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http://dx.doi.org/10.9721/KJFST.2018.50.6.688

Red ginseng-derived saponin fraction inhibits lipid accumulation and reactive oxygen species production by activating nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) pathway  

Kim, Chae-Young (Department of Integrated Biomedical and Life Science, Graduate School, Korea University)
Kang, Bobin (Department of Integrated Biomedical and Life Science, Graduate School, Korea University)
Hwang, Jisu (Department of Integrated Biomedical and Life Science, Graduate School, Korea University)
Choi, Hyeon-Son (Department of Food Science and Technology, College of Natural Science, Seoul Women's University)
Publication Information
Korean Journal of Food Science and Technology / v.50, no.6, 2018 , pp. 688-696 More about this Journal
Abstract
This study aimed to investigate the effects of red ginseng-derived saponin fraction (SF) on lipid accumulation, reactive oxygen species (ROS) production, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) signaling during adipocyte differentiation. SF effectively inhibited lipid accumulation, with the downregulation of adipogenic factors such as peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and CCAAT/enhancer-binding protein alpha ($C/EBP{\alpha}$). A high dose of SF decreased the protein levels of $PPAR{\gamma}$ and $C/EBP{\alpha}$ by over 90% compared to the control. SF-mediated downregulation of adipogenic factors was due to the regulation of early adipogenic factors including $C/EBP{\beta}$ and $Kr{\ddot{u}}ppel$-like Factor 2 (KLF2). In addition, SF ($200{\mu}g/mg$) decreased intracellular ROS generation by 40% during adipocyte differentiation. However, the SF significantly upregulated Nrf2 and its target proteins, hemoxygenase-1 (HO-1) and NADPH dehydrogenase quinone 1 (NQO1). Furthermore, SF ($200{\mu}g/mg$) promoted the nuclear translocation of Nrf2. The SF-mediated reduction of lipid accumulation was associated with the regulation of the Nrf2/Keap1 pathway.
Keywords
red ginseng-derived saponin fraction; lipid accumulation; ROS production; Nrf2/Keap1 pathway;
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1 Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem. Pharmacol. 58: 1685-1693 (1995)
2 Chang H. Effect of processing methods on the saponin contents of Panax ginseng leaf-tea. J. Food Sci. Nut.16: 46-53 (2003)
3 Chang YS, Chang YH, Sung JH. The effect of ginseng and caffeine products on the antioxidative activities of mouse kidney. J. Ginseng Res. 30: 15-21 (2006)   DOI
4 Chen HH, Chen YT, Huang YW, Tsai HJ, Kuo CC. 4-Ketopinoresinol, a novel naturally occurring ARE activator, induces the Nrf2/HO-1 axis and protects against oxidative stress-induced cell injury via activation of PI3K/AKT signaling. Free Radic. Biol. Med. 52: 1054-1066 (2012)   DOI
5 Choi HS, Jeon HJ, Lee OH, Lee BY. Indole-3-carbinol, a vegetable phytochemical, inhibits adipogenesis by regulating cell cycle and $AMPK{\alpha}$ signaling. Biochimie. 104: 127-136 (2014)   DOI
6 Choi KM, Lee YS, Sin DM, Lee S, Lee MK, Lee YM, Hong JT, Yun YP, Yoo HS. Sulforaphane inhibits mitotic clonal expansion during adipogenesis through cell cycle arrest. Obesity. 20: 1365-1371 (2012)   DOI
7 Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I. Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest. 114: 1752-1761 (2017)
8 Gaikwad A, Long DJ, Stringer JL, Jaiswal AK. In Vivo Role of NAD (P) H: quinone oxidoreductase1 (NQO1) in the regulation of intracellular redox state and accumulation of abdominal adipose tissue. J. Biol. Chem. 276: 22559-22564 (2001)   DOI
9 Halliwell B, Gutteridge JM, Cross CE. Free radicals, antioxidants, and human disease: where are we now?. J. Lab.Clin. Med. 119: 598-620 (1992)
10 He HJ, Wang GY, Gao Y, Ling WH, Yu ZW, Jin TR. Curcumin attenuates Nrf2 signaling defect, oxidative stress in muscle and glucose intolerance in high fat diet-fed mice. World J. Diabetes 3: 94-104 (2012)   DOI
11 Kersten S. Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Reports. 2: 282-286 (2001)   DOI
12 Keum YS, Park KK, Lee JM, Chun KS, Park JH, Lee SK, Kwon HJ, Surh YJ. Antioxidant and anti-tumor promoting activities of the methanol extract of heat-processed ginseng. Cancer Letters. 150: 41-48 (2000)   DOI
13 Kim DH, Kwak KH, Lee KJ, Kim SJ, Shin YC, Chun BG, Shin, KH. Effects of Korea red ginseng total saponin on repeated unpredictable stress-induced changes of proliferation of neural progenitor cells and BDNF mRNA expression in adult rat hippocampus. J. Ginseng Res. 28: 94-103 (2004).   DOI
14 Lee H, Lee YJ, Choi H, Ko EH, Kim JW. Reactive oxygen species facilitate adipocyte differentiation by accelerating mitotic clonal expansion. J. Biol. Chem. 284: 10601-10609 (2009)   DOI
15 Kim JH, Kang S, Jung YN, Choi H-S. Cholecalciferol inhibits lipid accumulation by regulating early adipogenesis in cultured adipocytes and zebrafish. Biochem. Biophys. Res. Commun. 469: 646-653 (2016)   DOI
16 Kim JY, Park JY, Kang HJ, Kim OY, Lee JH. Beneficial effects of Korean red ginseng on lymphocyte DNA damage, antioxidant enzyme activity, and LDL oxidation in healthy participants: a randomized, double-blind, placebo-controlled trial. Nutr. J.11: 47 (2012)   DOI
17 Konno C, Hikino H. Isolation and hypoglycemic activity of panaxans M, N, O and P, glycans of Panax ginseng roots. Int. J. Crude Drug Res. 25: 53-56 (1987)   DOI
18 Lee JW, Do JH. Antioxidative activity of ethanol extraction fraction from the Korean red tail ginseng. Kor. J. Food Sci. Technol. 33: 497-500 (2001).
19 Lee M, Kim I, Kim C, Kim Y. Effects of ginsenoside Rg3 on adipocyte fatty acid binding protein mRNA expression and glycerol-3-phosphate dehydrogenase activity during adipocytes differentiation. Kor. J. Lipidol. 21: 67-75 (2011)
20 Liu H, Wang J, Liu M, Zhao H, Yaqoob S, Zheng M, Cai D, Liu J. Antiobesity effects of ginsenoside Rg1 on 3T3-L1 preadipocytes and high fat diet-induced obese mice mediated by AMPK. Nutrients 10: 830-844 (2018)   DOI
21 Lowe CE, O'Rahilly S, Rochford JJ. Adipogenesis at a glance. J. Cell Sci. 124: 2681-2686 (2011)   DOI
22 Nam KY. The comparative understanding between red ginseng and white ginsengs, processed ginsengs (Panax ginseng CA Meyer). J. Ginseng Res. 29: 1-18 (2005)   DOI
23 Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. Transcriptional regulation of adipogenesis. Genes Dev. 14: 1293-1307 (2000)
24 Oakley FD, Abbott D, Li Q, Engelhardt JF. Signaling components of redox active endosomes: the redoxosomes. Antioxid. Redox Signal. 11: 1313-1333 (2009)   DOI
25 Panchal SK, Poudyal H, Brown L. Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats. J. Nutr. 142: 1026-1032 (2012)   DOI
26 Pi J, Leung L, Xue P, Wang W, Hou Y, Liu D,Yehuda-Shnaidman E, Lee, C, Lau J, Kurtz T W, Chan JY. Deficiency in the nuclear factor E2-related factor 2 transcription factor results in impaired adipogenesis and protects against diet-induced obesity. J. Biol. Chem. 285: 9292-9300 (2010)   DOI
27 Shin S, Wakabayashi N, Misra V, Biswal S, Lee GH, Agoston ES, Yamamoto M, Kensler TW. NRF2 modulates aryl hydrocarbon receptor signaling: influence on adipogenesis. Mol. Cell. Biol. 27: 7188-7197 (2007)   DOI
28 Spiegelman BM, Choy L, Hotamisligil GS, Graves RA, Tontonoz P. Regulation of adipocyte gene expression in differentiation and syndromes of obesity/diabetes. J. Biol. Chem. 268: 6823-6826 (1993)
29 Taguchi K, Motohashi H, Yamamoto M. Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells. 16: 123-140 (2011)   DOI
30 Suh HJ, Cho SY, Kim EY, Choi HS. Blockade of lipid accumulation by silibinin in adipocytes and zebrafish. Chem. Biol. Interact. 227: 53-62 (2015)   DOI
31 Tang W, Yan J, Wang T, Xia X, Zhuang X, Hong K, Li R, Liu P, Jiang H, Qiao J. Up-regulation of heme oxygenase-1 expression modulates reactive oxygen species level during the cryopreservation of human seminiferous tubules. Fertil. Steril. 102: 974-980 (2014)   DOI
32 Wang L, Chen Y, Sternberg P, Cai J. Essential roles of the PI3 kinase/Akt pathway in regulating Nrf2-dependent antioxidant functions in the RPE. Invest. Ophthalmol. Vis. Sci. 49: 1671-1678 (2008)   DOI
33 Wu Y, Huang XF, Bell C, Yu Y. Ginsenoside Rb1 improves leptin sensitivity in the prefrontal cortex in obese mice. CNS Neurosci. Ther. 24: 98-107 (2018)   DOI
34 Yoon S, Joo C. Study on the preventive effect of ginsenosides against hypercholesterolemia and its mechanism. Kor. J. Ginseng Sci. 17: 1-12 (1993)
35 Zhong Y, Liu T, Lai W, Tan Y, Tian D, Guo Z. Heme oxygenase-1-mediated reactive oxygen species reduction is involved in the inhibitory effect of curcumin on lipopolysaccharide-induced monocyte chemoattractant protein-1 production in RAW264.7 macrophages. Molecular Med. Reports. 7: 242-246 (2013)   DOI
36 Yuan Q, Jiang YW, Ma TT, Fang QH, Pan L. Attenuating effect of Ginsenoside Rb1 on LPS-induced lung injury in rats. J. Inflammation. 11: 40 (2014)   DOI
37 Zhang L, Zhang L, Wang X, Si H. Anti-adipogenic effects and mechanisms of ginsenoside Rg3 in pre-adipocytes and obese mice. Front. Pharmacol. 8: 113 (2017)
38 Zhang M, An C, Gao Y, Leak RK, Chen J, Zhang F. Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection. Prog. Neurobiol.100: 30-47 (2013)   DOI