• Journal of Ginseng Research
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• 제35권3호
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• pp.308-314
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• 2011

In the present study, we investigate anti-diabetic effect of pectinase-processed ginseng radix (GINST) in high fat diet-fed ICR mice. The ICR mice were divided into three groups: regular diet group, high fat diet control group (HFD), and GINSTtreated group. To induce hyperglycemia, mice were fed a high fat diet for 10 weeks, and mice were administered with 300 mg/kg of GINST once a day for 5 weeks. Oral glucose tolerance test revealed that GINST improved glucose tolerance after glucose challenge. Compared to the HFD control group, fasting blood glucose and insulin levels were decreased by 57.8% (p<0.05) and 30.9% (p<0.01) in GINST-treated group, respectively. With decreased plasma glucose and insulin levels, the insulin resistance index of the GINST-treated group was reduced by 68.1% (p<0.01) compared to the HFD control group. Pancreas of GINST-treated mice preserved a morphological integrity of islets and consequently having more insulin contents. In addition, GINST up-regulated the levels of phosphorylated AMP-activated protein kinase (AMPK) and its target molecule, glucose transporter 4 (GLUT4) protein expression in the skeletal muscle. Our results suggest that GINST ameliorates a hyperglycemia through activation of AMPK/GLUT4 signaling pathway, and has a therapeutic potential for type 2 diabetes.

• 한국체육학회지인문사회과학편
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• 제54권2호
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• pp.431-439
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• 2015

본 연구의 목적은 sarcopenic obese 흰쥐를 대상으로 사다리 등반 운동 또는 고단백식이 처치가 골격근의 단백질 합성과 인슐린 저항성에 미치는 영향을 규명하는 것이다. 50주령 SD계 수컷 흰쥐를 이용하여 6주간 고지방식이로 sarcopenic obese 쥐를 유도한 다음 4집단(Chow, HP, Ex, HPEx)으로 무선 배정하였다. 연구결과 8주간의 사다리 등반 운동은 sarcopenic obese 흰쥐의 인슐린 저항성과 체지방량을 감소시키고, mTOR 활성도를 유의하게 증가시켰다. 그러나 하지 근육양은 유의한 변화가 나타나지 않았고, 고지방식과 운동을 병행 처치한 경우 체지방과 인슐린 저항성이 개선되지 않았으며, 오히려 운동의 효과가 저해되는 것으로 나타났다. 이러한 결과를 통해 노화에 따른 sarcopenic obesity 개선을 위한 고단백식이는 그 양과 조성에 있어서 보다 면밀한 연구가 이루어져야 한다.

• 한국식품영양과학회지
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• 제46권2호
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• pp.267-272
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• 2017

본 연구에서는 팔미틴산을 처리한 지방간질환 간세포 모델과 비만/당뇨 동물 모델인 KK/HlJ 마우스를 이용하여 피세아테놀과 레스베라트롤 투여가 염증조절에 주는 영향을 알아보고자 하였다. 4주간의 피세아테놀과 레스베라트롤 섭취는 공복혈당과 경구당부하 검사 2시간 후 AUC를 감소시켜 혈당 조절 개선 효과를 보였다. 또한, 팔미틴산을 처리한 지방간질환 간세포 모델에 피세아테놀과 레스베라트롤을 처리한 결과 염증조절 경로인자인 TLR4와 $NF-{\kappa}B$의 발현을 유의적으로 감소시켰다. 이를 in vivo 비만/당뇨 동물 모델인 KK/HlJ 마우스의 간 조직에서 확인한 결과 피세아테놀 섭취는 NLRP3와 $NF-{\kappa}B$의 간 조직에서의 발현을 유의적으로 감소시켰고, IL-1 발현을 감소시키는 경향을 보였다. 하지만 동량의 레스베라트롤 섭취는 이와 같은 항염증 효과를 보이지 않았다. 결론적으로 혈당 조절 개선 효과와 항염증 효과에 있어 피세아테놀이 레스베라트롤보다 우수한 효과를 가지고, 피세아테놀의 항염증 효과는 혈당 조절 개선 효과에 부분적으로 기여할 것으로 제안한다.

• Nutrition Research and Practice
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• 제14권6호
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• pp.593-605
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• 2020

BACKGROUND/OBJECTIVES: Alzheimer's disease is common age-related neurodegenerative condition characterized by amyloid beta (Aβ) accumulation that leads cognitive impairment. In the present study, we investigated the protective effect of paeoniflorin (PF) against Aβ-induced neuroinflammation and the underlying mechanism in C6 glial cells. MATERIALS/METHODS: C6 glial cells were treated with PF and Aβ_25-35, and cell viability, nitric oxide (NO) production, and pro-inflammatory cytokine release were measured. Furthermore, the mechanism underlying the effect of PF on inflammatory responses and Aβ degradation was determined by Western blot. RESULTS: Aβ_25-35 significantly reduced cell viability, but this reduction was prevented by the pretreatment with PF. In addition, PF significantly inhibited Aβ_25-35-induced NO production in C6 glial cells. The secretion of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha was also significantly reduced by PF. Further mechanistic studies indicated that PF suppressed the production of these pro-inflammatory cytokines by regulating the nuclear factor-kappa B (NF-κB) pathway. The protein levels of inducible NO synthase and cyclooxygenase-2 were downregulated and phosphorylation of NF-κB was blocked by PF. However, PF elevated the protein expression of inhibitor kappa B-alpha and those of Aβ degrading enzymes, insulin degrading enzyme and neprilysin. CONCLUSIONS: These findings indicate that PF exerts protective effects against Aβ-mediated neuroinflammation by inhibiting NF-κB signaling, and these effects were associated with the enhanced activity of Aβ degradation enzymes.

• Molecules and Cells
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• 제40권6호
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• pp.393-400
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• 2017

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by lack of insulin and high glucose levels. T2DM can cause bone loss and fracture, thus leading to diabetic osteoporosis. Promoting osteogenic differentiation of osteoblasts may effectively treat diabetic osteoporosis. We previously reported that Sirtuin 1 (Sirt1), a $NAD^+$-dependent deacetylase, promotes osteogenic differentiation through downregulation of peroxisome proliferator-activated receptor (PPAR) ${\gamma}$. We also found that miR-132 regulates osteogenic differentiation by downregulating Sirt1 in a $PPAR{\beta}/{\delta}$-dependent manner. The ligand-activated transcription factor, $PPAR{\alpha}$, is another isotype of the peroxisome proliferator-activated receptor family that helps maintain bone homeostasis and promot bone formation. Whether the regulatory role of $PPAR{\alpha}$ in osteogenic differentiation is mediated via Sirt1 remains unclear. In the present study, we aimed to determine this role and the underlying mechanism by using high glucose (HG) and free fatty acids (FFA) to mimic T2DM in MC3T3-E1 cells. The results showed that HG-FFA significantly inhibited expression of $PPAR{\alpha}$, Sirt1 and osteogenic differentiation, but these effects were markedly reversed by $PPAR{\alpha}$ overexpression. Moreover, siSirt1 attenuated the positive effects of $PPAR{\alpha}$ on osteogenic differentiation, suggesting that $PPAR{\alpha}$ promotes osteogenic differentiation in a Sirt1-dependent manner. Luciferase activity assay confirmed interactions between $PPAR{\alpha}$ and Sirt1. These findings indicate that $PPAR{\alpha}$ promotes osteogenic differentiation via the Sirt1-dependent signaling pathway.

• Biomolecules & Therapeutics
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• 제19권3호
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• pp.348-356
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• 2011

Liriope platyphylla is a medical herb that has long been used in Korea and China to treat cough, sputum, neurodigenerative disorders, obesity and diabetes. The aims of this study were to study the antidiabetic effects of the aqueous extract of L. platyphylla (AEtLP) through pancreatic and extrapancreatic actions. AEtLP were orally administrated to ICR mice once a day for 7 days. Of three different concentrations of AEtLP, only 10% AEtLP were low toxic to liver, based on body weight and serum biochemical analyses. However, 10% AEtLP-treated mice displayed signifi cant reduction of the glucose concentration and increased insulin concentration; no changes were noted using 5% and 15% AEtLP. Also, the increase of glucose transporter (Glut)-1 expression in liver was dependent on the concentration of AEtLP, and was regulated by the phosphorylation of Akt. The lowest expression of Glut-3 was observed in 15% AEtLP treated mice, followed by 10% AEtLP- and 5% AEtLP-treated mice. This pattern of Glut-3 expression was roughly in accord with the phosphorylation of c-Jun N-teminal kinase (JNK) in the mitogen-activated protein kinase (MAPK) pathway. Furthermore, a signifi cant rise of the superoxide dismutase activity (SOD) was detected in AEtLP-treated mice. The fi ndings suggest that AEtLP should be considered as a diabetes therapeutic candidate to induce insulin secretion from pancreatic ${\beta}$-cells and glucose uptake in liver cells.

• Asian-Australasian Journal of Animal Sciences
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• 제31권1호
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• pp.138-148
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• 2018

Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0.8 mg ZEN/kg feed. Kidney samples were collected after treatment, and RNA-seq was used to investigate the effects on immune-related genes and gene networks. Results: A total of 186 differentially expressed genes (DEGs) were screened (120 upregulated and 66 downregulated). Gene ontology analysis revealed that the immune response, and cellular and metabolic processes were significantly controlled by these DEGs. The inflammatory stimulation might be an effect of the following enriched Kyoto encyclopedia of genes and genomes pathway analysis found related to immune and disease responses: cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, systemic lupus erythematosus (SLE), tuberculosis, Epstein-Barr virus infection, and chemical carcinogenesis. The effects of DON and ZEN on genome-wide expression were assessed, and it was found that the DEGs associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9, CXCL10, chemokine [C-C motif] ligand 4), proliferation (insulin like growth factor binding protein 4, IgG heavy chain, receptor-type tyrosine-protein phosphatase C, cytochrome P450 1A1, ATP-binding cassette sub-family 8), and other immune response networks (lysozyme, complement component 4 binding protein alpha, oligoadenylate synthetase 2, signaling lymphocytic activation molecule-9, ${\alpha}$-aminoadipic semialdehyde dehydrogenase, Ig lambda chain c region, pyruvate dehydrogenase kinase, isozyme 4, carboxylesterase 1), were suppressed by DON and ZEN. Conclusion: In summary, our results indicate that high concentrations of DON and ZEN suppress the inflammatory response in kidneys, leading to potential effects on immune homeostasis.

• Molecules and Cells
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• 제37권1호
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• pp.51-57
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• 2014

NOG1 is a nucleolar GTPase that is critical for 60S ribosome biogenesis. Recently, NOG1 was identified as one of the downstream regulators of target of rapamycin (TOR) in yeast. It is reported that TOR is involved in regulating lifespan and fat storage in Caenorhabditis elegans. Here, we show that the nog1 ortholog (T07A9.9: nog-1) in C. elegans regulates growth, development, lifespan, and fat metabolism. A green fluorescence protein (GFP) promoter assay revealed ubiquitous expression of C. elegans nog-1 from the early embryonic to the adult stage. Furthermore, the GFP-tagged NOG-1 protein is localized to the nucleus, whereas the aberrant NOG-1 protein is concentrated in the nucleolus. Functional studies of NOG-1 in C. elegans further revealed that nog-1 knockdown resulted in smaller broodsize, slower growth, increased life span, and more fat storage. Moreover, nog-1 over-expression resulted in decreased life span. Taken together, our data suggest that nog-1 in C. elegans may be an important player in regulating life span and fat storage via the insulin/IGF pathway.

• 생명과학회지
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• 제22권5호
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• pp.634-641
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• 2012

LP9M80-H는 맥문동($Liriope$ $platyphylla$)으로부터 메탄올과 헥산을 이용하여 추출한 새로운 추출물로서 ICR 마우스에서 인슐린분비를 촉진하며, 간과 뇌 조직에서 인슐린 신호경로를 활성화시키는 것으로 알려져 있다. 본 연구에서는 LP9M80-H가 당뇨와 비만의 치료에 미치는 효과를 조사하기 위하여, OLETF 모델동물에 LP9M80-H를 2주간 투여한 후 당뇨와 비만과 관련된 주요인자의 변화를 관찰하였다. 비록 체중은 두 집단간에 차이가 없었으나 복부 지방량은 vehicle 투여군보다 LP9M80-H 투여군에서 적었다. 또한, 혈중 포도당농도는 LP9M80-H를 투여한 OLETF 랫드가 대조군에 비하여 약간 낮았으나 인슐린의 농도는 유의적으로 크게 증가하였다. 혈청 내 3가지 주요 지질의 농도는 LP9M80-H를 투여한 OLETF 랫드에서 유의적으로 감소하였고, 지방의 산화를 촉진하는 아디포넥틴의 농도도 LP9M80-H를 투여한 OLETF 랫드에서 감소하였다. 더불어, 체내에 분비된 인슐린이 표적장기에 미치는 영향을 관찰하기 위하여 간조직에서 인슐린 수용체와 인슐린 수용체기질(iRS)의 발현을 관찰하였으며, 이러한 2가지 단백질은 LP9M80-H를 투여한 OLETF 랫드에서 vehicle 투여군에 비해 유의미하게 감소하였다. 또한, 인슐린 신호 경로의 다운스트림에 위치하는 포도당 수송체 중에서 Glut-2와 Glut-3 발현은 LP9M80-H를 투여한 OLETF 랫드에서 유의미하게 감소하는 반면에, Glut-4 발현은 일정하게 유지되었다. 따라서 이러한 결과는 LP9M80-H는 포도당 항상성과 지질농도의 조절을 통하여 당뇨와 비만의 증상을 완화시키는데 기여할 것으로 사료된다.

• Nutrition Research and Practice
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• 제17권4호
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• pp.682-697
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• 2023

BACKGROUND/OBJECTIVES: Tibetan tea is a kind of dark tea, due to the inherent complexity of natural products, the chemical composition and beneficial effects of Tibetan tea are not fully understood. The objective of this study was to unravel the composition of Tibetan tea using knowledge-guided multilayer network (KGMN) techniques and explore its potential antioxidant and hypolipidemic mechanisms in mice. MATERIALS/METHODS: The C57BL/6J mice were continuously gavaged with Tibetan tea extract (T group), green tea extract (G group) and ddH2O (H group) for 15 days. The activity of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in mice was detected. Transcriptome sequencing technology was used to investigate the molecular mechanisms underlying the antioxidant and lipid-lowering effects of Tibetan tea in mice. Furthermore, the expression levels of liver antioxidant and lipid metabolism related genes in various groups were detected by the real-time quantitative polymerase chain reaction (qPCR) method. RESULTS: The results showed that a total of 42 flavonoids are provisionally annotated in Tibetan tea using KGMN strategies. Tibetan tea significantly reduced body weight gain and increased T-AOC and SOD activities in mice compared with the H group. Based on the results of transcriptome and qPCR, it was confirmed that Tibetan tea could play a key role in antioxidant and lipid lowering by regulating oxidative stress and lipid metabolism related pathways such as insulin resistance, P53 signaling pathway, insulin signaling pathway, fatty acid elongation and fatty acid metabolism. CONCLUSIONS: This study was the first to use computational tools to deeply explore the composition of Tibetan tea and revealed its potential antioxidant and hypolipidemic mechanisms, and it provides new insights into the composition and bioactivity of Tibetan tea.