• Journal of Ginseng Research
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• v.47 no.3
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• pp.376-384
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• 2023

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.4
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• pp.1-8
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• 2022

Objectives This study is to investigate the effects and mechanisms of Gastrodia elata extract (GEE) on the high-fat diet-induced obesity model. Methods C57BL/6 mice were randomly assigned into 5 groups (n=10). Control group was fed normal diet (ND). Obesity group was fed 60% high fat diet (HFD). The other three groups were fed HFD with 100, 200, 500 mg/kg GEE. After five weeks, body weight, liver and epididymal fat weight, triglyceride concentration in liver and serum, sterol regulatory element-binding protein-1 (SREBP-1), acetyl-CoA carboxylase (ACC), fatty acid synthase, peroxisome proliferator-activated receptor 𝛾 (PPAR-𝛾), CCAAT/enhancer binding protein 𝛼 (C/EBP-𝛼) expression level, insulin concentration in serum were measured. Results The GEE (100, 200, and 500 mg/kg)-treated animals exhibited substantial decreases in body mass, liver weight and epididymal white adipose tissue collate to the HFD-fed group. GEE treatment also reduced hepatic and serum triglyceride level. Furthermore, GEE treatment significantly inhibited adipogenesis in the GEE group by reducing the protein expression of SREBP-1, ACC and the messenger RNA expression of PPAR𝛾, C/EBP-𝛼, which are adipocyte differentiation-related genes. Conclusions These research outcomes recommend that GEE is possibly valuable for the prevention of HFD-induced obesity via modification of various pathways related with adipogenesis and adipocyte differentiation.

• The Korea Journal of Herbology
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• v.34 no.6
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• pp.79-89
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• 2019

Objective : This study investigated the anti-diabetic effects of DM1, a herbal mixture with Atractylodis Rhizoma, Anemarrhenae Rhizoma, and Cinnamomi Cortex in high fat diet (HFD)-induced diabetic mice and the mechanism in C2C12 mouse skeletal muscle cells. Methods : The C57B/6 mice were fed high fat for 12 weeks, and then administrated DM1 extract (500 mg/kg, p.o.) for 4 weeks. The changes of body weight, calorie and water intakes, fasting blood glucose levels and the serum levels of glucose, insulin, triglyceride, HDL-cholesterol, AST and ALT were measured in mice. The histological changes of liver and pancreas tissues were also observed by H&E stain. C2C12 myoblasts were differentiated into myotubes and then treated with DM1 extract (0.5, 1, and 2 mg/㎖) for 24 hr. The expression of myosin heavy chain (MHC), PGC1α, Sirt1 and NRF1, and the AMPK phosphorylation were determined in the myotubes by western blot, respectively. Results : The DM1 extract administration significantly decreased the calorie and water intakes, glucose, triglyceride, AST and ALT levels and increased insulin and HDL-cholesterol in HFD-induced diabetic mice. DM1 extract inhibited lipid accumulation in liver tissue and improved glucose tolerance. In C2C12 myotubes, DM1 treatment increased the expression of MHC, PGC1α, Sirt-1, NRF-1 and the AMPK phosphorylation. Conclusion : In our results indicate that DM1 can improve diabetic symptoms by decreasing the obesity, glucose tolerance and fatty liver in HFD-induced diabetic mice, and responsible mechanism is might be related with energy enhancement.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.288-294
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• 2018

A few clues about correlation between endoplasmic reticulum (ER) stress and mulberry (Morus alba) leaves were investigated in only the experimental autoimmune myocarditis and streptozotocin-induced diabetes. To investigate whether a novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) could suppress ER in fatty liver, alterations in the key parameters for ER stress response were measured in high fat diet (HFD)-induced obese C57L/6 mice treated with EMfC for 12 weeks. The area of adipocytes in the liver section were significantly decreased in the HFD+EMfC treated group as compared to the HFD+Vehicle treated group, while their level was higher in HFD+Vehicle treated group than No treated group. The level of the eukaryotic initiation factor 2 alpha ($eIF2{\alpha}$) and inositol-requiring enzyme 1 beta ($IRE1{\alpha}$) phosphorylation and CCAAT-enhancer-binding protein homologous protein (CHOP) expression were remarkably enhanced in the HFD+Vehicle treated group. However, their levels were restored in the HFD+EMfC treated group, although some differences were detected in the decrease rate. Similar recovery was observed on the ER stress-induced apoptosis. The level of Caspase-3, Bcl-2 and Bax were decreased in the HFD+EMfC and HFD+orlistat (OT) treated group compared to the HFD+Vehicle treated group. The results of the present study therefore provide first evidence that EMfC with the anti-obesity effects can be suppressed ER stress and ER stress-induced apoptosis in the hepatic steatosis of HFD-induced obesity model.

• Journal of Acupuncture Research
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• v.24 no.1
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• pp.165-177
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• 2007

Objectives : This study anus to investigate the effects of Rosa Rugosae Radix (RU) herbal acupuncture on the metabolic syndrome in high-fat diet-fed mice. Methods : The experimental groups were fed with high-fat diet (HFD) for 8 weeks to induce metabolic syndrome. During the induction of metabolic syndrome, RU herbal acupuncture at a dosage of 50 mg/kg was carried out on the point of Sinsu(BL23) every day to measure the body weight, feed efficiency, blood glucose levels, insulin resistance index, lipid levels, blood pressure, and weight of liver and adipose tissues (brown adipose tissue from interscapular fat and white adipose tissue from epididymal fat). And after five weeks' induction of metabolic syndrome, RU herbal acupuncture was also performed for 6 weeks to measure the body weight and blood glucose levels. Results: 1. RU herbal acupuncture inhibited increasing body weight and blood glucose levels, with improved insulin resistance. 2. RU herbal acupuncture inhibited increasing levels of total cholesterol, LDL-cholesterol and free fatty acid, while increased HDL-cholesterol levels. 3. RU herbal acupuncture activated anti-hypertensive action. 4. RU herbal acupuncture inhibited increasing weight of white adipose tissues, but not in brown adipose tissues and liver. 5. RU herbal acupuncture lowered blood glucose levels and inhibited increasing body weight in metabolic syndrome-induced ICR mice. Conclusion : Rosa Rugosae Radix (RU) herbal acupuncture showed effectiveeness in prevention and management of metabolic syndrome in clinical application.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.238-246
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• 2020

Background: Dietary fat has been suggested to be the cause of various health issues. Obesity, hypertension, cardiovascular disease, diabetes, dyslipidemia, and kidney disease are known to be associated with a high-fat diet (HFD). Obesity and associated conditions, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD), are currently a worldwide health problem. Few prospective pharmaceutical therapies that directly target NAFLD are available at present. A Traditional Chinese Medicine, ginseng-plus-Bai-Hu-Tang (GBHT), is widely used by diabetic patients to control glucose level or thirst. However, whether it has therapeutic effects on fat-induced hepatic steatosis and metabolic syndrome remains unclear. Methods: This study was conducted to examine the therapeutic effect of GBHT on fat-induced obesity, hepatic steatosis, and insulin resistance in mice. Results: GBHT protected mice against HFD-induced body weight gain, hyperlipidemia, and hyperglycemia compared with mice that were not treated. GBHT inhibited the expansion of adipose tissue and adipocyte hypertrophy. No ectopic fat deposition was found in the livers of HFD mice treated with GBHT. In addition, glucose intolerance and insulin sensitivity in HFD mice was also improved by GBHT. Conclusion: GBHT prevents changes in lipid and carbohydrate metabolism in a HFD mouse model. Our findings provide evidence for the traditional use of GBHT as therapy for the management of metabolic syndrome.

• The Korea Journal of Herbology
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• v.27 no.4
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• pp.53-58
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• 2012

Objective : Obesity is often defined as a condition associated with accumulations of excessive body fats which resulting from disorder of energy balance in term of energy intake and energy expenditure. Methods : The effects of natural mixture (T) for inhibition of lipid metabolism on the liver, epididymal fat pads and pancreatic zymogen granules of high fat diet (HFD) supplied rats were observed by histopathology and histomorphometry. Results : As results of HFD supply, severe steatohepatitis such as increases of mean diameters of hepatocytes and the percentages regions of fatty changes was detected. In addition, hypertrophy of adipocytes (increase of mean diameters of epididymal fat pads) was also detected with dramatic decreases of pancreatic zymogen granules at histopathological and histomorphometrical observations. However, theses steatohepatitis and hypertrophy of adipocytes induced by HFD supply were inhibited by treatment of 5 % and 10 % T (T5, T10), respectively. Well corresponded as the results of adipocyte hypertrophy and steatohepatitis, the decreases of pancreatic zymogen granules were also dose-dependently inhibited by T treatment as compared with HFD control, respectively. Conclusion : In conclusion, based on the results, it is considered that test materials, T5 and T10, will be showed hepatoprotective and anti-obese effects, may be directly and/or indirectly mediated by pancreatic zymogen granules because they dose-dependently inhibited steatohepatitis, hypertrophy of adipocytes and decreases of pancreatic zymogen granules induced by HFD supply, respectively.

• Preventive Nutrition and Food Science
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• v.3 no.4
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• pp.344-350
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• 1998

Lipid lowering properties from three plant water extracts, Rosa rugosa, Crataegus pinnatifida and Polygonum cuspidatum, were tested by supplementing a 1% high-cholesterol diet with them in rats. Plasma triglyceride levels in Rosa fugosa, Crataegus pinnatifida and Polygonum cuspidatum groups were significantly lower compared to that of the control. by 29% , 24% and 47% respectively. hepatic trigylceride levels in Rosa rugosa and Crataegus pinnatifida groups were significantly lower compared to the control by 11% and 15% respectively. Hepatic HMG-CoA reductase activity in Rosa rugosa group was significantly greater compared to the control by 406%. Hepatic ACAT activity was significantly lower in Polygonum cuspidatum group compared to the control by 28%. by multiple regression results, only plasma cholesterol was associated significantly (p<0.05) with liver HMG-CoA reductase activity. Plasma cholesterol explained 12% of thevariance of the liver HMG-CoA redctase activity. In conclusion, we have showen that hot water extracts from Rosa rugosa, Crataegus pinnatifida and Polygonum cuspidatum lowered plasma triglycerides in rats fed on a high-cholesterol diet. Data suggests that these extracts could potentially prevent or treat hypertriglyceridemia induced by a high fat diet and fatty liver.

• Korean Journal of Acupuncture
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• v.22 no.3
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• pp.1-15
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• 2005

Objectives: This research was performed to investigate the effect of invasive low level laser acupuncture therapy(LLLAT) at Yolgyol(LU7), Yogu(LR5) and Yolgyol+Yogu(LU7+LR5) on weight gain, food intake, food efficiency, lipid metabolism, atherogenic index, HTR(HDL-cholesterol to total cholesterol ratio) and liver function in hyperlipidemia rats. Methods : Experimental groups were divided into high fat diet group(Control group), high fat diet and LLLAT at LU7(LU7 group), high fat diet and LLLAT at LR5(LR5 group), LLLAT at LU7 and LR5(LU7+LR5 group). Animals was treated by the LLLAT at 30mW-5min once a 2day during 5 weeks. Results: Body weight was decreased significantly in LU7+LR5 group when compared with control group. Food intake was increased significantly in LU7, LR5, LU7+LR5 group when compared with control group. Food efficiency was decreased significantly in LU7, LR5, LU7+LR5 group when compared with control group. In the lipid metabolism, total cholesterol and HDL-cholesterol was decreased significantly in LU7+LR5 group, LDL-cholesterol and phospholipids were decreased significantly in LR5, LU7+LR5 group, triglyceride and fee fatty acid were decreased significantly in LU7 group when compared with control group. Atherogenic index was decreased significantly in LU7, LR5, LU7+LR5 group when compared with control group. HTR was increased significantly in LU7 group when compared with conool group. In the liver function, the significance was not showed in AST and ALT, ALP was decreased significantly in LU7+LR5 group when compared with control group. Conclusions: LLLAT at LU7 and LR5 maybe can manage hyperlipidemia by controlling body weight, food intake, food efficiency ratio and lipid metabolism.

• Herbal Formula Science
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• v.22 no.1
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• pp.167-176
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• 2014

Objectives : This study investigated the improvement effects of Gangjihwan (DF) and combination of Gangjihwan and Gamisochehwan (GSH) on nonalcoholic fatty liver disease in a high fat diet-induced obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into five groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and atorvastatin, DF, and DF+GSH groups given a high fat diet with atorvastatin (10 mg/kg), DF (40 mg/kg), and DF+GSH (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, blood lipid markers, ALT concentrations, liver weight and histology were examined. Results : 1. Body weight gain was significantly decreased in DF, DF+GSH and atorvastatin groups compared with control. The extent of decreases was eminent in DF+GSH group. 2. Circulating concentrations of total cholesterol, HDL-cholesterol and LDL-cholesterol were decreased in DF, DF+GSH and atorvastatin groups compared with control. The decreases were significant in DF+GSH and atorvastatin groups. 3. Liver weights were decreased in DF, DF+GSH and atorvastatin groups compared with control. In particular, liver weight was significantly reduced only in DF+GSH group. 4. Hepatic lipid accumulation was significantly decreased in DF, DF+GSH and atorvastatin groups compared with control, and the magnitude of which was more effective in DF+GSH group than in DF-only group. 5. Circulating ALT concentrations were decreased in DF, DF+GSH and atorvastatin compared with control, but ALS levels were significantly reduced only in DF+GSH group. Conclusions : In conclusion, these results suggest that DF decreases body weight gain, improves blood lipid metabolism, and reduces liver weight and hepatic lipid accumulation, contributing to the improvement of nonalcoholic fatty liver disease. In addition, these effects were more effective in DF+GSH combination group than in DF-only group.