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Ginsenoside Rc modulates Akt/FoxO1 pathways and suppresses oxidative stress

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Abstract

Ginsenoside Rc (Rc), a protopanaxadiol type ginsenoside, is the active component mainly responsible for the therapeutic and pharmacologic properties of ginseng, which are derived from its suppression of superoxide-induced free radicals. Forkhead box O (FoxO1) regulates various genes involved in cellular metabolism related to cell death and response to oxidative stress, and Rc is known to prevent FoxO1 phosphorylation by activation of PI3K/Akt and subsequent inhibition of AMP-activated protein kinase (AMPK) in cells exposed to tert-butylhydroperoxide (t-BHP). In the current study, we attempted the mechanism of increased catalase expression by Rc through inhibition of FoxO1 activation resulting from t-BHP-induced production of reactive species (RS). We found that overexpression of catalase induced by Rc resulted in suppression of RS production in kidney human embryo kidney 293T cells (HEK293T) cells, and that oxidative stress induced activation of PI3K/Akt and inhibition of the AMPK pathway and FoxO1 phosphorylation, leading to down-regulation of catalase, a FoxO1-targeting gene. In addition, treatment of HEK293T cells with Rc resulted in cAMP-response element-binding protein (CREB)-binding protein (CBP) regulated FoxO1 acetylation. Our results suggest that Rc modulates FoxO1 phosphorylation through activation of PI3K/Akt and inhibition of AMPK and FoxO1 acetylation through interaction with CBP and SIRT1, and that this leads to upregulation of catalase under conditions of oxidative stress.

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Acknowledgments

A grant in 2011 from the Korea Society of Ginseng and by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A090582) and this work was carried out with the support of “Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ006522132013)” Rural Development Administration, Republic of Korea. This work was also supported by the R&D Program of MKE/KEIT (10040391, Development of Functional Food Materials and Device for prevention of Aging-associated Muscle Function Decrease). We also take this opportunity to thank the Aging Tissue Bank (Busan, Korea) for supplying research materials.

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Authors and Affiliations

  1. Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, 609-735, Republic of Korea

    Dae Hyun Kim, Chan Hum Park, Daeui Park, Yeon Ja Choi, Min Hi Park, Ki Wung Chung, So Ra Kim & Hae Young Chung

  2. Department of Biology, College of Natural Science, Chosun University, Gwangju, 501-759, Republic of Korea

    Jun Sik Lee

  3. Department of Pharmacy, College of Pharmacy, Pusan National University, Gumjung-gu, Busan, 609-735, Republic of Korea

    Hae Young Chung

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  1. Dae Hyun Kim
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Kim, D.H., Park, C.H., Park, D. et al. Ginsenoside Rc modulates Akt/FoxO1 pathways and suppresses oxidative stress. Arch. Pharm. Res. 37, 813–820 (2014). https://doi.org/10.1007/s12272-013-0223-2

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