• Korean Journal of Food Science and Technology
• /
• v.46 no.5
• /
• pp.630-635
• /
• 2014

Pine nut oil (PNO) is well known to impart beneficial effects in overweight individuals, but the mechanisms underlying PNO-mediated weight loss remain unclear. To investigate how PNO promotes weight loss, its composition was determined by gas chromatography coupled with mass spectrometry (GC-MS). In addition, the effects of PNO on cytotoxicity, lipid accumulation, expression of lipid metabolism-related biomarkers, and leptin secretion were assessed in 3T3-L1 cells. GC-MS analyses revealed that PNO contains several components, including linoleic acid, oleic acid, palmitic acid, and stearic acid. Moreover, PNO did not have a cytotoxic effect on 3T3-L1 cells. However, it inhibited the expression of peroxisome proliferator-activated receptor (PPAR) and adipocyte protein 2 (aP2). Finally, PNO significantly increased leptin secretion in a dose-dependent manner. Taken together, these results support the notion that PNO is useful for weight management in overweight individuals.

• Journal of Life Science
• /
• v.31 no.10
• /
• pp.873-884
• /
• 2021

The purpose of present study is to investigate the role of artesunate (ART) in enhancing anticancer effect of nonsteroidal anti-inflammatory drug (NSAID) on human cancer cells, and we elucidate a possible molecular mechanism of this combination effect. We showed that the combined effect of ART with NSAID such as celecoxib (CCB) or dimethyl-CCB (DMC) in various type of human cancer cells. After ART treatment, the expression of p62, nuclear factor erythroid 2-like 2 (NRF2) and cancer stemness (CS)-related proteins including CD44, CD133, aldehyde dehydrogenase 1 (ALDH1), octamer-binding transcription factor 4 (Oct4), mutated p53 (mutp53) and c-Myc was down-regulated. ART induced autophagy as reduction of the autophagy receptor p62, which was associated with up-regulation of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and simultaneous down-regulation of NRF2 and CS-related proteins was occurred in the human cancer cells. These results indicate a possibility that ART activates autophagy through ATF4-CHOP cascade leading to down-regulation of CS-related proteins and subsequently eradicated cancer stem cells. In addition, co-treatment with ART and imatinib was more effective than either drug alone on growth inhibition and apoptosis induction of cancer cells. In conclusion, induction of autophagy-dependent cell death by ART might play a critical role in mediating the synergistic effect of drug combination (ART/NSAID and ART/imatinib). Therefore, ART could be a promising candidate as a chemosensitizer to enhance the anticancer effects of NSAID and imatinib.

• Journal of Nutrition and Health
• /
• v.53 no.6
• /
• pp.583-595
• /
• 2020

Purpose: This study examined the effects of Sargassum horneri extracts on palmitic acid (PA)-induced endoplasmic reticulum (ER) stress in HepG2 cells. Methods: HepG2 cells were treated with varying concentrations of S. horneri extract or PA, and the cell viability was measured by water soluble tetrazolium salts analysis. The effective induction of ER stress and the effects of S. horneri were investigated through an examination of the ER stress-related genes, such as activating transcription factor 4 (ATF4), X-box binding protein (XBP1s), C/EBP homologous protein (CHOP), and 78-kDa glucose-regulated protein (GRP78) by quantitative reverse transcription polymerase chain reaction. The expression and activation levels of unfolded protein response (UPR) associated proteins, such as inositol-requiring enzyme-1α (IRE1α), eukaryotic translation initiation factor 2 alpha submit (eIF2α), and CHOP were examined by western blot analysis. Results: The treatment with PA increased the expression of UPR associated genes significantly and induced ER stress in a 12-hour treatment. Subsequent treatment with S. horneri reduced mRNA expression of ATF4, GRP78, and XBP1s. In addition, the protein levels of phosphate (p)-IRE1α, p-elF2α, and CHOP were also reduced by a treatment with S. horneri. An analysis of sirtuin (SIRT) mRNA expression in the S. horneri and PA-treated HepG2 cells showed that S. horneri increased the levels of SIRT2, SIRT6, and SIRT7, which indicates a possible role in reducing the expression of ER stress-related genes. Conclusion: These data indicate that S. horneri can exert an inhibitory effect on ER stress caused by PA and highlight its potential as an agent for managing various ER stress-related diseases.

• The Korea Journal of Herbology
• /
• v.33 no.6
• /
• pp.61-70
• /
• 2018

Objectives : Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of hepatic triglycerides (TG) that leads to inflammation and fibrosis. Crataegi Fructus ethanol extract (CE) is a korean traditional herb that used for digestive diseases. It has been investigated that CE has the effect that prevent hepatotoxicity caused by CCl4 or GaIN and regulate the inflammatory in several organs. However, a hypolipidemic effect of CF has not been reported. Methods : The purpose of this study is that examine the lipid accumulation inhibitory effect of CE on NAFLD. We checked the body and liver weight change of MCD-diet induced mice with/without administration of CE. The blood lipid levels of C57BL/6J mice were checked by biochemistry. Also we observed the liver histology of MCD-diet induced mice and investigate the molecular mechanisms in MCD-diet-induced NAFLD in C57BL/6J mice. Results : CE improved MCD-diet-induced lipid accumulation and TG and TC levels. Also, CE decreased hepatic lipogenesis such as SREBP-1, $C/EBP{\alpha}$, $PPAR{\gamma}$, ACC and FAS. Besides, we also found out that CE increased AMPK phosphorylation. These results indicated that CE has the same ability to activate AMPK and then reduce SREBP-1, and FAS expression, finally leading to inhibit hepatic lipogenesis and hepatic antioxidative ability. Conclusions : In this report, we found CE exerted a regulatory effect on lipid accumulation by decreasing lipogenesis in MCD-diet induced NAFLD model. Therefore, CE extract may be active in the prevention of fatty liver.

• Journal of Life Science
• /
• v.32 no.2
• /
• pp.94-100
• /
• 2022

Chronic infection by hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype, adaptive mutations, and environmental factors. The pregenomic RNA transcription of HBV for their replication is regulated by the core promoter activation. Core promoter mutations have been the reason for acute liver failure and are associated with HCC development. We obtained HBV genes from a patient in Myanmar who was infected with HBV and identified gene variations in the core promoter region. For measuring the relative transactivation activity of the core promoter, we prepared the core-promoter reporter construct. Among the gene variations of the core promoter, the mutations of C1731T and G1806A were associated with increase in the transactivation of the HBV core promoter. Through computer analysis for searching for a tentative transcription factor binding site, we showed that the mutations of C1713T and G1806A newly created C/EBPβ and XBP1-responsive elements of the core promoter, respectively. The ectopic expression of C/EBPβ largely increased the HBV core promoter containing the C1713T mutation and that of XBP1 activated the M95 promoter containing the G1806A mutation. Our efforts to treat and prevent HBV infections are hampered by the emergence of drug-resistant mutations and vaccine-escape mutations. Our results provide the biological properties and clinical significance of specific HBV core promoter mutations.

• Journal of Life Science
• /
• v.32 no.3
• /
• pp.210-221
• /
• 2022

This study investigated the mechanisms underlying the anti-cancer effects of non-steroidal anti-inflammatory drugs (NSAIDs) in human cancer cells in combination with either N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor, or MHY2245, a new synthetic sirtuin 1 inhibitor. The results showed both DAPT and MHY2245 as novel chemosensitizers of human colon cancer KM12 and human hepatocellular carcinoma SNU475 cells to NSAIDs involving celecoxib and 2, 5-dimethyl celecoxib. The NSAID-induced cytotoxicity of these cells was significantly increased by DAPT and MHY2245 in a cyclooxygenase-2 independent manner. In addition, DAPT and MHY2245 reduced levels of p62, Notch1 intracellular domain, and multiple cancer stemness (CS)-related markers including Notch1, CD44, CD133, octamer-binding transcription factor 4, mutated p53 and c-Myc. However, the level of activating transcription factor 4 (ATF4) was enhanced, probably indicating the down-regulation of multiple CS-related markers by DAPT or MHY2245-mediated autophagy induction. Moreover, the NSAID-mediated reduction of p62/nuclear factor erythroid-derived 2-like 2 and CS-related marker proteins and the up-regulation of C/EBP homologous protein (CHOP)/ATF4 were accelerated by DAPT and MHY2245. As such, the combination of NSAID and either DAPT or MHY2245 resulted in higher cytotoxicity than NSAID alone by accelerating the down-regulation of multiple CS-related markers and PARP activation, indicating that both inhibitors promote NSAID-mediated autophagic cell death, possibly through the CHOP/ATF4 pathway. In conclusion, either combination strategy may be useful for the effective treatment of human cancer cells expressing CS-related markers.

• Journal of the Korea Society of Computer and Information
• /
• v.29 no.1
• /
• pp.187-194
• /
• 2024

In this study, we examined the effects of Rubus crataegifolius leaf on the inhibition of differentiation and adipogenesis of 3T3-L1 preadipocytes to confirm their potential for use as an anti-obesity functional material. Rubus crataegifolius leaves water extracted using hot water were then concentrated for use, with an extract yield of 4.76%. The result of measuring the rate of 3T3-L1 cell survival of Rubus crataegifolius leaf extract (RCLE) showed growth inhibition of 13% at a concentration of 1,000 ㎍/mL. Thus, in this study, experiments were performed using RCLE treatment concentrations up to 500 ㎍/mL. Production of triglycedie in 3T3-L1 cells showed a dose-dependent decrease, and the rate of reduction was 28.7, 40.8, and 51.6% at concentrations of 100, 300, and 500 ㎍/mL, respectively, compared to the control group. In addition, the results confirmed that suppression of lipogenesis was achieved by suppressing the expression of peroxisome proliferator-activated receptor γ (PPAR γ), CCAAT/enhancer-binding protein α (C/EBP α), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and increasing the expression of p-activated protein kinase (p-AMPK). Based on these results, it is believed that Rubus crataegifolius leaf extract can be used in the effort to manage obesity by regulating factors related to adipocyte differentiation and adipogenesis.

• Korean Journal of Plant Resources
• /
• v.37 no.4
• /
• pp.307-313
• /
• 2024

In this study, the anti-obesity effect of Geranium wilfordii Maxim. extract was studied using 3T3-L1 cells. Geranium wilfordii Maxim. was extracted with water (NG-GT-T1L), 10% ethanol (NG-GT-T2L), 30% ethanol (NG-GT-T3L), 50% ethanol (NG-GT-T4L), 70% ethanol (NG-GT-T5L), and the effects on cell viability, lipid accumulation, triglyceride content, and protein expression in 3T3-L1 cells were confirmed. It was confirmed that NG-GT-T3L extract was superior to other extract conditions in reducing lipid accumulation and triglyceride content in the concentration range that did not show cytotoxicity. In addition, it was confirmed to suppress adipogenesis and lipogenesis by reducing the expression of peroxisome proliferator-activated receptor-gamma (PPARγ) and CCAAT/enhancer binding protein-α(C/EBPα) proteins that regulate adipogenesis, decreasing the expression of fatty acid synthetase (FAS) and stearoyl CoA desaturase-1 (SCD-1) proteins that regulate lipogenesis, and increasing the expression of AMP-activated protein kinase (AMPK) protein. From these research results, Geranium wilfordii Maxim. NG-GT-T3L extract is believed to have anti-obesity reduction effects through suppressing lipid accumulation and triglyceride accumulation and regulating adipogenesis and lipogenesis-related proteins.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.42 no.7
• /
• pp.1015-1021
• /
• 2013

Glycyrrhiza inflata Batal, an important species of licorice, is one of the most widely used medicinal plants for over 4000 years. Glycyrrhiza plant species has been well known for its various therapeutic activities such as anti-inflammatory, anti-allergic, and anti-ulcer. The purpose of this study was to determine the effects of Glycyrrhiza inflata Batal ethanol extracts (GBE) on adipocyte and osteoblast differentiation. Mesenchymal C3H10T1/2 cells were treated with sub-cytotoxic doses of GBE, and its effects on adipocyte differentiation were assessed. We found that GBE dose-dependently increased lipid accumulation and also induced the expression of adipocyte markers, such as $PPAR{\gamma}$ and its target genes, aP2, and adiponectin, in C3H10T1/2 cells. Consistently, similar effects of GBE on lipid accumulation were also observed in preadipocyte 3T3-L1 cells that further supports the pro-adipogenic activities of GBE. We also investigated the effects of GBE on osteoblast differentiation of mesenchymal C3H10T1/2 cells. As a results, we found that GBE increased the activity of alkaline phosphatase in a dose-dependent manner and also promoted the expression of osteoblast markers, such as ALP and RUNX2, during osteoblast differentiation of C3H10T1/2 cells. Similar pro-osteogenic effects of GBE were also observed in preosteoblast MC3T3-E1 cells. Finally, our data show that a major bioactive compound found in Glycyrrhiza inflata Batal, licochalcone A (LA) but not glycyrrhizic acid (GA), can mediate the pro-adipogenic and pro-osteogenic effects of GBE. Taken together, this study provides data to show the possibility of GBE and its bioactive component LA as putative strategies for type 2 diabetes and bone diseases.

• Journal of Life Science
• /
• v.20 no.7
• /
• pp.1054-1065
• /
• 2010

SH21B is a natural composition composed of seven herbs: Scutellaria baicalensis Georgi, Prunus armeniaca Maxim, Ephedra sinica Stapf, Acorus gramineus Soland, Typha orientalis Presl, Polygala tenuifolia Willd and Nelumbo nucifera Gaertner (Ratio 3:3:3:3:3:2:2). In our previous study, we reported that SH21B inhibited adipogenesis and fat accumulation in 3T3-L1 cells through modulation of various regulators in the adipogenesis pathway. The aim of this study was to analyze the transcriptome profiles for the anti-adipogenic effects of SH21B in 3T3-L1 cells. Total RNAs from SH21B-treated 3T3-L1 cells were reverse-transcribed into cDNAs and hybridized to Affymetrix Mouse Gene 1.0 ST array. From microarray analyses, we identified 2,568 genes of which expressions were changed more than two-fold by SH21B, and the clustering analyses of these genes resulted in 9 clusters. Three clusters among the 9 showed down-regulation by SH21B (cluster 4, cluster 6 and cluster 9), and two clusters showed up-regulation by SH21B (cluster 7 and cluster 8) during the adipogenesis of 3T3-L1 cells. It was found that many genes related to cell proliferation and adipogenesis were included in these clusters. Clusters 4, 6 and 9 included genes which were related with adipogenesis induction and cell cycle arrest. Clusters 7 and 8 included genes related to cell proliferation as well as adipogenesis inhibition. These results suggest that the mechanisms of the anti-adipogenic effects of SH21B may be the modulation of genes involved in cell proliferation and adipogenesis.