• Biomolecules & Therapeutics
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• 제32권2호
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• pp.214-223
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• 2024

Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression. The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300-CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.

• Journal of Ginseng Research
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• 제39권4호
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• pp.331-337
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• 2015

Background: The biological actions of various ginseng extracts have been studied for treating obesity and diabetes mellitus. However, few studies have evaluated the effects of fermented Korean Red Ginseng (Panax ginseng Meyer) on metabolic syndrome. The present study evaluated the antiobesity and antidiabetic effects of fermented red ginseng (FRG) on old-aged, obese, leptin-deficient (B6.V-Lepob, "ob/ob") mice. Methods: The animals were divided into three groups and given water containing 0%, 0.5%, and 1.0% FRG for 16 wk. The effect of FRG on ob/ob mice was determined by measuring changes in body weight, levels of blood glucose, serum contents of triglycerides, total cholesterol and free fatty acids, messenger RNA (mRNA) expressions of key factors associated with insulin action, such as insulin receptor (IR), lipoprotein lipase (LPL), glucose transporter 1 and 4 (GLUT1 and GLUT4), peroxisome proliferators-activated receptor gamma ($PPAR-{\gamma}$), and phosphoenolpyruvate carboxykinase (PEPCK) in the liver and in muscle, and histology of the liver and pancreas. Results: FRG-treated mice had decreased body weight and blood glucose levels compared with control ob/ob mice. However, anti-obesity effect of FRG was not evident rather than hypoglycemic effect in old aged ob/ob mice. The hyperlipidemia in control group was attenuated in FRG-treated ob/ob mice. The mRNA expressions of IR, LPL, GLUT1, GLUT4, $PPAR-{\gamma}$, and PEPCK in the liver and in muscle were increased in the FRG-treated groups compared with the control group. Conclusion: These results suggest that FRG may play a vital role in improving insulin sensitivity relative to reducing body weight in old-aged ob/ob mice.

• Food Science and Biotechnology
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• 제18권3호
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• pp.808-812
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• 2009

The ${\alpha}-glucosidase$ inhibitory and antioxidant effects of water chestnut (Trapa japonica Flerov.) were assessed to explore its possible use as an anti-diabetic agent. Methanol extracts of the fruit shell and meat of water chestnut were assayed for inhibitory activity against yeast ${\alpha}-glucosidase$ and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. Effect of fruit shell extract on postprandial glucose response was assessed. Compared with fruit meat, shell extract showed stronger inhibition against ${\alpha}-glucosidase$ with an $IC_{50}$ of 273 ${\mu}g/mL$. Oral administration of fruit shell extract (500 mg/kg) significantly lowered the postprandial area under the glucose response curve to starch (1 g/kg) in streptozotocin (STZ)-induced diabetic rats (p<0.01). Compared with fruit meat, shell extract showed stronger scavenging activity against DPPH, with an $IC_{50}$ of 27.1 ${\mu}g/mL$. The results indicate that the fruit shell of water chestnut was effective in controlling postprandial hyperglycemia and exerted an antioxidant effect. Therefore, water chestnut may be useful in treating diabetes.

• Journal of Microbiology and Biotechnology
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• 제30권4호
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• pp.490-496
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• 2020

Consumption of anti-inflammatory nutraceuticals may help treat or prevent inflammation-related illnesses such as diabetes, cardiovascular disease, and cancer. This study evaluated the effect of Croton hirtus L'Hér extract (CHE) on lipopolysaccharide (LPS)-induced nitric oxide (NO) production and nuclear factor kappa-B (NF-κB) signaling cascades. CHE significantly suppressed LPS-induced NO production and inducible nitric oxide synthase (iNOS) expression in RAW264.7 macrophages, although cyclooxygenase (COX)-2 expression was not affected. CHE also suppressed LPS-induced IκB kinase (IKK), IκB, and p65 phosphorylation in RAW264.7 cells. Western blot and immunofluorescence assays of cytosol and nuclear p65 and the catalytic subunit of NF-κB showed that CHE suppressed LPS-induced p65 translocation from the cytosol to the nucleus. CHE also suppressed LPS-induced Interleukin (IL)-6 and tumor necrosis factor (TNF)-α production in RAW264.7 cells. These results suggest that CHE prevents NO-mediated inflammation by suppressing NF-κB and inflammatory cytokines.

• Biomolecules & Therapeutics
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• 제25권2호
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• pp.158-164
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• 2017

Methylglyoxal (MGO) is a highly reactive metabolite of glucose which is known to cause damage and induce apoptosis in endothelial cells. Endothelial cell damage is implicated in the progression of diabetes-associated complications and atherosclerosis. Hypericin, a naphthodianthrone isolated from Hypericum perforatum L. (St. John's Wort), is a potent and selective inhibitor of protein kinase C and is reported to reduce neuropathic pain. In this work, we investigated the protective effect of hypericin on MGO-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Hypericin showed significant anti-apoptotic activity in MGO-treated HUVECs. Pretreatment with hypericin significantly inhibited MGO-induced changes in cell morphology, cell death, and production of intracellular reactive oxygen species. Hypericin prevented MGO-induced apoptosis in HUVECs by increasing Bcl-2 expression and decreasing Bax expression. MGO was found to activate mitogen-activated protein kinases (MAPKs). Pretreatment with hypericin strongly inhibited the activation of MAPKs, including P38, JNK, and ERK1/2. Interestingly, hypericin also inhibited the formation of AGEs. These findings suggest that hypericin may be an effective regulator of MGO-induced apoptosis. In conclusion, hypericin downregulated the formation of AGEs and ameliorated MGO-induced dysfunction in human endothelial cells.

• 한국산학기술학회논문지
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• 제19권10호
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• pp.243-253
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• 2018

본 연구 목적은 제2형 당뇨병 환자에서의 D-chiro-inositol(DCI)의 혈당강하 효과, 당뇨 자가관리(Summary of Diabetes Self-Care Activities, SDSCA) 및 삶의 질(SF-36 Version 2.0, Korean)에 미치는 요인을 파악하고자 하였다. 연구대상은 충남대학교병원 내분비대사내과에 내원한 제2형 당뇨병 환자 중에서 3제의 경구 혈당강하제를 12주 이상 투여 했음에도 불구하고 당화혈색소 7.0% 이상인 환자를 2015년 3월부터 2016년 5월까지 24주간 무작위 이중맹검 위약대조 임상시험으로 총 46명을 분석하였다. 연구결과, 실험군에서 DCI 투여 이후 당화혈색소 $8.75{\pm}0.79%$(베이스라인), $8.36{\pm}1.03%$(투여 12주), $8.65{\pm}0.81%$(투여 24주)으로 유의하게 감소하였으나(p<0.05), 대조군과의 변화량은 차이가 없었다. 흥미롭게도 실험군과 대조군에서 당뇨 자가관리 점수가 높아졌으며, 특히 실험군 변화량에서의 하부영역인 혈당검사 만이 유의한 차이를 보였고, 삶의 질은 투여 전 $73.05{\pm}16.85$점에서 투여후 $82.74{\pm}10.68$점으로 향상되었다. DCI 투여에 따른 실험군에서의 요인간 경로분석에서 공복 혈당 변화량은 당뇨 자가관리 변화량이 높을수록(${\beta}=-0.505$, t=-2.743) 높다고 확인되었다. 삶의 질 변화량에 가장 큰 영향을 준 변수는 공복 c-펩타이드 변화량이 높을수록(${\beta}=-0.445$, t=-2.668), 당뇨 자가관리 변화량이 높을수록(${\beta}=0.411$, t=2.024) 높은 것으로 확인되었다. 결론적으로 제2형 당뇨병 환자에게 DCI 투여는 투여 12주차에 혈당 강하 효과를 보이고, 24주차에는 없었지만, 혈당강하 효과는 환자의 당뇨 자가관리를 높이고 삶의 질을 향상시켰다. 본 연구에 기초하여 결과적인 지표와 제2형 당뇨병 환자의 주관적인 관점에서 평가될 수 있는 삶의 질에 대한 경로분석을 통하여 모형의 적합도에 관한 연구로써 그 의의가 있다고 본다.

• 약학회지
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• 제55권6호
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• pp.478-484
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• 2011

Non-alcoholic fatty liver disease is known to be frequently associated with obesity and type 2 diabetes. We examined the effects of EtOH extracts from Triticum aestivum on lipid accumulation during the differentiation of 3T3-L1 preadipocytes to screening the candidate materials in preventing non-alcoholic fatty liver disease. The lipid level in adipocytes was determined by Oil Red O staining. The treatment of 50% ethanol, but not water and 100% ethanol extracts, from Triticum aestivum at concentration of 0.5 $mg/ml$ inhibited lipid accumulation in 3T3-L1 cells, revealing no cell toxicity. Thus, the fractions of $CH_2Cl_2$, EtOAc and BuOH were separated from 50% EtOH extract to characterize anti-adipogenic effect. The $CH_2Cl_2$ fraction at concentration of $50{\mu}g/ml$ effectively inhibited the lipid accumulation in the adipocytes compared to those of EtOAc and BuOH at concentration of $50{\mu}g/ml$. The intracellular triglyceride accumulation also was significantly reduced by treatment of $CH_2Cl_2$ fraction in concentration-dependent manner. Western blot analysis showed that the $CH_2Cl_2$ fraction attenuated the intracelluar level of fatty acid synthase(FAS) accompanied by attenuated expression of Peroxidase proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) adipogenic transcription factor. These results suggest that $CH_2Cl_2$ fraction from 50% EtOH extract of Triticum aestivum may has the potent anti-adipogenic effects by inhibiting the transactivation of $PPAR{\gamma}$.

• Journal of Nutrition and Health
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• 제53권6호
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• pp.570-582
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• 2020

본 연구는 상지추출물과 stilbene 화합물인 MSA, ORT의 항비만 효능을 비교 분석하고자 식이성 비만 마우스 모델을 이용하여 HFD에 실험물질을 첨가한 식이를 13주 동안 급여하였다. 연구결과, 실험물질들의 항비만 효능은 ORT, ME, MSA, MW군 순이었으며, 특히 ME와 ORT의 급여는 고지방식이에 의한 체중 및 체지방 증가, 혈당 증가, 이상지질혈증 및 지방간 개선에 있어 양성대조군인 GC군과 비슷한 효과를 보였다. 향후 관련 기작 규명 및 안전성 확보, 그리고 최대 유효성 도출을 위한 추출 조건 확립 및 용량 검증 등의 연구가 수행된다면 체중조절용 기능성 식품으로의 개발을 기대해 볼 수 있을 것으로 사료된다.

• Journal of Microbiology and Biotechnology
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• 제25권12호
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• pp.2146-2152
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• 2015

Apios americana Medik (hereinafter Apios) has been reported to treat diseases, including cancer, hypertension, obesity, and diabetes. The therapeutic effect of Apios is likely to be associated with its anti-inflammatory activity. This study was conducted to evaluate the protective effects of Apios in animal models of acute lung injury induced by lipopolysaccharide (LPS) or pandemic H1N1 2009 influenza A virus (H1N1). Mice were exposed to LPS or H1N1 for 2-4 days to induce acute lung injury. The treatment groups were administered Apios extracts via oral injection for 8 weeks before LPS treatment or H1N1 infection. To investigate the effects of Apios, we assessed the mice for in vivo effects of Apios on immune cell infiltration and the level of pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. After induction of acute lung injury, the numbers of neutrophils and total cells were lower in the Apios-treated groups than in the non-Apios-treated LPS and H1N1 groups. The Apios groups tended to have lower levels of tumor necrosis factor-a and interleukin-6 in BAL fluid. In addition, the histopathological changes in the lungs were markedly reduced in the Apios-treated groups. These data suggest that Apios treatment reduces LPS- and H1N1-induced lung inflammation. These protective effects of Apios suggest that it may have therapeutic potential in acute lung injury.

• Nutrition Research and Practice
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• 제1권3호
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• pp.184-188
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• 2007

The major goal in the treatment of diabetes mellitus is to achieve near-normal glycemic control. To optimize both fasting blood glucose and postprandial glucose levels is important in keeping blood glucose levels as close to normal as possible. ${\alpha}-Glucosidase$ is the enzyme that digests dietary carbohydrate, and inhibition of this enzyme could suppress postprandial hyperglycemia. The purpose of this study was to test the inhibitory activity of methanol extract of Euonymus alatus on ${\alpha}-glucosidase$ in vitro and in vivo to evaluate its possible use as an anti-diabetic agent. Yeast ${\alpha}-glucosidase$ inhibitory activities of methanol extract of E. alatus were measured at concentrations of 0.50, 0.25, 0.10, and 0.05 mg/ml. The ability of E. alatus to lower postprandial glucose was studied in streptozotocin-induced diabetic rats. A starch solution (1 g/kg) with and without E. alatus extract (500 mg/kg) was administered to diabetic rats by gastric intubation after an overnight fast. Plasma glucose levels were measured at 30, 60, 90, 120, 180, and 240 min. Plasma glucose levels were expressed in increments from baseline, and incremental areas under the response curve were calculated. Extract of E. alatus, which had an $IC_{50}$ value of 0.272 mg/ml, inhibited yeast ${\alpha}-glucosidase$ activity in a concentration-dependent manner. A single oral dose of E. alatus extract significantly inhibited increases in blood glucose levels at 60 and 90 min (p<0.05) and significantly decreased incremental response areas under the glycemic response curve (p<0.05). These results suggest that E. alatus has an antihyperglycemic effect by inhibiting ${\alpha}-glucosidase$ activity in this animal model of diabetes mellitus.