• The Korean journal of internal medicine
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• v.33 no.6
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• pp.1210-1223
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• 2018

Background/Aims: The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. Methods: High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. Results: HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. Conclusions: These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.

• Journal of Life Science
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• v.29 no.4
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• pp.470-477
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• 2019

White jelly fungus (Tremella fuciformis Berk) is effective for hypertension, diabetes, obesity, lung disease, beauty, and has been known as an elixir of life in ancient Chinese dynasty. In this study, we investigated the anti-obesity and diabetic effects of the fermented white jelly fungus extract by the bioconversion process. We fed an obesity-inducing mouse with 5% non-fermented Tremella fuciformis (TF), 2.5% fermented Tremella fuciformis (FTF), and 5% FTF containing High Fats Diet (HFD) and HFD for 8 weeks, respectively. The oral glucose tolerance test (OGTT) was performed analysis after 7 weeks of feeding and the dietary intake, food efficiency ratio, body weight, liver, epididymal fat weight, and serum insulin level were measured after 8 weeks of feeding. Also, HOMA-IR was analyzed. The concentrations of serum total cholesterol, triglycerides test was analyzed. The FTF compare with 5% TF and HFD confirmed that 5% FTF reduced body weight, tissue weight, triglycerides concentration, HOMA-IR, respectively. As a result, we confirmed that the fermented white jelly fungus has the anti-obesity effect. Finally, this study can be used a basic data for obesity treatment using fermented white jelly fungus.

• Journal of Ginseng Research
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• v.43 no.1
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• pp.116-124
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• 2019

Background: Ginsenosides are known as the principal pharmacological active constituents in Panax medicinal plants such as Asian ginseng, American ginseng, and Notoginseng. Some ginsenosides, especially the 20(R) isomers, are found in trace amounts in natural sources and are difficult to chemically synthesize. The present study provides an approach to produce such trace ginsenosides applying biotransformation through Escherichia coli modified with relevant genes. Methods: Seven uridine diphosphate glycosyltransferase (UGT) genes originating from Panax notoginseng, Medicago sativa, and Bacillus subtilis were synthesized or cloned and constructed into pETM6, an ePathBrick vector, which were then introduced into E. coli BL21star (DE3) separately. 20(R)-Protopanaxadiol (PPD), 20(R)-protopanaxatriol (PPT), and 20(R)-type ginsenosides were used as substrates for biotransformation with recombinant E. coli modified with those UGT genes. Results: E. coli engineered with $GT95^{syn}$ selectively transfers a glucose moiety to the C20 hydroxyl of 20(R)-PPD and 20(R)-PPT to produce 20(R)-CK and 20(R)-F1, respectively. GTK1- and GTC1-modified E. coli glycosylated the C3-OH of 20(R)-PPD to form 20(R)-Rh2. Moreover, E. coli containing $p2GT95^{syn}K1$, a recreated two-step glycosylation pathway via the ePathBrich, implemented the successive glycosylation at C20-OH and C3-OH of 20(R)-PPD and yielded 20(R)-F2 in the biotransformation broth. Conclusion: This study demonstrates that rare 20(R)-ginsenosides can be produced through E. coli engineered with UTG genes.

• 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 Oriental Neuropsychiatry
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• v.30 no.3
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• pp.209-220
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• 2019

Objectives: As a general emotion, everyone can temporarily experience depression, but depressive disorder is a disease that excessively affects daily life. Among the various causes of depression, the deficiency of monoamine-based neurotransmitters such as serotonin and epinephrine are considered significant. Thus, antidepressants that target monoamines are used frequently. However, side effects such as nausea, vomiting, insomnia, anxiety, and sexual dysfunction are observed. Thus, it is necessary to develop a new therapeutic agent with fewer side effects. In this study, we investigated the antidepressant effect of JG02, used to treat depression by normalizing the flow of qi (氣) in Korean medicine. Methods: C57BL/6 mice were selected and randomly divided into six groups: normal, control, amitriptyline, and JG02 (50, 125, 250 mg/kg), respectively. Except for normal, depression was induced by applying restraint stress at the same time for six hours daily for 14 consecutive days. Saline, amitriptyline or JG02 samples were orally administered two hours before applying the stress. After that, a forced swimming test and an open field test were performed. Additionally, serum corticosterone, serotonin mRNA, BDNF mRNA, and protein in the hippocampal region were measured and compared. Results: JG02 decreased immobility time rate in the FST and increased the zone transition number and travel distance in the OFT. Also, JG02 inhibited the release of serum corticosterone, and increased serotonin, BDNF gene expression, and BDNF protein in the hippocampus. Conclusions: In this study, JG02 showed significant antidepressant effects on the chronic restraint stress mice model. When further research is performed based on JG02, the development of a new antidepressant is considered highly possible.

• Journal of the Korean Applied Science and Technology
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• v.36 no.3
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• pp.804-812
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• 2019

The purpose of this study was to investigate the effects of different types of exercise training on neurodegeneration and cognitive function in mice with impaired glucose tolerance (IGT). Thirty-six male C57BL/6 mice were randomly assigned to the control (CO, n = 9) and impaired glucose tolerance (IGT, n = 27) groups. The IGT group consumed 45% high fat diet for 4 weeks and received 40 mg/kg of streptozotocin twice in the lower abdomen to induce IGT. After the IGT induction period, the IGT group was subdivided into IGT + sedentary (IGT, n = 9), IGT + endurance exercise (IGTE, n = 9), and IGT + resistance exercise (IGTR, n = 9). The IGTE and IGTR groups performed treadmill and ladder climbing exercises 5 times per week for 8 weeks, respectively. Fasting glucose and glycated hemoglobin (HbA1c) levels were significantly higher in IGT group than in CO, IGTE, and IGTR groups (p < 0.05). HOMA-IR was significantly higher in IGT group than CO group (p < 0.05). Hippocampal catalase (CAT) was significantly lower in IGT group than in CO group (p < 0.05), while beta-amyloid ($A{\beta}$) was significantly higher in IGT group than in CO group (p < 0.05). Hippocampal tau was significantly higher in IGT group than in CO, IGTE, and IGTR groups (p < 0.05). The Y-maze test performance for cognitive function was significantly lower in IGT group than in CO, IGTE, and IGTR groups (p <0.05). These results suggest that IGT induces neurodegeneration and negatively affects cognitive function, while regular exercise may be effective in alleviating neurodegeneration and cognitive decline regardless of exercise type.

• Toxicological Research
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• v.35 no.4
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• pp.361-369
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• 2019

1,2-Dichloropropane (1,2-DCP) has been used as an industrial solvent and a chemical intermediate, as well as in soil fumigants. Human exposure may occur during its production and industrial use. The target organs of 1,2-DCP are the eyes, respiratory system, liver, kidneys, central nervous system, and skin. Repeated or prolonged contact may cause skin sensitization. In this study, 1,2-DCP was dissolved in corn oil at 0, 2.73, 5.75, and 8.75 mL/kg. The skin of mice treated with 1,2-DCP was investigated using western blotting, hematoxylin and eosin staining, and immunohistochemistry. 1,2-DCP was applied to the dorsal skin and both ears of C57BL/6J mice. The thickness of ears and the epidermis increased significantly following treatment, and the appearance of blood vessels was observed in the dorsal skin. Additionally, the expression of vascular endothelial growth factor, which is tightly associated with neovascularization, increased significantly. The levels of protein kinase-B (PKB), phosphorylated PKB, mammalian target of rapamycin (mTOR), and phosphorylated mTOR, all of which are key components of the phosphoinositide 3-kinase/PKB/mTOR signaling pathway, were also enhanced. Taken together, 1,2-DCP induced angiogenesis in dermatitis through the PI3K/PKB/mTOR pathway in the skin.

• Journal of Life Science
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• v.29 no.5
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• pp.607-613
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• 2019

The purpose of this study was to investigate the effects of either chrysin or exercise on the inflammasome and thermogenic markers in the livers of high-fat fed mice. C57BL/6 mice were randomly assigned to four groups: normal diet control (NC; n=5), high-fat diet control (HC; n=5), high-fat diet with chrysin (Hch; n=5), and high-fat diet with moderate exercise (HME; n=5). The mice were fed a high-fat diet (60% of calories from fat) or normal diet (18% of calories from fat). Chrysin was supplemented orally as 50mg/kg/day dissolved in a 0.1ml solution of dimethyl sulfoxide. The exercised mice ran on a treadmill at 12-20 m/min for 30-60 min/day, 5 times/week, for 16 weeks. After the intervention, the epididymal fat and liver weights were significantly decreased in the HME group compared with HC and Hch groups. The adipocyte size was effectively decreased in the Hch and HME groups compared with the HC group. The inflammasome markers NLRP3, $IL-1{\beta}$, and caspase1 were significantly decreased in the Hch and HME groups compared with the HC group. The thermogenic markers $PGC-1{\alpha}$ and BMP7 were significantly lower in the HC than in the NC group. However, the HME group showed an increase in the thermogenic markers. In conclusion, chrysin and moderate exercise have positive effects on obese metabolic complications induced by high-fat diets by reducing inflammasome genes. However, chrysin supplementation had no effect on thermogenic gene expression. Moderate exercise would therefore seem to be more effective in controlling obesity-induced metabolic deregulation.

• Korean Journal of Medicinal Crop Science
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• v.28 no.6
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• pp.421-427
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• 2020

Morus alba, Anti-obesity, C57BL/6 Mice, Expression, Flavonoid, Gene, Mulberry Background: The seed oil of Zanthoxylum schinifolium S. et Z. (sancho) is a traditional cooking oil that has long been sold at a very high price however, depending on the method of extraction and storage, this oil becomes rancid occurs very quickly. Therefore, this study aimed to find a material that prevents rancidity and improves the storage properties of sancho oil. Methods and Results: Sancho oil was extracted using an extraction press, and acid values were compared with commercially available vegetable oils, sancho oil had a higher acid value than other vegetable oils. A very high acid value was observed in sancho oil stored for 6 months, regardless of temperature, requiring an effective storage method. The high acid value and the decrease in turbidity of sancho oil are dependent on the days of sedimentation. Treatment with sodium bicarbonate by concentration resulted in minimal changes in acid value over time. However, minor differences were detected among the treatment concentrations. Ascorbic acid was added to maximize the effect of sodium bicarbonate, and it was observed that ascorbic acid did not improve the antioxidant effect. The sodium bicarbonate and ascorbic acid mixture resulted in minimal change in acid value at temperature up to 25℃. Conclusions: Sancho oil becomes rancid very quicky and requires efficient storage techniques. Sodium bicarbonate and ascorbic acid have been proven to be useful as safe anti-racidity agents without causing harm to humans.

• Journal of Korean Medicine for Obesity Research
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• v.20 no.2
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• pp.69-77
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• 2020

Objectives: In this study, we investigated the antiobesity and antidiabetic effects of polyherbal extract, DM2 consisting of Atractylodis Rhizoma, Anemarrhenae Rhizoma, Cinnamomi Cortex, and Moutan Radicles Cortex in high fat diet-induced obesity mice. Methods: DM2 extract was prepared with a hot water. Six-week-old male C57BL/6N mice were fed a high-fat diet (HFD) for 8 weeks and then administrated with DM2 extract (500 mg/kg, p.o.) for 4 weeks. The changes of physiological markers, body weight (BW), food and water intakes, and the levels of fasting blood glucose (FBG) were measured once a week for 4 weeks in mice. The the serum levels of glucose, insulin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (T-CHO), triglyceride, and low density lipoprotein cholesterol in sera were measured in mice using autometic chemical analyzer and enzyme linked immunosorbant assay. We also observed the histological changes of liver and pancreatic tissues with Hematoxylin & Eosin staining. Results: In physiological change, the increases of BW, calorie intake, and FBG in HFD-induced obese mice were significantly decreased after administration of DM2 extract for 4 weeks. The decrease of water intake was significantly increased in DM2 extract-administrated mice. In serological change, the administration of DM2 extract in obesity mice was significantly decreased the serum levels of glucose, insulin, T-CHO, AST, and ALT levels. We also found that DM2 extract inhibited the increase of lipid droplets in liver and the structural destruction of pancreatic tissues in obesity mice. Conclusion: Our study demonstrated that DM2 extract has antiobesity antidiabetic effects with body weight loss, decrease of glucose and insulin levels, and lipid accumulation on liver tissue.