• Journal of Ginseng Research
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• 제44권4호
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• pp.664-671
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• 2020

Background: Ginsenoside compound-Mc1 (Mc1) is a member of the deglycosylated ginsenosides obtained from ginseng extract. Although several ginsenosides have a cardioprotective effect, this has not been demonstrated in ginsenoside Mc1. Methods: We treated H9c2 cells with hydrogen peroxide (H₂O₂) and ginsenoside Mc1 to evaluate the antioxidant effects of Mc1. The levels of antioxidant molecules, catalase, and superoxide dismutase 2 (SOD2) were measured, and cell viability was determined using the Bcl2-associated X protein (Bax):B-cell lymphoma-extra large ratio, a cytotoxicity assay, and flow cytometry. We generated mice with high-fat diet (HFD)-induced obesity using ginsenoside Mc1 and assessed their heart tissues to evaluate the antioxidant effect and the fibrosis-reducing capability of ginsenoside Mc1. Results: Ginsenoside Mc1 significantly increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the H9c2 cells. The expression levels of catalase and SOD2 increased significantly after treatment with ginsenoside Mc1, resulting in a decrease in the production of H₂O₂-mediated reactive oxygen species. Treatment with ginsenoside Mc1 also significantly reduced the H₂O₂-mediated elevation of the Bax:Bcl2 ratio and the number of DNA-damaged cells, which was significantly attenuated by treatment with an AMPK inhibitor. Consistent with the in vitro data, ginsenoside Mc1 upregulated the levels of catalase and SOD2 and decreased the Bax:B-cell lymphoma-extra large ratio and caspase-3 activity in the heart tissues of HFD-induced obese mice, resulting in reduced collagen deposition. Conclusion: Ginsenoside Mc1 decreases oxidative stress and increases cell viability in H9c2 cells and the heart tissue isolated from HFD-fed mice via an AMPK-dependent mechanism, suggesting its potential as a novel therapeutic agent for oxidative stress-related cardiac diseases.

• 한국응용과학기술학회지
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• 제36권3호
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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.

• Journal of Yeungnam Medical Science
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• 제36권1호
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• pp.26-35
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• 2019

Background: Dysregulation of hepatic glucose production (HGP) contributes to the development of type 2 diabetes mellitus. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), has various ancillary effects in addition to common blood pressure-lowering effects. The effects and mechanism of telmisartan on HGP have not been fully elucidated and, therefore, we investigated these phenomena in hyperglycemic HepG2 cells and high-fat diet (HFD)-fed mice. Methods: Glucose production and glucose uptake were measured in HepG2 cells. Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase ${\alpha}$ ($G6Pase-{\alpha}$), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ${\zeta}$ ($PKC{\zeta}$) were assessed by western blot analysis. Animal studies were performed using HFD-fed mice. Results: Telmisartan dose-dependently increased HGP, and PEPCK expression was minimally increased at a $40{\mu}M$ concentration without a change in $G6Pase-{\alpha}$ expression. In contrast, telmisartan increased phosphorylation of IRS-1 at Ser302 ($p-IRS-1-Ser^{302}$) and decreased $p-IRS-1-Tyr^{632}$ dose-dependently. Telmisartan dose-dependently increased $p-PKC{\zeta}-Thr^{410}$ which is known to reduce insulin action by inducing IRS-1 serine phosphorylation. Ectopic expression of dominant-negative $PKC{\zeta}$ significantly attenuated telmisartan-induced HGP and $p-IRS-1-Ser^{302}$ and -inhibited $p-IRS-1-Tyr^{632}$. Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) antagonist, did not alter this effect. Finally, in the livers from HFD-fed mice, telmisartan increased $p-IRS-1-Ser^{302}$ and decreased $p-IRS-1-Tyr^{632}$, which was accompanied by an increase in $p-PKC{\zeta}-Thr^{410}$. Conclusion: These results suggest that telmisartan increases HGP by inducing $p-PKC{\zeta}-Thr^{410}$ that increases $p-IRS-1-Ser^{302}$ and decreases $p-IRS-1-Tyr^{632}$ in a $PPAR{\gamma}$-independent manner

• 한국약용작물학회지
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• 제28권6호
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• pp.395-411
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• 2020

Background: This study investigated the anti-obesity effect of the flavonoid rich fraction (FRF) and its constituent, rutin obtained from the leaf of Morus alba L., on the lipid accumulation mechanism in 3T3-L1 adipocyte and C57BL/6 mouse models. Methods and Results: In Oil Red O staining, FRF (1,000 ㎍/㎖) treatments showed inhibition rate of 35.39% in lipid accumulation compared to that in the control. AdipoRedTM assay indicated that the triglyceride content in 3T3-L1 adipocytes treated with FRF (1,000 ㎍/㎖) was reduced to 23.22%, and free glycerol content was increased to 106.04% that of the control. FRF and its major constituent, rutin affected mRNA gene expression. Rutin contributed to the inhibition of Sterol regulatory element binding protein-1c (SREBP-1c) gene expression, and inhibited the transcription factors SREBP-1c, peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). In addition, the effect of FRF administration on obesity development in C57BL/6 mice fed high-fat diet (HFD) was investigated. FRF suppressed weight gain, and reduced liver triglyceride and leptin secretion. FRF exerted potential anti-inflammatory effects by improving insulin resistance and adiponectin levels, and could thus be used to help counteract obesity. The mRNA expressions of PPAR-γ, FAS, ACC, and CPT-1 were determined in liver tissue. Quantitative real-time PCR analysis was also performed to evaluate the expression of IL-1β, IL-6, and TNF-α in epididymal adipose tissue. Compared to the control group, mice fed the HFD showed the up-regulation in PPAR-γ, FAS, IL-6, and TNF-α genes, and down-regulation in CPT1 gene expression. FRF treatement markedly reduced the expression of PPAR-γ, FAS, IL-6, and TNF-α compared to those in HFD control, whereas increased the expression level of CPT1. Conclusions: These results suggest that the FRF and its major active constituent, rutin, can be used as effective anti-obesity agents.

• Journal of Nutrition and Health
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• 제57권2호
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• pp.196-210
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• 2024

본 연구에서는 정향과 마가목 복합물 (SS)의 항비만 효과를 알아보기 위해 실험을 진행하였다. SS 투여는 3T3-L1 세포 내 TG와 TC가 유의적으로 감소하는 효과를 나타냈으며, 지질 합성 관련 유전자와 지방산 산화 관련 유전자 발현을 조절하는 효과를 보여주었다. 비만이 유도된 C57BL/6 mice에서 SS 투여는 혈청 내 leptin 호르몬 수치를 감소시켰으며, AMPK/ACC/SREBP-1 경로를 경유하여 TG 합성을 억제하였다. 또한, 조직병리학적 분석을 통해 지질 축적과 지방세포의 크기가 감소된 것을 확인하였다. 따라서 SS는 비만의 예방과 치료를 위한 잠재력을 갖춘 소재로 사료된다.

• Toxicological Research
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• 제30권1호
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• pp.49-54
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• 2014

In this study, we investigated the hepatoprotective effects of aged black garlic (ABG) in rodent models of liver injury. ABG inhibited carbon tetrachloride-induced elevation of aspartate transaminase (AST) and alanine transaminase (ALT), which are markers of hepatocellular damage, in SD rats. D-galactosamine-induced hepatocellular damage was also suppressed by ABG treatment. However, ABG does not affect the elevation of alkaline phosphatase (ALP), a marker of hepatobilliary damage, in rats treated with carbon tetrachloride or D-galactosamine. We also examined the effect of ABG on high-fat diet (HFD)-induced fatty liver and subsequent liver damage. ABG had no significant effect on body weight increase and plasma lipid profile in HFD-fed mice. However, HFD-induced increase in AST and ALT, but not ALP, was significantly suppressed by ABG treatment. These results demonstrate that ABG has hepatoprotective effects and suggest that ABG supplementation might be a good adjuvant therapy for the management of liver injury.

• 한국발생생물학회지:발생과생식
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• 제19권4호
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• pp.235-242
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• 2015

Black soybean teata is helpful to preventing obesity through enhancing energy expenditure and suppressing accumulation in mesenteric adipose tissue. The ethanol testa-extract of Cheongja #3 black soybean (ETCBS) is also have similar effects on obesity. So far, it is not clear whether the ethanol testa extract of black soybean can have effect on the characters of subcutaneous adipose stem cells such as proliferation, activity, and adipogenicity. The doubling time was different between subcutaneous adipose-derived stem (ADS) and visceral ADS cells. By the in vitro culture and passage, the doubling time was increased both of them. The shape was not different between groups and their passages were not cause the change of shapes. In the case of visceral ADS cells, the doubling time was 62.3 h or 40.3 h in control or high fat diet administrated mice, respectively, but not modified in subcutaneous ADS cells. ETCBS administration caused of increased the doubling time from 62.3 h to 84.2 h. ETCBS had suppressive effects on the cellular activity of subcutaneous ADS cells. The intensity of Oil Red O staining was very faint in 100 and $200{\mu}g/mL$ ETCBS treated groups. The amounts of accumulated triglyceride were also significantly low in 100 and $200{\mu}g/mL$ treated groups. From these results we know that the doubling times and the effects of ETCBS are different by the anatomical origin of ADS cells. It also suggested that ETCBS may suppress the differentiation of subcutaneous ADS cells into the precursors and maturing of adipocytes.

• BMB Reports
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• 제53권6호
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• pp.317-322
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• 2020

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. NAFLD can further progress to irreversible liver failure such as non-alcoholic steatohepatitis (NASH) fibrosis and cirrhosis. However, specific regulator of NASH-fibrosis has yet to be established. Here, we found that glutathione peroxidase 7 (GPx7) was markedly expressed in NASH fibrosis. Although GPx7 is an antioxidant enzyme protecting other organs, whether GPx7 plays a role in NASH fibrosis has yet to be studied. We found that knockdown of GPx7 in transforming growth factor-β (TGF-β) and free fatty acids (FFA)-treated LX-2 cells elevated the expression of pro-fibrotic and pro-inflammatory genes and collagen synthesis. Consistently, GPx7 overexpression in LX-2 cells led to the suppression of ROS production and reduced the expression of pro-fibrotic and pro-inflammatory genes. Further, NASH fibrosis induced by choline-deficient amino acid defined, high fat diet (CDAHFD) feeding was significantly accelerated by knockdown of GPx7, as evidenced by up-regulated liver fibrosis and inflammation compared with CDAHFD control mice. Collectively, these results suggest that GPx7 might be a novel therapeutic target to prevent the progression and development of NAFLD.

• 한국식품영양학회지
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• 제29권6호
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• pp.998-1007
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• 2016

본 연구에서는 상추 추출물이 혈관내피세포의 염증반응에 미치는 영향 및 지질대사 개선 효과를 확인하기 위해 HUVEC을 이용한 in vitro 실험 및 고콜레스테롤혈증 모델을 이용한 동물실험을 수행하였다. 상추 추출물은 HUVEC에서 TNF-${\alpha}$에 의해 증가되는 세포접착단백질 ICAM-1, VCAM-1의 발현을 억제하였고 TNF-${\alpha}$에 의해 촉진되는 HUVEC와 단핵구 세포의 부착을 감소시켰다. 또한 상추 추출물은 TNF-${\alpha}$에 의해 증가되는 염증성 사이토카인 IL-6, IL-8 및 동맥경화 유발 케모카인 MCP-1의 생성을 농도 의존적으로 억제하였다. 고콜레스테롤혈증 동물모델에서 고콜레스테롤 식이군 및 상추 추출물이 첨가된 고콜레스테롤 식이군의 체중증가량 및 식이섭취량은 유의적인 차이를 보이지 않았다. 고콜레스테롤 식이군의 혈중 총 콜레스테롤 함량은 정상 식이군에 비해 크게 증가하였고 상추추출물이 첨가된 고콜레스테롤 식이군의 콜레스테롤 함량은 유의적으로 감소하였다. 고콜레스테롤 식이군의 혈중 중성지방 함량은 정상 식이군에 비해 약간 감소하였지만 유의적인 차이는 보이지 않았다. 상추 추출물이 첨가된 고콜레스테롤 식이군의 경우 혈중 중성지방 함량은 고콜레스테롤 식이군과 비교하였을 때 유의적인 차이를 보이지 않았다. 고콜레스테롤 식이군의 HDL-콜레스테롤 함량은 정상 식이군에 비해 감소하였고 상추 추출물이 첨가된 경우 HDL-콜레스테롤 함량은 고콜레스테롤 식이군에 비해 유의적으로 증가하였다. LDL-콜레스테롤 함량은 고콜레스테롤 식이군에서 크게 증가하였고 상추 추출물이 첨가된 경우 감소하였다. 혈청의 동맥경화지수 및 심혈관지수는 고콜레스테롤 식이군에서 정상 식이군에 비해 유의적으로 증가하였고 상추 추출물이 첨가된 고콜레스테롤 식이군에서 유의한 감소를 나타내었다. 이상의 연구결과는 상추 추출물이 혈관내피세포의 염증반응을 억제하여 혈관협착을 방지할 수 있고 혈중 지질대사의 개선 효과를 보여 혈액순환개선 및 동맥경화, 심혈관질환의 예방과 치료에 효과가 있다는 것을 의미한다.

• 생명과학회지
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• 제33권4호
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• pp.315-324
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• 2023

폴리코사놀의 콜레스테롤 감소 효과에 대한 기전은 아직 명확하게 규명되지 못하고 있다. 최근 몇몇 연구들은 지방산 합성 경로를 통한 콜레스테롤 합성의 조절에 sterol regulatory element-binding proteins(SREBP-1c)의 역할을 제시하였다. 그러나 현재까지 SREBP-1c에 의해 조절되는 지방산 합성에서 폴리코사놀의 효과에 대한 연구는 전무하다. 그러므로 본 연구의 목표는 SREBP-1c에 의해 매개되는 지방산 합성이 폴리코사놀의 콜레스테롤 감소 효과와 관계하는지를 조사하는 것이다. 7주령의 C57BL/6 수컷 생쥐를 7개군(군당 7마리)으로 나누고 8주간 다음과 같이 처리하였다; 1) 정상식이군(정상 대조군), 2) 고지방식이군(high-fat diet, HFD, 음성대조군), 3) 고지방식이+에탄올처리군(Pol-0), 4) 고지방식이+1 mg/kg 폴리코사놀처리군(Pol-1), 5) 고지방식이+2 mg/kg 폴리코사놀처리군(Pol-2), 6) 고지방식이+4 mg/kg 폴리코사놀처리군(Pol-4),7) 고지방식이+simvastatin 50 ㎍/kg 처리군(양성 대조군). 폴리코사놀과 simvastatin은 고지방식이를 유지하는 동안 매일 동일 시간에 처리하였으며 체중과 음식섭취량은 8주 동안 매주 측정하였다. 8주 후, 혈중 콜레스테롤 수치를 측정하였으며, 간의 조직학적 분석과 SREBP-1c와 지방산의 발현을 조사하였다. 폴리코사놀은 농도-의존적으로 체중과 음식섭취량을 감소시켰다. 혈중 콜레스테롤 수치는 Pol-1과 Pol-4군에서 유의하게 감소하였으며, SREBP-1c와 FAS의 발현 역시 Pol-4 군에서 유의하게 감소하였다. 이러한 결과들은 폴리코사놀의 콜레스테롤 감소 효과가 SREBP-1c와 FAS의 발현 억제에 기인하여 일어날 수 있음을 시사한다.