• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.442-448
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• 2015

We evaluated the chondroprotective effects of wogonin by investigating its effects on the gene expression and production of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as on production of MMP-3 in the rat knee. Rabbit articular chondrocytes were cultured in a monolayer, and RT-PCR was used to measure interleukin-$1{\beta}$ (IL-$1{\beta}$)-induced expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), and type II collagen. In rabbit articular chondrocytes, the effects of wogonin on IL-$1{\beta}$-induced production and proteolytic activity of MMP-3 were investigated using western blot analysis and casein zymography, respectively. The effect of wogonin on MMP-3 protein production was also examined in vivo. In rabbit articular chondrocytes, wogonin inhibited the expression of MMP-3, MMP-1, MMP-13, and ADAMTS-4, but increased expression of type II collagen. Furthermore, wogonin inhibited the production and proteolytic activity of MMP-3 in vitro, and inhibited production of MMP-3 protein in vivo. These results suggest that wogonin can regulate the gene expression and production of MMP-3, by directly acting on articular chondrocytes.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3259-3264
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• 2012

Curcumin (CM) possesses anti-cancer activity against a variety of tumors. Matrix metalloproteinases (MMPs) play an important role in remodeling the extracellular matrix and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs) family. Control of MMP and TIMP activity are now of great significance. In this study, the effect of CM is investigated on metastatic MMPs and anti-metastatic TIMPs genes on MDA breast cancer cells cultured in a mixture of DMEM and Ham's F12 medium and treated with different concentrations of CM (10, 20 and $40{\mu}M$ for various lengths of time. Reverse transcription followed by quantitative real time PCR was used to detect the gene expression levels of MMPs and TIMPs in CM-treated versus untreated cases and the data were analyzed by one-way ANOVA. At high concentrations of curcumin, TIMP-1, -2, -3 and -4 genes were up-regulated after 48 hours of treatment, their over-expression being accompanied by down-regulation of MMP-2 and MMP-9 gene expression levels in a concentration- and time-dependent manner. These results suggest that curcumin plays a role in regulating cell metastasis by inhibiting MMP-2 and MMP-9 and up-regulating TIMP1 and TIMP4 gene expression in breast cancer cells.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.27 no.3
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• pp.106-114
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• 2014

Objective : UV irradiatiion causes skin-aging involving coarse wrinkles, thickning, dyspigmentation, and rough skin surface. This study was aimed to elucidate the anti-winkle activity of complex diet of Korean red ginseng (RG) and fish oil (FO) on UV-induced Photoaging. Methods : To investigated photo-protective effects of Korean red ginseng and fish oil on UV-induced damaged skins, SKH hairless female mice were randomly divided into six groups [control, UV, UV/RG, UV/FO, UV/RG/FO(low), UV/RG/FO(high)]and orally administered three times a week respectively. UV radiation was applied to the backs of the mice three times a week for 8 weeks. Expressions of matrix metalloproteinase (MMP)-3, MMP-13 and tissue inhibitor matrix metalloproteinase (TIMP)-1 in skin were measured by immunohistochemical staining. Results : In this study, UVB-induced epidermal hypertropy was diminished by RG group or FO group or complex group of RG and FO. Expression levels of MMP-3 and MMP-13 were reduced and expression level of TIMP-1 was increased by RG group or FO group or complex group of RG and FO. Especially MMP-3 and MMP-13 were markedly reduced by diet of FO and complex diet of RG and FO compared with untreated group. Conclusions : This results suggest that complex diet of RG and FO have a anti-wrinkle activity on UV-induced photo-aging and intrinsic aging.

• Korean Journal of Food Science and Technology
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• v.51 no.5
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• pp.466-472
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• 2019

This study was conducted to investigate anti-photoaging effects of collagen hydrolysate containing collagen tripeptides (CTP) in both HaCaT cells and SKH-1 hairless mice. CTP treatment was nontoxic to HaCaT cells and improved expression of biomarkers associated with aging of skin, such as, collagen 1A, metalloproteinase (MMP)-1, and MMP-13 after subjecting mice to ultraviolet B (UVB) irradiation. In animal studies, the depth and width of wrinkles in the skin of mice were determined upon subjecting them to UVB irradiation. However, positive effects on wrinkles on the skin of mice were seen following CTP supplementation. Collagen content and density of mouse skin were restored following CTP supplementation for 14 weeks after UVB irradiation. These results were based on the effects of CTP on protein levels of collagen 1A, MMP-1, and MMP-13. Therefore, CTP might have positive effects on the number, depth, and width of wrinkles caused by UVB irradiation in SKH-1 hairless mice.

• Journal of Periodontal and Implant Science
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• v.43 no.1
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• pp.24-29
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• 2013

Purpose: Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix, and they are inducible enzymes depending on an inflammatory environment such as periodontitis and bacterial infection in periodontal tissue. Gingival inflammation has been postulated to be correlated with the production of MMP-2 and MMP-9. The objective of this study was to quantify the expression and activity of MMP-9 and -2, and to determine the correlation between activity and expression of these MMPs in human gingival tissues with periodontitis. Methods: The gingival tissues of 13 patients were homogenized in $500{\mu}L$ of phosphate buffered saline with a protease inhibitor cocktail. The expression and activity of MMP-2 and -9 were measured by enzyme-linked immunosorbent assay and Western blot analysis, and quantified by a densitometer. For the correlation line, statistical analysis was performed using the Systat software package. Results: MMP-9 was highly expressed in all gingival tissue samples, whereas MMP-2 was underexpressed compared with MMP-9. MMP-9 activity increased together with the MMP-9 expression level, with a positive correlation (r=0.793, P=0.01). The correlation was not observed in MMP-2. Conclusions: The expression of MMP-2 and -9 might contribute to periodontal physiological and pathological processes, and the degree of MMP-9 expression and activity are predictive indicators relevant to the progression of periodontitis.

• Journal of Environmental Science International
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• v.15 no.8
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• pp.799-809
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• 2006

Hydrobromic acid salts of new N, N, O tridentate ligands containing phenol, 2-[(2-Methylamino- ethyl- amino)-methyl]-phenol(H-MMP. 2HBr), 5-Bromo-2-[(2-Methylamino-ethylamino)-methyl]-phenol (Br- MMP. 2HBr), 5-Chloro-2-[(2-Methylamino-ethylamino)-methyl]-phenol(Cl-MMP. 2HBr), 5-Methyl-2-[(2-Methylamino-ethylamino)-methyl]-phenol(Me-MMP. 2HBr), 5-Methoxy-2-I(2-Methylamino-ethylamino)- methyl]-phenol(MeO- MMP. 2HBr) and. 1-[(2-Methylamino-ethylamino)- methyl]-naphthalen-2-ol(Nap- MMP. 2HBr) were synthesized. The synthesized ligands were confirmed by C. H. N. atomic analysis, UV-visible and IR spectroscopies, $^1$H NMR, $^{13}$C NMR and mass analysis. The potentiometry study revealed that the proton dissociation constants(logK$_n^H$) of the synthesized ligands and stability constants (logK$_{ML}$, logK$_{LM2}$) of transition metal complexes of Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Pb(II) ions occurred in three steps and the order of the calculated overall proton dissociation constants(log$\beta_p$) and stability constants (logK$_{ML}$) of ligands was Br-MMP. 2HBr < Cl-MMP 2HBr < H-MMP. 2HBr < Nap-MMP. 2HBr < Me-MMP. 2HBr < MeO-MMP. 2HBr. The order showed a similar trend to that of Hammett substituent constants($\delta_p$). The synthesized ligands usually form 2:1(ML$_2$) complexes with transition metal ions. The order of the stability constants of each transition metal ions was Co(II) < Ni(II) < Cu(II) ;> Zn(II) ;> Cd(II) ;> Pb(II).

• Ocean and Polar Research
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• v.41 no.2
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• pp.79-88
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• 2019

In this study, the inhibitory effect of Atriplex gmelinii C. A. Mey. against the activity of MMP-2 and MMP-9 secreted from phorbol-12-myristate-13-acetate (PMA)-stimulated HT-1080 cells was evaluated by gelatin zymography and enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase-chain reaction (RT-PCR), and Western blot assay. Specimens of the halophyte A. gmelinii were extracted twice for 24 hr with methylene chloride ($CH_2Cl_2$), and then twice with methanol (MeOH), in turn. Each extract significantly inhibited the enzymatic activities in gelatin zymography and MMP ELISA kit, and expression of MMP-2 and 9 in mRNA and protein levels. Two crude extracts were combined and then the combined crude extracts were fractionated into n-hexane, 85% aqueous methanol (85% aq.MeOH), n-butanol (n-BuOH), and water ($H_2O$) fractions, according to solvent polarity. Among solvent-partitioned fractions, the 85% aq.MeOH fraction showed the strongest inhibitory effect against MMP-2 and -9 in gelatin zymography and MMP ELISA kit. In RT-PCR, all solvent-partitioned fractions significantly suppressed mRNA expression of MMP-2 and -9. On the other hand, in Western blot assay, all solvent-partitioned fractions except $H_2O$ significantly reduced expression levels of protein. HT 1080 cell migration was most significantly inhibited by the n-BuOH fraction followed by the 85% aq.MeOH and $H_2O$ fractions. These results suggest that A. gmelinii could be used as a potential source to inhibit tumor cell metastasis.

• Genomics & Informatics
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• v.21 no.1
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• pp.9.1-9.13
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• 2023

Matrix metalloproteinase-9 (MMP-9) is a zinc and calcium-dependent proteolytic enzyme involved in extracellular matrix degradation. Overexpression of MMP-9 has been confirmed in several disorders, including cancers, Alzheimer's disease, autoimmune diseases, cardiovascular diseases, and dental caries. Therefore, MMP-9 inhibition is recommended as a therapeutic strategy for combating various diseases. Cinnamic acid derivatives have shown therapeutic effects in different cancers, Alzheimer's disease, cardiovascular diseases, and dental caries. A computational drug discovery approach was performed to evaluate the binding affinity of selected cinnamic acid derivatives to the MMP-9 active site. The stability of docked poses for top-ranked compounds was also examined. Twelve herbal cinnamic acid derivatives were tested for possible MMP-9 inhibition using the AutoDock 4.0 tool. The stability of the docked poses for the most potent MMP-9 inhibitors was assessed by molecular dynamics (MD) in 10 nanosecond simulations. Interactions between the best MMP-9 inhibitors in this study and residues incorporated in the MMP-9 active site were studied before and after MD simulations. Cynarin, chlorogenic acid, and rosmarinic acid revealed a considerable binding affinity to the MMP-9 catalytic domain (ΔG_binding < -10 kcal/ mol). The inhibition constant value for cynarin and chlorogenic acid were calculated at the picomolar scale and assigned as the most potent MMP-9 inhibitor from the cinnamic acid derivatives. The root-mean-square deviations for cynarin and chlorogenic acid were below 2 Å in the 10 ns simulation. Cynarin, chlorogenic acid, and rosmarinic acid might be considered drug candidates for MMP-9 inhibition.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1657-1662
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• 2012

Fucosyltransferase IV (FUT4) has been implicated in cell adhesion, motility, and tumor progression in human epidermoid carcinoma A431 cells. We previously reported that it promotes cell proliferation through the ERK/MAPK and PI3K/Akt signaling pathways; however, the molecular mechanisms underlying FUT4-induced cell invasion remain unknown. In this study we determined the effect of FUT4 on expression of matrix metalloproteinase (MMP)-12 induced by EGF in A431 cells. Treatment with EGF resulted in an alteration of cell morphology and induced an increase in the expression of MMP-12. EGF induced nuclear translocation of nuclear factor kB (NF-${\kappa}B$) and resulted in phosphorylation of $IkB{\alpha}$ in a time-dependent manner. In addition, ERK1/2 and p38 MAPK were shown to play a crucial role in mediating EGF-induced NF-${\kappa}B$ translocation and phosphorylation of $I{\kappa}B{\alpha}$ when treated with the MAPK inhibitors, PD98059 and SB203580, which resulted in increased MMP-12 expression. Importantly, we showed that FUT4 up-regulated EGF-induced MMP-12 expression by promoting the phosphorylation of ERK1/2 and p38 MAPK, thereby inducing phosphorylation/degradation of $I{\kappa}B{\alpha}$, NF-${\kappa}B$ activation. Base on our data, we propose that FUT4 up-regulates expression of MMP-12 via a MAPK-NF-${\kappa}B$-dependent mechanism.

• Biomedical Science Letters
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• v.18 no.2
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• pp.104-111
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• 2012

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases which degrade extracellular matrix (ECM) during embryogenesis, wound healing, and tissue remodeling. Dysregulation of MMP activity is also associated with various pathological inflammatory conditions. In this study, we examined the expression pattern of MMPs during PMA-induced differentiation of THP-1 monocytic cells into macrophages. We found that MMP1, MMP8, MMP3, MMP10, MMP12, MMP19, MMP9, and MMP7 were upregulated during differentiation whereas MMP2 remained unchanged. Expression of MMPs increased in a time-dependent manner; MMP1, MMP8, MMP3, MMP10, and MMP12 increased beginning at 60 hr post PMA treatment whereas MMP19, MMP9, and MMP7 increased beginning at 24 hr post PMA treatment. To identify signal transduction pathways involved in PMA-induced upregulation of MMPs, we treated PMA-differentiated THP-1 cells with specific inhibitors for PKC, MEK1, NF-${\kappa}B$, PI3K, p38 MAPK and PLC. We found that inhibition of the MEK1 pathway blocked PMA-induced upregulation of all MMPs to varying degrees except for MMP-2. In addition, expression of select MMPs was inhibited by PI3K, p38 MAPK and PLC inhibitors. In conclusion, we show that of the MMPs examined, most MMPs were up-regulated during differentiation of monocyte into macrophage via the MEK1 pathway. These results provide basic information for studying MMPs expression during macrophage differentiation.