• Title/Summary/Keyword: AMP-activated Protein Kinase (AMPK)

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Ethanol Extract of Schisandra chinensis (Turcz.) Baill. Reduces AICAR-induced Muscle Atrophy in C2C12 Myotubes (마우스 C2C12 근관세포에서 AICAR로 유도된 근위축에 미치는 오미자 추출물의 영향)

  • Kang, Young-Soon;Park, Cheol;Han, Min-Ho;Hong, Su-Hyun;Hwang, Hye-Jin;Kim, Byung Woo;Kim, Cheol Min;Choi, Yung Hyun
    • Journal of Life Science
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    • v.25 no.3
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    • pp.293-298
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    • 2015
  • Muscle atrophy, known as a sarcopenia, is defined as a loss of muscle mass resulting from a reduction in the muscle fiber area or density due to a decrease in muscle protein synthesis and an increase in protein breakdown. Schisandrae fructus (SF) extract of the fruits of Schisandra chinensis (Turcz) Baillon has been used as a tonic in traditional medicine for thousands of years. Although a great deal of work has been carried out on the therapeutic potential of SF, its pharmacological mechanisms of action in muscle diseases actions remain unclear. In the present study, we investigated the inhibitory effects of SF ethanol extracts on the production of muscle atrophy factors in C2C12 myotubes stimulated with 5-aminoimidazole-4-carboxamide-ribonucleotide (AICAR), an AMP-activated kinase (AMPK) activator, and sought to determine the underlying mechanisms of action. AICAR upregulated atrophy-related ubiquitin ligase muscle RING finger-1 (MuRF-1) and stimulated the levels of the forkhead box O3a (FoxO3a) transcription factor in the C2C12 myotubes. SF supplementation effectively and concentration- dependently counteracted AICAR-induced muscle cell atrophy and reversed the increased expression of MuRF-1 and FoxO3a. Our study demonstrates that SF can reverse the muscle cell atrophy caused by AICAR through regulation of the AMPK and FoxO3a signaling pathways, followed by inhibition of MuRF-1.

Comprehensive analysis of miRNAs, lncRNAs and mRNAs profiles in backfat tissue between Daweizi and Yorkshire pigs

  • Chen Chen;Yitong Chang;Yuan Deng;Qingming Cui;Yingying Liu;Huali Li;Huibo Ren;Ji Zhu;Qi Liu;Yinglin Peng
    • Animal Bioscience
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    • v.36 no.3
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    • pp.404-416
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    • 2023
  • Objective: Daweizi (DWZ) is a famous indigenous pig breed in China and characterized by tender meat and high fat percentage. However, the expression profiles and functions of transcripts in DWZ pigs is still in infancy. The object of this study was to depict the transcript profiles in DWZ pigs and screen the potential pathway influence adipogenesis and fat deposition, Methods: Histological analysis of backfat tissue was firstly performed between DWZ and lean-type Yorkshire pigs, and then RNA sequencing technology was utilized to explore miRNAs, lncRNAs and mRNAs profiles in backfat tissue. 18 differentially expressed (DE) transcripts were randomly selected for quantitative real-time polymerase chain reaction (QPCR) to validate the reliability of the sequencing results. Finally, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were conducted to investigate the potential pathways influence adipocyte differentiation, adipogenesis and lipid metabolism, and a schematic model was further proposed. Results: A total of 1,625 differentially expressed transcripts were identified in DWZ pigs, including 27 upregulated and 45 downregulated miRNAs, 64 upregulated and 119 down-regulated lncRNA, 814 upregulated and 556 downregulated mRNAs. QPCR analysis exhibited strong consistency with the sequencing data. GO and KEGG analysis elucidated that the differentially expressed transcripts were mainly associated with cell growth and death, signal transduction, peroxisome proliferator-activated receptors (PPAR), AMP-activated protein kinase (AMPK), PI3K-Akt, adipocytokine and foxo signaling pathways, all of which are strongly involved in cell development, lipid metabolism and adipogenesis. Further analysis indicated that the BGIR9823_87926/miR-194a-5p/AQP7 network may be effective in the process of adipocyte differentiation or adipogenesis. Conclusion: Our study provides comprehensive insights into the regulatory network of backfat deposition and lipid metabolism in pigs from the point of view of miRNAs, lncRNAs and mRNAs.

Antioxidant and Anti-Obesity Effect of SM17 in High-Fat Diet Induced C57BL/6 Mice (고지방식이로 비만을 유도한 C57BL/6 마우스에서 SM17의 항산화 및 항비만 효과)

  • Kim, Soo Hyun;Kim, Su Ji;Kim, Kyeong Jo;Lee, Ah Reum;Roh, Seong-Soo;Lee, Young Cheol
    • The Korea Journal of Herbology
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    • v.32 no.5
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    • pp.47-55
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    • 2017
  • Objectives : Obesity is caused by the excess accumulation of fat in the body due to energy imbalance, and it causes various diseases. The aim of this study was to investigate an anti-obesity efficacy and an antioxidant activity of water from herbal mixture extract (SM17). Methods : The antioxidant activities were evaluated through radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals. To evaluated anti-obesity effect of SM17, we used a high fat diet fed mouse model. The SM17 (150 mg/kg body weight/day, p.o.) was treated every day for 6 weeks to C57BL/6 mice. Body weight and food intake were measured every day. The changes of reactive oxygen species (ROS), alanine aminotransferanse (ALT), aspartate aminotransferase (AST), triglycerids (TG) and total cholesterol (TC) in serum were analyzed after experiment. Also, expression of lipid metabolism related proteins were investigated by western blot analysis. Results : It was effective in antioxidant measurements, SM17 administration inhibited the biomarkers of lipid metaboism in serum and tissues. The administration of SM17 showed a significant reduction of body and tissue weight. Morever, it decreased ROS, ALT, AST, TG and TC in serum, compared with those of the obese mice. Adipogenesis-related protein expressions increased in obese mice compared to normal mice. However, SM17 group exhibited the down-expression of these proteins. Conclusion : A SM17 aqueous extract has a great effect on the stimulation (AMPK) activation, and may have a benefit to reduce a fatty acid metabolism through inhibition of lipid accumulation.

Antioxidant and Antidiabetic Activities of Jerusalem Artichoke Composites Containing Gynura procumbens, Momordica charantia, and Curcuma longa via AMPK Activation (명월초, 여주 및 울금을 포함한 돼지감자 복합물의 항산화 및 AMPK 활성화를 통한 항당뇨 활성)

  • Lee, Soo-Jung;Hu, Wen-Si;Pyo, Jae-Ho;Ryu, Ji Hyeon;Kang, Dawon;Jeong, Bo-Young;Sung, Nak-Ju
    • Journal of Life Science
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    • v.28 no.1
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    • pp.26-36
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    • 2018
  • This study was performed to identify the antioxidant and ${\alpha}$-glucosidase inhibitory activities of water and 70% ethanol extracts of the three following herbs: G. procumbens, M. charantia, and C. longa. In addition, the antioxidant and antidiabetic activities of five types of Jerusalem artichoke composites (JA1 - 5), which were prepared by adding ethanol extracts of several herbs to Jerusalem artichoke concentrate, were studied and compared. The results showed that the total phenol and flavonoid contents of the ethanol extracts were higher than those of the water extracts. The DPPH and ABTS radical scavenging activities and reducing power depended on the total phenol and flavonoid contents. The antioxidant activities of ethanol extracts from G. procumbens and C. longa were comparable. Moreover, the ${\alpha}$-glucosidase inhibitory activity of the ethanol extracts ($2,000{\mu}g/ml$) from each herb was found to be over 50%. In contrast, the five types of JA composites showed higher total phenol and flavonoid contents than those of JA concentrate. In addition, increased antioxidant and ${\alpha}$-glucosidase inhibitory activities were observed, with that of JA1 being the highest. However, all concentrations ($1{\sim}100{\mu}g/ml$) of JA tested did not affect the cell viability of Chang cells. In addition, JA induced the activation of AMP-activated protein kinase (AMPK) in Chang cells and significantly increased the glucose uptake in C2C12 cells. Therefore, it could be concluded that the JA composites (JA1 - 5) mixed with G. procumbens, M. charantia, and C. longa extracts were effective in increasing the extracts' antioxidant and antidiabetic activities.

Study on the in vitro and in vivo anti-obesity effects of a combination of Syzygium aromaticum L. and Sorbus commixta Hedl. (정향과 마가목 복합물의 in vitro와 in vivo 항비만 효과 연구)

  • Ji Heon Yu;Hui Yeon An;Seong-Soo Roh;Mi-Rae Shin
    • Journal of Nutrition and Health
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    • v.57 no.2
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    • pp.196-210
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    • 2024
  • Purpose: This study investigated the anti-obesity effects of a combination of Syzygium aromaticum L. and Sorbus commixta Hedl. (SS) in vitro and in vivo. Methods: The extracts of Syzygium aromaticum extract (SA) and Sorbus commixta extract (SC) were prepared individually using distilled water. They were mixed in a 1:2 ratio for use in the experiment. To assess the anti-obesity potential of SS in vitro, we examined cell proliferation, cellular triglyceride (TG), and total cholesterol (TC) levels, as well as lipogenesis and β-oxidation in 3T3-L1 cells. To confirm its anti-obesity potential in vivo, C57BL/6J mice were fed a 60% high-fat diet (HFD) to induce obesity. SA alone, SC alone, and their combination compound, SS (at a dosage of 200 mg/kg) were orally administered for 6 weeks. Thereafter, to conduct a comparative evaluation, serum analysis, western blotting of liver tissues, and histopathological analysis were performed. Results: Both SS200 and SS400 significantly inhibited the cellular TG and TC contents in the 3T3-L1 cells. Furthermore, treatment of the cells with SS (at a dose 200 and 400 ㎍/mL) also led to a noticeable regulation of key lipogenic and β-oxidation factors. Treatment of obese mice with SS resulted in a greater reduction in serum leptin and TG levels compared to treatment with the individual compounds (SA and SC). Furthermore, activation of AMP-activated protein kinase α by SS treatment resulted in the suppression of sterol regulatory element-binding proteins (SREBP)-1, leading to the inhibition of acetyl-CoA carboxylase (ACC) expression. Conclusion: Our results suggest that SS may have the potential to prevent obesity through a reduction in the TG and TC levels and regulation of lipogenesis and β-oxidation.

Anti-diabetic effect and mechanism of Korean red ginseng extract in C57BL/KsJ db/db mice

  • Yuan, Hai-Dan;Shin, Eun-Jung;Chung, Sung-Hyun
    • Proceedings of the Ginseng society Conference
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    • 2007.12a
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    • pp.57-58
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    • 2007
  • Purpose: Ginseng is a well-known medical plant used in traditional Oriental medicine. Korean red ginseng (KRG) has been known to have potent biological activities such as radical scavenging, vasodilating, anti-tumor and anti-diabetic activities. However, the mechanism of the beneficial effects of KRG on diabetes is yet to be elucidated. The present study was designed to investigate the anti-diabetic effect and mechanism of KRG extract in C57BL/KsJ db/db mice. Methods: The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. During the experiment, body weight and blood glucose levels were measured once every week. At the end of treatment, we measured Hemoglobin A1c (HbA1c), blood glucose, insulin, triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). Morphological analyses of liver, pancreas and white adipose tissue were done by histological observation through hematoxylin-eosin staining. Pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. To elucidate an action of mechanism of KRG, DNA microarray analyses were performed, and western blot and RT-PCR were conducted for validation. Results: Compared to the DC group mice, body weight gain of PIO treated group mice showed 15.2% increase, but the other group mice did not showed significant differences. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in RGL, 18.3% in RGH, 67.7% in MET, 52.3% in GPZ, 56.9% in PIO-treated group. With decreased plasma glucose levels, the insulin resistance index of the RGL-treated group was reduced by 27.7% compared to the DC group. Insulin resistance values for positive drugs were all markedly decreased by 80.8%, 41.1% and 68.9%, compared to that of DC group. HbA1c levels in RGL, RGH, MET, GPZ and PIO-treated groups were also decreased by 11.0%, 6.4%, 18.9%, 16.1% and 27.9% compared to that of DC group, and these figure revealed a similar trend shown in plasma glucose levels. Plasma TG and NEFA levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the RGL-treated group compared to those in DC group. Histological analysis of the liver of mice treated with KRG revealed a significantly decreased number of lipid droplets compared to the DC group. The control mice exhibited definitive loss and degeneration of islet, whereas mice treated with KRG preserved islet architecture. Compared to the DC group mice, KRG resulted in significant reduction of adipocytes. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin production, but decreased glucagon production. KRG treatment resulted in stimulation of AMP-activated protein kinase (AMPK) phosphorylation in the db/db mice liver. To elucidate mechanism of action of KRG extract, microarray analysis was conducted in the liver tissue of mice treated with KRG extract, and results suggest that red ginseng affects on hepatic expression of genes responsible for glycolysis, gluconeogenesis and fatty acid oxidation. In summary, multiple administration of KRG showed the hypoglycemic activity and improved glucose tolerance. In addition, KRG increased glucose utilization and improved insulin sensitivity through inhibition of lipogenesis and activation of fatty acid $\beta$-oxidation in the liver tissue. In view of our present data, we may suggest that KRG could provide a solid basis for the development of new anti-diabetic drug.

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