• BMB Reports
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• v.45 no.12
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• pp.713-718
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• 2012

Gangliosides play important roles in the control of several biological processes, including proliferation and transmembrane signaling. In this study, we demonstrate the effect of ganglioside GM1 on the proliferation of mouse induced pluripotent stem cells (miPSCs). The proliferation rate of miPSCs was lower than in mouse embryonic stem cells (mESCs). Fluorescence activated cell sorting analysis showed that the percentage of cells in the G2/M phase in miPSCs was lower than that in mESCs. GM1 was expressed in mESCs, but not miPSCs. To confirm the role of GM1 in miPSC proliferation, miPSCs were treated with GM1. GM1-treated miPSCs exhibited increased cell proliferation and a larger number of cells in the G2/M phase. Furthermore, phosphorylation of mitogen-activated protein kinases was increased in GM1-treated miPSCs.

• Journal of Life Science
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• v.30 no.6
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• pp.532-541
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• 2020

In this study, we describe the inhibition of adipocyte differentiation by the lactic acid bacteria (LAB) fermentation product of Chrysanthemum indicum L. (CI) extract to control obesity. Preparation of LAB-fermented products was performed to overcome the cytotoxicity of CI extract. During fermentation and 3T3-L1 cell line experiment, cytotoxicity was not induced in the CI fermentation products over 1 day in culture. Fermented materials from highly proliferative cultures were selected for treatment of 3T3-L1 cells and for comparison with unfermented control groups. Cell survival and undifferentiated cell populations were decreased differentiation population in all experimental groups compared with controls, as measured using fluorescence-activated cell sorting analysis. Akt pathway activity increased upon treatment with these fermented extracts in 3T3-L1 cells. Gli2 depleted at the protein level in association with adipocyte differentiation. LAB KCTC 3115- and 3109-fermented extract treatment caused controlled Gli2 protein accumulation. Moreover, KCTC 3115 and 3109 were found to reduce C/EBPα and FAS was depleted, whereas pACC was increased at the protein level upon treatment with the fermentation products of each of the four LAB used in this study. With Lactococcus lactis subsp. lactis KCTC 3115 fermentation, the regulation of adipose differentiation and hedgehog signaling were also suppressed, thereby inhibiting the differentiation of progenitor cells. The basis for the activation of hedgehog signaling may provide insights into the treatment of obesity and the inhibition of adipocyte differentiation.

• Journal of Life Science
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• v.30 no.10
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• pp.835-843
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• 2020

Obesity, the world's leading metabolic disease, is a serious health problem in both industrialized and developing countries. Natural substances are of great interest in preventative medicine, especially in the field of metabolic syndromes-from insulin resistance to obesity and diabetes. In the present study, we investigated the effect of A. pullulans SM-2001 Extract (Polycan^®) on the adipocyte differentiation of 3T3-L1 preadipocytes and the anti-obesity effect of 3T3-L1 adipocytes. Although β-glucan has been found to have health benefits in the regulation of the immune system and blood cholesterol levels, its role in obesity has not been fully investigated. Polycan^® suppressed lipid accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity without affecting cell viability in 3T3-L1 preadipocytes and adipocytes. Polycan^® also inhibited cellular lipid accumulation through down-regulation of transcription factors, such as PPARγ and C/EBPα, and induced dose-dependent phosphorylation of AMP-activated protein kinase (AMPK)-a cellular energy sensor-while the total AMPK protein content remained unchanged. Taken together, this shows that the activation of AMPK by Polycan^® in adipocytes plays a critical role in Polycan^®-induced inhibition of adipocyte differentiation. Our results show that Polycan^® has an anti-obesity action in vitro, suggesting a potential novel preventative agent for obesity and other metabolic diseases.

• Tuberculosis and Respiratory Diseases
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• v.75 no.4
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• pp.140-149
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• 2013

Background: Plasminogen activator inhibitor type 1 (PAI-1), an important regulator of plasminogen activator system which controls degradation of extracellular membrane and progression of tumor cells, and PAI-1 gene polymorphic variants have been known as the prognostic biomarkers of non-small cell lung cancer patients. Recently, experimental in vitro study revealed that transforming growth factor-${\beta}1$ initiated PAI-1 transcription through epithelial growth factor receptor (EGFR) signaling pathway. However, there is little clinical evidence on the association between PAI-1 A15T gene polymorphism and prognosis of Korean population with pulmonary adenocarcinoma and the influence of activating mutation of EGFR kinase domain. Methods: We retrospectively reviewed the medical records of 171 patients who were diagnosed with pulmonary adenocarcinoma and undergone EGFR mutation analysis from 1995 through 2009. Results: In all patients with pulmonary adenocarcinoma, there was no significant association between PAI-1 A15T polymorphic variants and prognosis for overall survival. However, further subgroup analysis showed that the group with AG/AA genotype had a shorter 3-year survival time than the group with GG genotype in patients with EGFR mutant-type pulmonary adenocarcinoma (mean survival time, 24.9 months vs. 32.5 months, respectively; p=0.015). In multivariate analysis of 3-year survival for patients with pulmonary adenocarcinoma harboring mutant-type EGFR, the AG/AA genotype carriers had poorer prognosis than the GG genotype carriers (hazard ratio, 7.729; 95% confidence interval, 1.414-42.250; p=0.018). Conclusion: According to our study of Korean population with pulmonary adenocarcinoma, AG/AA genotype of PAI-1 A15T would be a significant predictor of poor short-term survival in patients with pulmonary adenocarcinoma harboring mutant-type EGFR.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.6
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• pp.829-835
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• 2014

This study investigated the neuroprotective effects of bread containing extract from Cirsium setidens (CS) or Aster scaber (AS) against $H_2O_2$-induced death of human brain neuroblastoma SK-N-SH cells. Treatment with bread containing extract from CS (CSB) or AS (ASB) reduced $H_2O_2$ cytotoxicity in SK-N-SH cells, the intracellular ROS level, and the phospho-p38 mitogen-activated protein kinase (MAPK) level. In the sensory evaluation, wild vegetable flavor scores of CSB were higher than those of ASB and bread containing 0% CS or AS (NB). In terms of appearance, color, flavor, softness, and overall acceptability, CSB and ASB showed higher scores than NB, but no differences were observed between CSB and ASB. These results indicate that CSB and ASB have potent health benefits in terms of neuroprotection against oxidative stress mediated through antioxidant activity and inhibition of p38 phosphorylation in brain neural cells. Thus, CS and AS could be considered as a health functional material.

• KSBB Journal
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• v.30 no.5
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• pp.223-229
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• 2015

In this study, extract from Artemisia annua in L. (AAE) is known as a medicinal herb that is effective against cancer. The cell cycle is regulated by the activation of cyclin-dependent kinase (CDK)/cyclin complex. We will focus on regulation of CDK2 by cyclin E. cyclin E is associated with CDK2 to regulate progression from G1 into S phase. Akt is known to play an important role in cell proliferation and cell survival. Activation of Akt increases mTOR activity that promotes cell proliferation and cancer growth. In this study, we investigated that AAE-induced cell cycle arrest at G1/S phase in HCT116 colon cancer. Treatment of AAE shows that reduced activation of Akt decreases mTOR/Mdm2 activity and then leads to increase the activation of p53. The active p53 promotes activation of p21. p21 induces inactivation of CDK2/cyclin E complex and occurs cell cycle arrest at G1/S phase. We treated LY294002 (Akt inhibitor) and Rapamycin (mTOR inhibitor) to know the relationship between the signal transduction of proteins associated with cell cycle arrest. These results suggest that AAE induces cell cycle arrest at G1/S phase by Akt/mTOR pathway in HCT116 colon cancer cell.

• Herbal Formula Science
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• v.23 no.2
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• pp.189-198
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• 2015

Objectives : Sparganii Rhizoma is frequently used in traditional herbal medicine for treatment of blood stasis, amenorrhea and functional dyspepsia and has been reported to exhibit anti-oxidant, anti-proliferation and anti-angiogenesis peoperties. In this study, we investigated the cytoprotective effect and underlying mechanism of Sparganii Rhizoma water extract (SRE) against oxidative stress-induced mitochondrial dysfunction and apoptosis in hepatocyte. Methods : To determine the effects of SRE on oxidative stress, we induced synergistic cytotoxicity by co-treatment of arachidonic acid (AA) and iron in the HepG2 cell, a human derived hepatocyte cell line. Results : Treatment of SRE increased relative cell viability and altered the expression levels of apoptosis-related proteins such as Bcl-xL, Bcl-2 and procaspase-3. And SRE also inhibited the mitochondrial dysfunction and excessive reactive oxygen species production induced by AA+iron. In addition, SRE activated of AMP-activated protein kinase (AMPK), a potential target for cytoprotection, by increasing the phosphorylation of AMPKα at Thr-172. Morever, SRE increased phosphorylation of acetyl-CoA carboxylase, a direct downstream target of AMPK. Conclusion : These results indicated that SRE has the ability to protect against oxidative stress-induced hepatocyte damage, which may be mediated with AMPK pathway.

• The Journal of Korean Medicine
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• v.31 no.3
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• pp.79-97
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• 2010

Background: Peripheral nerve injuries are commonly encountered clinical problems and often result in severe functional deficit. Bee venom acupuncture has traditionally been used to treat several inflammatory diseases and chronic pain conditions. Objectives: The aims of this study were to compare the effects of bee venom (general bee venom, BV) and sweet bee venom (allergen-removed bee venom, SBV) acupuncture on the recovery rate of locomotor function, the expression of brain-derived neurotrophic factor (BDNF) in the sciatic nerve, and the expression of c-Fos in the brain following sciatic crushed nerve injury in rats, and to evaluate differences due to administration areas. Method: Walking track analysis, Western blot for BDNF and tyrosine receptor kinase B (TrkB), and immunohistochemistry for c-Fos were performed. In this study, comparative analyses of the effects of BV and SBV acupuncture in relation to administration sites, contralateral side or ipsilateral side, were conducted. Results: In the present result, sciatic function index (SFI) in walking track analysis significantly decreased following sciatic crushed nerve injury. The expressions of BDNF and TrkB in the sciatic nerve increased after induction of sciatic crushed nerve injury. C-Fos expression in the ventrolateral periaqueductal gray (vlPAG) and paraventricular nucleus (PVN) also increased. BV and SBV acupuncture treatment improved the SFI in walking track analysis. Treatment with SBV at 1mg/kg showed more potent enhancing effect on SFI compared to BV. Treatment with 1mg/kg BV or 1mg/kg SBV acupuncture suppressed the BDNF and TrkB expression in the sciatic nerve. BV and SBV acupuncture treatment also suppressed c-Fos expression in the PVN and vlPAG regions. Treatment with SBV at 1mg/kg showed more potent suppressing effect on c-Fos expression compared to BV when injected into the contralateral side of the injured nerve. Generally we could not find significant difference in the effects between contralateral side and ipsilateral side of the injured nerve. Conclusion: We have shown that BV and SBV acupuncture treatment can be used as the effective therapeutic modality to ameliorate the symptoms of sciatic crushed nerve injury.

• Korean Journal of Acupuncture
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• v.23 no.3
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• pp.133-160
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• 2006

Objectives : Scolopendrae Corpus has a broad array of clinical applications in Korean medicine, including treatment of inflammatory conditions such as arthritis. To explore the global gene expression profiles in human Raw cell lines treated with Scolopendrae Corpus herbal-acupuncture solution (SCHAS), cDNA microarray analysis was performed. Methods : The Raw 264.7 cells were treated with lipopolysaccharide (LPS), SCHAS, or both. The primary data was normalized by the total spots of intensity between two groups, and then normalized by the intensity ratio of reference genes such as housekeeping genes in both groups. The expression ratio was converted to log2 ratio. Normalized spot intensities were calculated into gene expression ratios between the control and treatment groups. Greater than 2 fold changes between two groups were considered to be of significance. Results : Of the 8 K genes profiled in this study, with a cut-off level of two-fold change in the expression, 20 genes (BCL2-related protein A1, MARCKS-like 1, etc.) were upregulated and 5 genes (activated RNA polymerase II transcription cofactor 4, calcium binding atopy-related autoantigen 1, etc.) downregulated following LPS treatment. 139 genes (kell blood group precursor (McLeod phenotype), ribosomal protein S7, etc.) were upregulated and 42 genes (anterior gradient 2 homolog (xenopus laevis), phosphodiesterase 8B, etc.) were downregulated following SCHAS treatment. And 10 genes (yeast saccharomyces cerevisiae intergeneic sequence 4-1, mitogen-activated protein kinase 1, etc.) were upregulated and 8 genes (spermatid perinuclear RNA binding protein, nuclear receptor binding protein 2, etc.) were downregulated following co-stimulation of SCHAS and LPS. Discussions : It is thought that microarrays will play an ever-growing role in the advance of our understanding of the pharmacological actions of SCHAS in the treatment of arthritis. But further studies are required to concretely prove the effectiveness of SCHAS.

• Korean Journal of Food Science and Technology
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• v.41 no.4
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• pp.405-412
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• 2009

The purpose of this study was to determine the inhibitory effect of a glycoprotein isolated from Cudrania tricuspidata Bureau (CTB glycoprotein, 75 kDa) on immunoglobulin E (IgE)-induced allergic inflammation in RBL-2H3 cells. This experiment evaluated the production of intracellular reactive oxygen species (ROS), the activities of mitogenactivated protein kinase (MAPK), transcription factor (c-jun), and cyclooxygenase (COX)-2, and histamine release in cells. The results showed that the CTB glycoprotein inhibited histamine release and COX-2 expression induced by IgE in the cells. The CTB glycoprotein also had suppressive effects on the expressions of ERK1/2, p38 MAPK, c-jun, and the production of intracellular ROS in IgE-treated RBL-2H3 cells. The activities of c-jun and COX-2 were collectively blocked by ERK1/2 inhibitor (PD98059) and p38 MAPK inhibitor (SKF86002), respectively. Hence, we speculate that CTB glycoprotein might be a component with potential use in the preparation of health supplements for the prevention of allergic diseases.