• The Korea Journal of Herbology
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• v.32 no.1
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• pp.83-89
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• 2017

Objectives : The present study was designed to determine the effects of mixture of Achyranthis Japonicae Radix, Scutellariae Radix, and Acanthopanacis Cortex on monosodium iodoacetate (MIA)-induced osteoarthritis in rats. The mixture was composed of Achyranthis Japonicae Radix, Scutellariae Radix, and Acanthopanacis Cortex extracts. Methods : Arthritis was induced by injection of MIA into knee joints of rats. At the end of experiment, gross examination on the articular structures of knee joints were performed. Proteoglycan (PG) contents in articular cartilages were analysed as well. Tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$) and $interleukin-1{\beta}$ ($IL-1{\beta}$) contents in synovial fluids were measured by ELISA method and matrix metalloproteinase 2 (MMP2), MMP9, and tissue inhibitors of metalloproteinase 1 (TIMP1) mRNA were measured by a realtime PCR. Results : The surfaces of the articular cartilage were observed. The severity of osteoarthritis in the treated group were alleviated compared with control group. PG contents in articular cartilages of the treated group were increased compared with control group. $IL-1{\beta}$ contents in synovial fluids of the treated group were significantly decreased compared with control group. MMP2 and MMP9 mRNA contents in articular cartilages were significantly decreased compared with control group and TIMP1 mRNA contents were increased compared with control group. Conclusions : On the basis of these results, we concluded that Achyranthis Japonicae Radix-containing mixture treatment has anti-arthritic effects on the MIA-induced osteoarthritis in rats. And the effects were related with the reduction of $IL-1{\beta}$ in synovial membranes and the consequent reduction of MMP2 and MMP9 expressions.

• Restorative Dentistry and Endodontics
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• v.24 no.1
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• pp.200-211
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• 1999

The periapical response to injury is a complex interaction of inflammatory, immune, neural, vascular and synthetic activity. TGF-${\beta}$ is a potent modulator of proliferation and differentiation in various tissue, seems to lead to an increase in extracellular matrix. MMP are a family of proteolytic enzyme that mediate the degradation of extracellular matric macromolecules, but little is known about theirs possible role in periapical tissue. The purpose of this study is to investigate the differential expression of TGF-${\beta}$ and MMP-1 in tooth follicle, periapical abscess, granuloma and cyst. The expression of TGF-${\beta}$ and MMP-1 in Periapical tissue was evaluated by immunohistochemical staining and Western blot analysis. Correlationship among the periapical lesions were stastically analyzed. The degree of MMP-1 expression in periapical abscess was higher than in any other periapical lesion, and stastically significant. TGF-${\beta}$ expression is the prominent in granuloma than other periapical lesion, which was stastically significant. The increased expression of MMP and TGF-${\beta}$ was not co-related with inflammatory cell infiltration degree of the periapical cyst. The expression degree of MMP and TGF-${\beta}$ was not co-related with periapical abscess and cyst, but expression of MMP and TGF-${\beta}$ showed strong positive co-relationship with periapical granuloma, which was stastically significant. TGF-${\beta}$ expression by Western blot analysis was prominent in granuloma and cyst, and similar to the results by imunohistochemistry. MMP-1 expression is less than TGF-${\beta}$, but there is not extreme difference between periapical lesion. These results suggest that TGF-${\beta}$ and MMP may be involved in tissue remodeling and has an important role in progress or mediation of periapical lesions.

• Natural Product Sciences
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• v.18 no.1
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• pp.52-59
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• 2012

In our continuous efforts to procure the active materials from natural products in the protective effects of oxidative stress or UV damage to skin cells we found the Prunus persica flesh extract (PPFE) is considerable to meet the demand to protect the skin damage. PPFE attenuated cell damage induced by hypoxanthine-xanthine oxidase in cultured human keratinocytes, indicating that PPFE has the potential of the scavenging effect of reactive oxygen species (ROS) in human skin cell. Moreover, PPFE significantly suppressed UVA-induced ROS production determined by the oxidation of 2,7-dichlorodihydrofluorescein diacetate (DCFH) using FACS analysis. Additional study revealed that UVA irradiation of HaCaT human keratinocytes increased the gelatinolytic activities of matrix metalloproteinase-2, and -9 (MMP-2, -9) and mRNA expression of MMP-9 analyzing by a real-time reverse transcriptase-polymerase chain reaction (RT-PCR), and these events were significantly suppressed by the treatment with PPFE. These results suggest that PPFE might be applicable as natural ingredients for skin antiaging agents via UV-induced ROS scavenging activity and suppression of MMP expression in the skin cells.

• Animal cells and systems
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• v.13 no.2
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• pp.113-118
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• 2009

Extracts derived from various medical mushrooms have been reported to have antitumor and immuno-modulatory properties. In order to investigate the antitumor activity of keumsa Linteusan, the water extract of Phellinus Iimteus, HT1080 cells, a human fibrosarcoma cell line, were treated with it and changes in cellular migration potential was tested in vitro. At a concentration range below 1,000 $\mu$g/mL, Linteusan blocked, in a dose dependent manner, the migration of cells through Matrigel as well as Boyden chamber without affecting the viability of the cells. Prolonged treatment of HT1080 cells with Linteusan suppressed TNFa induced production of matrix metalloproteinase (MMP)-9 as well as basal level expression of MMP-2. Linteusan also affected the adhesion of the cells to fibronectin-coated surfaces. The effect of Linteusan on cell signaling pathways was also tested. Linteusan specifically affected TNF-$\alpha$ induced phosphorylation of AKT in a dose-dependent manner, while phosphorylation levels of ERK remained unaffected. These data indicate that Linteusan blocks the migration of HT1080 cells by affecting various processes associated with cell migration such as the expression of matrix degradingenzymes,cell adhesion, and AKT-medicated cellular signaling pathways.

• Toxicological Research
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• v.35 no.1
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• pp.93-101
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• 2019

Tetrabromobisphenol A (TBBPA), the most common industrial brominated flame retardant, acts as a cytotoxic, neurotoxic, and immunotoxicant, causing inflammation and tumors. However, the mechanism of TBBPA-induced matrix metalloproteinase-9 (MMP-9) expression in human breast cancer cells is not clear. In human breast cancer MCF-7 cells, treatment with TBBPA significantly induced the expression and promoter activity of MMP-9. Transient transfection with MMP-9 mutation promoter constructs verified that $NF-{\kappa}B$ and AP-1 response elements are responsible for the effects of TBBPA. Furthermore, TBBPA-induced MMP-9 expression was mediated by $NF-{\kappa}B$ and AP-1 transcription activation as a result of the phosphorylation of the Akt and MAPK signaling pathways. Moreover, TBBPA-induced activation of Akt/MAPK pathways and MMP-9 expression were attenuated by a specific NADPH oxidase inhibitor, and the ROS scavenger. These results suggest that TBBPA can induce cancer cell metastasis by releasing MMP-9 via ROS-dependent MAPK, and Akt pathways in MCF-7 cells.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.192.2-192.2
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• 2003

Apigenin-7-O-${\beta}$-D-glucoside, chrysoeriol, and luteolin were isolated from the aqueous ethanolic extract of Zostera marina L. leaves as the scavengers of reactive oxygen species (ROS) with the SC$\_$50/ values of 0.18 mM, 0.68 mM, and 0.18 mM against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 0.04 mM, 0.03 mM, and 0.01 mM against superoxide radicals in the xanthine/xanthine oxidase system, respectively. The luteolin suppressed the expression of matrix metalloproteinase-1 (MMP-1) up to 44% at 4.0 ${\mu}$M. (omitted)

• Food Science and Preservation
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• v.24 no.1
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• pp.93-99
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• 2017

Collagen synthesis is decreased and matrix metalloproteinase-1 (MMP-1) levels are increased in naturally aged human skin, and these alterations cause changes such as skin wrinkling and decreased elasticity. As a part of our ongoing search for bioactive ingredients, MMP-1 inhibitory and type-1 procollagen synthesis inducing activities of aqueous methanolic extract of manufactured gambir product from Uncaria gambir were investigated in in vitro bioassay systems. In addition, total phenolic contents were quantified using a spectrophotometric method. Among tested samples, 40% MeOH eluate from 80% methanolic extract of manufactured U. gambir using open column chromatography packed with Diaion HP-20 resin showed significant MMP-1 inhibitory activities with an $IC_{50}$ value of $15.6{\pm}1.3{\mu}g/mL$. Furthermore, type-1 procollagen synthesis promoting property of 40% MeOH eluate ($IC_{50}$ value; $6.9{\pm}0.7{\mu}g/mL$) from 80% methanolic extract of manufactured gambir was higher than other eluates. Additionally, the present investigation revealed that 40% MeOH eluate of manufactured gambir product contained a high level of total phenolic compounds. The result suggests a distinct relationship between anti-wrinkle activity and total phenolic contents, and manufactured gambir product could be considered a new effective source of natural bioactive ingredients. Systematic investigation of manufactured gambir product will be performed for further development of its biological properties.

• Applied Biological Chemistry
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• v.46 no.1
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• pp.60-65
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• 2003

MMP-1 inhibitory compounds were isolated from 120 Korean traditional edible plants. UP- 1 activity significantly increased linearly with increasing UVB dose in normal human foreskin fibroblast HS68 cell, showing maximum activity at approximately 35 $mJ/cm^2$, whereas in HaCaT cell, normal human keratinocyte, no increase was observed. Maximum secretion of MMP-1 after UVB treatment occurred around 36-48 k after treatment. MMP-1 inhibitory compound isolated from cold-water fraction of Cataegus pinnatifida Bunge showed the mort potent activity. The MMP-1 inhibitory compound was deduced as a peptide based on the fact that pronase digestion decreased the activity whereas periodate oxidation did not. The most potent UP- 1-inhibitory protein, CP-2Va-2, showing an activity of 88.5% against MMP-1, was isolated through sequential column chromatography on DEAE-Toyopearl 650C, Butyl-Toyopearl 650M, and Bio-Gel P-30. Molecular weight of CP-2Va-2 determined through high performance liquid chromatography and SDS PACE was 19 and 20 kDa. respectively, signifying a monomeric structure.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1615-1621
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• 2013

Background: Matrix metalloproteinase 9 (MMP-9) is related to tumor invasion and metastasis. However, the role of MMP-9 expression in breast cancer survival remains controversial. The purpose of this study was to accomplish a more accurate estimation of the association between MMP-9 expression and survival results in breast cancer patients through meta-analysis. Methods: A meta-analysis of published studies investigating the effects of positive MMP-9 expression on both relapse free survival (RFS) and overall survival (OS) was performed. Relevant literature was confirmed by searching electronic databases including PubMed, Ovid, EMBASE and China National Knowledge Infrastructure (CNKI) before November 1, 2012. Individual hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled HRs with 95% CIs were used to evaluate the strength of the association between positive MMP-9 expression and survival results of breast cancer patients. Funnel plot and Egger's regression tests were used to evaluate publication bias. Heterogeneity and sensitivity analysis was also conducted. All the work was completed using STATA. Results: A total of 2,344 patients from 15 evaluative studies were finally included. Pooled HRs and 95% CIs suggested that MMP-9 overexpression had an unfavorable impact on both OS (HR: 1.70, 95% CI: 1.41-2.04) and RFS (HR: 1.54, 95% CI: 1.17-2.01) in breast cancer patients. There was no significant heterogeneity observed in the studies reported for OS (P=0.360, $I^2$=8.8%), but not RFS (P=0.002, $I^2$=67%). Publication bias was absent among the studies both in OS and RFS cases (t=-0.54, P=0.605 and t=1.71, P=0.131, respectively). Omission of any single study had little effect on the combined risk estimates on sensitivity analysis. Conclusion: The results of this meta-analysis suggest that positive MMP-9 expression confers a higher risk of relapse and a worse survival in patients with breast cancer. Larger prospective studies are now needed to evaluate the clinical utility of MMP-9 expression.

• Molecules and Cells
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• v.42 no.3
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• pp.218-227
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• 2019

This study was designed to determine the effects of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on vascular smooth muscle cell (VSMC) apoptosis and extracellular matrix (ECM) disruption in a murine abdominal aortic aneurysm (AAA) model. After injection of PVT1-silencing lentiviruses, AAA was induced in Apolipoprotein E-deficient ($ApoE^{-/-}$) male mice by angiotensin II (Ang II) infusion for four weeks. After Ang II infusion, mouse serum levels of pro-inflammatory cytokines were analysed, and aortic tissues were isolated for histological, RNA, and protein analysis. Our results also showed that PVT1 expression was significantly upregulated in abdominal aortic tissues from AAA patients compared with that in controls. Additionally, Ang II treatment significantly increased PVT1 expression, both in cultured mouse VSMCs and in AAA murine abdominal aortic tissues. Of note, the effects of Ang II in facilitating cell apoptosis, increasing matrix metalloproteinase (MMP)-2 and MMP-9, reducing tissue inhibitor of MMP (TIMP)-1, and promoting switching from the contractile to synthetic phenotype in cultured VSMCs were enhanced by overexpression of PVT1 but attenuated by knockdown of PVT1. Furthermore, knockdown of PVT1 reversed Ang II-induced AAA-associated alterations in mice, as evidenced by attenuation of aortic diameter dilation, marked adventitial thickening, loss of elastin in the aorta, enhanced aortic cell apoptosis, elevated MMP-2 and MMP-9, reduced TIMP-1, and increased pro-inflammatory cytokines. In conclusion, our findings demonstrate that knockdown of lncRNA PVT1 suppresses VSMC apoptosis, ECM disruption, and serum pro-inflammatory cytokines in a murine Ang II-induced AAA model.