• Journal of Ginseng Research
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• 제46권2호
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• pp.255-265
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• 2022

Background: Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective. Methods: The mice model of acute myocardial ischemia (AMI) and oxygen glucose deprivation (OGD)-induced cardiomyocytes injury were applied to explore the protective effect and mechanism of Rb1. Meanwhile, the comprehensive metabolomics profiling was conducted by high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) and a tandem liquid chromatography and mass spectrometry (LC-MS). Results: Rb1 treatment profoundly reduced the infarct size and attenuated myocardial injury. The metabolic network map of 65 differential endogenous metabolites was constructed and provided a new inspiration for the treatment of AMI by Rb1, which was mainly associated with mitophagy. In vivo and in vitro experiments, Rb1 was found to improve mitochondrial morphology, mitochondrial function and promote mitophagy. Interestingly, the mitophagy inhibitor partly attenuated the cardioprotective effect of Rb1. Additionally, Rb1 markedly facilitated the phosphorylation of AMP-activated protein kinase α (AMPKα), and AMPK inhibition partially weakened the role of Rb1 in promoting mitophagy. Conclusions: Ginsenoside Rb1 protects acute myocardial ischemia injury through promoting mitophagy via AMPKα phosphorylation, which might lay the foundation for the further application of Rb1 in cardiovascular diseases.

• 생명과학회지
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• 제32권7호
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• pp.542-549
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• 2022

Polymethoxyflavones (PMFs)는 주로 감귤류에서 발견되는 플라보노이드로 다양한 생리활성을 나타낸다고 알려져 있다. 본 연구에서는 제주재래귤인 진귤(Citrus sunki Hort. ex Tanaka)에서 PMFs를 다량 함유하는 분획물(PMFs-rich fraction, PRF)을 획득하는 방법을 확립하여 3T3-L1 세포에서 지방대사에 미치는 영향을 분석하였다. PRF는 3T3-L1 전구지방세포의 지방생성(lipogenesis)을 농도 의존적으로 억제하였다. PRF는 peroxisome proliferator-activated receptor 𝛾 (PPAR𝛾)와 CCAAT/enhancer binding protein 𝛼 (CEBP𝛼) 발현을 억제함으로써 fatty acid synthase (FAS), adipocyte fatty-acid-binding protein 2 (aP2)의 발현을 억제하여 지방생성을 억제함을 확인할 수 있었다. 성숙한 3T3-L1 지방세포에 PRF를 처리하면, cAMP 의존성 protein kinase A (PKA)/sterol regulatory element-binding protein 1 (HSL)의 활성화가 일어나 지방분해(lipogenesis)는 촉진됨을 확인할 수 있었다. 그리고 PRF는 AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC)의 인산화를 증가시켜 지방산화를 촉진할 수 있음을 확인하였다. 이 연구결과는 진귤 잎 유래 PRF는 3T3-L1 전구지방세포의 분화를 억제하고 성숙한 지방세포에서 지방분해 및 지방산 산화를 촉진하는 활성을 나타내어 항비만 소재로서의 활용가능성을 제시하였다.

• 대한본초학회지
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• 제28권1호
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• pp.23-31
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• 2013

Objectives : The purpose of this study was to determine the anti-obesity effect and molecular mechanism of YY312, a herbal extract composed of Imperatae Rhizoma, Citri Unshius Pericarpium Immaturus, and Evodiae Fructus, on a high-fat diet-induced animal model and on 3T3-L1 cells. Methods : C57BL/6 mice were fed for 6 weeks with a normal diet or a high-fat diet (HFD). Then they orally administered daily with 300 mg/kg YY312 for next 10 weeks. Body weight and food consumption were recorded weekly and daily, respectively. Tissue weights, serum lipid, and glucose levels were analyzed at the end of the study. Additionally, the effects of YY312 on adipocyte differentiation in 3T3-L1 cells were examined. After differentiating 3T3-L1 cells were treated with YY312, Oil-red O staining, RT-PCR, and Western blotting were performed for lipid accumulation, mRNA expression of adipogenesis gene, and AMP-activated protein kinase (AMPK) phosphorylation, respectively. Results : YY312-administered mice showed a significant reduction of body weights and abdominal adipose tissue weights. YY312 also reduced the serum levels of triglycerides and total cholesterol, compared with the HFD group. Treatment with YY312 inhibited lipid accumulation and blocked expression of adipogenic transcription factors and lipogenesis genes, including peroxisome proliferator-activated receptor ${\gamma}$, CCAT/enhancer binding protein ${\alpha}$ and fatty acid synthase. YY312 increased AMPK phosphorylation in 3T3-L1 adipocytes. Conclusions : This study showed that herbal extract YY312 has an anti-obesity effect in vitro and in vivo. Thus, YY312 could be developed as a supplement for reduction of body weight gain induced by an HFD.

• 대한본초학회지
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• 제34권6호
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• pp.79-89
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• 2019

Objective : This study investigated the anti-diabetic effects of DM1, a herbal mixture with Atractylodis Rhizoma, Anemarrhenae Rhizoma, and Cinnamomi Cortex in high fat diet (HFD)-induced diabetic mice and the mechanism in C2C12 mouse skeletal muscle cells. Methods : The C57B/6 mice were fed high fat for 12 weeks, and then administrated DM1 extract (500 mg/kg, p.o.) for 4 weeks. The changes of body weight, calorie and water intakes, fasting blood glucose levels and the serum levels of glucose, insulin, triglyceride, HDL-cholesterol, AST and ALT were measured in mice. The histological changes of liver and pancreas tissues were also observed by H&E stain. C2C12 myoblasts were differentiated into myotubes and then treated with DM1 extract (0.5, 1, and 2 mg/㎖) for 24 hr. The expression of myosin heavy chain (MHC), PGC1α, Sirt1 and NRF1, and the AMPK phosphorylation were determined in the myotubes by western blot, respectively. Results : The DM1 extract administration significantly decreased the calorie and water intakes, glucose, triglyceride, AST and ALT levels and increased insulin and HDL-cholesterol in HFD-induced diabetic mice. DM1 extract inhibited lipid accumulation in liver tissue and improved glucose tolerance. In C2C12 myotubes, DM1 treatment increased the expression of MHC, PGC1α, Sirt-1, NRF-1 and the AMPK phosphorylation. Conclusion : In our results indicate that DM1 can improve diabetic symptoms by decreasing the obesity, glucose tolerance and fatty liver in HFD-induced diabetic mice, and responsible mechanism is might be related with energy enhancement.

• Nutrition Research and Practice
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• 제9권1호
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• pp.22-29
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• 2015

BACKGROUND/OBJECTIVES: Recently, anthocyanins have been reported to have various biological activities. Furthermore, anthocyanin-rich purple corn extract (PCE) ameliorated insulin resistance and reduced diabetes-associated mesanginal fibrosis and inflammation, suggesting that it may have benefits for the prevention of diabetes and diabetes complications. In this study, we determined the anthocyanins and non-anthocyanin component of PCE by HPLC-ESI-MS and investigated its anti-diabetic activity and mechanisms using C57BL/KsJ db/db mice. MATERIALS/METHODS: The db/db mice were divided into four groups: diabetic control group (DC), 10 or 50 mg/kg PCE (PCE 10 or PCE 50), or 10 mg/kg pinitol (pinitol 10) and treated with drugs once per day for 8 weeks. During the experiment, body weight and blood glucose levels were measured every week. At the end of treatment, we measured several diabetic parameters. RESULTS: Compared to the DC group, Fasting blood glucose levels were 68% lower in PCE 50 group and 51% lower in the pinitol 10 group. Furthermore, the PCE 50 group showed 2-fold increased C-peptide and adiponectin levels and 20% decreased HbA1c levels, than in the DC group. In pancreatic islets morphology, the PCE- or pinitol-treated mice showed significant prevention of pancreatic ${\beta}$-cell damage and higher insulin content. Microarray analyses results indicating that gene and protein expressions associated with glycolysis and fatty acid metabolism in liver and fat tissues. In addition, purple corn extract increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6pase) genes in liver, and also increased glucose transporter 4 (GLUT4) expressions in skeletal muscle. CONCLUSIONS: Our results suggested that PCE exerted anti-diabetic effects through protection of pancreatic ${\beta}$-cells, increase of insulin secretion and AMPK activation in the liver of C57BL/KsJ db/db mice.

• Journal of Microbiology and Biotechnology
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• 제23권5호
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• pp.637-643
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• 2013

We have demonstrated that 1-deoxynojirimycin (DNJ) isolated from Bacillus subtilis MORI could enhance the levels of adiponectin and its receptors in differentiated 3T3-L1 adipocytes, which has been shown to be effective in lowering blood glucose levels and enhancing insulin sensitivity. DNJ was not toxic to differentiated 3T3-L1 adipocytes for up to a concentration of $5{\mu}M$. In terms of expression levels of adiponectin and its receptors (AdipoR1 and AdipoR2), DNJ in concentrations as low as $0.5{\mu}M$ elevated both mRNA and protein levels of adiponectin and transcript levels of AdipoR1 and AdipoR2. In addition, DNJ increased phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK) in a statistically significant manner. Finally, treatment with DNJ resulted in increased mRNA expression of glucose transporter 4 (GLUT4), which encodes for a glucose transporter, along with a significant increase in glucose uptake into the adipocytes based on results of a 2-deoxy-D-[$^3H$] glucose uptake assay. Our findings indicate that DNJ may greatly facilitate glucose uptake into adipose tissues by increasing the action of adiponectin via its up-regulated expression as well as its receptor genes. In addition, the glucose-lowering effects of DNJ may be achieved by an increased abundance of GLUT4 protein in the plasma membrane, as a consequence of the increased transcript levels of the GLUT4 gene and the activation of AMPK.

• 생명과학회지
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• 제29권10호
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• pp.1152-1158
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• 2019

겹삼잎국화는 한국에서 복통, 위염에 민간요법으로 사용되는 약초로 알려져있다. 하지만, 겹삼잎국화를 민간요법으로 사용되고 있으나 이 약초에 대한 연구는 거의 수행되어지지 않았다. 본 연구에서는 겹삼잎국화의 의학적 효과를 증명하기 위해 항비만 관련 연구를 수행하였다. 70% 에탄올을 이용한 겹삼잎국화 추출물의 항 비만 효과에 대한 연구를 위해 3T3-L1 지방전구세포를 사용하였으며, 지방전구세포가 지방세포로 성숙하는 것을 방지하고 이에 관련된 단백질 인자의 발현을 확인하기 위해 Oil Red O 염색법과 웨스턴 블롯, PCR을 통한 mRNA 분석이 수행되었다. DM (인슐린 칵테일)을 처리하여 지방전구세포의 성숙을 유도한 후, 겹삼잎국화 에탄올 추출물을 처리한 결과, $100{\mu}g/ml$ 농도에서 지방세포 분화 억제 효과와 세포 내 트리글리세리드(TG)의 수준이 현저하게 감소한 것을 확인하였다. 또한, 지방전구세포의 성숙에 관여하는 여러가지 단백질 등의 인자 발현율 또한 확인하였다. 겹삼잎국화 에탄올 추출물로 인해 $PPAR{\gamma}$, $C/EBP{\alpha}$, LPL, FAS와 같은 지방 세포의 성숙을 유도하는 인자가 조절되었으며, Acetyl-CoA carboxylase, AMP-activated protein kinase (AMPK) 등과 같은 단백질의 발현도 억제하여 분자적 기전 또한 규명하였다. 결론적으로, 겹삼잎국화 에탄올 추출물은 지방전구세포의 활성에 영향을 끼치지 않으며 지방세포로의 성숙을 유도하는 인자 및 단백질의 발현을 선택적으로 조절하여 항 비만 효과를 갖는 것으로 확인되었다.

• 대한본초학회지
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• 제33권6호
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• pp.61-70
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• 2018

Objectives : Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of hepatic triglycerides (TG) that leads to inflammation and fibrosis. Crataegi Fructus ethanol extract (CE) is a korean traditional herb that used for digestive diseases. It has been investigated that CE has the effect that prevent hepatotoxicity caused by CCl4 or GaIN and regulate the inflammatory in several organs. However, a hypolipidemic effect of CF has not been reported. Methods : The purpose of this study is that examine the lipid accumulation inhibitory effect of CE on NAFLD. We checked the body and liver weight change of MCD-diet induced mice with/without administration of CE. The blood lipid levels of C57BL/6J mice were checked by biochemistry. Also we observed the liver histology of MCD-diet induced mice and investigate the molecular mechanisms in MCD-diet-induced NAFLD in C57BL/6J mice. Results : CE improved MCD-diet-induced lipid accumulation and TG and TC levels. Also, CE decreased hepatic lipogenesis such as SREBP-1, $C/EBP{\alpha}$, $PPAR{\gamma}$, ACC and FAS. Besides, we also found out that CE increased AMPK phosphorylation. These results indicated that CE has the same ability to activate AMPK and then reduce SREBP-1, and FAS expression, finally leading to inhibit hepatic lipogenesis and hepatic antioxidative ability. Conclusions : In this report, we found CE exerted a regulatory effect on lipid accumulation by decreasing lipogenesis in MCD-diet induced NAFLD model. Therefore, CE extract may be active in the prevention of fatty liver.

• Biomolecules & Therapeutics
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• 제25권6호
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• pp.609-617
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• 2017

Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of ${\alpha}$-mangostin (${\alpha}M$) and ${\gamma}$-mangostin (${\gamma}M$) extracted from the pericarp of Garcinia mangostana L.. Both ${\alpha}$M and ${\gamma}M$ reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels. They also induced autophagy by increasing levels of microtubule-associated protein 1A/1B light chain 3B (LC3II) in both cell lines while decreasing sequestosome 1 (p62) in MIA PaCa-2. Both ${\alpha}$M and ${\gamma}M$ induced autophagy through increasing phosphorylation levels of AMP-activated protein kinase (p-AMPK) and p38-mitogen activated protein kinase (p-p38) while decreasing phosphorylation level of mammalian target of rapamycin complex 1 (p-mTOR). Of various microRNAs (miRNA), miR-18a was found to be a putative regulatory miRNA for autophagy induced by ${\alpha}$M or ${\gamma}M$. In combination with gemcitabine, a compound frequently used in pancreatic cancer treatment, ${\alpha}$M and ${\gamma}M$ showed synergistic anti-cancer effects in MIA PaCa-2. Collectively, these results suggest that ${\alpha}$M and ${\gamma}M$ can induce apoptosis and autophagy in pancreatic cancer cells and that their anti-cancer effect is likely to be associated with miR-18a. In conclusion, ${\alpha}$M and ${\gamma}M$ might be used as a potential new therapy for pancreatic cancer.

• Nutrition Research and Practice
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• 제16권3호
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• pp.298-313
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• 2022

BACKGROUND/OBJECTIVES: The effectiveness of natural compounds in improving athletic ability has attracted attention in both sports and research. Gynostemma pentaphyllum (Thunb.) leaves are used to make traditional herbal medicines in Asia. The active components of G. pentaphyllum, dammarane saponins, or gypenosides, possess a range of biological activities. On the other hand, the anti-fatigue effects from G. pentaphyllum extract (GPE) and its effective compound, gypenoside L (GL), remain to be determined. MATERIALS/METHODS: This study examined the effects of GPE on fatigue and exercise performance in ICR mice. GPE was administered orally to mice for 6 weeks, with or without treadmill training. The biochemical analysis in serum, glycogen content, mRNA, and protein expressions of the liver and muscle were analyzed. RESULTS: The ExGPE (exercise with 300 mg/kg body weight/day of GPE) mice decreased the fat mass percentage significantly compared to the ExC mice, while the ExGPE showed the greatest lean mass percentage compared to the ExC group. The administration of GPE improved the exercise endurance and capacity in treadmill-trained mice, increased glucose and triglycerides, and decreased the serum creatine kinase and lactate levels after intensive exercise. The muscle glycogen levels were higher in the ExGPE group than the ExC group. GPE increased the level of mitochondrial biogenesis by enhancing the phosphorylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein and the mRNA expression of nuclear respiratory factor 1, mitochondrial DNA, peroxisome proliferator-activated receptor-δ, superoxide dismutase 2, and by decreasing the lactate dehydrogenase B level in the soleus muscle (SOL). GPE also improved PGC-1α activation in the SOL significantly through AMPK/p38 phosphorylation. CONCLUSIONS: These results showed that GPE supplementation enhances exercise performance and has anti-fatigue activity. In addition, the underlying molecular mechanism was elucidated. Therefore, GPE is a promising candidate for developing functional foods and enhancing the exercise capacity and anti-fatigue activity.