• Journal of Ginseng Research
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• v.44 no.3
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• pp.461-474
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• 2020

Background: Ginseng effectively reduces fatigue in both animal models and clinical trials. However, the mechanism of action is not completely understood, and its molecular targets remain largely unknown. Methods: By screening for proteins that interact with the primary components of ginseng (ginsenosides) in an affinity chromatography assay, we have identified muscle-type creatine kinase (CK-MM) as a potential target in skeletal muscle tissues. Results: Biolayer interferometry analysis showed that ginsenoside metabolites, instead of parent ginsenosides, had direct interaction with recombinant human CK-MM. Subsequently, 20(S)-protopanaxadiol (PPD), which is a ginsenoside metabolite and displayed the strongest interaction with CK-MM in the study, was selected as a representative to confirm direct binding and its biological importance. Biolayer interferometry kinetics analysis and isothermal titration calorimetry assay demonstrated that PPD specifically bound to human CK-MM. Moreover, the mutation of key amino acids predicted by molecular docking decreased the affinity between PPD and CK-MM. The direct binding activated CK-MM activity in vitro and in vivo, which increased the levels of tissue phosphocreatine and strengthened the function of the creatine kinase/phosphocreatine system in skeletal muscle, thus buffering cellular ATP, delaying exercise-induced lactate accumulation, and improving exercise performance in mice. Conclusion: Our results suggest a cellular target and an initiating molecular event by which ginseng reduces fatigue. All these findings indicate PPD as a small molecular activator of CK-MM, which can help in further developing better CK-MM activators based on the dammarane-type triterpenoid structure.

• Korean Journal of Food Science and Technology
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• v.46 no.4
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• pp.489-497
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• 2014

We examined the effects of unripe black raspberry water extract (UBR-W) on lipid metabolism and oxidative stress in mice. C57BL/6J mice were divided into 4 groups: those administered a control diet (CTL), high-fat diet (HFD), UBR-W and simvastatin for 12 weeks. In the HFD group, LDL cholesterol were significantly higher than in the CTL group. However, the UBR-W treated group showed dose-dependent reduction of plasma LDL levels. Hepatic total lipid, TC, and malondialdehyde were significantly increased in hyperlipidemic mice. However, supplementation with either UBR-W or simvastatin effectively reduced these lipid profiles and lipid peroxidation. UBR-W increased mRNA expression of the LDL receptor, sterol regulatory element binding protein 2 (SREBP2), 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase and ATP-binding cassette transporter A1 (ABCA1) compared to that observed in the HFD group. In addition, UBR-W and simvastatin showed significantly reduced oxidized LDL uptake by the scavenger receptor CD36. These results suggest that UBR-W is useful for treatment and prevention of hyperlipidemia and lipid peroxidation.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.12
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• pp.1654-1660
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• 2009

This study was conducted to investigate the effects of different fattening periods i.e. 25, 27 and 29 months of age (25 mo, 27 mo and 29 mo), on feed consumption, body weight gain, carcass parameters, and lipogenic gene expression in 45 Korean native steers (Hanwoo). Daily DM intake was higher in steers on 29 mo compared with those on 25 mo or 27 mo. Daily body weight gain was higher in steers on 25 mo compared with those on 27 mo or 29 mo during fattening and overall experimental periods. Therefore, feed conversion ratio was lower in 25 mo compared with 27 mo or 29 mo during the fattening and whole experimental periods. As expected, slaughter and carcass weights were higher in the order of 29 mo>27 mo>25 mo. Carcass yield grade was relatively lower in 29 mo reflecting higher back fat thickness compared with other treatments, while carcass quality grade was not largely influenced by the treatments. By investigation with an ultra-sound scanning technique, the marbling score was significantly and numerically higher in 25 mo compared with 27 mo or 29 mo. The mRNA levels of stearoyl-CoA desaturase (SCD) gene were gradually increased in the late fattening stages (p<0.01) and mRNA of acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACL) and glucose transporter 4 (GLUT4) gene were highly expressed in 29 mo compared with 25 mo and 27 mo (p<0.05). However, gene expressions of adipocyte fatty acid binding protein 4 (FABP4) and lipoprotein lipase (LPL) were not significantly different among the treatments. Thus the present results indicated that different fattening period has no major effect on carcass characteristics, although 25 mo had a lower carcass weight compared with 27 mo or 29 mo.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.2
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• pp.169-176
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• 2017

Non-alcoholic fatty liver disease (NAFLD) is caused by chronic lipid accumulation due to dysregulation of lipid metabolism in the liver, and it is associated with various human diseases such as obesity, dyslipidemia, hypertension, and diabetes. Histone acetylation is a representative epigenetic mechanism regulated by histone acetyltransferases (HATs) and deacetylases. We observed that tartary buckwheat sprout (TBS) suppressed lipid accumulation in HepG2 cells through its anti-HAT activity. We showed that TBS was a novel HAT inhibitor with specificity for the major HAT enzyme p300. Importantly, TBS reduced acetylation of total and histone proteins, H3K9, H3K36, and H4K8, resulting in decreased transcriptional activities of sterol regulatory element-binding protein 1c, ATP citrate lyase, and fatty acid synthase. These results suggest that TBS inhibits the NAFLD transcription-modulating activity of lipogenesis-related genes through modification of histone acetylation.

• Journal of Life Science
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• v.19 no.8
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• pp.1159-1163
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• 2009

It has been postulated that endoplasmic (ER) stress is involved in the development of several diseases. However, the detailed molecular mechanisms have not been fully understood. Therefore, we characterized a genetic network of genes induced by ER stress using cDNA microarray and gene set expression coherence analysis (GSECA), and identified gene function as well as several transcription regulators associated with ER stress. We analyzed time-dependent gene expression profiles in thapsigargin-treated Sk-Hep1 using an oligonucleotide expression chip, and then selected functional gene sets with significantly high expression coherence which was processed into functional clusters according to the expression similarities. The functions related to sugar binding, lysosome, ribosomal protein, ER lumen, and ER to golgi transport increased, whereas the functions with mRNA processing, DNA replication, DNA repair, cell cycle, electron transport chain and helicase activity decreased. Furthermore, functional clusters were investigated for the enrichment of regulatory motifs using GSECA, and several transcriptional regulators associated with regulation of ER-induced gene expression were found.

• Journal of Life Science
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• v.17 no.4 s.84
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• pp.462-469
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• 2007

In this study, we isolated, characterized, and compared the vasa homologous genes of diploid and triploid Paragonimus westermani and localized VASA homologous proteins in both lung fluke types. Open reading frames of Pw-vasa-2n and Pw-vasa-3n were of 1812 bp, and encoded deduced proteins of 622 amino acids with calculated molecular weights of 69.0 kDa and 68.9 kDa and pI's of 9.11 and 9.03, respectively. A comparison of these two VASA deduced protein sequences showed that only 6 of the 622 amino acids differed. The deduced sequences of Pw-VASA-2n and Pw-VASA-3n contained eight consensus sequences characteristic of the DEAD-box protein family and their N-terminal regions contained four arginine-glycine-glycine (RGG) motifs. These two lung fluke VASA-like proteins were more similar to those of other VASA proteins than to those of other DEAD-family proteins isolated from several organisms (planarian, zebra fish, mouse, and human). vasa homologous gene transcription and VASA protein expressions in triploid type lung flukes was slightly stronger than in the diploid type. Immunostaining showed that testes and a portion of the ovaries of both diploid and triploid lung flukes reacted strongly to anti-Pw-VASA antibody.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.408-419
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• 2023

Background: Ginsenoside compound K (CK), the main active metabolite in Panax ginseng, has shown good safety and bioavailability in clinical trials and exerts neuroprotective effects in cerebral ischemic stroke. However, its potential role in the prevention of cerebral ischemia/reperfusion (I/R) injury remains unclear. Our study aimed to investigate the molecular mechanism of ginsenoside CK against cerebral I/R injury. Methods: We used a combination of in vitro and in vivo models, including oxygen and glucose deprivation/reperfusion induced PC12 cell model and middle cerebral artery occlusion/reperfusion induced rat model, to mimic I/R injury. Intracellular oxygen consumption and extracellular acidification rate were analyzed by Seahorse multifunctional energy metabolism system; ATP production was detected by luciferase method. The number and size of mitochondria were analyzed by transmission electron microscopy and MitoTracker probe combined with confocal laser microscopy. The potential mechanisms of ginsenoside CK on mitochondrial dynamics and bioenergy were evaluated by RNA interference, pharmacological antagonism combined with co-immunoprecipitation analysis and phenotypic analysis. Results: Ginsenoside CK pretreatment could attenuate mitochondrial translocation of DRP1, mitophagy, mitochondrial apoptosis, and neuronal bioenergy imbalance against cerebral I/R injury in both in vitro and in vivo models. Our data also confirmed that ginsenoside CK administration could reduce the binding affinity of Mul1 and Mfn2 to inhibit the ubiquitination and degradation of Mfn2, thereby elevating the protein level of Mfn2 in cerebral I/R injury. Conclusion: These data provide evidence that ginsenoside CK may be a promising therapeutic agent against cerebral I/R injury via Mul1/Mfn2 mediated mitochondrial dynamics and bioenergy.