• Journal of Life Science
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• v.26 no.5
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• pp.584-591
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• 2016

Saururus chinensis is a perennial plants, its flavonoid compound is known to exhibit anti-oxidative activity. This study was aimed to investigate the effect of Water Extract and Solvent Fractions of Saururus chinensis on antioxidant, anti-inflammatory and anti-invasive of Phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP-2) and MMP-9 activities. Plant samples were fractionated into hexane, CHCl₃, ethyl acetate, butanol, and water fractions, and each of these was assayed individually. The water fraction showed the highest extraction yield at 9.25%(w/w). Anti-oxidative activity was analyzed by DPPH assay. Cell viability was detected by the MTS assay. Anti-inflammatory activity was assayed by the nitric oxide (NO) production in mouse macrophage Raw 264.7 cells. The activity and mRNA expression of MMP-2 and MMP-9 in human oral squamous carcinoma YD-10B cells were examined by zymography and RT-PCR. As results, MMP-2/-9 activation was increased in PMA induced YD-10B cells. In PMA-treated YD-10B cells, the increased mRNA expression and protein activation of MMP-2/-9 were significantly inhibited in the ethyl acetate fraction. The ethyl acetate fraction showed the highest anti-oxidative activity at 73.38%. The ethyl acetate fraction at non-cytotoxic concentrations significantly exhibited the anti-inflammatory activity of Raw 264.7 cells in dose-dependent manner. In conclusion, these findings demonstrate that the ethyl acetate fraction obtained from a chinensis water extract potentiates a promising therapeutic anti-invasive agent and, therefore, as an anti-cancer drug for cancer prevention and therapy in oral cancer.

• Journal of Life Science
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• v.31 no.11
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• pp.980-986
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• 2021

Natural products have always been an attractive source in terms of novel anti-metastatic compounds which can hinder MMP expression and activity. Corydalis heterocarpa is a salt marsh plant found in the seashores throughout Korea. Its yellow flowers and spikes have been an ingredient in folk medicine to treat spasm and contractions. The present study assessed the potential of different solvent-based fractions from the crude extract of Corydalis heterocarpa (CHE), a halophyte with reported bioactivities, to suppress the PMA-induced MMP expression in human fibrosarcoma HT-1080 cells. The solvent fractions which were named after the solvent used for fractionation (n-hexane, 85% aqueous (aq.) methanol (MeOH), n-butanol (BuOH), and H₂O were shown to inhibit the both elevated mRNA and protein expression levels of MMP-2 and MMP-9 and simultaneously relieved the suppression on the expression of the endogenous MMP inhibitors TIMP-1 and TIMP-2. Results indicated that the CHE fractions might intervene with the PMA-induced activation of the MAPK signaling which is the upstream activator of MMP overexpression. Among tested samples, 85% aq. MeOH and n-hexane fractions of CHE was determined to be the most active and future studies to isolate the bioactive substances responsible for the regulation of the MMP expression are, therefore, urged. In conclusion, C. heterocarpa was shown to be a potential source of anti-metastatic compounds and n-Hexane and MeOH fractions might yield lead molecules to develop novel MMP inhibitors.

• The Journal of Korean Medicine
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• v.41 no.4
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• pp.12-26
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• 2020

Objectives: The aim of this study is to investigate the mechanisms involved in the anti-inflammatory and anti-tumor effects of Rhus verniciflua Stokes (RVS) on PMA-differentiated human monocytic leukemia THP-1 cells. Methods: Cells were treated with various concentrations of RVS decoction (0-300㎍/ml) for 24, 48, and 72h. Cell viability was evaluated by MTS/PMS assay. The expressions of MMP-2, MMP-9, TIMP-1, TIMP-2, iNOS and COX-2 mRNA and proteins were measured using RT-PCR and western blotting, respectively. Results: RVS suppressed expression of MMP-2 and MMP-9 mRNA. It also down-regulated iNOS and COX-2 mRNA and protein expression. RVS inhibited NF-𝜅B p65 activity and the phosphorylation of Akt and MAPK (ERK and p38 MAPK). Instead, the phosphorylation of JNK is increased at a very low concentration but decreased at higher concentrations. Conclusion: RVS is regarded to inhibit the expression of MMP and TIMP as well as iNOS and COX-2 gene expression via directly inhibiting the activation of NF-𝜅B and phosphorylation of MAPK pathway in THP-1 cells. This suggests RVS have potential to be used as a therapeutic agent for acute myeloid leukemia (AML).

• BMB Reports
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• v.44 no.7
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• pp.462-467
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• 2011

Up-regulation of selected matrix metalloproteinases (MMPs) such as MMP-9 contributes to inflammatory processes during the development of various skin diseases, such as atopic dermatitis. In this study, we examined the effect of a cell-permeable superoxide dismutase (Tat-SOD) on TNF-${\alpha}$-induced MMP-9 expression in human keratinocyte cells (HaCaT). When Tat-SOD was added to the culture medium of HaCaT cells, it rapidly entered the cells in dose- and time-dependent manners. Tat-SOD decreased TNF-${\alpha}$-induced reactive oxygen species (ROS) generation. Tat-SOD also inhibited TNF-${\alpha}$-induced NF-${\kappa}B$ DNA binding activity. Treatment of HaCaT cells with Tat-SOD significantly inhibited TNF-${\alpha}$-induced mRNA and protein expression of MMP-9, as measured by RT-PCR and Western blot analysis. In addition, Tat-SOD suppressed TNF-${\alpha}$-induced gelatinolytic activity of MMP-9. Taken together, our results indicate that Tat-SOD can suppress TNF-${\alpha}$-induced MMP-9 expression via ROS-NF-${\kappa}B$-dependent mechanisms in keratinocytes, and therefore can be used as an immunomodulatory agent against inflammatory skin diseases related to oxidative stress.

• Journal of Nutrition and Health
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• v.41 no.3
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• pp.224-231
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• 2008

We examined the effect of indole-3-carbinol (I3C, $C_9H_9NO$), an autolysis product of a glucosinolate and a glucobrassicin in vegetables, on MMP-2, -9 activities and TIMP-l and -2 inductions via microtubule-associated protein kinase (MAPK) signaling pathway in prostate cancer cell line, PC3 cells. Our results indicated that I3C inhibited cell growth of PC3 cells in dose (0,50, 100 ,${\mu}M$) and time (0,24,48 and 72 h) dependent manners. Using gelatin zymography for MMP activity, we demonstrated that I3C significantly decrease MMP-2 and -9 activities in PC3 cells. We also observed that I3C decreased the proteins and mRNA levels of MMP-2 and -9 in PC3 cells as well. Inversely, expressions of TIMP-l and -2 protein and mRNA in PC3 cells were increased by I3C in a dose dependent manner. In another experiment, we showed that I3C inhibited PC3 cells invasiveness by using marigel invasion assay and we also found that I3C suppressed MMP transcriptional activity by MAPK signaling pathways. Taken together, our results suggest that I3C may contribute to the potential beneficial food component to prevent the cancer metastasis in prostate cancer cells. (KoreanJNutr2008; 41(3): 224~23I)

• Journal of Ginseng Research
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• v.46 no.4
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• pp.536-542
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• 2022

Background: In aged skin, reactive oxygen species (ROS) induces degradation of the extracellular matrix (ECM), leading to visible aging signs. Collagens in the ECM are cleaved by matrix metalloproteinases (MMPs). Syringaresinol (SYR), isolated from Panax ginseng berry, has various physiological activities, including anti-inflammatory action. However, the anti-aging effects of SYR via antioxidant and autophagy regulation have not been elucidated. Methods: The preventive effect of SYR on skin aging was investigated in human HaCaT keratinocytes in the presence of H₂O₂, and the keratinocyte cells were treated with SYR (0-200 ㎍/mL). mRNA and protein levels of MMP-2 and -9 were determined by real-time PCR and Western blotting, respectively. Radical scavenging activity was researched by 2,2 diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. LC3B level was assessed by Western blotting and confocal microscopy. Results: SYR significantly reduced gene expression and protein levels of MMP-9 and -2 in both H₂O₂-treated and untreated HaCaT cells. SYR did not show cytotoxicity to HaCaT cells. SYR exhibited DPPH and ABTS radical scavenging activities with an EC₅₀ value of 10.77 and 10.35 ㎍/mL, respectively. SYR elevated total levels of endogenous and exogenous LC3B in H₂O₂-stimulated HaCaT cells. 3-Methyladenine (3-MA), an autophagy inhibitor, counteracted the inhibitory effect of SYR on MMP-2 expression. Conclusion: SYR showed antioxidant activity and up-regulated autophagy activity in H₂O₂-stimulated HaCaT cells, lowering the expression of MMP-2 and MMP-9 associated with skin aging. Our results suggest that SYR has potential value as a cosmetic additive for prevention of skin aging.

• Molecules and Cells
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• v.41 no.6
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• pp.532-544
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• 2018

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.31 no.1 s.49
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• pp.103-109
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• 2005

UV irradiation leads to distinct changes in skin connective tissue, which is degradation of collagen. Many of these alterations in the extracellular matrix are mediated by matrix metalloproteinases. In this study, to develop a new anti-aging agent, we screened the antioxidant activity of solvent fractions from ethanolic extract of Melothria Heterophylla. Among the four solvent fractions tested, the EtOAc fraction exhibited the highest antioxidant activity. It was investigated the inhibitory effect of the EtOAc fraction on the expression and activity of MMP-1 in UVA-irradiated human dermal fibroblasts. The EtOAc fraction inhibited the activity of MMP-1 in a dose dependent manner with the $IC_{50}$ values of $9{\mu}g/mL$. Also, UVA-induced MMP-1 expression was reduced about $90\%$ by $100{\mu}g/mL$ of the EtOAc fraction but MMP-1 mRNA expression was not inhibited. Therefore, we conclude that the EtOAc fraction significantly inhibits MMP-1 expression at the protein level. From these results, we suggest that the EtOAc fraction from M. heterophylla could be used as a new anti-aging agent for the photo-damaged skin.

• ALGAE
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• v.29 no.4
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• pp.355-366
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• 2014

Fucoxanthin is known to be an effective cell proliferation inhibitor with anti-tumor and anti-angiogenic activities. However, there is a lack of data regarding the biological effects of cis isomers of fucoxanthin. To assess the potential therapeutic properties of 9'-cis-(6'R) fucoxanthin (FcA), and 13-cis and 13'-cis-(6'R) fucoxanthin complex (FcB) isolated from Sarggassum siliquastrum, we investigated their inhibitory effects on matrix metalloproteinases (MMPs) in phorbol 12-myristate 13-acetate (PMA)-induced human fibrosarcoma (HT1080) cells. FcA and FcB reduced MMP-2 and MMP-9 protein and mRNA levels, as well as the migration of these cells, in a dose-dependent manner. Additionally, FcA and FcB increased levels of MMPs inhibition factors such as tissue inhibitor of metalloproteinase-1. FcA and FcB significantly inhibited the transcriptional activity of nuclear factor ${\kappa}B$ (NF-${\kappa}B$) and by inhibiting c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases. Our results demonstrate that suppression of the NF-${\kappa}B$, JNK, and p38 signaling pathways may inhibit PMA-induced MMP-2 and MMP-9 activity. Therefore, FcA and FcB may be useful in noninvasive therapeutic strategies against fibrosarcoma metastasis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.5
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• pp.494-498
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• 2014

It is well known that Desomodii Herba (DH) has an effect to eliminate dampness, relieve jaundice and to clear away toxic material, relieve swelling in Korean Medicine. However, the effect of DH on breast cancer invasion is unknown. In this study, we investigated the inhibitory effect of DH extracts (DHE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in MCF-7, human breast cancer cells. DHE inhibits TPA-induced MMP-9 protein and mRNA expressions in a dose-dependent fashion. DHE also inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-${\kappa}B$). These results indicate that DHE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-${\kappa}B$ pathway in MCF-7 cells.