• Title/Summary/Keyword: Matrix Metalloproteinase(MMP)

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Screening of Anti-angiogenic Activity from Plant Extracts (식물 추출물의 혈관신생 억제 효능 검색)

  • Kim, Joon-Sik;Park, Byoung-Young;Park, Eun-Kyu;Lee, Hee-Suk;Hahm, Jong-Cheon;Bae, Ki-Hwan;Kim, Min-Young
    • Korean Journal of Pharmacognosy
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    • v.37 no.4 s.147
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    • pp.253-257
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    • 2006
  • We examined anti-angiogenic effects of water extracts from 32 plant materials (20 Korean medicinal plants and 12 western herbs) using cell-based anti-angiogenic assay, HUVEC tube formation assay, and then we found that 7 plant extracts inhibited HUVEC tube formation strongly. The plant materials which showed anti-angiogenic effects are Cinnamomi Ramulus, Atractylodis Rhizoma alba, Polygalae Radix, Myristicae Semen, Artemisiae Iwayomogii Herba, leaves of Rosmarinus officinalis, and leaves of Melissa officinalis. We also investigated inhibitory effects of these anti-angiogenic herbal extracts on MMP (matrix metalloproteinase) activity which has important roles in angiogenesis. Among extracts tested in this study, water extract of Melissa officinalis showed the most potent anti-angiogenic and MMP inhibitory activity.

Effect of Rhei Rhizoma on Brain Edema Induced by MCAO in Rats (대황(大黃)이 뇌허혈 손상에 의한 뇌부종에 미치는 영향)

  • Kang, Kyung-Hwa;Sohn, Nak-Won;Kim, Bum-Hoi
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.4
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    • pp.866-871
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    • 2009
  • Brain edema is a major importance in the pathophysiology of CNS injuries including stroke. Ischemic brain edema results from both cytotoxic edema, which is severe in astrocytes at early stage, and vasogenic edema caused by excessive blood-brain barrier (BBB) permeability. The present study was performed to determine the effect of Rhei Rhizoma on brain edema induced by middle cerebral artery occlusion (MCAO) in the rats. The neurological symptom, total infarct volume and edema index caused by MCAO were measured. The changes of Matrix Metalloproteinase-9 (MMP-9) and inducible nitric oxide synthase (iNOS) immunoreactivities were also observed. We found that Rhei Rhizoma extract improved the neurological symptom and attenuated the total infarct volume and brain edema caused by ischemic insult. Rhei Rhizoma extract also attenuated the expression of MMP-9 and iNOS. This results suggest that Rhei Rhizoma has a protective effect on the brain edema caused by ischemic insult.

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.

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.

Luteolin Inhibits the Activity, Secretion and Gene Expression of MMP-3 in Cultured Articular Chondrocytes and Production of MMP-3 in the Rat Knee

  • Kang, Bun-Jung;Ryu, Jiho;Lee, Choong Jae;Hwang, Sun-Chul
    • Biomolecules & Therapeutics
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    • v.22 no.3
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    • pp.239-245
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    • 2014
  • We investigated whether luteolin affects the gene expression, secretion and activity of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as production of MMP-3 in the rat knee to evaluate the potential chondroprotective effects of luteolin. Rabbit articular chondrocytes were cultured in a monolayer and IL-$1{\beta}$-induced gene expression levels of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), ADAMTS-5 and type II collagen were measured by reverse transcription - polymerase chain reaction (RT-PCR). Effects of luteolin on interleukin- $1{\beta}$ (IL-$1{\beta}$)-induced secretion and enzyme activity of MMP-3 in rabbit articular chondrocytes were investigated by western blot analysis and casein zymography, respectively. The effect of luteolin on MMP-3 protein production was also examined in vivo. The results were as follows: (1) luteolin inhibited the gene expression levels of MMP-3, MMP-1, MMP-13, ADAMTS-4 and ADAMTS-5. However, it increased the gene expression level of collagen in rabbit articular chondrocytes; (2) luteolin inhibited the secretion and activity of MMP-3; (3) luteolin inhibited in vivo production of MMP-3 protein. These results suggest that luteolin can regulate the gene expression, secretion and activity of MMP-3, by directly acting on articular chondrocytes.

Expression of Matrix Metalloproteinase-2, Cathepsin D and E-cadherin in Human Gastric Adenocarcinomas (위선암에서 Matrix Metalloproteinase-2, Cathepsin D 및 E-cadherin의 발현)

  • Lee Sang Kuon;Park Seung Cheol;Kim Won Woo;Kim Wook;Lee Kyo Young;Jeon Hae Myung;Kim Eung Kook;Koh Yong Bok
    • Journal of Gastric Cancer
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    • v.2 no.3
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    • pp.151-156
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    • 2002
  • Purpose: The prognosis of gastric cancer depends on the depth of invasion, lymph-node metastasis, invasion to adjacent tissues, and distant metastasis. Recently, it is known that tumor-associated proteases and adhesion molecules have been shown to play a relevant role in the process of progression and metastasis. The purpose of our study was to demonstrate the value of MMP-2 (matrix metalloproteinase), cathepsin D and E-cadherin as prognostic factors. Materials and Methods: In this study, formalin-fixed, paraffin-embedded tissue blocks from 69 patients with gastric cancer were immunohistochemically studied using antibodies to MMP-2, cathepsin D, and E-cadherin, and their expressions were analyzed according to the pathologic stage, lymph-node metastasis, histological differentiation, and patient survival. The medical records of these patients were retrospectively reviewed. Results: Increased expression of MMP-2 significantly correlated with advanced pathologic stage (P=0.026). Patients with lymph-node metastasis also had increased expression of MMP-2. Those patients with increased expression of MMP-2 showed a poorer survival; nevertheless, it was not statistically significant. Increased expression of cathepsin D significantly correlated with advanced pathologic stage (p=0.029). However, no correlation was observed between advanced pathologic stage and either lymph-node status or histological differentiation. Patients with increased expression of cathepsin D had a poorer survival, but that result was not statistically significant. No association was found between reduced expression of E-cadherin and pathologic stage, lymph-node status, or histological differentiation. Also, no correlation was found between the expression of E-cadherin and survival. In addition, when a combination of MMP-2 and cathepsin D expressions was analyzed, if both were negative, the survival seems to be longer, but it was not statistically significant. Conclusions: In patients with gastric cancer, expressions of MMP-2 and cathepsin D correlated with tumor stage; therefore, they may be considered as prognostic factors.

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Possible Role of Matrix Metalloproteinase in Osteolytic Intracranial Meningiomas

  • Moon, Hyung-Sik;Jung, Shin;Jung, Tae-Young;Cao, Van Thang;Moon, Kyung-Sub;Kim, In-Young
    • Journal of Korean Neurosurgical Society
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    • v.47 no.1
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    • pp.11-16
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    • 2010
  • Objective: Abnormalities of the bone are frequently encountered in patients with meningioma, and hyperostosis and endostosis are common bone alterations in these tumors. Extensive bony destruction is very unusual in patients with meningioma. We report six cases of intracranial meningioma associated with an osteolytic lesion of the skull and discuss the underlying mechanisms that may be responsible for bone destruction in patients with meningioma. Methods: Six patients were classified into three groups, severe, moderate and mild, according to the degree of osteolytic bony destruction. The tumor was classified as intracranial or extracranial, depending on its location. We investigated the potential role of matrix metalloproteinase (MMP) in meningioma-associated osteolysis. The levels of MMP expression were determined by gelatin zymography, reverse transcription-quantitative PCR analysis (RT-PCR) and immunohistochemical analysis. Results: Complete surgical removal of the lesion was performed in each patient. Histological examination revealed benign meningioma in four cases, and two cases of atypical meningioma. Patients did not have a poor prognosis except one case of recurred atypical meningioma. Gelatin zymography and RT-PCR detected high levels of MMP-2 in almost all extracranial masses in comparison with the intracranial masses and MMP9 in two. There was no difference in the severity of bone destruction. Immunohistochemical analysis revealed MMP-2 expression in the vicinity of the bone destruction, and a few MMP-9-positive stainings were observed. Conclusion: Osteolysis of the skull in patients with meningiomas might not be indicative of malignant pathological features and poor prognosis. Invasion to the extracranial portion and osteolysis might be associated with MMP-2 expression in meningioma.

Inhibitory Activity of the Extracts from the Pigmented Rice Brans on Inflammatory Reactions (유색미 겨 추출물의 염증반응 억제활성)

  • Choi, Sun-Phil;Kang, Mi-Young;Nam, Seok-Hyun
    • Applied Biological Chemistry
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    • v.47 no.2
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    • pp.222-227
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    • 2004
  • Effects of the extracts from bran part of the pigmented rices on inflammation was evaluated by determining their inhibitory action on the production of nitric oxides, histamines and matrix metalloproteinase(MMP) from inflammatory leukocytes. Effects on the production of nitric oxides in a macrophage cell line, RAW264.7 cells, were determined, demonstrating that any significant difference was not detected between the normal rice and the pigmented rice extracts. Inhibitory effects on the histamine-release from a basophilic cell line, RBL-2H3, were examined, showing 3.6 to 5.4-fold increase in the inhibitory activity compared to that of the normal rices. Among the pigmented rice cultivars tested, especially, inhibitory activity of LK1-3-6-12-1-1 was the greatest. Using RAW264.7 cells, we examined the effect of the pigmented rice extracts on the MMP activity. The results showed that the enzyme activity increased with the increasing concentration of the normal rice extract. However, the pigmented rice extracts, except LK1A-2-12-1-l, acted to decrease the MMP activity with their increasing concentrations. The results described above showed the superiority of the pigmented rice extracts in inhibition on release of histamine and MMP, pivotal factors for causing inflammatory responses, from the leukocytes.

Effects of matrix metallproteinases on dentin bonding and strategies to increase durability of dentin adhesion (상아질 접착에 대한 matrix metalloproteinase (MMP)의 영향과 이를 극복하기 위한 전략)

  • Lee, Jung-Hyun;Chang, Ju-Hea;Son, Ho-Hyun
    • Restorative Dentistry and Endodontics
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    • v.37 no.1
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    • pp.2-8
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    • 2012
  • The limited durability of resin-dentin bonds severely compromises the longevity of composite resin restorations. Resin-dentin bond degradation might occur via degradation of water-rich and resin sparse collagen matrices by host-derived matrix metalloproteinases (MMPs). This review article provides overview of current knowledge of the role of MMPs in dentin matrix degradation and four experimental strategies for extending the longevity of resin-dentin bonds. They include: (1) the use of broadspectrum inhibitors of MMPs, (2) the use of cross-linking agents for silencing the activities of MMPs, (3) ethanol wet-bonding with hydrophobic resin, (4) biomimetic remineralization of water-filled collagen matrix. A combination of these strategies will be able to overcome the limitations in resin-dentin adhesion.

DIFFERENT EFFECTS OF QUERCETIN ON MATRIX METALLOPROTEINASES EXPRESSION IN EARLY AND LATE PASSAGE HUMAN FIBROBLASTS

  • Eum, Sung-Yong;Oh, Jang-Hee;Park, Jong-Min;Chung, An-Sik
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.158-158
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    • 2001
  • Bioflavonoids have been regarded as therapeutic agents for a wide range of disease including cancer. The increase of matrix metalloproteinases expression is a key event in several pathological conditions, e.g., dermal photocarcinogenesis, tumor initiation, invasion and metastasis. In this study, we investigated effects of quercetin, a major bioflavonoid in human diet, on matrix metalloproteinase (MMR)-1, MMP-2, MMP-3, MMP-9 mRNA expression during cellular aging in cultured human foreskin fibroblast. (omitted)

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