• Journal of Veterinary Clinics
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• v.27 no.4
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• pp.348-365
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• 2010

Artemisia capillaries THUNB is a perennial herb that belongs to the family compositae spp. and the most common plant among the various herbal folk remedies used in treatment of abdominal pain, hepatitis, chronic liver disease, jaundice and coughing in Korea. The object of this study is to observe the dosage-dependent anti-obestic effects of an aqueous extracts of dried aqueous extracts of stems of Artemisia capillaris Thunberg. [Artemisiae capillaris Herba, In-Jin in Korean, INJ] on 45%/Kcal high fat diet (HFD) supplied mice. 45%/Kcal rodent HFD are supplied to ICR mice from 1 week before initiation of INJ administration throughout the 12 weeks, and after the end of 12 weeks of 62.5, 125 and 250 mg/kg/day of INJ administration, the efficacy was divided into five categories 1) hypoglycemic, 2) hepato-protective, 3) nephroprotective, 4) hypolipemic, and 5) anti- obesity effects. The effects were compared to those of simvastatin (for hypolipemic activity), silymarin (for hepatoprotective and free radical scavenger effects) and metformin (for hypoglycemic and related anti-obesity effects). 7 animals per group (8 groups; total 56adapted mice on HFD were selected base on the body weight at 6 days after initiation of HFD supply) were used in this experiment. INJ and all three different reference drugs were directly suspended or dissolved in distilled water, and administered at a volume of 10 mL/kg, once a day for 84 days from 1 week after HFD supply. As results of 91 days of continuous HFD supply, mice showed marked obese states, hyperglycemia, hyperlipemia, liver damages and kidney damages. These mean the obesity, diabetes, diabetic hepatopathies, nephropathies and hyperlipemia were induced by HFD supply. After end of 84 days of continuous treatment of three different dosages of INJ, all diabetes related complications were inhibited; relatively favorable anti-obesity, hypolipemic, hepatoprotective, hypoglycemic and nephroprotective effects. These favorable effects showed relatively good dose-relations between all three different dosages of INJ treated, and INJ 250 mg/kg showed enough favorable effects on diabetes and related four complications tested as compared with one of each three different references. Otherwise, the efficacy of 62.5 and 125 mg/kg of INJ was somewhat slighter than those of all three reference drugs. Therefore, the suitable effective dosage of INJ is considered as 250 mg/kg/day in the present study. The overall anti-obesity effects of INJ 250 mg/kg-treated group was similar or more favorable than those of metformin 250 mg/kg-treated group, and INJ 250 mg/kg showed slighter hypoglycemic effects with silymarin 100 mg/kg and metformin 250 mg/kg, similar hypolipemic effects with simvastatin 10 mg/kg, and similar hepatoprotective effects with silymarin 100 mg/kg, and similar nephroprotective effects with that of silymarin 100 mg/kg and metformin 250 mg/kg, respectively. Obese, hyperglycemia, hyperlipemia, steatohepatitis and related nephropathies induced by HFD supply were dramatically inhibited by 84 days of continuous treatment of all three different dosages of INJ. It is, therefore expected that INJ extracts will be a favorable alternative agent for diet-related diabetes and complications.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.352-357
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• 2006

This experimental study was designed to investigate the effects of Acanthopanax sessiliflorus $S_{EEM}$ leaves, stems, roots (ACL, ACS, ACR) on the change of weight and the serum total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride, free fatty acid, total lipid and phospholipid level in obese mice induced Dy high fat diet. Experimental groups were as follows ; Normal group was fed with normal diet and administered with distilled water during 7 weeks, Control group was fed with high fat diet and administered with distilled water during 7 weeks, Sample A group was fed with high fat diet and administered with ACL of 500 mg/kg/mouse/day during 7 weeks, Sample B group was fed with high fat diet and administered with ACS of 500 mg/kg/mouse/day during 7 weeks, Sample C group was fed with high fat diet and administered with ACR of 500 mg/kg/mouse/day during 7 weeks. The results were as follows ; 1. Sample A group, Sample B group and Sample C group were significantly decreased the serum total lipid level in comparison with Control group. 2. Sample A group was decreased the body weight (4 weeks, 7 weeks), the serum total cholesterol level, the serum LDL-cholesterol level, the serum triglyceride level, the serum free fatty acid and phospholipid level but increased the serum HDL-cholesterol level in comparison with Control group. 3. Sample B group was increased the serum HDL-cholesterol level but decreased the body weight (4weeks), the serum total cholesterol level, the serum free fatty acid and triglyceride level in comparison with Control group. 4. Sample B group was significantly decreased the body weight (7 weeks), the serum LDL-cholesterol and phospholipid level in comparison with Control group. 5. Sample C group was increased the serum HDL-cholesterol level but decreased the body weight (4 weeks) and the serum free fatty acid level in comparison with Control group. 6. Sample C group was significantly decreased the body weight (7 weeks), the serum total cholesterol level, the serum LDL-cholesterol and triglyceride level in comparison with Control group. According to above results, I suggest ACR is able to be used for the obesity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.6
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• pp.667-673
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• 2009

The antihyperlipidemic and glycemic control effects of mycelia of Inonotus obliquus including protein-bound polysaccharides extract were investigated. In high fat diet-induced obese C57BL/6J mice, the mycelia of Inonotus obliquus including protein-bound polysaccharides extract showed significant decrease in epididymal fat tissue weight, blood triglyceride and VLDL level, triglyceride and total cholesterol level in liver, serum insulin and HOMA-IR level and AUC. Oral glucose tolerance test glucose level reduction were 4.9% (M150L; ${\beta}$-glucan 1.303 mg/kg bw), 9.5% (M150; ${\beta}$-glucan 2.606 mg/kg bw) after 180 min of glucose loading compared to H-C group. Besides, the mycelia of Inonotus obliquus including protein-bound polysaccharides extract treatment significantly increased glycogen contents in liver and adiponectin level in high fat diet-induced obese mice. In conclusion, the results showed that the mycelia of Inonotus obliquus including protein-bound polysaccharides extract possesses significant antihyperlipidemic and glycemic control effects in C57BL/6J mice.

• Korean Journal of Pharmacognosy
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• v.45 no.3
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• pp.194-199
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• 2014

The roots of Paeonia lactiflora (PL) has been traditionally used as analgesic, spasmolytic and tonic in Korea, China, and Japan. As part of a search for herbal medicine to treat diabetes and obesity, we confirmed hypoglycemic effect of PL through high fat diet-induced obese and diabetic mice experiments in vivo. Treatment of ethanolic extract from PL led to a significant decrease in glucose level, which is comparable to that of an antidiabetic drug metformin. In addition, PL selectively stimulates the transcriptional activities of both peroxisome proliferator-activated receptor $(PPAR){\alpha}$ and ${\gamma}$, and inhibits enzymatic activity of protein tyrosine phosphatase 1B (PTP1B), which are predicted to be therapeutic target in treatment of type2 diabetes and obesity. Especially, the n-hexane fraction (Hx) from PL ethanol extract showed more potent activities on $PPAR{\alpha}$ and than others and exihibited moderate inhibitory activity against PTP1B.

• Nutrition Research and Practice
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• v.17 no.1
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• pp.164-173
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• 2023

BACKGROUND/OBJECTIVES: Hyperglycemia is a major cause of diabetes and diabetesrelated diseases. Sodium butyrate (NaB) is a short-chain fatty acid derivative that produces dietary fiber by anaerobic bacterial fermentation in the large intestine and occurs in foods, such as Parmesan cheese and butter. Butyrate has been shown to prevent obesity, improve insulin sensitivity, and ameliorate dyslipidemia in diet-induced obese mice. Therefore, this study examined the effects and mechanism of NaB on the secretion of inflammatory cytokines induced by high glucose (HG) in THP-1 cells. MATERIALS/METHODS: THP-1 cells were used as an in vitro model for HG-induced inflammation. The cells were cultured under normal glycemic or hyperglycemic conditions with or without NaB (0-25 μM). Western blotting and quantitative polymerase chain reaction were used to evaluate the protein and mRNA levels of nuclear factor-κB (NF-κB), interleukin-6, tumor necrosis factor-α, acetylated p65, acetyl CREB-binding protein/p300 (CBP/p300), and p300 using THP-1 cells. Histone acetyltransferase (HAT), histone deacetylase (HDAC), and pro-inflammatory cytokine secretion activity were analyzed using an enzyme-linked immunosorbent assay. RESULTS: HG significantly upregulated histone acetylation, acetylation levels of p300, NF-κB activation, and inflammatory cytokine release in THP-1 cells. Conversely, the NaB treatment reduced cytokine release and NF-κB activation in HG-treated cells. It also significantly reduced p65 acetylation, CBP/p300 HAT activity, and CBP/p300 gene expression. In addition, NaB decreased the interaction of p300 in acetylated NF-κB and TNF-α. CONCLUSIONS: These results suggest that NaB suppresses HG-induced inflammatory cytokine production through HAT/HDAC regulation in monocytes. NaB has the potential for preventing and treating diabetes and its related complications.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.642-648
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• 2008

The aim of this study is to investigate Chegameuiin-tang water extracts (CETE) have potent anti-obesity activities in a high fat diet-induced obesity mouse model. In this study, we designed three group (normal diet group, high fat diet group, high fat diet plus CETE group for 13-week oral administration). Increases in body weight and fat storage were inhibited by 13-week oral administration of CETE at a 500 mg/kg concentration in this animal model, while the amount of food intake was not affected. Results from blood lipid analysis showed that the levels of triglyceride, total cholesterol and LDL-cholesterol were significantly lowered by CETE administration, also HDL-cholesterol was increased more than high fat diet-induced obese mouse. To understand the underlying mechanism at the molecular level, the effects of CETE were examined on the expression of the genes involved in lipogenesis and lipolysis by real-time PCR. In epididymal fat of CETE-treated mice, the mRNA level of lipogenic genes such as sterol regulatory element binding protein 1 and fatty acid synthase were decreased, which was well correlated with the reduction of the epididymal fat weight. Also, CETE administration inhibited decreases of the hormone-sensitve lipase and lipoprotein lipase mRNA expressions, which are genes related with lipolysis. These results suggest that Chegameuiin-tang may have great potential as a novel anti-obesity agent.

• Korean Journal of Food Science and Technology
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• v.42 no.5
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• pp.586-592
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• 2010

This study investigated the effects of Stevia rebaudian bertoni leaf extract on lipid profiles in C57BL/6J mice, as compared to stevioside. Fourty mice were divided into four groups: NC (normal diet and DW), HC (high fat diet and DW), HLSV (high fat diet and stevia leaf extract, 1 mL/kg/day), and HSS (high fat diet and stevioside, 1 mL/kg/day). Serum triglyceride concentrations were significantly lower in the HLSV and HSS groups than in the HC group. Epididymal fat pad weights were significantly lower in the HLSV and HSS groups than in the HC group. We also evaluated the serum and liver carnitine levels (NEC, AIAC, ASAC, TCNE) of all the groups. These results were supported by the mRNA expression of enzymes related to lipid metabolism (ACC, PPAR${\alpha}$, ACS, CPT-I) assessed by RT-PCR. Overall, the results show the antiobesity effects of stevia leaf extract as compared to stevioside in high fat diet induced obese mice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.9
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• pp.1235-1243
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• 2011

In this study, we investigated the antioxidative activity (scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and superoxide anion radical) and anti-obesity effects of black bean chungkugjang extract (BBCE). DPPH free radical-scavenging activity and superoxide anion radical-scavenging activity ($SC_{50}$ value) of BBCE were $162.7{\pm}2.8$ ppm, and $205.62{\pm}3.6$ ppm, respectively. The anti-obesity effects of BBCE were investigated by measuring Oil Red O staining in 3T3-L1 adipocytes. BBCE reduced the content of Oil Red O dye in 3T3-L1 adipocytes. We also examined the effects of BBCE on adiposity, serum lipid, and leptin levels in obese mice fed a high-fat diet. Mice were fed the BBCE experimental diets for 7 weeks, after which they were sacrificed. ICR male mice were randomly divided into three groups, one normal diet group (ND group) and two high fat diet groups with or without BBCE supplementation (HFD group and HFD-BBCE group). The results showed that weight gain and the food efficiency ratio significantly decreased upon addition of BBCE compared to those of the HFD group. Further, white adipose tissue weights of epididymal, mesenteric, and retroperitoneal areas in the HFD-BBCE group were reduced to 34.8%, 7.1%, and 40.6%, respectively, compared to that of the HFD group. The serum levels of triglycerides, total cholesterol, LDL-cholesterol, and leptin in the HFD-BBCE group were significantly lower than those of the HFD group. Based on these results, it can be concluded that BBCE may have beneficial effects on reducing fat mass and serum lipid content.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.464-472
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• 2009

The aim of this study was to investigate the effects of Cheonghyul-san on the generation of peroxynitrite ($ONOO^-$), nitric oxide (NO) and superoxide anion radical ( ${\cdot}\;O_2^-$), and on the expression of NF-${\kappa}$B-dependent proinflammatory proteins in ob/ob mice. Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57BL/6J black mice) and control obese (ob/ob mice) groups have received the standard chow. The experimental groups were fed with a diet of chow supplemented with 7.5, 15 and 30 mg Cheonghyul-san per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein-2 (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blot was performed using anti-IKK-${\alpha}$, anti-phospho I${\kappa}$B-${\alpha}$, anti-NF-${\kappa}$B (p50, p65), anti-COX-2, anti-iNOS, anti-VCAM-1 antibodies, respectively. Cheonghyul-san prevented $H_2O_2$-induced cell death. Cheonghyul-san inhibited the generation of $ONOO^-$, NO and ${\cdot}\;O_2^-$ in the $H_2O_2$-treated LLC-$PK_1$ cells. The generation of $ONOO^-$, NO and ${\cdot}\;O_2^-$ were inhibited in the Cheonghyul-san-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Cheonghyul-san-administered groups. Cheonghyul-san inhibited the protein expression levels of phospho-I${\kappa}$B-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}$B (p50, p65), COX-2, iNOS and VCAM-1 genes. These results suggest that Cheonghyul-san is an effective scavenger of $ONOO^-$, ${\cdot}\;O_2^-$ and NO, and has an inhibitory effect on the expression of NF-${\kappa}$B-dependent inflammatory genes in ob/ob mice. Therefore, Cheonghyul-san might be used as a potential therapeutic drug against the diabetes- and obesity-related proinflammatory diseases.

• 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.