• The Korean Journal of Physiology and Pharmacology
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• v.12 no.3
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• pp.125-129
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• 2008

The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of matrix metallopeptidase 2 (MMP2) are associated with obesity. MMP2 is an enzyme with proteolytic activity against matrix and nonmatrix proteins, particularly basement membrane constituents. To identify the relationship between polymorphisms of MMP2 and overweight/obese, we genotyped 5 SNPs (rs17242319, rs1053605, rs243849, rs2287074, and rs10775332) of the coding region of MMP2 using the Golden Gate assay on an Illumina BeadStation 500 GX. One hundred and forty two overweight/obese ($BMI\;{\ge}\;23$) and 145 normal (BMI 18 to < 23) subjects were analyzed. SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were used for the analysis of genetic data. A linkage disequilibrium (LD) block was discovered among the 5 SNPs selected, including rs17242319, rs1053605, rs243849, and rs2287074. Of the 5 polymorphisms, 2 synonymous SNPs [rs17242319 (Gly226Gly) and rs10775332 (Phe602Phe)] were found significant associations with overweight/obese. Recently, rs1132896 replaced rs17242319 as a new number (SNP database, BUILD 129). In haplotype analysis using Haploview, a haplotype (haplotype: CCCA) containing a meaningful polymorphism (rs17242319) was found to be significantly different. The results suggest that MMP2 may be associated with overweight/obese in Korean population.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.92-92
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• 2018

Solanum nigrum L. (SNL), generally known as black nightshade, is traditionally used as medicine to reduce inflammation caused by several diseases like asthma, chronic bronchitis and liver cirrhosis. In this study, anti-inflammatory effects of SNL extract were examined and possible molecular mechanisms of the anti-inflammatory effects were investigated. The inhibitory effects of SNL extract on nitric oxide (NO), pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6) and Matrix metallopeptidase 9 (MMP-9) productions were dissected using lipopolysaccharide (LPS) stimulated murine macrophage-like cell line Raw264.7 cells and human microglial cell line BV2 cells. We further investigated whether SNL extract could suppress the phosphorylation of ERK1/2, JNK, and p38 and the nuclear expression of nuclear factor $NF-{\kappa}B$ p65 in LPS-stimulated Raw264.7 cells and BV2 cells. As a result, we showed that the SNL extract significantly decreased the production of pro-inflammatory cytokines, NO, and MMP-9. In addition, the SNL strongly inhibited the phosphorylation of ERK1/2, JNK, p38 and nuclear translocation of $NF-{\kappa}B$ p65 in activated cells. We confirmed that the extracts of SNL effectively inhibits the anti-inflammatory and may be used as a therapeutic to various inflammatory diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.377-384
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• 2010

The present study examined whether metformin treatment prevents isoporterenol-induced cardiac hypertrophy in mice. Chronic subcutaneous infusion of isoproterenol (15 mg/kg/24 h) for 1 week using an osmotic minipump induced cardiac hypertrophy measured by the heart-to-body weight ratio and left ventricular posterior wall thickness. Cardiac hypertrophy was accompanied with increased interleukin-6 (IL-6), transforming growth factor (TGF)-${\beta}$, atrial natriuretic peptide (ANP), collagen I and III, and matrix metallopeptidase 2 (MMP-2). Coinfusion of metformin (150 mg/kg/24 h) with isoproterenol partially inhibited cardiac hypertrophy that was followed by reduced IL-6, TGF-${\beta}$, ANP, collagen I and III, and MMP-2. Chronic subcutaneous infusion of metformin did not increase AMP-activated protein kinase (AMPK) activity in heart, although acute intraperitoneal injection of metformin (10 mg/kg) increased AMPK activity. Isoproterenol increased nitrotyrosine levels and mRNA expression of antioxidant enzyme glutathione peroxidase and metformin treatment normalized these changes. These results suggest that metformin inhibits cardiac hypertrophy through attenuating oxidative stress.

• Journal of Life Science
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• v.22 no.9
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• pp.1254-1260
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• 2012

The moringa (Moringa oleifera Lam.) plant is used both as food and an anti-allergic agent. In this study, we investigated skin protection effects of methanol extracts from the root, seed, fruit, and leaves of moringa in HaCaT keratinocyte cells. To investigate the pharmacological potential of various moringa extracts on TNF-${\alpha}$-induced collagen degradation in HaCaT cells, we measured the activity of matrix metallopeptidase-9,2 (MMP-9,2) by zymography analysis. Our results showed that all the moringa extracts inhibit the TNF-${\alpha}$-induced enzyme activity of MMP-9. In particular, moringa root extracts significantly suppressed MMP-9 and MMP-2 in a dose-dependent manner. Next, to investigate the anti-inflammation effect of the moringa extracts, we examined cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and interleukin-6 (IL-6) expression of the extracts. The results showed that both the root extracts and the seed extracts decreased the TNF-${\alpha}$-induced expression of COX-2. In addition, the root and leaf extracts reduced the expression of IL-6. However, none of the moringa extracts affected the expression of iNOS. The results suggest that moringa root extracts down-regulate MMP-9, COX-2, and IL-6 and that the root extracts offer superior skin protection effects compared with other extracts of moringa in HaCaT cells.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.261-268
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• 2013

The ginseng plant (Panax ginseng Meyer) has a large number of active ingredients including steroidal saponins with a dammarane skeleton as well as protopanaxadiol and protopanaxatriol, commonly known as ginsenosides, which have antioxidant, anticancer, antidiabetic, anti-adipocyte, and sexual enhancing effects. Though several discoveries have demonstrated that ginseng saponins (ginsenosides) as the most important therapeutic agent for the treatment of osteoporosis, yet the molecular mechanism of its active metabolites is unknown. In this review, we summarize the evidence supporting the therapeutic properties of ginsenosides both in vivo and in vitro, with an emphasis on the different molecular agents comprising receptor activator of nuclear factor kappa-B ligand, receptor activator of nuclear factor kappa-B, and matrix metallopeptidase-9, as well as the bone morphogenetic protein-2 and Smad signaling pathways.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.2
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• pp.116-122
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• 2019

The aim of this study is to evaluate the anti-inflammatory effect of Hataedock treatment using Coptidis Rhizome and Glycyrrhiza Uralensis (CG) mixed extract in allergic rhinitis induced NC/Nga mice. We divided NC/Nga mice into 3 groups as follows; allergic rhinitis-induced group after CG Hataedock treatment (CGT, n=10), no treatment group (Ctrl), allergic rhinitis elicited group (ARE). To induce allergic rhinitis, NC/Nga mice of 3 weeks age were sensitized on 7, 8 and 9week by Ovalbumin (OVA) antigen in intranasal space. Hataedock using CG extract was administered on week 3 in allergic rhinitis-induced group (CGT) after Hataedock treatment. To identify distribution of Interlukin (IL)-4, Cluster of differentiation 40 (CD40), high-affinity IgE receptor ($Fc{\varepsilon}RI$), substance P, Matrix metallopeptidase 9 (MMP-9), Nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) p65, Inducible nitric oxide synthase (iNOS) and Cycloxygenase-2 (COX-2), we used histological examination. CGT significantly inhibited IL-4 and CD40 response compared with ARE. The reduction of Th2 cytokine expression decreased inflammatory mediators such as $Fc{\varepsilon}RI$, substance P, MMP-9, $NF-{\kappa}B$ p65, iNOS and COX-2. Such immunological improvement induced reduction of respiratory epithelial damage and mucin secretion in goblet cell. These results indicate that Hataedock treatment suppresses allergic rhinitis through modulating of Th2 responses and diminishing various inflammatory mediators in nasal mucosal tissue. It might have potential applications for prevention and treatment of allergic rhinitis.

• Nutrition Research and Practice
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• v.9 no.3
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• pp.256-261
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• 2015

BACKGROUND/OBJECTIVES: Yacon (Samallanthus sonchifolius), a common edible plant grown throughout the world, is well known for its antidiabetic properties. It is also known to have several other pharmacological properties including anti-inflammatory, anti-oxidant, anti-allergic, and anti-cancer effects. To date, the effect of yacon on gliomas has not been studied. In this study, we investigated the effects of yacon on the migration and proliferation of C6 glioma cells stimulated by fetal bovine serum (FBS). MATERIALS/METHODS: Cell growth and proliferation were determined by evaluating cell viability using an EZ-Cytox Cell Viability Assay Kit. FBS-induced migration of C6 glioma cells was evaluated by performing the scratch wound healing assay and the Boyden chamber assay. We also used western blot analysis to determine the expression levels of extracellular signal-regulated kinase 1/2 (ERK1/2), a major regulator of migration and proliferation of glioma cells. Matrix metallopeptidase (MMP) 9 and TIMP-1 levels were measured by performing reverse transcription PCR. RESULTS: Yacon ($300{\mu}g/mL$) reduced both the FBS-induced proliferation of C6 glioma cells and the dose-dependent migration of the FBS-stimulated C6 cells. FBS-stimulated C6 glioma cells treated with yacon (200 and $300{\mu}g/mL$) showed reduced phosphorylation of ERK1/2 and inhibition of MMP 9 expression compared to those shown by the untreated FBS-stimulated C6 cells. In contrast, yacon (200 and $300{\mu}g/mL$) induced TIMP-1 expression. CONCLUSIONS: On the basis of these results, we suggest that yacon may exert an anti-cancer effect on FBS-stimulated C6 glioma cells by inhibiting their proliferation and migration. The most likely mechanism for this is down-regulation of ERK1/2 and MMP9 and up-regulation of TIMP-1 expression levels.

• BMB Reports
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• v.52 no.12
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• pp.706-711
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• 2019

Cisplatin (Cis-DDP) is one of the most widely used anti-cancer drugs. It is applicable to many types of cancer, including lung, bladder, and breast cancer. However, its use is now limited because of drug resistance. p90 ribosomal S6 kinase (p90RSK) is one of the downstream effectors in the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathway and high expression of p90RSK is observed in human breast cancer tissues. Therefore, we investigated the role of p90RSK in the Cis-DDP resistance-related signaling pathway and epithelial-mesenchymal transition (EMT) in breast cancer cells. First, we discovered that MDA-MB-231 cells exhibited more Cis-DDP resistance than other breast cancer cells, including MCF-7 and BT549 cells. Cis-DDP increased p90RSK activation, whereas the inactivation of p90RSK using a small interfering RNA (siRNA) or dominant-negative kinase mutant plasmid overexpression significantly reduced Cis-DDP-induced cell proliferation and migration via the inhibition of matrix metallopeptidase (MMP)2 and MMP9 in MDA-MB-231 cells. In addition, p90RSK activation was involved in EMT via the upregulation of mRNA expression, including that of Snail, Twist, ZEB1, N-cadherin, and vimentin. We also investigated NF-κB, the upstream regulator of EMT markers, and discovered that Cis-DDP treatment led to NF-κB translocation in the nucleus as well as its promoter activity. Our results suggest that targeting p90RSK would be a good strategy to increase Cis-DDP sensitivity in triple-negative breast cancers.

• Journal of Periodontal and Implant Science
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• v.53 no.1
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• pp.20-37
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• 2023

Purpose: Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system. Methods: The targets and pathways of parthenolide and naringin were predicted. Three cell models were used to assess the anti-inflammatory effects of parthenolide and the osteogenic effects of naringin. First, the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) and the bone mineral density (BMD) of surgical defects were measured in a rat model of periodontitis with periodontal fenestration defects. Additionally, the mRNA expression levels of matrix metallopeptidase 9 (MMP9) and alkaline phosphatase (ALP) were measured. Furthermore, the number of inflammatory cells and osteoclasts, as well as the protein expression levels of tumor necrosis factor-alpha (TNF-α) and levels of ALP were determined. Results: Target prediction suggested prostaglandin peroxidase synthase (PTGS2) as a potential target of parthenolide, while cytochrome P450 family 19 subfamily A1 (CYP19A1) and taste 2 receptor member 31 (TAS2R31) were potential targets of naringin. Parthenolide mainly targeted inflammation-related pathways, while naringin participated in steroid hormone synthesis and taste transduction. In vitro experiments revealed significant antiinflammatory effects of parthenolide on RAW264.7 cells, and significant osteogenic effects of naringin on bone marrow mesenchymal stem cells and MC3T3-E1 cells. DDDS loaded with parthenolide and naringin decreased the CEJ-ABC distance and increased BMD and ALP levels in a time-dependent manner. Inflammation was significantly alleviated after 14 days of DDDS treatment. Additionally, after 56 days, the DDDS group exhibited the highest BMD and ALP levels. Conclusions: DDDS loaded with parthenolide and naringin in a rat model achieved significant synergistic anti-inflammatory and osteogenic effects, providing powerful preclinical evidence.

• The Journal of Pediatrics of Korean Medicine
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• v.37 no.4
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• pp.53-62
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• 2023

Objectives The aim of this study was to identify the effect of Baekho-tang extract on epidermal barrier recovery and inflammation relief in atopic dermatitis-induced mice through Endocanabinoid system (ECS) regulation. Methods In this study, we used 4-week-old NC/Nga mice were divided into 4 group: lipid barrier elimination group (LBEG), palmitoylethanolamide treated group after lipid barrier elimination (PEAT), Baekho-tang extract treatment group after lipid barrier elimination (BHTT) and control group (Ctrl). Each group was assigned 10 animals. We identified that cannabinoid receptor (CB) 1, CB2, CD (Cluster of Differentiation) 68, inducible nitric oxide synthase (iNOS), substance P and Matrix metallopeptidase 9 (MMP-9) through our immunohistochemistry. Results We discovered that when compared to PEAT, 8-hydroxydeoxyguanosine, a marker of oxidative stress in the epidermal barrier, and CB1 and CB2, markers of ECS modulation, were less activated in BHTT. These results led to an anti-inflammatory response in BHTT, with a significant decrease in several inflammatory mediators such as CD 68, iNOS, substance P and MMP-9 compared to PEAT and LBEG. Conclusions These results suggest that the Baekho-tang extract can reduce the inflammation of atopic dermatitis by restoring the structural damage of the skin lipid barrier through ECS modulation.