Browse > Article
http://dx.doi.org/10.4162/nrp.2016.10.1.3

Oligonol promotes anti-aging pathways via modulation of SIRT1-AMPK-Autophagy Pathway  

Park, Seul-Ki (Department of Biomedical Sciences, College of Medicine, Korea University)
Seong, Rak-Kyun (Department of Biomedical Sciences, College of Medicine, Korea University)
Kim, Ji-Ae (Department of Biomedical Sciences, College of Medicine, Korea University)
Son, Seok-Jun (BK21 Plus Graduate Program, Department of Animal Science and Institute of Rare Earth for Biological Application, Chonbuk National University)
Kim, Younghoon (BK21 Plus Graduate Program, Department of Animal Science and Institute of Rare Earth for Biological Application, Chonbuk National University)
Yokozawa, Takako (Institute of Natural Medicine, University of Toyama)
Shin, Ok Sarah (Department of Biomedical Sciences, College of Medicine, Korea University)
Publication Information
Nutrition Research and Practice / v.10, no.1, 2016 , pp. 3-10 More about this Journal
Abstract
BACKGROUND/OBJECTIVES: Oligonol, mainly found in lychee fruit, is an antioxidant polyphenolic compound which has been shown to have anti-inflammatory and anti-cancer properties. The detailed mechanisms by which oligonol may act as an anti-aging molecule have not been determined. MATERIALS/METHODS: In this study, we evaluated the ability of oligonol to modulate sirtuin (SIRT) expression in human lung epithelial (A549) cells. Oligonol was added to A549 cells and reactive oxygen species production, mitochondrial superoxide formation, and p21 protein levels were measured. Signaling pathways activated upon oligonol treatment were also determined by western blotting. Furthermore, the anti-aging effect of oligonol was evaluated ex vivo in mouse splenocytes and in vivo in Caenorhabditis elegans. RESULTS: Oligonol specifically induced the expression of SIRT1, whose activity is linked to gene expression, metabolic control, and healthy aging. In response to influenza virus infection of A549 cells, oligonol treatment significantly up-regulated SIRT1 expression and down-regulated viral hemagglutinin expression. Oligonol treatment also resulted in the activation of autophagy pathways and the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, oligonol-treated spleen lymphocytes from old mice showed increased cell proliferation, and mRNA levels of SIRT1 in the lungs of old mice were significantly lower than those in the lungs of young mice. Additionally, in vivo lethality assay revealed that oligonol extended the lifespan of C. elegans infected with lethal Vibrio cholerae. CONCLUSIONS: These data demonstrated that oligonol may act as an anti-aging molecule by modulating SIRT1/autophagy/AMPK pathways.
Keywords
Oligonol; SIRT1; senescence; aging;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Wu Y, Li X, Zhu JX, Xie W, Le W, Fan Z, Jankovic J, Pan T. Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson's disease. Neurosignals 2011;19:163-74.   DOI
2 Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, Bruns NE, Tsokos M, Alt FW, Finkel T. A role for the NAD-dependent deacetylase SIRT1 in the regulation of autophagy. Proc Natl Acad Sci U S A 2008;105: 3374-9.   DOI
3 Salminen A, Kaarniranta K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev 2012;11:230-41.   DOI
4 Rubinsztein DC, Marino G, Kroemer G. Autophagy and aging. Cell 2011;146:682-95.   DOI
5 Fujii H, Nakagawa T, Nishioka H, Sato E, Hirose A, Ueno Y, Sun B, Yokozawa T, Nonaka G. Preparation, characterization, and antioxidative effects of oligomeric proanthocyanidin-L-cysteine complexes. J Agric Food Chem 2007;55:1525-31.   DOI
6 Shin OS, Yanagihara R, Song JW. Distinct innate immune responses in human macrophages and endothelial cells infected with shrew-borne hantaviruses. Virology 2012;434:43-9.   DOI
7 Jung KJ, Lee EK, Kim SJ, Song CW, Maruyama N, Ishigami A, Kim ND, Im DS, Yu BP, Chung HY. Anti-inflammatory activity of SMP30 modulates NF-kappaB through protein tyrosine kinase/phosphatase balance. J Mol Med (Berl) 2015;93:343-56.   DOI
8 Kim JI, Park S, Lee I, Lee S, Shin S, Won Y, Hwang MW, Bae JY, Heo J, Hyun HE, Jun H, Lim SS, Park MS. GFP-expressing influenza A virus for evaluation of the efficacy of antiviral agents. J Microbiol 2012;50:359-62.   DOI
9 Kim Y, Mylonakis E. Caenorhabditis elegans immune conditioning with the probiotic bacterium Lactobacillus acidophilus strain NCFM enhances gram-positive immune responses. Infect Immun 2012;80: 2500-8.   DOI
10 Kim HI, Kim JA, Choi EJ, Harris JB, Jeong SY, Son SJ, Kim Y, Shin OS. In vitro and in vivo antimicrobial efficacy of natural plantderived compounds against Vibrio cholerae of O1 El Tor Inaba serotype. Biosci Biotechnol Biochem 2015;79:475-83.   DOI
11 Gangehei L, Ali M, Zhang W, Chen Z, Wakame K, Haidari M. Oligonol a low molecular weight polyphenol of lychee fruit extract inhibits proliferation of influenza virus by blocking reactive oxygen speciesdependent ERK phosphorylation. Phytomedicine 2010;17:1047-56.   DOI
12 Koyuncu E, Budayeva HG, Miteva YV, Ricci DP, Silhavy TJ, Shenk T, Cristea IM. Sirtuins are evolutionarily conserved viral restriction factors. MBio 2014;5:pii: e02249-14.
13 Lee JW, Park S, Takahashi Y, Wang HG. The association of AMPK with ULK1 regulates autophagy. PLoS One 2010;5:e15394.   DOI
14 Jin J, Iakova P, Jiang Y, Medrano EE, Timchenko NA. The reduction of SIRT1 in livers of old mice leads to impaired body homeostasis and to inhibition of liver proliferation. Hepatology 2011;54:989-98.   DOI
15 Maruyama N, Ishigami A, Kondo Y. Pathophysiological significance of senescence marker protein-30. Geriatr Gerontol Int 2010;10 Suppl 1:S88-98.   DOI
16 Ermolaeva MA, Schumacher B. Insights from the worm: the C. elegans model for innate immunity. Semin Immunol 2014;26:303-9.   DOI
17 Cinar HN, Kothary M, Datta AR, Tall BD, Sprando R, Bilecen K, Yildiz F, McCardell B. Vibrio cholerae hemolysin is required for lethality, developmental delay, and intestinal vacuolation in Caenorhabditis elegans. PLoS One 2010;5:e11558.   DOI
18 Sahu SN, Lewis J, Patel I, Bozdag S, Lee JH, LeClerc JE, Cinar HN. Genomic analysis of immune response against Vibrio cholerae hemolysin in Caenorhabditis elegans. PLoS One 2012;7:e38200.   DOI
19 Sakurai T, Nishioka H, Fujii H, Nakano N, Kizaki T, Radak Z, Izawa T, Haga S, Ohno H. Antioxidative effects of a new lychee fruit- derived polyphenol mixture, oligonol, converted into a low- molecular form in adipocytes. Biosci Biotechnol Biochem 2008;72: 463-76.   DOI
20 Fujii H, Yokozawa T, Kim YA, Tohda C, Nonaka G. Protective effect of grape seed polyphenols against high glucose-induced oxidative stress. Biosci Biotechnol Biochem 2006;70:2104-11.   DOI
21 Fujii H, Nishioka H, Wakame K, Magnuson BA, Roberts A. Acute, subchronic and genotoxicity studies conducted with Oligonol, an oligomerized polyphenol formulated from lychee and green tea extracts. Food Chem Toxicol 2008;46:3553-62.   DOI
22 Salminen A, Ojala J, Kaarniranta K, Kauppinen A. Mitochondrial dysfunction and oxidative stress activate inflammasomes: impact on the aging process and age-related diseases. Cell Mol Life Sci 2012;69:2999-3013.   DOI
23 Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell 2012;48:158-67.   DOI
24 Li X, Fang P, Mai J, Choi ET, Wang H, Yang XF. Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers. J Hematol Oncol 2013;6:19.   DOI
25 West AP, Brodsky IE, Rahner C, Woo DK, Erdjument-Bromage H, Tempst P, Walsh MC, Choi Y, Shadel GS, Ghosh S. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature 2011;472:476-80.   DOI
26 Rutanen J, Yaluri N, Modi S, Pihlajamaki J, Vanttinen M, Itkonen P, Kainulainen S, Yamamoto H, Lagouge M, Sinclair DA, Elliott P, Westphal C, Auwerx J, Laakso M. SIRT1 mRNA expression may be associated with energy expenditure and insulin sensitivity. Diabetes 2010;59:829-35.   DOI
27 Agarwal B, Baur JA. Resveratrol and life extension. Ann N Y Acad Sci 2011;1215:138-43.   DOI
28 Fulco M, Sartorelli V. Comparing and contrasting the roles of AMPK and SIRT1 in metabolic tissues. Cell Cycle 2008;7:3669-79.   DOI
29 Park JY, Kim Y, Im JA, You S, Lee H. Inhibition of Adipogenesis by Oligonol through Akt-mTOR Inhibition in 3T3-L1 Adipocytes. Evid Based Complement Alternat Med 2014; 2014:895272.
30 Park CH, Yokozawa T, Noh JS. Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, attenuates diabetes-induced renal damage through the advanced glycation end product-related pathway in db/db mice. J Nutr 2014;144:1150-7.   DOI
31 Canto C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, Auwerx J. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 2009;458:1056-60.   DOI
32 Lee SJ, Chung IM, Kim MY, Park KD, Park WH, Moon HI. Inhibition of lung metastasis in mice by oligonol. Phytother Res 2009;23: 1043-6.   DOI
33 Fujii H, Sun B, Nishioka H, Hirose A, Aruoma OI. Evaluation of the safety and toxicity of the oligomerized polyphenol Oligonol. Food Chem Toxicol 2007;45:378-87.   DOI
34 Tomobe K, Fujii H, Sun B, Nishioka H, Aruoma OI. Modulation of infection-induced inflammation and locomotive deficit and longevity in senescence-accelerated mice-prone (SAMP8) model by the oligomerized polyphenol Oligonol. Biomed Pharmacother 2007; 61:427-34.   DOI
35 Kundu JK, Hwang DM, Lee JC, Chang EJ, Shin YK, Fujii H, Sun B, Surh YJ. Inhibitory effects of oligonol on phorbol ester-induced tumor promotion and COX-2 expression in mouse skin: NF-kappaB and C/EBP as potential targets. Cancer Lett 2009;273:86-97.   DOI
36 Park CH, Noh JS, Fujii H, Roh SS, Song YO, Choi JS, Chung HY, Yokozawa T. Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, attenuates gluco-lipotoxicity-mediated renal disorder in type 2 diabetic db/db mice. Drug Discov Ther 2015;9:13-22.   DOI
37 Guarente L. Sirtuins, aging, and metabolism. Cold Spring Harb Symp Quant Biol 2011;76:81-90.
38 Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003;425:191-6.   DOI
39 Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol 2010;5:253-95.   DOI
40 Korkina LG, Pastore S, Dellambra E, De Luca C. New molecular and cellular targets for chemoprevention and treatment of skin tumors by plant polyphenols: a critical review. Curr Med Chem 2013;20: 852-68.