• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.128-128
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• 1998

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases that degrade extracellular matrix and basement membrane. These enzymes are play important roles in tumor cell invasion and metastasis, as well as angiogenesis and other connective tissue diseases. In our screening program for inhibitors of MMP-2 from fungal metabolites, we have isolated novel non-peptidic inhibitors of MMPs, designated gelastatin A and B from the culture broth of Westerdykella multispora F50733. The structures of gelastatin A and B were determined to be 3-(5E-hexa-2E,4E-dienylidene-2-oxo-5,6-dihydro-2H-pyran-3yl)-propanoic acid and 3-(5Z-hexa-2E,4E-dienylidene-2-oxo-5,6-dihydro-2H-pyran-3yl)-propanoic acid, respectively. Gelastatin A and B exist as a mixture of two stereoisomers in a ratio of 2: 1. The 2: 1 mixture of gelastatin A and B inhibited activated MMP-2 and MMP-9 with an IC$\sub$50/ value of 0.63, 5.29 ${\mu}$M, respectively. They inhibited the invasion of B16F10 melanoma cells through basement membrane Matrigel with dose dependent.

• Journal of Life Science
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• v.26 no.6
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• pp.673-679
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• 2016

The development of safe and effective anti-cancer compounds has been seriously required to prevent and treat development of tumor in recent years. Among them, natural compounds derived traditional medicinal stuffs have been paid to attention as an anti-cancer candidate. In this study, aesculetin is a main component of a widely known as a medicinal stuff. It was reported that aesculetin has various biological effects such as anti-inflammatory and anti-bacterial, but its effect related to cell invasion was not discovered. Therefore, in this study, the effect of aesculetin on antioxidant and matrix metalloproteases (MMPs) was investigated in human fibrosarcoma cells, HT1080. First of all, aesculetin showed the scavenging activity of DPPH radical and reducing power in a dose dependent manner. As a result of cytotoxicity, the nontoxic concentration of aesculetin was below 2 μM in HT1080 cells performed by MTT assay. In addition, aesculetin displayed the inhibitory effect on MMP-9 activity related to cell invasion in experiment carried out by gelatin zymography assay. Furthermore, aesculetin increased the expression level of TIMP-1 but decreased the expression level of MMP-9 stimulated with PMA in western blot assay. Furthermore, aesculetin remarkably inhibited cell invasion related to metastasis a dose dependent manner. Above results suggest that aesculetin could exert chemopreventive effect through inhibition of activity and expression of MMP-9 related to cell invasion.

• YAKHAK HOEJI
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• v.48 no.6
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• pp.358-363
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• 2004

Matrix metalloproteinases (MMPs) are known to play an important role in photoaging by mediating the degradation of extracellular matrix proteins. In this study, to develop a n ew anti-aging agent, we investigated the antioxidant activity and the inhibitory effect of Melothria heterophylla extract on expression of MMP-1 in UVA-irradiated human dermal fibroblasts and MMP-1 activity. The M.heterophylla extract was found to scavenge radicals and reactive oxygen species (ROS) with the $SC_{50}$ values of $13{\mu}g/ml$ against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and $20{\mu}g/ml$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. UVA-induced MMP-1 expression was reduced about 80% by $100{\mu}g/ml$ of the M.heterophylla extract but MMP-1 Mrna expression was not inhibited. Therefore, we conclude that the M.heterophylla extract significantly inhibits MMP-1 expression at the protein level. Also, the M.heterophylla extract inhibited MMP-1 activity in a dose dependent manner. From these results, we suggest that the M.heterophylla extract can be used as a new anti-aging agent by antioxidant activity, regulation of UVA-induced MMP-1 production, and inhibition of MMP-1 activity.

• Journal of Life Science
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• v.22 no.8
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• pp.1092-1098
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• 2012

This study was carried out to discover the skin wrinkle reducing components in the seeds of Arctium lappa. The isolation of a methylene chloride-soluble fraction of 70% ethanol extract from the seeds of Arctium lappa using a procollagen type-1 synthesis and MMP-1 activity resulted in the isolation and identification of four lignin compounds: arctiin, arctigenin, matairesinol, and diarctigenin. All structures were confirmed via NMR and MS spectroscopic data. To determine cell viability and procollagen type-1 synthesis, human dermal fibroblasts were treated with 10-100 ${\mu}M$. As a result, none of the four compounds showed cytotoxicity up to 50 ${\mu}M$. We also investigated their procollagen type-1 synthesis and MMP-1 inhibition activity and found that arctiin had the highest activity in terms of both procollagen synthesis and MMP-1 inhibition among all four compounds. Putting all the data together, we suggest that arctiin be used in cosmetics as an anti-wrinkle material.

• Analytical Science and Technology
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• v.16 no.3
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• pp.179-184
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• 2003

Root bark of Ulmus davidiana Plancn. var. japonica Nakai was extracted by using several solvents with different polarities. Each extract was treated on the MMPs obtained from SK-Hep-1 in order to investigate inhibition effect. Zymography of MMPs showed that MeOH extract has significant inhibition effect. On the GC-MS analysis the highest mass to charge ratio (m/z) of the purified substance was 281. Also, on zymography of MMPs the substance showed 47% inhibition effect at the concentration of $314.7{\mu}g/g$. Cell viability of SK-Hep-1 was 60% at $31.47{\mu}g/g$.

• Microbiology and Biotechnology Letters
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• v.41 no.4
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• pp.449-455
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• 2013

Human skin is constantly exposed to environmental conditions such as UV rays, polluted air, and chemical products. UV rays, in particular, affect skin in many ways causing wrinkles, fine wrinkles, rough skin, and xeroderma through a skin aging process. The purpose of this study was to investigate the anti-wrinkling effect of Juniperus rigida Sieb., derived from a common cedar tree found the world over. Measuring the elastase to investigate wrinkling efficacy, it was shown that at a concentration level of $1,000{\mu}g/ml$ of the two extracts, the water extract exhibited a lower than 10% inhibition activity, while the ethanol extract exhibited a 68.5% inhibition activity. Collagenase inhibition activity in the water extract and ethanol extract were 44.9% in the former and 97.2% in the latter extract, which in the case of the ethanol extract, is similar to ascorbic acid (99.6%). Moreover, measuring the biosynthesis of collagen by fibroblast, a concentration level of $50{\mu}g/ml$ of ethanol extract produced 151.52% of biosynthetic promotion, proving that the ethanol extract acts as a superb anti-wrinkling agent. The result of an investigation conducted on the influence of the ethanol extract on MMP-1 caused by UVA showed that at a concentration level of $1,00{\mu}g/ml$ of the ethanol extract of J. rigida Sieb a 67.1% inhibition activity was noted. At a concentration level of $50{\mu}g/ml$ of the ethanol extract of J. rigida Sieb a 35% and 39% inhibition ratio to MMP-1 protein and mRNA were observed respectively, thereby restraining the appearance of the collagen breakdown enzyme MMP-1 and wrinkle creation by skin photo-aging.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5709-5714
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• 2012

Objective: To evaluate the effects of curcumin on matrixmetalloproteinase-9 (MMP-9) and invasion ability induced by transforming growth factor-${\beta}1$ (TGF-${\beta}1$) in MDA-MB-231 cells and potential mechanisms. Methods: Human breast cancer MDA-MB-231 cells were used with the CCK-8 assay to measure the cytotoxicity of curcumin. After treatment with 10 ng/ml TGF-${\beta}1$, with or without curcumin (${\leq}10{\mu}M$), cell invasion was checked by transwell chamber. The effects of curcumin on TGF-${\beta}1$-stimulated MMP-9 and phosphorylation of Smad2, extracellular-regulated kinase (ERK), and p38 mitogen activated protein kinases (p38MAPK) were examined by Western blotting. Supernatant liquid were collected to analyze the activity of MMP-9 via zymography. Following treatment with PD98059, a specific inhibitor of ERK, and SB203580, a specific inhibitor of p38MAPK, Western blotting and zymography were employed to examine MMP-9 expression and activity, respectively. Results: Low dose curcumin (${\leq}10{\mu}M$) did not show any obvious toxicity to the cells, while $0{\sim}10{\mu}mol/L$ caused a concentration-dependent reduction in cell invasion provoked by TGF-${\beta}1$. Curcumin also markedly inhibited TGF-${\beta}1$-regulated MMP-9 and activation of Smad2, ERK1/2 and p38 in a dose- and time-dependent manner. Additionally, PD98059, but not SB203580, showed a similar pattern of inhibition of MMP-9 expression. Conclusion: Curcumin inhibited TGF-${\beta}1$-stimulated MMP-9 and the invasive phenotype in MDA-MB-231 cells, possibly associated with TGF-${\beta}$/Smad and TGF-${\beta}$/ERK signaling.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.2
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• pp.247-251
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• 2004

UV radiation exerts various influences in the skin, including photoaging and inflammation (1). The MMPs (Matrix metalloproteinases), which are induced by UV irradiation, can degrade matrix proteins, and these results in a collagen deficiency in photodamaged skin that leads to skin wrinkling. It has been known that the production of PGE$_2$ stimulates MMPs expression, and inhibits procollagen (2). Thus, it is possible that the induction of MMPs and the inhibition of matrix protein synthesis by UV -induced PGE$_2$ may play some role in UV-induced collagen deficiency in photoaged skin. Fructose-1,6-diphosphate (FDP), a glycolytic metabolite, is reported to have cytoprotective effects against ischemia and postischemic reperfusion injury of brain and heart, presumably by augmenting anaerobic carbohydrate metabolism (3). And also, FDP significantly prevent skin aging by decreasing facial winkle compared with vehicle alone after 6 months of use. We studied the mechanism of anti-aging effect of FDP on UVB-irradiated HaCaT keratinocyte model. FDP has protective role in UVB injured keratinocyte by attenuating prostaglandin E$_2$ (PGE$_2$) production and COX-2 expression. And FDP also suppressed UVB-induced MMP-2 expression. Further, to delineate the inhibition of UVB-induced COX-2 and MMPs expression with cell signaling pathways, treatment of FDP to HaCaT keratinocytes resulted in marked inhibition of UVB-induced phosphorylation of ERK1/2, JNK. It also prevents UV induced NFB translocation, which are activated by cellular inflammatory signal. Our results indicate that FDP has protecting effects in UV-injured skin aging by decreasing UVB-induced COX-2 and MMPs expression, which are possibly through blocking UVB-induced signal cascades.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.2
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• pp.242-248
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• 2010

The present study was designed in order to determine whether Lonicerae flos (LF) could mitigate rheumatoid arthritis through inhibition of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 by regulation of macrophage migration inhibitory factor (MIF). We found that MIF mRNA expression in synoviocytes stimulated with phorbol-12-myristate-13-acetate dose-dependantly decreased by LF extract treatment (0.4 - 1.0 mg/$m{\ell}$). The distribution of MIF, COX-2 and MMP-9 positive reacted cells in LPS induced arthritis of mice were decreased by LF (45 mg/kg/day) treatment for 28 days. These data likely indicate that LF may act as MIF inhibitor and may be possible to develop useful agent for rheumatoid arthritis.

• Fisheries and Aquatic Sciences
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• v.21 no.6
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• pp.16.1-16.7
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• 2018

Background: Matrix metalloproteinases (MMPs) are linked with several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Brown seaweeds are being extensively studied for their bioactive molecule content against cancer progression. In this context, Sargassum horneri was reported to possess various bioactivities including antiviral, antimicrobial, and anti-inflammatory partly due to its phenolic compound content. Methods: In this study, potential of S. horneri was evaluated through anti-MMP effect in HT1080 fibrosarcoma cells. S. horneri crude extract was fractionated with organic solvents, namely, water ($H_2O$), n-buthanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and n-hexane. The non-toxicity of fraction samples (Sargassum horneri solvent-partitioned extracts (SHEs)) was confirmed by cell-viability assay. SHEs were tested for their ability to inhibit MMP enzymatic activity through gelatin digestion evaluation and cell migration assay. Expressions of MMP-2 and MMP-9 and tissue inhibitors of MMP (TIMPs) were evaluated by reverse transcription and Western blotting. Results: All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to gelatin zymography. Except $H_2O$ fraction, fractions hindered the cell migration significantly. All tested fractions suppressed both mRNA and protein levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Conclusion: Overall, current results suggested that S. horneri has potential to be a good source for anti-MMP agents, and further investigations are underway for better understanding of the action mechanism and isolation and elucidation of the bioactive molecules.