• 대한본초학회지
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• 제32권1호
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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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• 제24권1호
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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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• 제18권1호
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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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• 제13권2호
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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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• 제35권1호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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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)

• 한국식품저장유통학회지
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• 제24권1호
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• pp.93-99
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• 2017

건조한 아선약을 80% 메탄올로 침지 추출하여 얻어진 추출물에 대해 Diaion HP-20 수지를 충진제로 사용한 칼럼크로마토그래피를 수해하여 6종의 용리액을 얻었으며, 얻어진 추출물에 대하여 MMP-1 저해 및 type-1 procollagen 합성 촉진 활성을 평가하였다. 먼저 MMP-1 저해활성은 총페놀성 화합물의 함량이 상대적으로 높은 40% 메탄올 용리액에서 $IC_{50}$값이 $15.6{\pm}1.3{\mu}g/mL$으로 positive control로 녹차의 주름개선 성분인 (-)-EGCG의 $IC_{50}$값인 $38.4{\pm}2.3{\mu}g/mL$ 보다 우수한 활성이었다. 또한 type-1 procollagen 합성촉진 활성은 총페놀성 화합물 함량이 가장 높은 40% 메탄올 용리액에서 우수한 $EC_{50}$값이 $6.9{\pm}0.7{\mu}g/mL$을 나타내었으며, 양성대조구인 (-)-EGCG의 효능과 동등한 활성이었다. 본 실험에 사용된 아선약 시료의 경우 다양한 화합물이 공존하는 추출물 및 용리액 상태이며 이들 시료에 우수한 효능의 성분의 존재 및 추출물에 존재하는 화합물의 우수한 상승효과의 가능성을 시사하였다. 향후 각종 칼럼크로마토 그래피를 활용한 이들 주름개선 효능 관련 물질의 분리를 통한 활성물질의 구조 결정 및 활성 기작에 대한 연구를 수행할 예정이며, 본 연구결과는 천연물 유래의 우수한 MMP-1 저해 및 type-1 procollagen 합성 촉진 활성을 가지는 새로운 천연 소재 발굴을 위한 기초자료로 활용 가능할 것으로 사료된다.

• Applied Biological Chemistry
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• 제46권1호
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• pp.60-65
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• 2003

피부노화는 크게 생리적 노화(chmnological aging)와 광노화(photoaging)로 나누어 진다. 진피세포와 표피세포에서 광노화는 MMP(Matrix metalloproteinase)의 분비량이 증가하면서 MMP와 TIMP(Tissue inhibitors of metalloproteinase)의 균형을 깨뜨려 진피층을 붕괴가 유도된다. 본 연구는 광노화 및 암 전이 과정, 관절염 등 여러 질병에서 주목받고 있는 MMP-1의 생성 억제활성물질을 120여종의 식용식물(edible plants)로부터 활성물질을 분리, 정제하고 정제물질의 일부 물리화학적 성질을 규명하였다. 표피세포(HaCaT)와 진피세포(HS68) 세포주를 이용하여 다양한 강도의 UVB를 조사하여 생성되는 MMP-1의 양과 감수성을 검토한 결과 HS68에서 UVB의 조사량에 비례하여 MMP 분비량이 증가되는 반면, HaCaT세포의 MMP 분비량은 유의적 차이를 보이지 않았다. MMP-1 생성량이 가장 높은 UVB 조사량은 35 $mJ/cm^2$ 내외이었고, UVB조사 후 분비되는 MMP-1의 양은 36-48시간대에 가장 높게 나타났다. MMP-1의 생성 억제활성을 검색한 결과 아가위(Crataegus pinnatifida Bunge)의 냉수분획층(CP)에서 최대활성을 나타내었다. CP를 periodate 산화 처리에서는 변화가 없으나 pronase 처리시 활성이 감소되는것으로 단백질이 활성의 본체임을 확인하였다. 정제는 CP의 ultrafiltration처리, DEAE-Tayopearl 650c, Butyl-Tayopearl 650M의 이온교환크로마토그래프와 Bio-Gel P-30겔 여과 크로마토그래프 통해서 MMP-1 억제 활성 분획층 CP-2Va-2를 정제하였다. CP-2Va-2의 MMP-1억제활성은 88.5%이었으며, 분자량은 HPLC로 확인한 결과 19kDa, SDS-PAGE에서는 20 kDa 확인됨으로써 monomer구조임을 알 수 있었다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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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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• 제42권3호
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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.