• The Korea Journal of Herbology
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• v.37 no.2
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• pp.1-11
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• 2022

Objectives : Although the anti-obesity effect of Schizandrae Fructus water extract has been demonstrated, its underlying mechanism is still unclear. Therefore, we aimed to evaluate the anti-obesity effect of Schizandrae Fructus water extract through the p-AMP-activated protein kinase (p-AMPK), sirtuin1 (Sirt1), and peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling in 60% high-fat diet (HFD)-induced obese mouse model. Methods : Male C57BL/6 mice were divided into four groups. The Normal group was fed a normal diet and the obese groups were fed 60% HFD. Except for the Control group, the GG group was supplemented with 0.5% Garcinia gummigutta and the SCW group was supplemented with 0.5% Schizandrae Fructus water extract. After 6 weeks, obesity-related biomarkers in serum were measured and the expressions of protein for lipid-related factors in liver tissue were analyzed by western blot. Results : Treatment with SCW significantly down-regulated body weight compared to the Control group. SCW down-regulated levels of triglyceride and total cholesterol in serum and significantly increased p-AMPK, Sirt1, and PGC-1α in liver tissue. In addition, the expressions of fatty acid oxidation-related proteins such as peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1A (CPT-1A), uncoupling protein 1 (UCP1), and uncoupling protein 3 (UCP3) were significantly up-regulated. However, fatty acid synthesis-related proteins including sterol regulatory element-binding protein-1 (SREBP-1), phospho-Acetyl-CoA Carboxylase (p-ACC), and fatty acid synthase (FAS) were significantly down-regulated. Conclusions : Taken together, SCW treatment showed anti-obesity effect by regulating both fatty acid oxidation-related and fatty acid synthesis-related proteins through AMPK/Sirt1/PGC-1α signaling in 60% HFD-induced obese mice.

• Molecules and Cells
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• v.38 no.12
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• pp.1037-1043
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• 2015

The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. 1 TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-$phosphoelF2{\alpha}$-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance.

• 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 Ginseng Research
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• v.39 no.3
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• pp.230-237
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. Methods: A genetically engineered $Apc^{Min/+}$ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. Results: After oral ginseng administration (10-20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-$1{\alpha}$ (IL-$1{\alpha}$), IL-$1{\beta}$, IL-6, tumor necrosis factor-${\alpha}$, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Conclusion: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.2.1-2.12
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• 2018

Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is well-known that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

• Korean Journal of Pharmacognosy
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• v.44 no.1
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• pp.75-82
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• 2013

Previous studies have shown that Aloe QDM complex, which is consisted of chromium (Cr), aloesin (ALS) and processed Aloe vera gel (PAG), exert antidiabetic activity in a high fat diet-induced mouse model of type 2 diabetes. In this study we examined the mechanism of the antidiabetic activity of the Aloe QDM complex. Rat myoblast cell line L6 cells were cultured in the presence of Cr, ALS, and PAG alone and in combinations, and then the capability of the cells to uptake glucose was examined using radiolabeled glucose. All of the 3 agents, Cr, ALS and PAG, exerted glucose uptake-enhancing activity in L6 cells. The most potent capability to uptake glucose was observed when L6 cells were cultured with the Aloe QDM complex. The activity of the Aloe QDM complex to enhance glucose uptake was prominent in conditions where existing insulin concentrations are low. We also examined the effects of the Aloe QDM complex on the plasma membrane expression of GLUT4 in L6 cells. The Aloe QDM complex increased the content of GLUT4 in the plasma membrane, while decreasing the content of GLUT4 in the light microsome. Taken together, these results show that the antidiabetic activity of the Aloe QDM complex is at least in part due to the stimulation of glucose uptake into the muscle cells, and this activity of the Aloe QDM complex is mediated through the enhancement of the translocation of GLUT4 into the plasma membrane.

• 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 the Korean Applied Science and Technology
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• v.36 no.4
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• pp.1153-1163
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• 2019

In women, obesity rises with menopause. By comparing the dose-dopendent effects of genistein on regulation of body weight and lipid levels with swimming exercise in female ovariectomized (OVX) mice, an animal model of postmenopausal women, the effective dose of genistein on obesity control was investigated. Ovariectomized female mice were divided into control group, swimming exercise group and genistein concentration (0.005%, 0.05%, 0.1% wt/wt) treatment group and all mice fed high-fat diet for 8 weeks. The three different genistein doses as well as swimming decreased body weight, white adipose tissue mass, plasma lipid levels and lipid accumulation in liver, compared with control OVX mice. These decrease effectiveness of genistein showed dose-dependent manner, and is most effective at 0.1% genistein concentration, and paralleled effects of swimming on body weight, white adipose tissue, plasma lipid levels and lipid accumulation in liver. This present findings indicate that optimal dose of genistein in feamle OVX mice have a similar effect to swimming exercise on improvement of obesity. Intake of dietary genistein supplements will help obesity prevention in postmenopausal women.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.10a
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• pp.5-5
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• 2019

DMZ는 살아있는 생물다양성의 보고로 지난 60여년동안 자연적으로 재생이 일어나고 환경적인 강제 보존 영향으로 높은 생태학적인 가치가 유지되고 있으며, 최근에는 남북교류에 대한 활발한 의지로 DMZ생태자원의 남북공동활용 방안에 대한 이슈가 급부상하고 있다. 이에 본 연구진은 3년전부터 DMZ에서 자생하는 식물에 대한 조사를 진행하여 총 200여종 이상의 자생식물의 표본과 추출물들을 보유하고 있으며, 이 추출물들을 활용 in vitro 와 in vivo 평가를 통해 비임상 평가에서 유효한 효과를 나타내는 후보물질들을 다수 찾아낼 수 있었다. 그 중 조팝나무(Spiraea prunifolia var. simpliciflora)는 쌍떡잎식물 장미과에 속하는 낙엽활엽관목으로 동북아시아 지역에 널리 분포되며 우리나라에서는 중부지방에 주로 서식한다고 알려져 있다. 예로부터 해열 및 소염, 신경통완화 치료등에 이용해왔다고 알려져 있으며 그 속에는 다양한 terpenoids, flavonoid 및 phenolic 화합물이 다량 함유되어 있다고 알려져 있다. 본 연구에서는 조팝나무 추출물을 이용하여 전구지방세포에서의 지방세포분화 억제 및 관련 유전자들의 활성을 확인한 후 고지방식이로 유도된 high-fat diet mouse model을 이용하여 체지방 감소 및 내장지방감소, 간 조직내의 지방량 감소등을 확인하였으며, 혈액분석을 통해 총콜레스테롤과 고중성지방등 동맥경화와 심혈관계 질환을 유도시킬수 있는 지표들에서 억제 활성도 확인하였다. 특히 내장 지방의 경우는 Micro-CT를 통해 정밀한 분석을 진행하였고, 체지방뿐만 아니라 전체 체중감소도 나타나는 것을 확인하였다. 현재 실험을 통해 적출된 간 조직과 지방조직을 이용하여 항 비만 활성의 작용기전을 지속적으로 확인하고 있으며, 이 결과는 국제적인 연구저널에 보고되어 향후 체지방 감소 또는 항 비만 치료제로 개발되는 비임상 연구자료로 활용될 계획이다. 이미 조팝나무에 대한 연구결과는 특허로 출원이 완료되어 PCT출원까지 진행중에 있으며 개별인정형 건강기능식품 개발 기업에 기술이전이 될 예정이다. 또한 원활한 원료 수급을 위해 기초단체 소속 농업기술센터와 원료 재배 및 대량 수급에 관한 논의를 마친 상태로 접경지역 근처 농가소득 증대로도 이어지는 제품화 사례이기도 하다. 이는 접경지역에서 자생하는 원료의 활성을 과학적으로 검증하여 기업과의 연계를 통해 기초시군 단체의 농가 소득과도 연계한 우수한 제품개발 사례로 향후에도 이와 같은 연구성과가 지속적으로 도출되기를 기대해본다.