• 한국식품영양학회지
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• 제30권5호
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• pp.1035-1041
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• 2017

(-)-Epigallocatechin-3-gallate (EGCG) is a major catechin found in green tea. It is reported that EGCG possesses various health benefits including anti-cancer, antioxidant, anti-diabetes, and anti-obesity. The objective of this study was to investigate the effects of EGCG on adipogenesis via activation of AMP-activated protein kinase (AMPK) pathway in 3T3-L1 preadipocytes. In order to determine the effects of EGCG on adipogenesis, preadipocyte differentiation was induced in the presence or absence of EGCG ($0{\sim}100{\mu}M$) for a period of 6 days. EGCG significantly inhibited fat accumulation and suppressed the expression of adipogenic specific proteins including peroxisome proliferator-activated receptor (PPAR)-${\gamma}$. Also, EGCG markedly increased the activation of AMPK and acetyl-CoA carboxylase (ACC) and the production of intracellular reactive oxygen species (ROS). However, any pretreatment with a specific AMPK inhibitor, compound C, abolished the inhibitory effects of the EGCG on $PPAR{\gamma}$ expression. This study suggests that EGCG has anti-adipogenic effects through modulation of the AMPK signaling pathway and therefore, may be a promising antiobesity agent.

• 대한한의학방제학회지
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• 제31권1호
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• pp.41-51
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• 2023

Objectives : Raphani Semen (Raphanus sativus L.) is known for the various beneficial effects in Korean medicine. This study aimed to investigate the effect of Raphani Semen extract (RSE) against arachidonic acid (AA)+iron-induced oxidative stress in cells. Methods : Ingredients, their target information, oxidative stress liver injury-related proteins was obtained from various network pharmacology databases and software. A hypergeometric test and enrichment analysis were conducted to evaluate associations between protein targets of RSE. The cell viability was assessed by MTT assay, and immunoblot analysis was used to confirm the molecular mechanisms. Results : A compound-target network of RSE was constructed, which consisted of 336 edges between 18 ingredients and 123 protein targets. PI3K-Akt signaling pathway, ErbB signaling pathway, HIF-1 signaling pathway, PPAR signaling pathway, and AMPK signaling pathway was significantly associated with protein targets of RSE. RSE protected HepG2 cells against AA+iron-induced oxidative stress as mediated with AMPK signaling. Conclusion : RSE was found to protect the cells against oxidative stress via the AMPK signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5455-5461
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• 2014

Background: Saponins are a major active component for the traditional Chinese medicine, Rubus parvifolius L., which has shown clear antitumor activities. However, the specific effects and mechanisms of saponins of Rubus parvifolius L. (SRP) remain unclear with regard to human chronic myeloid leukemia cells. The aim of this study was to investigate inhibition of proliferation and apoptosis induction effects of SRP in K562 cells and further elucidate its regulatory mechanisms. Materials and Methods: K562 cells were treated with different concentrations of SRP and MTT assays were performed to determine cell viability. Apoptosis induction by SRP was determined with FACS and DAPI staining analysis. Western blotting was used to detect expression of apoptosis and survival related genes. Specific inhibitors were added to confirm roles of STAT3 and AMPK pathways in SRP induction of apoptosis. Results: Our results indicated that SRP exhibited obvious inhibitory effects on the growth of K562 cells, and significantly induced apoptosis. Cleavage of pro-apoptotic proteins was dramatically increased after SRP exposure. SRP treatment also increased the activities of AMPK and JNK pathways, and inhibited the phosphorylation expression level of STAT3 in K562 cells. Inhibition of the AMPK pathway blocked the activation of JNK by SRP, indicating that SRP regulated the expression of JNK dependent oon the AMPK pathway. Furthermore, inhibition of the latter significantly conferred resistance to SRP pro-apoptotic activity, suggesting involvement of the AMPK pathway in induction of apoptosis. Pretreatment with a STAT3 inhibitor also augmented SRP induced growth inhibition and cell apoptosis, further confirming roles of the STAT3 pathway after SRP treatment. Conclusions: Our results demonstrated that SRP induce cell apoptosis through AMPK activation and STAT3 inhibition in K562 cells. This suggests the possibility of further developing SRP as an alternative treatment option, or perhaps using it as adjuvant chemotherapeutic agent for chronic myeloid leukemia therapy.

• 생명과학회지
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• 제25권3호
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• pp.285-292
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• 2015

본 연구에서는 3T3-L1 지방전구세포가 지방세포로 분화되는 과정에서 진피 에탄올 추출물(ethanol extracts of citrus peel, EECP)이 유발하는 항비만 효능에 대해서 조사하였다. 3T3-L1 세포의 생존율 및 증식에 영향을 미치지 않는 농도의 EECP를 처리하였을 경우 지방세포에서 특징적으로 나타나는 lipid droplet의 형성과 triglyceride의 생성도 억제되는 것으로 나타났다. EECP가 유발하는 지방세포로의 분화억제에는 PPARγ, C/EBPα, C/EBPβ 및 SREBP-1c 등과 같은 adipogenic transcription factors의 발현억제가 관여하는 것으로 나타났으며, 그 결과로 aP2 및 Leptin과 같은 adipocyte expressed genes의 발현도 억제되는 것으로 조사되었다. 또한 EECP는 AMPK 및 ACC의 인산화를 유발하였으며, AMPK 억제제인 Compound C를 이용하여 AMPK의 활성을 억제하였을 경우 EECP에 의한 AMPK의 인산화와 adipogenic transcription factors의 억제현상이 회복되었다. 이상의 결과에서 EECP는 AMPK signaling pathway를 통하여 항비만 효능을 가진다는 것을 알 수 있었으며, 향후 비만 예방 및 억제와 관련된 기능성 소재로서의 진피의 활용 가능성을 제시한 것으로서 그 가치가 매우 높을 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.203-210
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• 2015

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Previous studies have shown that activation of AMPK results in suppression of cardiac myocyte hypertrophy via inhibition of the p70S6 kinase (p70S6K) and eukaryotic elongation factor-2 (eEF2) signaling pathways. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac hypertrophy. However, the molecular mechanisms has not been well investigated. In this study, we found that EGCG could significantly reduce natriuretic peptides type A (Nppa), brain natriuretic polypeptide (BNP) mRNA expression and decrease cell surface area in H9C2 cardiomyocytes stimulated with phenylephrine (PE). Moreover, we showed that AMPK is activated in H9C2 cardiomyocytes by EGCG, and AMPK-dependent pathway participates in the inhibitory effects of EGCG on cardiac hypertrophy. Taken together, our findings provide the first evidence that the effect of EGCG against cardiac hypertrophy may be attributed to its activation on AMPK-dependent signaling pathway, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy.

• Nutrition Research and Practice
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• 제18권4호
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• pp.479-497
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• 2024

BACKGROUND/OBJECTIVES: Activating brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can protect against obesity and obesity-related metabolic conditions. Cryptotanshinone (CT) regulates lipid metabolism and significantly ameliorates insulin resistance. Adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), a receptor for cellular energy metabolism, is believed to regulate brown fat activity in humans. MATERIALS/METHODS: The in vivo study included high-fat-fed obese mice administered orally 200/400 mg/kg/d CT. They were evaluated through weight measurement, the intraperitoneal glucose tolerance test (IPGTT), intraperitoneal insulin tolerance test (IPITT), cold stimulation test, serum lipid (total cholesterol, triglycerides, and low-density lipoprotein) measurement, hematoxylin and eosin staining, and immunohistochemistry. Furthermore, the in vitro study investigated primary adipose mesenchymal stem cells (MSCs) with incubation of CT and AMPK agonists (acadesine)/inhibitor (Compound C). Cells were evaluated using Oil Red O staining, Alizarin red staining, flow cytometry, and immunofluorescence staining to identify and observe the osteogenic versus adipogenic differentiation. Quantitative real-time polymerase chain reaction and the Western blot were used to observe related gene expression. RESULTS: In the diet-induced obesity mouse model mice CT suppressed body weight, food intake, glucose levels in the IPGTT and IPTT, serum lipids, the volume of adipose tissue, and increased thermogenesis, uncoupling protein 1, and the AMPK pathway expression. In the in vitro study, CT prevented the formation of lipid droplets from MSCs while activating brown genes and the AMPK pathway. AMPK activator enhanced CT's effects, while the AMPK inhibitor reversed the effects of CT. CONCLUSION: CT promotes adipose tissue browning to increase body thermogenesis and reduce obesity by activating the AMPK pathway. This study provides an experimental foundation for the use of CT in obesity treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4033-4039
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• 2013

Links between cancer and metabolism have been suggested for a long time but compelling evidence for this hypothesis came from the recent molecular characterization of the LKB1/AMPK signaling pathway as a tumor suppressor axis. Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells. In addition, AMPK plays a central role in the control of cell growth, proliferation and autophagy through the regulation of mTOR activity, which is consistently deregulated in cancer cells. Targeting of AMPK/mTOR is thus an attractive strategy in the development of therapeutic agents against non-small-cell lung cancer (NSCLC). In this review, the LKB1/AMPK/mTOR signaling pathway is described, highlighting its protective role, and opportunities for therapeutic intervention, and clinical trials in NSCLC.

• Food Science and Biotechnology
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• 제17권5호
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• pp.1047-1051
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• 2008

Overexpression of HER2 in breast cancer cells is considered to induce the expression of acetyl-CoA carboxylase $\alpha$ (ACACA) and fatty acid synthase (FASN) through activation of mammalian target of rapamycin (mTOR) signaling pathway. Resveratrol, a red wine polyphenol, has been shown to induce apoptosis in several cancers by interfering in several signaling pathways. Present study elucidated the mechanism by which resveratrol downregulates ACACA and FASN in breast cancer cells. Resveratrol activated AMP-activated protein kinase (AMPK) and downregulated mTOR in BT-474 cells. These effects of resveratrol were mimicked by AICAR, an AMPK activator, and exogenously expressed constitutively active AMPK, while they were abolished by a dominant-negative mutant of AMPK. The downregulation of mTOR was not accompanied with changes in Akt, the upstream regulator of mTOR. These findings indicate that the downregulation of ACACA and FASN by resveratrol is mediated by the downregulation of mTOR signaling pathway via activation of AMPK.

• 생명과학회지
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• 제32권2호
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• pp.86-93
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• 2022

Lupeol은 pentacyclic triterpene의 일종으로 다양한 질병에 약리 효과가 있는 것으로 보고되어 있으나, lupeol이 포도당 흡수에 미치는 영향은 아직 보고된 바 없다. 본 연구에서 3T3-L1 지방세포에서 포도당 흡수에 대한 lupeol의 효과를 조사하였다. 그 결과, Lupeol은 3T3-L1 지방세포에서 GLUT4를 원형질막으로 이동시켜 포도당 흡수를 촉진하였으며, 이는 PI3K/AKT 및 AMPK 경로의 활성화와 관련되어 있었다. PI3K/AKT 경로에서 lupeol은 PI3K를 활성화시키는 insulin receptor substrate 1의 인산화와 AKT의 인산화를 촉진하지만 비정형 단백질 키나아제 C isoforms ζ 및 λ의 인산화는 촉진하지 않았다. 반면, lupeol은 5 'AMP-activated protein kinase의 인산화를 촉진하였고, Lupeol의 의한 AMPK의 활성화는 원형질막-GLUT4의 발현과 세포내 포도당 흡수를 증가시키는 것으로 확인되었다. 3T3-L1 지방세포에서 lupeol에 의한 포도당 흡수 효과는 PI3K 억제제인 wortmannin 및 AMPK 억제제인 Compound C에 의해 억제됨을 통해 확인하였다. 본 연구 결과는 lupeol이 3T3-L1 지방세포에서 PI3K/AKT 및 AMPK 경로를 통해 원형질막 GLUT4의 발현을 자극함으로써 인슐린 감수성을 증가시켜 포도당 흡수를 촉진할 수 있음을 제시하고 있다.

• 한국식품영양과학회지
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• 제42권8호
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• pp.1197-1203
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• 2013

본 연구는 2주간의 지구성 운동과 ginsenoside $Rb_1$이 쥐골격근의 AMPK insulin signaling($tAMPK{\alpha}$, $pAMPK{\alpha}$ $Thr^{172}$)과 PI3K insulin signaling pathway(pIRS-1 $Tyr^{612}$, PI3K $p^{85}$, pAkt $Ser^{473}$) 발현 및 glucose uptake에 미치는 영향을 분석하였다. 골격근내 glucose uptake에서는 비교집단과 비교하여 운동집단(59.4%), $Rb_1$집단(70.5%) $Rb_1/Ex$집단(58.6%)에서 유의하게 증가하였다. 2주간의 지구성 운동과 ginsenoside $Rb_1$이 AMPK insulin signaling pathway에 미치는 효과를 조사한 결과 비교집단에 비해 $AMPK{\alpha}$(Ex, 28.6%; $Rb_1$, 28.5%; $Rb_1/Ex$, 29.8%), $pAMPK{\alpha}$ $Thr^{172}$(Ex, 35.1%; $Rb_1$, 35.3%; $Rb_1/Ex$, 30.9%)의 발현이 유의하게 증가한 것을 알 수 있었다. 2주간의 지구성 운동과 ginsenoside $Rb_1$이 PI3K insulin signaling pathway에 미치는 효과를 알아본 결과 비교집단과 비교하여 IRS-1, PI3K $p^{85}$에서는 유의한 차이가 없었으나 pAkt $Ser^{473}$은 $Rb_1$ 집단에서 유의하게 증가한 것을 알 수 있었다. 이상의 결과를 종합해 볼 때, ginsenoside $Rb_1$은 운동과 더불어 근육 세포내 AMPK의 활성화와 근육 내 glucose uptake를 증가시켜 제2형 당뇨병 예방과 치료에 효과가 있을 것으로 생각된다. 그러나 본 연구의 결과로 PI3K insulin signaling pathway의 항당뇨 효과는 설명하기는 부족하다고 판단되며 추후 본 연구의 결과를 기초로 ginsenoside $Rb_1$의 농도, 처치시간, 처치방법을 고려한 후속 연구가 필요할 것으로 생각된다.