASMC migration and may offer a therapeutic approach to block HASMC migration.

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Anti-metastatic Effect of Samguikoeui-Tang Via Inhibition of Matrix Metalloproteinases Activities (금속단백분해효소의 활성 저해를 통한 삼귀고의탕의 전이억제 효과)

  • Kim, Sung-Moo;Rhee, Yun-Hee;Lee, Joo-Ho;Kim, Sung-Hoon;Lee, Eun-Ok
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.6
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    • pp.1470-1474
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    • 2008
  • This study was performed to examine the anti-metastatic effect of ethanol extract of Samguikoeui-Tang (SGKE), a formula consisting of four oriental herbs, in highly-metastatic HT1080 human fibrosarcoma cells. SGKE significantly inhibited the adhesion of HT1080 cells to matrigel at nontoxic concentrations in a dose-dependent manner, while it did not exert cytotoxicity against HT1080 cells up to the concentration of 100 ${\mu}g$/ml. Also, SGKE depressed the activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) by gelatin zymography. However, SGKE did not affect the mRNA expression of MMP-2 and TIMP-2, an inhibitor of MMP-2, by RT-PCR analysis. In addition, the effect of SGKE on HT1080 cell invasion was determined using Boyden chamber assay. SGKE suppressed the invasion of HT1080 cells in a dose-dependent manner. Taken together, these results suggest that SGKE has an anti-metastatic effect via inhibition of MMP-2 and -9 activities.

Inhibitory Effect of Methanol Extract of Magnolia officinalis on Matrix Metalloproteinase-2

  • Lee, Dong-Yup;Kim, Cheorl-Ho;Kim, Dong-Soo
    • Preventive Nutrition and Food Science
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    • v.11 no.3
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    • pp.191-197
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    • 2006
  • Matrix metalloproteinase-2 (MMP-2) is a key enzyme involved in tumor invasiveness. The plant of Magnolia officinalis Rehd. et Wils. is often included as an ingredient in various herbal remedies recommended for cancer theraphies in Korea. Various extracts prepared from stems of M. officinalis were tested for cytotoxic activity on human hepatocellular carcinoma cell line, SK-Hep cells using the XTT assay method. Then, the inhibitory effect was examined on MMP-2 activity using gelatin zymography. Methanol (MeOH) extract of M. officinalis caused the strongest inhibition of the MMP-2 activity, as measured by gelatin zymography method for enzyme activity. $IC_{50}$ values of fractions on MMP-2 activity were in a range of $4.9{\sim}11.3\;{\mu}g/mL$. Among each fraction, butanol and ethylacetate (EtOAc) fractions showed the strong inhibitory activities ($IC_{50}=10.7\;and\;4.9\;{\mu}g/mL$, respectively). When the M. officinalis's constituents such as magnolol, honokiol, (-)-epigallocatechin gallate (EGCG) and ovovatol were examined for inhibitory effects on MMP-2 activity, EGCG showed strong inhibitory activity. However, MeOH extract of M. officinalis was dose-dependently inhibited to MMP-2 activity. The MeOH extract, hexane and EtOAc fractions $(IC_{50}\;of\;>200\;{\mu}g/mL)$ exhibited weak cytotoxicity activity, while butanol $(IC_{50}=80\;{\mu}g/mL)$ and chloroform fractions $(IC_{50}=90\;{\mu}g/mL)$ exhibited relatively strong cytotoxic activity. From these results, M. officinalis could be suitable for cancer treatment and chemopreventive drugs.

Extracts of Aster species Inhibit Invasive Phenotype and Motility of H-ras MCF10A Human Breast Epithelial Cells Possibly via Downregulation of MMP-2 and MMP-9

  • Ahn, Seong-Min;Lee, Kang-Ro;Moon, A-Ree
    • Biomolecules & Therapeutics
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    • v.10 no.4
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    • pp.240-245
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    • 2002
  • Cancer metastasis represents the most important cause of cancer death and antitumor agents that may inhibit this process have been extensively pursued. Invasion and metastasis of malignantly transformed cells involve degradation of the extracellular matrix (ECM) components by matrix metalloproteinases (MMP), especially MMP-2 and -9. We previously showed that H-ras-induced invasive phenotype may involve MMP-2, rather than MMP-9, in MCF10A cells. In the present study, we investigated the chemopreventive effect of Aster, a widely used culinary vegetable in Korea. We screened twelve extracts from three Aster species (Aster scaber, Aster oharai and Aster glehni) for the inhibitory effect on MMP activities of H-ras MCF10A human breast epithelial cells. All of the extracts tested in this study efficiently inhibited the gelatinolytic activities of MMP-2 and MMP-9. A more prominent inhibition was observed in MMP-2 activity compared to MMP-9. Out of twelve extracts, eight extracts showed>90% inhibition of MMP-2 activity in H-ras MCF10A cells while only one extract showed>90% inhibition of MMP-9 activity. We selected three extracts (AO-3, AG-3 and AS-EA) for further studies since they exerted a marked inhibition in the ratio of MMP-2 to MMP-9. Treatment with AO-3, AG-3 and AS-EA in H-ras MCF10A cells caused a significant inhibition of invasive phenotype and migration, proving a chemopreventive potential of these extracts. Taken together, our results demonstrate that extracts of Aster effectively inhibit invasion and migration of highly malignant human breast cells, possibly via downregulation of MMP-2 and MMP-9.