• Journal of Sasang Constitutional Medicine
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• v.29 no.2
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• pp.136-153
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• 2017

Objectives This experimental study was designed to investigate the effect of Phaseolus angularis shell on metabolic syndrome. Methods Each 5 C57BL/6J mice were randomly assigned to normal diet group, high-fat diet(HFD) control group, high-fat diet plus 15.6 mg/kg/day of Orlistat(HFD-Orlistat) group, high-fat diet plus 100mg/kg/day of Phaseolus angularis shell extract(HFD-PAS_E) group. Weight, the blood chemical and hematologic parameter was med. The mRNA expression was assayed through Reverse transcriptase polymerase chain reaction(RT-PCR). Results In HFD-PAS_E group, the body weight gain, weight of liver, and the level of LDL-Cholesterol were significantly decreased and the level of HDL-Cholesterol were significantly increased. The size of adipocyte in HFD-PAS_E group was smaller than HFD group's. In HFD-PAS_E group, the expression of leptin, PPAR-${\gamma}$, AP2/FABP4 mRNA in liver adipocyte tissue was decreased, the expression of Adiponectin, UCP-2 mRNA in liver adipocyte tissue was increased and the expression of Leptin, C/EBP-a, AP2/FABP4 mRNA in epididymal adipocyte tissue was decreased. Conclusion These results suggest that Phaseolus angularis shell has inhibitory effects on metabolic syndrome by reducing the body weight and the levels of lipid contents in high-fat-diet induced obese mice.

• Animal cells and systems
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• v.16 no.2
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• pp.87-94
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• 2012

Nur77 is a member of the nuclear receptor 4A (NR4A) subgroup, which has been implicated in energy metabolism. Although Nur77 is found in adipose tissue, where TR4 plays a key role in lipid homeostasis, the role of Nur77 in adipogenesis is still controversial. Although the Nur77 responsive element (AAAGGTCA) is partially overlapped with TR4-binding sites (AGGTCA $n$ AGGTCA: $n$=0-6), the regulatory role of Nur77 in TR4 function associated with adipocyte biology remains unclear. Here, we found that Nur77 inhibits adipogenesis and TR4 transcriptional activity. Treatment with a Nur77 agonist, 1,1-bis(3'-indolyl)-1-($p$-anisyl)-methane, during 3T3-L1 adipocyte differentiation reduced adipogenesis. In reporter gene analysis, Nur77 specifically suppressed TR4 transcription activity but had little effect on $PPAR{\gamma}$ transcription activity. Consistently, Nur77 also suppressed TR4-induced promoter activity of the TR4 target gene PEPCK, which is known to be important for glyceroneogenesis in adipose tissue. Furthermore, Nur77 suppressed TR4 binding to TR4 response elements without direct interaction with TR4, suggesting that Nur77 may inhibit TR4 transcription activity via binding competition for TR4-binding sites. Furthermore, DIM-C-$pPhOCH_3$ substantially suppressed TR4-induced PEPCK expression in 3T3-L1 adipocytes. Together, our data demonstrate that Nur77 plays an inhibitory role in TR4-induced PEPCK expression in 3T3-L1 adipocytes.

• Journal of Pharmaceutical Investigation
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• v.40 no.6
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• pp.357-362
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• 2010

To enhance therapeutic effects of insulin-sensitizing adipokine, ADN gene and potent agonists, rosiglitazone for the $PPAR{\gamma}$, cationic liposomes as non-viral vectors were formulated. The particle size and zeta potential of drug loaded and unloaded cationic liposomes were investigated. The complex formation between cationic liposomes and negatively charged plasmid DNA was confirmed and the protection from DNase was observed. In vitro transfection was investigated in HepG2, HeLa, and HEK293 cells by mRNA expression of ADN. Encapsulation efficacy of rosiglitazone-loaded liposomes was determined by UV detection. Particle sizes of cationic liposomes were in the range of 110-170 nm and those of rosiglitazone-loaded cationic liposomes were in the range of 130-180 nm, respectively. Gel retardation of complexes indicated that the complex was formed at weight ratios of cationic lipid to plasmid DNA higher than 20:1. Both complexes protected plasmid DNA from DNase either drug free or drug loading. Encapsulation efficiency of rosiglitazone-loaded emulsion was increased by drug dose. The mRNA expression levels of ADN were dose-dependently increased in cells transfected with plasmid DNA. Therefore, cationic liposomes could be potential co-delivery system for drug and gene.

• Journal of Microbiology and Biotechnology
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• v.22 no.6
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• pp.806-813
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• 2012

Adipocyte differentiation is strongly associated with obesity, which causes metabolic disorders. In this study, we investigated the inhibitory effects of widdrol on 3T3-L1 preadipocyte growth and differentiation. Widdrol decreased lipid droplet accumulation and down-regulated adipogenic transcription factors such as C/$EBP{\alpha}$, C/$EBP{\beta}$, and $PPAR{\gamma}$. Widdrol blocked preadipocyte proliferation and differentiation through the inhibition of mitotic clonal expansion, which was accompanied by the failure of degradation of p21, a cyclin-dependent kinase inhibitor. Cell-cycle analysis clearly indicated that widdrol actively induces cell-cycle arrest at the G1-S phage transition, causing cells to remain in the preadipocyte state. Moreover, widdrol increased p21 expression and inhibited Rb phosphorylation in preadipocyte incubated in a hormone medium. Therefore, these findings clearly suggest that widdrol blocks preadipocyte growth and differentiation through the inhibition of mitotic clonal expansion by p21-and Rb-dependent G1 arrest and can be developed as a potent anti-adipogenic agent for reducing obesity.

• Journal of Microbiology and Biotechnology
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• v.26 no.11
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• pp.1836-1844
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• 2016

Adipogenesis is one of the cellular processes and a highly controlled program. Nowadays, inhibition of adipogenesis has received attention as an effective way to regulate obesity. In the current study, we investigated the inhibition effect of a chloroform extract of Pleurotus eryngii var. ferulae 'Beesan No. 2' (CEBT) on adipogenesis in 3T3-L1 murine preadipocytes. Pleurotus eryngii var. ferulae is one of many varieties of King oyster mushroom and has been reported to have various biological activities, including antitumor and anti-inflammation effects. Biological activities of 'Beesan No. 2', a new cultivar of Pleurotus eryngii var. ferulae, have not yet been reported. In this study, we found that CEBT suppressed adipogenesis in 3T3-L1 cells through inhibition of key adipogenic transcription factors, such as peroxisome proliferatoractivated receptor ${\gamma}$ and CCAAT/enhancer binding protein ${\alpha}$. Additionally, CEBT reduced the expression of the IRS/PI3K/Akt signaling pathway and its downstream factors, including mammalian target of rapamycin and p70S6 kinase, which stimulate adipogenesis. Furthermore, ${\beta}-catenin$, a suppressor of adipogenesis, was increased in CEBT-treated cells. These results indicate that Pleurotus eryngii var. ferulae 'Beesan No. 2' effectively inhibited adipogenesis, so this mushroom has potential as an anti-obesity food and drug.

• Journal of the East Asian Society of Dietary Life
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• v.24 no.3
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• pp.335-350
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• 2014

Compared to the large numbers of studies on the diabetes, hyperlipidemia and cancer therpeutic effects of ginseng, the anti-obese effect and mechanisms of ginsengs have not been studied as much. To determine the effects of ginseng on obesity, 14 keywords (ginseng, ginsenoside, obesity, weight, fat, diet, overeat, appetite, lipid, 3T3-L1, adipocyte, food intake, adipogenesis and lipolysis) were combined in searching a database. Fifty-six articles published from 1983 to 2012 as well as 656 patents registered until Aug $17^{th}$, 2012, were screened for anti-obese effects of ginseng. In the classification of experimental methods, 16 papers on 3T3-L1 cells, 38 papers on animals and three papers on human were reviewed. In terms of obese mechanisms of action, the most commonly used biomarkers were in order of lipid profiles > weight change > blood glucose > adipocytokine. Most ginseng studies on obesity focused on AMPK, $PPAR{\gamma}$, GLUT-4, PI3K and SREBP-1. Korean white ginseng extracts and Re repressed the lipogenesis genes such as PPARc2, SREBP-1c, LPL, FAS and DGAT1. However, ginseng or ginsenosides, PD (Rb1) and PT (Re), showed different or contradictory results. Water and ethanol extraction of ginseng showed contradictory effects on the secretion of inflammatory cytokines, wheras IL-6 was repressed by ethanol extracts and TNF-${\alpha}$ repressed by Re in vitro. Based on the literature, further studies on anti-obese mechanisms of ginseng, such as the inflammation-related obesity or cross signals between the adipocytes and the environments, are needed, instead of more studies on its hypolipidemic and hypoglycemic effects.

• Journal of Life Science
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• v.20 no.7
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• pp.1113-1120
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• 2010

This study investigated the efficacy of macelignan and hot water with Chinese traditional herb (CTH) extract on altering severe diabetic conditions in C57BL/KsJ-db/db mice. Previously, the anti-diabetic effects of macelignan were partly reported as a PPAR $\alpha/\gamma$-dual agonist. Here, we futher studied whether a combination of macelignan and CTH had more beneficial effects or not. The macelignan and CTH compound significantly decreased fasting blood glucose and HbA1c compared to macelignan-treated mice, and also significantly improved postprandial glucose, insulin sensitivity, and plasma lipid profiles (FFA, and TG). On the other hand, insulin levels were not significantly changed compared to the diabetic control group. There were no significant changes in the concentrations of total cholesterol and HDL-cholesterol, but there were changes in HTR and AI. These results suggest that the macelignan and CTH compound ameliorates hyperglycemia and efficiently improves postprandial glucose, insulin sensitivity, and hyperlipidemia compared with macelignan in db/db mice. Moreover, the macelignan and CTH compound seems to be more potent in affecting diabetic complications than macelignan.

• IMMUNE NETWORK
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• v.9 no.3
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• pp.98-105
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• 2009

Background: It has been recently noticed that type 2 diabetes (T2D), one of the most common metabolic diseases, causes a chronic low-grade inflammation and activation of the innate immune system that are closely involved in the pathogenesis of T2D. Cordyceps militaris, a traditional medicinal mushroom, produces a component compound, cordycepin (3'-deoxyadenosine). Cordycepin has been known to have many pharmacological activities including immunological stimulating, anti-cancer, and anti-infection activities. The molecular mechanisms of cordycepin in T2D are not clear. In the present study, we tested the role of cordycepin on the anti-diabetic effect and anti-inflammatory cascades in LPS-stimulated RAW 264.7 cells. Methods: We confirmed the levels of diabetes regulating genes mRNA and protein of cytokines through RT-PCR and western blot analysis and followed by FACS analysis for the surface molecules. Results: Cordycepin inhibited the production of NO and pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ in LPS-activated macrophages via suppressing protein expression of pro-inflammatory mediators. T2D regulating genes such as $11{\beta}$-HSD1 and PPAR${\gamma}$ were decreased as well as expression of co-stimulatory molecules such as ICAM-1 and B7-1/-2 were also decreased with the increment of its concentration. In accordance with suppressed pro-inflammatory cytokine production lead to inhibition of diabetic regulating genes in activated macrophages. Cordycepin suppressed NF-${\kappa}B$ activation in LPS-activated macrophages. Conclusion: Based on these observations, cordycepin suppressed T2D regulating genes through the inactivation of NF-${\kappa}B$ dependent inflammatory responses and suggesting that cordycepin will provide potential use as an immunomodulatory agent for treating immunological diseases.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.397-404
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• 2020

Adiponectin secretion-promoting compounds have therapeutic potentials in human metabolic diseases. Diallyl biphenyl-type neolignan compounds, magnolol, honokiol, and 4-O-methylhonokiol, from a Magnolia officinalis extract were screened as adiponectin-secretion promoting compounds in the adipogenic differentiation model of human bone marrow mesenchymal stem cells (hBM-MSCs). In a target identification study, magnolol, honokiol, and 4-O-methylhonokiol were elucidated as PPARα and PPARγ dual modulators. Diallyl biphenyl-type neolignans affected the transcription of lipid metabolism-associated genes in a different way compared to those of specific PPAR ligands. The diallyl biphenyl-type neolignan structure provides a novel pharmacophore of PPARα/γ dual modulators, which may have unique therapeutic potentials in diverse metabolic diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.1
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• pp.17-24
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• 2019

Cymbopogon citratus, commonly know as lemongrass, prossesses strong antioxidant, anti-tumor and anti-inflammatory properties. Howerver, its anti-obesity activity remains to be elucidated. This study investigated the effect of ethanol extract of Cymbopogon citratus on adipogenesis, and its underlying mechanism, in 3T3-L1 preadipocytes. The results demonstrated that ethanol extracts of Cymbopogon citratus effectively suppressed intercellular lipid accumulation at non-toxic concentrations, and was associated with the down-regulation of adipocyte-specific transcription factors, including $C/EBP{\alpha}$ and $PPAR{\gamma}$, and phosphorylation of $AMPK{\alpha}$. Furthermore, ethanol extracts of Cymbopogon citratus increased p21 and p21 expression, while the expression of CDK2, cyclin A and cyclin B1 was reduced. As a result, ethanol extracts of Cymbopogon citratus seems to induce G0/G1 cell cycle arrest of 3T3-L1 cells. On the other hand, ERK and Akt signaling pathways were not involved in anti-adipogenesis by ethanol extracts of Cymbopogon citratus. Taken together, theses results suggest that ethanol extracts of Cymbopogon citratus inhibits adipocyte differentiation in 3T3-L1 cells and can be used as a safe and efficient natural substance to manage anti-obesity.