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      • KCI등재

        Ginsenosides attenuate bioenergetics and morphology of mitochondria in cultured PC12 cells under the insult of amyloid beta-peptide

        Kenneth Kin Leung Kwan,Huang Yun,Tina Ting Xia Dong,Karl Wah Keung Tsim 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.4

        Background: Mitochondrial dysfunction is one of the significant reasons for Alzheimer"s disease (AD). Ginsenosides, natural molecules extracted from Panax ginseng, have been demonstrated to exert essential neuroprotective functions, which can ascribe to its anti-oxidative effect, enhancing central metabolism and improving mitochondrial function. However, a comprehensive analysis of cellular mitochondrial bioenergetics after ginsenoside treatment under Aβ-oxidative stress is missing. Methods: The antioxidant activities of ginsenoside Rb₁, Rd, Re, Rg₁ were compared by measuring the cell survival and reactive oxygen species (ROS) formation. Next, the protective effects of ginsenosides of mitochondrial bioenergetics were examined by measuring oxygen consumption rate (OCR) in PC12 cells under Aβ-oxidative stress with an extracellular flux analyzer. Meanwhile, mitochondrial membrane potential (MMP) and mitochondrial dynamics were evaluated by confocal laser scanning microscopy. Results: Ginsenoside Rg₁ possessed the strongest anti-oxidative property, and which therefore provided the best protective function to PC12 cells under the Ab oxidative stress by increasing ATP production to 3 folds, spare capacity to 2 folds, maximal respiration to 2 folds and non-mitochondrial respiration to 1.5 folds, as compared to Aβ cell model. Furthermore, ginsenoside Rg1 enhanced MMP and mitochondrial interconnectivity, and simultaneously reduced mitochondrial circularity. Conclusion: In the present study, these results demonstrated that ginsenoside Rg₁ could be the best natural compound, as compared with other ginsenosides, by modulating the OCR of cultured PC12 cells during oxidative phosphorylation, in regulating MMP and in improving mitochondria dynamics under Aβ-induced oxidative stress.

      • KCI등재

        Ginseng extracts modulate mitochondrial bioenergetics of live cardiomyoblasts: a functional comparison of different extraction solvents

        Yun Huang,Kenneth Kin Leung Kwan,Ka Wing Leung,Ping Yao,HuaiyouWang,Tina Tingxia Dong,Karl Wah Keung Tsim 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.4

        Background: The root of Panax ginseng, a member of Araliaceae family, has been used as herbal medicineand functional food in Asia for thousands of years. According to Traditional Chinese medicine, ginseng isthe most widely used “Qi-invigorating” herbs, which provides tonic and preventive effects by resistingoxidative stress, influencing energy metabolism, and improving mitochondrial function. Very few reportshave systematically measured cell mitochondrial bioenergetics after ginseng treatment. Methods: Here, H9C2 cell line, a rat cardiomyoblast, was treated with ginseng extracts having extractedusing solvents of different polarity, i.e., water, 50% ethanol, and 90% ethanol, and subsequently, theoxygen consumption rate in healthy and tert-butyl hydroperoxideetreated live cultures was determinedby Seahorse extracellular flux analyzer. Results: The 90% ethanol extracts of ginseng possessed the strongest antioxidative and tonic activities tomitochondrial respiration and therefore provided the best protective effects to H9C2 cardiomyocytes. Byincreasing the spare respiratory capacity of stressed H9C2 cells up to three-folds of that of healthy cells,the 90% ethanol extracts of ginseng greatly improved the tolerance of myocardial cells to oxidativedamage. Conclusion: These results demonstrated that the low polarity extracts of ginseng could be the bestextract, as compared with others, in regulating the oxygen consumption rate of cultured cardiomyocytesduring mitochondrial respiration.

      • KCI등재
      • KCI등재

        Alectinib (CH5424802) antagonizes ABCB1- and ABCG2-mediated multidrug resistance in vitro, in vivo and ex vivo

        Ke Yang,Yifan Chen,Kenneth Kin Wah To,Fang Wang,Delan Li,Likun Chen,Liwu Fu 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

        Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo. Mechanistically, alectinib increased the intracellular accumulation of ABCB1/ABCG2 substrates such as doxorubicin (DOX) and Rhodamine 123 (Rho 123) by inhibiting the efflux function of the transporters in ABCB1- or ABCG2-overexpressing cells but not in their parental sensitive cells. Furthermore, alectinib stimulated ATPase activity and competed with substrates of ABCB1 or ABCG2 and competed with [125I] iodoarylazidoprazosin (IAAP) photolabeling bound to ABCB1 or ABCG2 but neither altered the expression and localization of ABCB1 or ABCG2 nor the phosphorylation levels of AKT and ERK. Alectinib also enhanced the cytotoxicity of DOX and the intracellular accumulation of Rho 123 in ABCB1-overexpressing primary leukemia cells. These findings suggest that alectinib combined with traditional chemotherapy may be beneficial to patients with ABCB1- or ABCG2-mediated MDR.

      • SCIESCOPUSKCI등재

        Ginseng extracts modulate mitochondrial bioenergetics of live cardiomyoblasts: a functional comparison of different extraction solvents

        Huang, Yun,Kwan, Kenneth Kin Leung,Leung, Ka Wing,Yao, Ping,Wang, Huaiyou,Dong, Tina Tingxia,Tsim, Karl Wah Keung The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.4

        Background: The root of Panax ginseng, a member of Araliaceae family, has been used as herbal medicine and functional food in Asia for thousands of years. According to Traditional Chinese medicine, ginseng is the most widely used "Qi-invigorating" herbs, which provides tonic and preventive effects by resisting oxidative stress, influencing energy metabolism, and improving mitochondrial function. Very few reports have systematically measured cell mitochondrial bioenergetics after ginseng treatment. Methods: Here, H9C2 cell line, a rat cardiomyoblast, was treated with ginseng extracts having extracted using solvents of different polarity, i.e., water, 50% ethanol, and 90% ethanol, and subsequently, the oxygen consumption rate in healthy and tert-butyl hydroperoxideetreated live cultures was determined by Seahorse extracellular flux analyzer. Results: The 90% ethanol extracts of ginseng possessed the strongest antioxidative and tonic activities to mitochondrial respiration and therefore provided the best protective effects to H9C2 cardiomyocytes. By increasing the spare respiratory capacity of stressed H9C2 cells up to three-folds of that of healthy cells, the 90% ethanol extracts of ginseng greatly improved the tolerance of myocardial cells to oxidative damage. Conclusion: These results demonstrated that the low polarity extracts of ginseng could be the best extract, as compared with others, in regulating the oxygen consumption rate of cultured cardiomyocytes during mitochondrial respiration.

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