• Molecular Medicine Reports
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• v.21 no.3
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• pp.1374-1382
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• 2020

Arctigenin is a natural lignan that is found in burdock with anti-viral, -oxidative, -inflammatory and anti-tumor activities. In the current study, the effect of arctigenin on metastatic potential was examined in 4T-1 mouse triple-negative breast cancer cells. The results indicated that arctigenin inhibited cell motility and invasiveness, which was determined using wound healing and transwell invasion assays. Arctigenin suppressed matrix metalloprotease-9 (MMP-9) activity via gelatin zymography, and protein expression of cyclooxygenase-2 (COX-2) and MMP-3. Furthermore, arctigenin attenuated the mRNA expression of metastatic factors, including MMP-9, MMP-3 and COX-2. Based on these results, the effect of arctigenin on the mitogen-activated protein kinase (MAPK)/activating protein-1 (AP-1) signaling pathway was assessed in an attempt to identify the regulatory mechanism responsible for its anti-metastatic effects. Arctigenin was demonstrated to inhibit the phosphorylation of extracellular signal-regulated protein kinase (ERK) and c-Jun N- terminal kinase (JNK), and the nuclear translocations of the AP-1 subunits, c-Jun and c-Fos. In summary, the present study demonstrated that in 4T-1 mouse triple-negative breast cancer cells the anti-metastatic effect of arctigenin is mediated by the inhibition of MMP-9 activity and by the inhibition of the metastasis-enhancing factors MMP-9, MMP-3 and COX-2, due to the suppression of the MAPK/AP-1 signaling pathway. The results of the current study demonstrated that arctigenin exhibits a potential for preventing cell migration and invasion in triple negative breast cancer.

• Journal of the Korean Academy of Clinical Electrophysiology
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• v.6 no.1
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• pp.17-30
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• 2008

This study was investigated the effects of pain and functional recovery when low frequency electrical stimulation and aquatic exercise applied to sciatic nerve injured rats. The rats were assigned into four groups; Group I(n=20, control group), Group II(n=20, low frequency electrical stimulation group), Group III(n=20, aquatic exercise group), Group (n=20, applied low frequency electrical stimulation and aquaatic exercise group). Each IV group measured hot plate examination, sciatic nerve functional index(SFI), c-fos.. In hot plate examination, group II, IV showed effect than group Iat 14 days after injured(p<0.01) and group III, Ⅳ showed effect than group I at 21, 28 days after in-jured(p<0.01, p<0.001). In SFI, group II, III, IV showed effect II, III, IV than group I and group IV showed effect than group II at 14, 21 days after injured(p<0.001). group II, III, IV showed effect than group I at 28 days after injured(II = p<0.01, III and IV = p<0.001). Effects of pain and function recovery when low frequency electrical stimulation and aqua-exercise applied to sciatic nerve injured rats, group Ⅳ were most effected to sciatic nerve injured rats. As well as group II and III were effected to sciatic nerve injured rats.

• Biotechnology and Bioprocess Engineering:BBE
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• v.10 no.5
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• pp.444-450
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• 2005

Epidermal growth factor (EGF) activates many intracellular effector molecules, which subsequently influence the expression levels of many genes involved in cell growth, apoptosis and signal transduction, etc. In this study, the early response of gene expressions due to EGF treatment was monitored using oligonucleotide DNA microarrays in rat schwannoma cell lines. An immunoblotting experiment showed the successful activation of EGF receptors and an effector protein, STAT5, due to EGF treatment. The microarray study showed that 35 genes were significantly induced and 2 were repressed within 60 min after the treatment. The list of induced genes included early growth response 1, suppressor of cytokine signaling 3, c-fos, interferon regulatory factor 1 and early growth response 2, etc. According to the microarray data, six of these were induced by more than 10-fold, and showed at least two different induction patterns, indicating complicated regulatory mechanisms in the EGF signal transduction.

• The Journal of Korean Medicine
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• v.20 no.2
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• pp.88-97
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• 1999

To characterize the effects of Gilgyung-Tang(GGT) on cellular proliferation and viability of normal lung fibroblast cells, we examined the cell cycle progression and cell cycle-related gene expression in T3891 using a flow cytometry and a quantitative RT-PCR analysis. 1. The significant surpression effect of cellular proliferations of GGT was observed in proportion to a certain concentration and time. 2. GGT was identified to induce apoptotic death of damaged cells by treatment with a DNA-damage agent and etoposide, while it stimulated the recovery of cellular viability of normal cells. 3 The significant reductions of mRNA expression of PCAN, c-Fos treated by GGT were observed. 4. The significant inductions of mRNA expression of p53, CDKN1. Gadd45 treated by GGT were observed. 5. The apoptosis caused by the reduction of Bcl-2 genes was significant and the Bax genes were increased. but the amount of Fas genes were not changed. These results strongly suggest that GGT triggers arrest of the cell cycle at G1 phase, and thus causes an inhibition of cellular proliferation of human normal lung cells through the transcriptional up-regulation of cell cycle inhibitory genes and down-regulation of induction of cell cycle stimulating genes respectably.

• Journal of Korean Biological Nursing Science
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• v.18 no.4
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• pp.274-279
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• 2016

Purpose: Adolescents who experienced the alcohol consumption have gradually increased. Adolescence is a critical period of the neural plasticity in the brain. Neural plasticity is mediated by neurotrophins and has an impact on cognitive function. Environmental enrichment ameliorates the cognitive function and increases neurotrophins. Thus, we investigated the neuroprotective effect of environmental enrichment on ethanol induced cognitive impairment in adolescent rats. Methods: The ethanol groups and the controls groups were injected with ethanol (0.5g/kg) and phosphate buffered saline, respectively, through intraperitoneal from 28th day of birth for 11 days. The environmental enrichment groups were provided larger cages containing toys than the standard cage. Passive avoidance test and Y-maze test were performed to evaluate the spatial memory. Results: Environmental enrichment+ethanol group showed higher alterations than the standard environment+ethanol group in Y-maze test (p<.05). In hippocampus, The environmental enrichment+ethanol group showed significantly higher level of the number of c-fos positive celsl and density of tropomyosin receptors kinase B receptor than the standard environment+ethanol group (p<.05). Conclusion: So, we suggested that the environmental enrichment played a role as a prophylaxis for prevention of memory impairment induced by ethanol exposure in adolescence.

• The Journal of Korean Obstetrics and Gynecology
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• v.29 no.2
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• pp.66-82
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• 2016

Objectives : This study was conducted to evaluate the effect of Kanghwalsokdan-tang Gamibang water extract (KSG) on osteoporosis. Methods : RANKL-stimulated RAW 264.7 was used to evaluate inhibitory effect of KSG osteoclast differentiation and gene expression. We counted TRAP (+) multinucleated cells and measured TRAP activity and mRNA expressions of osteoclastogenesis-related genes (NFATc1, MITF, JNK1, cathepsin K, MMP-9) to figure out the effect of KSG on osteoclast. Osteoblastogenesis was also determined in rat calvarial cell. Alkaline phosphatase (ALP) activity, bone matrix protein and collagen synthesis were measured by using murine calvarial cell. Results : KSG inhibited the differentiation of osteoclast precursor cell and expression of genes related osteoclastogenesis like NAFTc1, MITF, c-fos, JNK1, Cathepsin K, MMP-9 and TRAP. KSG increased cell division and function of osteoblast separated from the skull of a rat and ALP synthesis, biosynthesis of bone matrix protein and collagen. Conclusions : Reviewing these results, KSG has efficacy on osteoclast inhibition and osteoblast activation. After further study, KSG will be able to apply for osteoporosis treatment and prevention.

• The Journal of Internal Korean Medicine
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• v.27 no.4
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• pp.915-926
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• 2006

Objectives : Yanggyuksanhwa-tang is a prescription used for cerebral infarction clinically it is known that this formula reduces body fat, serum cholesterol and triglyceride in hyperglycemia and obesity patients. According to previous research data, controlling these types of lipid is considered to decrease the risk of cerebral infarction. Based on this fact, we investigated the relationship between hyperlipidemia and cerebral infarction, and the effect of Yanggyuksanhwa-tang on hyperlipidemic cerebral infarction. Methods : We induced cerebral infarction by middle cerebral artery occlusion (MCAO) in high-fat diet rats, and the rats were administered Yanggyuksanhwa-tang. Results : Infarct area and serum lipid were measured, and the level of elements such as c-Fos, Bax and caspase-3 in penumbra of infarct were expressed by immunohistochemical staining. Conclusions : Yanggyuksanhwa-tang showed neuroprotective effect through preventing neuronal cell apoptosis as well as reducing serum lipid level in hyperlipidemic condition.

• The Journal of Korean Medicine
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• v.38 no.3
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• pp.59-72
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• 2017

Objectives: This study was performed to evaluate effects of Sochungryong-tang Extract(SRE) on osteoclast differentiation and bone resorptionin order to find out the possibility for clinical use in preventing and treating osteoporosis. Methods: To evaluate the effect of SRE on osteoclast differentiation, we induced RAW 264. 7 cells to be differentiated to osteoclasts by RANKL (receptor activator of nuclear $factor-{\kappa}B$ ligand). We measured effect on TRAP (Tartrate-resistant acid phosphatase), NFATc, cathepsin K, MMP-9, inflammation related factors, histogenesis factors and bone resorption. Results: SRE decreased osteoclast differentiation, and also decreased expression of bone resorbing factors such as MMP-9, cathepsin K, TRAP, NFATc1, MITF, c-Fos, osteoclast stimulatory transmembrane protein, calcitonin receptor in RANKL-induced osteoclast. SRE also decreased Cyclooxygenase-2, indusible nitric oxide synthase, $TNF-{\alpha}$, which are thought to be related with the inflammatory bone destruction. Conclusion: SRE inhibits osteoclast differentiation and bone resorption. The results indicate that the BHT extract can potentially be applied for preventing and treating osteoporosis.

• International Journal of Oral Biology
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• v.36 no.4
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• pp.187-194
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• 2011

Periodontitis is an inflammatory disorder of the periodontium, characterized by destruction of the tooth supporting tissues including alveolar bone and mediated by various pro-inflammatory mediators. Here, we demonstrated that HP08-0106, composed of four crude drugs-Gardenia jasminoides Grandiflora, Angelica gigas Nakai, Rehmannia glutinosa, and Schizonepeta tenuifolia in a weight ratio of 2:2:1:2, perturbs inflammatory responses, osteoclast formation in LPS-induced RAW 264.7 cells and alveolar bone resorption in ligature-induced periodontitis. HP08-0106 decreased the protein level of iNOS and COX2 as well as the secreted level of IL-$1{\beta}$, indicating that HP08-0106 has antiinflammatory effects. HP08-0106 also inhibited the expression of genes associated with osteoclastogenesis including c-Fos, MMP-9 and TRAP. Moreover, HP08-0106 exhibited a protective effect from alveolar bone loss in ligature-induced periodontitis animal models. Our results strongly suggest that HP08-0106 represent an important therapeutic tool to treat inflammatory disorders associated with bone loss such as periodontitis.

• BMB Reports
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• v.52 no.7
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• pp.469-474
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• 2019

Kruppel-like factor 2 (KLF2) has been implicated in the regulation of cell proliferation, differentiation, and survival in a variety of cells. Recently, it has been reported that KLF2 regulates the p65-mediated transactivation of $NF-{\kappa}B$. Although the $NF-{\kappa}B$ pathway plays an important role in the differentiation of osteoclasts and osteoblasts, the role of KLF2 in these bone cells has not yet been fully elucidated. In this study, we demonstrated that KLF2 regulates osteoclast and osteoblast differentiation. The overexpression of KLF2 in osteoclast precursor cells inhibited osteoclast differentiation by downregulating c-Fos, NFATc1, and TRAP expression, while KLF2 overexpression in osteoblasts enhanced osteoblast differentiation and function by upregulating Runx2, ALP, and BSP expression. Conversely, the downregulation of KLF2 with KLF2-specific siRNA increased osteoclast differentiation and inhibited osteoblast differentiation. Moreover, the overexpression of interferon regulatory protein 2-binding protein 2 (IRF2BP2), a regulator of KLF2, suppressed osteoclast differentiation and enhanced osteoblast differentiation and function. These effects were reversed by downregulating KLF2. Collectively, our data provide new insights and evidence to suggest that the IRF2BP2/KLF2 axis mediates osteoclast and osteoblast differentiation, thereby affecting bone homeostasis.