• The Korea Journal of Herbology
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• v.37 no.5
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• pp.17-26
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• 2022

Objective : The aim of the present study is to examine hepatic lipid-lowering and anti-inflammatory effects of silymarin combined with Jakyakgamcho-tang on non-alcoholic fatty liver disease in a high fat diet-induced obese mice model. Methods : C57BL/6 mice were divided into four dietary groups: (1) Normal, (2) Control (60% high-fat diet), (3) Control + silymarin 50 mg/kg/day (Silymarin), (4) Control + Silymarin 50 mg/kg/day + Jakyakgamcho-tang 100 mg/kg/day (SPG). After 12 weeks administration, mice were sacrificed and lipids and inflammation-related biomarkers were analyzed liver and plasma. Results : Silymarin and SPG treatments significantly lowered body and liver weights compared to the Control. Serumlipids (triglyceride (TG), total cholesterol) and pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin 1𝛽, and IL-6) concentrations were significantly lowered in the Silymarin and SPG groups than the Control group. Silymarin and SPG treatments suppressed hepatic TG level and hepatic lipid droplets compared to the Control. Theses two treatments significantly increased hepatic kinase B1 and AMP-activated protein kinase protein levels, and significantly decreased hepatic key lipogenic enzymes (acetyl-CoA carboxylase, fatty acid synthase and stearyl coenzyme A desaturase 1) protein levels than the Control. SPG also significantly increased hepatic fatty acid oxidation-related protein (peroxisome proliferator-activated receptor alpha and uncoupling protein 2) levels than the Control. Conclusions: Silymarin and SPG suppressed hepatic lipid accumulation by regulating hepatic protein expression, and lowered blood pro-inflammatory cytokines concentrations though the synergic effect of silymarin and Jakyakgamchotang was not clear.

• 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.

• Herbal Formula Science
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• v.22 no.1
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• pp.113-122
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• 2014

Objectives : This study investigated the improvement effects of Pakistani (DF-a) and Chinese Ephedra herba-containing Gangjihwan (DF-b) 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-a, and DF-b groups given a high fat diet with atorvastatin (10 mg/kg), DF-a (80 mg/kg), and DF-b (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-a, DF-b, and atorvastatin groups compared with control. The extent of decreases was eminent in DF-a group. 2. Circulating concentrations of total cholesterol and LDL-cholesterol were significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control. The decreases were most effective in atorvastatin group. 3. Liver weights were decreased in DF-a, DF-b, and atorvastatin groups compared with control. In particular, liver weight was significantly reduced in DF-b group. 4. Hepatic lipid accumulation was significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control, and the magnitude of which was most effective in DF-b group. 5. Circulating ALT concentrations were decreased in DF-a, DF-b, and atorvastatin groups compared with control, but ALS levels were significantly reduced only in DF-b group. Conclusions : In conclusion, these results suggest that DF-a and DF-b decrease body weight gain, improve blood lipid metabolism, and reduce liver weight and hepatic lipid accumulation, contributing to the improvement of nonalcoholic fatty liver disease. In addition, these effects were similar between Pakistani and Chinese Ephedra herba-containing Gangjihwan.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.201-209
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• 2018

G protein-coupled receptor 119 (GPR119) is expressed in the pancreas and gastrointestinal tract, and its activation promotes insulin secretion in the beta cells of the pancreatic islets as well as the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells, consequently improving glucose-stimulated insulin secretion. Due to this dual mechanism of action, the development of small-molecule GPR119 agonists has received significant interest for the treatment of type 2 diabetes. We newly synthesized 1,2,4-triazolone derivatives of GPR119 agonists, which demonstrated excellent outcomes in a cyclic adenosine monophosphate (cAMP) assay. Among the synthesized derivatives, YH18968 showed cAMP=2.8 nM; in GLUTag cell, GLP-1secretion=2.3 fold; in the HIT-T15 cell, and insulin secretion=1.9 fold. Single oral administration of YH18968 improved glucose tolerance and combined treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor augmented the glucose lowering effect as well as the plasma level of active GLP-1 in normal mice. Single oral administration of YH18968 improved glucose tolerance in a diet induced obese mice model. This effect was maintained after repeated dosing for 4 weeks. The results indicate that YH18968 combined with a DPP-4 inhibitor may be an effective therapeutic candidate for the treatment of type 2 diabetes.

• Journal of Life Science
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• v.24 no.8
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• pp.827-836
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• 2014

There is a rising trend in obesity due to various factors, including changes in eating habits, lack of exercise, and genetic and psychological factors. Citrus peel has been reported to prevent obesity via antioxidative, antihypertensive, and LDL cholesterol-lowering effects. This study investigated the effects of citrus peel extract fermented with or without Aspergillus oryzae in a mouse model of diet-induced obesity. The animals were divided into four groups: a high-fat diet group (HFD), a normal fat diet (NFD) group, a citrus peel extract (CP) group, and a citrus peel extract fermented with A. oryzae (CPA) group. The citrus peel extract improved lipid metabolism and weight loss in the high-fat diet-induced obese mouse model. As expected, the body weight was higher in the HFD group compared with the NFD, CP, and CPA groups. However, the concentrations of total cholesterol (TG) and triglyceride (TC) in the serum and liver of the CP and CPA groups were lower than in the HFD group. There were no significant differences in the HDL cholesterol concentration among the groups. Taken together, our results suggest that extract of citrus peel biotransformed with A. oryzae had more antiobesity activity than citrus peel not transformed by A. oryzae through the fermentation of metabolites.

• Journal of Life Science
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• v.28 no.7
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• pp.786-794
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• 2018

Silkworm (Bombyx mori) pupae have been widely worked in wound dressing, hepatoprotective activity, antigenotoxicity, control of glucose level and anti-cancer activity. To investigate the anti-obesity activity of ethanol extract of silkworm pupae powder fermented with Cordyceps militaris (ESfC), the free glycerol release and cAMP concentration as well as fat accumulation were measured in the primary adipocytes of SD (Sprague Dawley) rats and high fat diet (HFD)-treated C57BL/6 mice treated with 12 weeks. Firstly, the presence of the cordycepin with lipid lowering effect was confirmed in ESfC using HPLC analysis. The level of free glycerol and cAMP concentration was significantly increased in the primary adipocytes treated with high dose of ESfC ($400{\mu}g/ml$) although these levels were consistently maintained in other dose ESfC treated groups. In HFD-induced obesity model, the increased fat weight and size of adipocytes in HFD+Vehicle treated group was recovered in HFD+ESfC treated group. Also, the liver weight and the number of lipid droplets were higher in HFD+Vehicle treated group than No treated group. But, this level was significantly decreased in HFD+ESfC treated group compared with HFD+Vehicle treated group. Furthermore, a similar recovery was detected on the phosphorylation of periliphin and HSL, and ATGL expression. Overall, the results of the present study provide some scientific evidences that ESfC can stimulate lipolysis in primary adipocytes and prevent fat accumulation in HFD-treated obesity model, and therefore have the potential for use as anti-obesity agents to treat obese patient.

• Nutrition Research and Practice
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• v.14 no.6
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• pp.580-592
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• 2020

BACKGROUND/OBJECTIVES: The present study aimed to further investigate the potential health beneficial effects of long-term seaweed supplementation on lipid metabolism and hepatic functions in DIO mice. MATERIALS/METHODS: Four brown seaweeds (Undaria pinnatifida [UP], Laminaria japonica [LJ], Sargassum fulvellum [SF], or Hizikia fusiforme [HF]) were added to a high fat diet (HFD) at a 5% ratio and supplemented to C57BL/6N mice for 16 weeks. Triglycerides (TGs) and total cholesterol (TC) in the liver, feces, and plasma were measured. Fecal bile acid (BA) levels in feces were monitored. Hepatic insulin signaling- and lipogenesis-related proteins were evaluated by Western blot analysis. RESULTS: Fasting blood glucose levels were significantly reduced in the LJ, SF, and HF groups compared to the HFD group by the end of 16-week feeding period. Plasma TG levels and hepatic lipid accumulation were significantly reduced in all 4 seaweed supplemented groups, whereas plasma TC levels were only suppressed in the UP and HF groups compared to the HFD group. Fecal BA levels were significantly elevated by UP, LJ, and SF supplementation compared to HFD feeding only. Lastly, regarding hepatic insulin signaling-related proteins, phosphorylation of 5'-AMP-activated protein kinase was significantly up-regulated by all 4 types of seaweed, whereas phosphorylation of protein kinase B was up-regulated only in the SF and HF groups. Lipogenesis-related proteins in the liver were effectively down-regulated by HF supplementation in DIO mice. CONCLUSIONS: Brown seaweed consumption showed hypotriglyceridemic effects in the prolonged DIO mouse model. Specifically, combinatory regulation of BA excretion and lipogenesis-related proteins in the liver by seaweed supplementation contributed to the reduction of plasma and hepatic TG levels, which inhibited hyperglycemia in DIO mice. Thus, the discrepant and species-specific functions of brown seaweeds provide novel insights for the selection of future targets for therapeutic agents.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.2
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• pp.193-202
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• 2010

In vitro activities of Codonopsis lanceolata (CL) 70% ethanol extract and its fractions (hexane, chloroform, ethyl acetate, butanol and water) were examined by total polyphenol content, reducing power, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), 2,2-diphenyl-$\beta$-picrylhydrazyl (DPPH), and oxygen radical absorbance capacity (ORAC) assays. The ethyl acetate fraction from CL ethanol extract (CLEA) showed the highest total polyphenol content (22.7 mg/g) among five fractions, and also exhibited an excellent reducing power (0.42~1.27 at $250\sim1,000\;{\mu}g/mL$). CLEA at $100\sim400\;{\mu}g/mL$ concentrations had 27.7~70.3% of ABTS radical scavenging activity and the highest DPPH radical scavenging activity (81.6% at $400\;{\mu}g/mL$). CLEA had dominantly higher $ORAC_{{ROO}{\cdot}}$activity compared to other fractions. CLEA and butanol fraction had significantly higher $ORAC_{{OH}{\cdot}}$ activities than 70% ethanol extract, hexane, chloroform and water fractions. The CLEA exhibited the highest antioxidant activity in CL 70% ethanol extract and its fractions. Thus, effect of CLEA treatment on antioxidant gene expression under the oxidative stress conditions by a high fat diet in animal model was studied by microarray and RT-PCR methods. The 31 antioxidant genes were expressed but the genes were not up-regulated at least a two-fold by CLEA treatment. We concluded that CLEA does not have an indirect antioxidant effect but a direct antioxidant effect by up-regulation of antioxidant genes in high fat diet-induced obese mice.