• Journal of Ginseng Research
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• v.32 no.3
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• pp.187-193
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• 2008

The present study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng in C57BL/KsJ db/db mice. The db/db mice were divided into three groups: diabetic control group (DC), Korean red ginseng group (KRG, 100 mg/kg) and metformin group (MET, 300 mg/kg), and treated with drugs once per day for 10 weeks. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in KRG-, 67.7% in MET-treated group. With decreased plasma glucose and insulin levels, the insulin resistance index of the KRG-treated group was reduced by 27.6% compared to the DC group. The HbA1c levels in KRG and MET-treated groups were also decreased by 11.0% and 18.9% compared to that of DC group, respectively. Plasma triglyceride and non-esterified fatty acid levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the KRG-treated group compared to those in DC group. Histological analyses of the liver and fat tissue of mice treated with KRG revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the DC group. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin contents, but decreased glucagon production. To elucidate action mechanism of KRG, effects on AMP-activated protein kinase (AMPK) and its downstream target proteins responsible for fatty acid oxidation and gluconeogenesis were explored in the liver. KRG activated AMPK and acetyl-coA carboxylase (ACC) phosphorylations, resulting in stimulation of fatty acid oxidation. KRG also caused to down regulation of SREBP1a and its target gene expressions such as FAS, SCD1 and GPAT. In summary, our results suggest that KRG exerted the anti-diabetic effect through AMPK activation in the liver of db/db mice.

• Journal of Nutrition and Health
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• v.51 no.4
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• pp.275-286
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• 2018

Purpose: Our previous study demonstrated that persimmon (Diospyros kaki Thumb.) at different stages of ripening provided different protective effects against high-fat/cholesterol diet (HFD)-induced dyslipidemia in rats. In this study, we compared the metabolites profile and gene expressions related to triglyceride (TG)/cholesterol metabolism in vitro and in vivo after treating with persimmon water extracts (PWE) or tannin-enriched persimmon concentrate (TEP). Methods: Primary and secondary metabolites in test materials were determined by GC-TOF/MS, UHPLC-LTQ-ESI-IT-MS/MS, and UPLC-Q-TOF-MS. The expression of genes related to TG and cholesterol metabolism were determined by RT-PCR both in HepG2 cells stimulated by oleic acid/palmitic acid and in liver tissues obtained from Wistar rats fed with HFD and PWE at 0, 150, 300, and 600 mg/d (experiment I) or TEP at 0, 7, 14, and 28 mg/d (experiment II) by oral gavage for 9 weeks. Results: PLS-DA analysis and heatmap analysis demonstrated significantly differential profiling of metabolites of PWE and TEP according to processing of persimmon powder. In vitro, TEP showed similar hypolipidemic effects as PWE, but significantly enhanced hypocholesterolemic effects compared to PWE in sterol regulatory element-binding protein 2 (SREBP2), HMG-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesterol $7{\alpha}-hydroxylase$ (CYP7A1), and low density lipoprotein receptor (LDLR) gene expression. Consistently, TEP and PWE showed similar hypolipidemic capacity in vivo, but significantly enhanced hypocholesterolemic capacity in terms of SREBP2, HMGCR, and bile salt export pump (BSEP) gene expression. Conclusion: These results suggest that column extraction after hot water extraction may be a good strategy to enhance tannins and long-chain fatty acid amides, which might cause stimulation of hypocholesterolemic actions through downregulation of cholesterol biosynthesis gene expression and upregulation of LDL receptor gene expression.

• Nutrition Research and Practice
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• v.13 no.3
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• pp.196-204
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• 2019

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease triggered by epigenetic alterations, including lysine acetylation at histone or non-histone proteins, affecting the stability or transcription of lipogenic genes. Although various natural dietary compounds have anti-lipogenic effects, their effects on the acetylation status and lipid metabolism in the liver have not been thoroughly investigated. MATERIALS/METHODS: Following oleic-palmitic acid (OPA)-induced lipid accumulation in HepG2 cells, the acetylation status of histone and non-histone proteins, HAT activity, and mRNA expression of representative lipogenic genes, including $PPAR{\gamma}$, SREBP-1c, ACLY, and FASN, were evaluated. Furthermore, correlations between lipid accumulation and HAT activity for 22 representative natural food extracts (NExs) were evaluated. RESULTS: Non-histone protein acetylation increased following OPA treatment and the acetylation of histones H3K9, H4K8, and H4K16 was accelerated, accompanied by an increase in HAT activity. OPA-induced increases in the mRNA expression of lipogenic genes were down-regulated by C-646, a p300/CBP-specific inhibitor. Finally, we detected a positive correlation between HAT activity and lipid accumulation (Pearson's correlation coefficient = 0.604) using 22 NExs. CONCLUSIONS: Our results suggest that NExs have novel applications as nutraceutical agents with HAT inhibitor activity for the prevention and treatment of NAFLD.

• Journal of the Korean Data and Information Science Society
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• v.26 no.3
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• pp.677-685
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• 2015

Disease of human and economic traits of livestocks are affected a lot by gene combination effect rather than a single gene effect. In this study, we used SNPHarvester method that supplement existing method in order to investigate the interaction of these genes. The used genes are SREBPs (g.3270+10274 C>T, g.13544 T>C) and FABP4 (g.2634+1018 A>T, g.2988 A>G, g.3690 G>A, g.3710 G>C, g.3977-325 T>C, g.4221 A>G) that are closely related to the fatty acid composition affecting the meatiness of Korean cattle. The economic traits which are used are oleic acid (C18:1), monounsaturated fatty acid (MUFA), marbling score (MS). First, we have utilized the SNPHarvester method in order to find excellent gene combination, and then used the multifactor dimensionality reduction method in order to identify excellent genotype in gene combination.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.3
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• pp.288-295
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• 2014

Bojungchiseub-tang (BJCST) has been used in symptoms and signs of edema, dampness-phlegm, kidney failure, and so on. BJCST is also expected to have strong anti-obesity activities. However, little is known about the mechanisms of its inhibitory effects on adipocyte differentiation and adipogenesis. In the present study, we examined the effects and mechanism of BJCST on transcription factors and adipogenic genes of 3T3-L1 preadipocytes to understand its inhibitory effects on adipocyte differentiation and adipogenesis. Our results showed that BJCST significantly inhibited differentiation and adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner. To elucidate the mechanism of the effects of BJCST on lowering lipid content in 3T3-L1 adipocytes, we examined whether BJCST modulate the expressions of transcription factors to induce adipogenesis and adipogenic genes related to regulate accumulation of lipids. As a result, the expression of steroid regulatory element-binding protein (SREBP)1, cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins ${\alpha}$ ($C/EBP{\alpha}$), $C/EBP{\beta}$, $C/EBP{\delta}$, and peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) genes, which induce the adipose differentiation, liver X receptor $(LXR){\alpha}$ and fatty acid synthase (FAS) genes, which induce lipogenesis and adipose-specific aP2, Adipsin, lipoprotein lipase (LPL), CD36, TGF-${\beta}$, leptin and adiponectin genes, which compose fat formation were decreased. BJCST also reduced the expression of acyl CoA oxidase (ACO) and uncoupling protein (UCP) genes related to lipid oxidation. In conclusion, BJCST could regulate transcript factor related to induction of adipose differentiation and inhibited the accumulation of lipids and expression of adipogenic genes.

• Nutrition Research and Practice
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• v.15 no.5
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• pp.568-578
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• 2021

BACKGROUND/OBJECTIVES: Psidium guajava L. (guava) leaves have been shown to exhibit hypoglycemic and antidiabetic effects in rodents. This study investigated the effects of guava leaf extract on adipogenesis, glucose uptake, and lipolysis of adipocytes to examine whether the antidiabetic properties are mediated through direct effects on adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with 25, 50, 100 ㎍/mL of methanol extract from guava leaf extract (GLE) or 0.1% dimethyl sulfoxide as a control. Lipid accumulation was evaluated with Oil Red O Staining and AdipoRed assay. Immunoblotting was performed to measure the expression of adipogenic transcription factors, fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). Glucose uptake under basal or insulin-stimulated condition was measured using a glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose. Lipolysis from fully differentiated adipocytes was measured by free fatty acids release into the culture medium in the presence or absence of epinephrine. RESULTS: Oil Red O staining and AdipoRed assay have shown that GLE treatment reduced lipid accumulation during adipocyte differentiation. Mitotic clonal expansion, an early essential event for adipocyte differentiation, was inhibited by GLE treatment. GLE inhibited the expression of transcription factors involved in adipocyte differentiation, such as peroxisome proliferator-activated receptor 𝛄 (PPAR𝛄), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP-1c). FAS expression was also decreased while the phosphorylation of AMPK was increased by GLE treatment. In addition, GLE increased insulin-induced glucose uptake into adipocytes. In lipid-filled mature adipocytes, GLE enhanced epinephrine-induced lipolysis but reduced basal lipolysis dose-dependently. CONCLUSIONS: The results show that GLE inhibits adipogenesis and improves adipocyte function by reducing basal lipolysis and increasing insulin-stimulated glucose uptake in adipocytes, which can be partly associated with antidiabetic effects of guava leaves.

• KSBB Journal
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• v.24 no.6
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• pp.549-555
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• 2009

4 kinds of Regional Special Natural Products (RSNPs), such as Anthrisci radix, Psoraleae semen, Siegesbeckiae herba and Corni fructus were examined to verify for anti-obesity effect. $PPAR\gamma$ (peroxisome proliferator-activated receptor $\gamma$) from 3T3-L1 cell concerning adipocyte differentiation was suppressed by different concentraton of 4 RSNPs with western blot, when treated RSNPs' extract and MDI (IBMX, Dexamethasone, Insulin) at the same time. Also, SREBP-1 (Sterol regulatory element binding protein) controlling lipogenesis and $PPAR\gamma$ expression levels were reduced by these 4 RSNPs' extract, when these chemicals after differentiation of 3T3-L1 cell. And lipid droplets were reduced by 7.5%, 14.4%, 18.3% and 30% at different concentration of Anthrisci radix from Oil Red O staining. Also, it was reduced by 2%, 4.9%, 9.3% and 38% at different concentration of Psoraleae semen. For Siegesbeckiae herba, it was inhibited by 1.4%, 6.4%, 16.4% and 30.1%, respectively. And Corni fructus was also showed by 0.9%, 6.3%, 13.7% and 33% at same concentration of Siegesbeckiae herba. These 4 kinds of RSNPs were expected for a useful material for anti-obesity materials.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.4
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• pp.279-288
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• 2016

To observe the potential hepatoprotective effects of Gongjin-dan on the acute ethanol (EtOH)-induced liver damages in C57BL/6 mice with its possible action mechanisms. EtOH-mediated acute hepatic damages were induced by oral administration of EtOH total 3 doses. The changes on the body weight, liver weight, albumin, TG, AST, ALP, ALT, hepatic TG contents, hepatic antioxidant defense system, TNF-α, CYP 2E1 activity and mRNA expressions of hepatic lipogenic genes - SREBP-1c, SCD1, ACC1, FAS, PPARγ and DGAT2 or genes involved in fatty acid oxidation - PPARα, ACO and CPT1 were observed with final liver histopathological inspections after 15 days of continuous administration of silymarin 200 mg/kg, Gongjin-dan (GJD) 400, 200 and 100 mg/kg. The results were compared with silymarin 200 mg/kg treated mice. Marked decreases of body and liver weights, increases of serum AST, ALT, Albumin and TG levels, hepatic TG contents, TNF-α level, CYP 2E1 activity and mRNA expressions of hepatic lipogenic genes or decreases mRNA expressions of genes involved in fatty acid oxidation were observed with histopathological changes related hepatosteatosis increases of immunolabelled hepatocytes, as the results of a binge drinking of EtOH in the present study. Also destroys of hepatic antioxidant defense systems were demonstrated in EtOH control mice as compared with intact vehicle control mice, respectively. The results suggest that oral administration of 400, 200 and 100 mg/kg of GJD favorably protected the liver damages from acute mouse EtOH intoxications.

• The Journal of Pediatrics of Korean Medicine
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• v.24 no.3
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• pp.92-105
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• 2010

Objectives: The purpose of this study is to investigate the effects of Daecheongryong-tang (DCRT) on the adipogenesis in 3T3-L1 preadipocytes. Methods: 3T3-L1 preadipocytes were differentiated with adipogenic reagents by incubating for 2 days in the absence or presence of DCRT ranging 0.25 and 2%. The effect of DCRT on adipogenesis was examined by Oil red O staining, and the protein, RNA, and RT-PCR were measured. Results: Our results showed that DCRT decreased the TG content by ORO staining. To elucidate the mechanism of the effects of DCRT on lowering TG content in 3T3-L1 adipocytes, we examined the DCRT modulate expressions of transcription factors to induce adipogenesis and adipogenic genes which is related to the regulation of accumulation of lipids. As a result, the expression of SREBP1, C/$EBP{\beta}$, C/$EBP{\delta}$, C/$EBP{\alpha}$, and $PPAR{\gamma}$ genes, which induce the adipose differentiation and adipose-specific aP2, adipsin, LPL, CD36, TGF-${\beta}$ and adiponectin genes which regulates fat formations, were decreased. In addition, DCRT reduced the expression of iNOS and IL-6 in 3T3-L1 adipocytes, resulting in inflammation. Conclusions: DCRT could regulate transcript factor related to induction of adipose differentiation, inhibit the accumulation of lipids and expression of the adipogenic genes.

• Korean Journal of Medicinal Crop Science
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• v.24 no.4
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• pp.309-316
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• 2016

Background: This study represents the first report that the anti-obesity activity of ethanol extracts of Aronia melanocarpa can be enhanced through ultrasonification at a frequency of 120 kHz at $60^{\circ}C$ (UE). Methods and Results: The amounts of cyanidin-3-O-galactose (cya-gal), a major anthocyanin in A. melanocarpa were higher by up to 402.4 mg/100 g, as compared with 221.4 mg/100 g and 322.1 mg/100 g, for hot water at $100^{\circ}C$ and 70% ethanol at $80^{\circ}C$ respectively. This result should cause the higher antioxidant activities of the UE than extract of hot water and ethanol in DPPH free radical scavenging. It was confirmed that the high antioxidant activity of UE could play an important role in inhibiting the production of proteins related to adipocyte differentiation, such as peroxisome proliferator activated receptor-${\gamma}$ (PPAR-${\gamma}$) and sterol regulatory element binding protein 1 (SREBP1). Conclusions: Ultrasonification at a frequency of 120 kHz at $60^{\circ}C$ should result in better anti-obesity activity than that observed using other processes. It was also observed for the first time that the anti-obesity activity of A. melanocarpa was associated with its antioxidant activity, possibly due to the higher elution of intact cya-gal, owing to efficient low temperature ultrasonification extraction. These results could also be applied to improve other biological activities of medicinal herbs that contain many types of heat-labile bioactive substances.