Abstract
In this chapter we discuss the bioavailability of resveratrol and its related derivatives in red wines. Many of the effects of resveratrol in vitro can be replicated in vivo. However, resveratrol has very low bioavailability and is rapidly metabolized to yield plasma and tissue levels that are several-fold lower than those typically used in experiments with cultured cells. Here we provide an overview of the metabolism of resveratrol in vivo and present data describing its bioavailability in rodents and humans. We discuss some of the strategies that have been used to enhance resveratrol’s uptake and increase its bioavailability, and comment on the possibility that its metabolites share some of resveratrol’s biological activities.
Keywords
- Human Lung Fibroblast Cell
- Resveratrol Concentration
- Cancerous Mammary Cell Line
- Mouse Myoblast Cell Line
- Human Lung Fibroblast Cell Line
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Almeida L, Vaz-da-Silva M, Falcao A, Soares E, Costa R, Loureiro AI, Fernandes-Lopes C, Rocha JF, Nunes T, Wright L, Soares-da-Silva P (2009) Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers. Mol Nutr Food Res 53:S7–S15
Amri A, Chaumeil JC, Sfar S, Charrueau C (2012) Administration of resveratrol: what formulation solutions to bioavailability limitations? J Control Release 158:182–193
Asensi M, Medina I, Ortega A, Carretero J, Bano MC, Obrador E, Estrela JM (2002) Inhibition of cancer growth by resveratrol is related to its low bioavailability. Free Radic Biol Med 33:387–398
Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342
Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, Ducharme MP, Booth TD, Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE (2007) Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev 16:1246–1252
Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M, Booth TD, Vasilinin G, Sen A, Schinas AM, Piccirilli G, Brown K, Steward WP, Gescher AJ, Brenner DE (2010) Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res 70:9003–9011
Coimbra M, Isacchi B, van Bloois L, Torano JS, Ket A, Wu X, Broere F, Metselaar JM, Rijcken CJ, Storm G, Bilia R, Schiffelers RM (2011) Improving solubility and chemical stability of natural compounds for medicinal use by incorporation into liposomes. Int J Pharm 416:433–442
Delmas D, Lin HY (2011) Role of membrane dynamics processes and exogenous molecules in cellular resveratrol uptake: consequences in bioavailability and activities. Mol Nutr Food Res 55:1142–1153
Delmas D, Jannin B, Cherkaoui Malki M, Latruffe N (2000) Inhibitory effect of resveratrol on the proliferation of human and rat hepatic derived cell lines. Oncol Rep 7:847–852
Edwards JA, Beck M, Riegger C, Bausch J (2011) Safety of resveratrol with examples for high purity, trans-resveratrol, resVida. Ann NY Acad Sci 1215:131–137
Gokce EH, Korkmaz E, Dellera E, Sandri G, Bonferoni MC, Ozer O (2012) Resveratrol-loaded solid lipid nanoparticles versus nanostructured lipid carriers: evaluation of antioxidant potential for dermal applications. Int J Nanomedicine 7:1841–1850
Hoshino J, Park EJ, Kondratyuk TP, Marler L, Pezzuto JM, van Breemen RB, Mo S, Li Y, Cushman M (2010) Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites. J Med Chem 53:5033–5043
Hsu CL, Lin YJ, Ho CT, Yen GC (2012) Inhibitory effects of garcinol and pterostilbene on cell proliferation and adipogenesis in 3T3-L1 cells. Food Funct 3:49–57
Jannin B, Menzel M, Berlot JP, Delmas D, Lancon A, Latruffe N (2004) Transport of resveratrol, a cancer chemopreventive agent, to cellular targets: plasmatic protein binding and cell uptake. Biochem Pharmacol 68:1113–1118
Juan ME, Maijo M, Planas JM (2010) Quantification of trans-resveratrol and its metabolites in rat plasma and tissues by HPLC. J Pharm Biomed Anal 51:391–398
Kuhnle G, Spencer JP, Chowrimootoo G, Schroeter H, Debnam ES, Srai SK, Rice-Evans C, Hahn U (2000) Resveratrol is absorbed in the small intestine as resveratrol glucuronide. Biochem Biophys Res Commun 272:212–217
Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122
Lasa A, Churruca I, Eseberri I, Andres-Lacueva C, Portillo MP (2012) Delipidating effect of resveratrol metabolites in 3T3-L1 adipocytes. Mol Nutr Food Res 56:1559–1568
Lau BY, Fajardo VA, McMeekin L, Sacco SM, Ward WE, Roy BD, Peters SJ, Leblanc PJ (2010) Influence of high-fat diet from differential dietary sources on bone mineral density, bone strength, and bone fatty acid composition in rats. Appl Physiol Nutr Metab 35:598–606
Lee MF, Pan MH, Chiou YS, Cheng AC, Huang H (2011) Resveratrol modulates MED28 (Magicin/EG-1) expression and inhibits epidermal growth factor (EGF)-induced migration in MDA-MB-231 human breast cancer cells. J Agric Food Chem 59:11853–11861
Lin HS, Yue BD, Ho PC (2009) Determination of pterostilbene in rat plasma by a simple HPLC-UV method and its application in pre-clinical pharmacokinetic study. Biomed Chromatogr 23:1308–1315
Marier JF, Vachon P, Gritsas A, Zhang J, Moreau JP, Ducharme MP (2002) Metabolism and disposition of resveratrol in rats: extent of absorption, glucuronidation, and enterohepatic recirculation evidenced by a linked-rat model. J Pharmacol Exp Ther 302:369–373
McCormack D, Schneider J, McDonald D, McFadden D (2011) The antiproliferative effects of pterostilbene on breast cancer in vitro are via inhibition of constitutive and leptin-induced Janus kinase/signal transducer and activator of transcription activation. Am J Surg 202:541–544
McCormack DE, Mannal P, McDonald D, Tighe S, Hanson J, McFadden D (2012) Genomic analysis of pterostilbene predicts its antiproliferative effects against pancreatic cancer in vitro and in vivo. J Gastrointest Surg 16:1136–1143
Miksits M, Wlcek K, Svoboda M, Kunert O, Haslinger E, Thalhammer T, Szekeres T, Jager W (2009) Antitumor activity of resveratrol and its sulfated metabolites against human breast cancer cells. Planta Med 75:1227–1230
Nutakul W, Sobers HS, Qiu P, Dong P, Decker EA, McClements DJ, Xiao H (2011) Inhibitory effects of resveratrol and pterostilbene on human colon cancer cells: a side-by-side comparison. J Agric Food Chem 59:10964–10970
Richard T, Poupard P, Nassra M, Papastamoulis Y, Iglesias ML, Krisa S, Waffo-Teguo P, Merillon JM, Monti JP (2011) Protective effect of ε-viniferin on β-amyloid peptide aggregation investigated by electrospray ionization mass spectrometry. Bioorg Med Chem 19:3152–3155
Robb EL, Winkelmolen L, Visanji N, Brotchie J, Stuart JA (2008b) Dietary resveratrol administration increases MnSOD expression and activity in mouse brain. Biochem Biophys Res Commun 372:254–259
Santos AC, Veiga F, Ribeiro AJ (2011) New delivery systems to improve the bioavailability of resveratrol. Expert Opin Drug Deliv 8:973–990
Teng Z, Yuan C, Zhang F, Huan M, Cao W, Li K, Yang J, Cao D, Zhou S, Mei W (2012) Intestinal absorption and first-pass metabolism of polyphenol compounds in rat and their transport dynamics in Caco-2 cells. PLoS One 7:e29647
Teskac K, Kristl J (2010) The evidence for solid lipid nanoparticles mediated cell uptake of resveratrol. Int J Pharm 390:61–69
Vitaglione P, Sforza S, Galaverna G, Ghidini C, Caporaso N, Vescovi PP, Fogliano V, Marchelli R (2005) Bioavailability of trans-resveratrol from red wine in humans. Mol Nutr Food Res 49:495–504
Vitrac X, Desmouliere A, Brouillaud B, Krisa S, Deffieux G, Barthe N, Rosenbaum J, Merillon JM (2003) Distribution of [14C]-trans-resveratrol, a cancer chemopreventive polyphenol, in mouse tissues after oral administration. Life Sci 72:2219–2233
Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK (2004) High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 32:1377–1382
Wang X, Song R, Bian HN, Brunk UT, Zhao M, Zhao KS (2012) Polydatin, a natural polyphenol, protects arterial smooth muscle cells against mitochondrial dysfunction and lysosomal destabilization following hemorrhagic shock. Am J Physiol 302:R805–R814
Wen X, Walle T (2006) Methylated flavonoids have greatly improved intestinal absorption and metabolic stability. Drug Metab Dispos 34:1786–1792
Wenzel E, Somoza V (2005) Metabolism and bioavailability of trans-resveratrol. Mol Nutr Food Res 49:472–481
Wenzel E, Soldo T, Erbersdobler H, Somoza V (2005) Bioactivity and metabolism of trans-resveratrol orally administered to Wistar rats. Mol Nutr Food Res 49:482–494
Zghonda N, Yoshida S, Araki M, Kusunoki M, Mliki A, Ghorbel A, Miyazaki H (2011) Greater effectiveness of ε-viniferin in red wine than its monomer resveratrol for inhibiting vascular smooth muscle cell proliferation and migration. Biosci Biotechnol Biochem 75:1259–1267
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2013 The Author(s)
About this chapter
Cite this chapter
Stuart, J.A., Robb, E.L. (2013). Bioavailability of Resveratrol, Pterostilbene, and Piceid. In: Bioactive Polyphenols from Wine Grapes. SpringerBriefs in Cell Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6968-1_4
Download citation
DOI: https://doi.org/10.1007/978-1-4614-6968-1_4
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-6967-4
Online ISBN: 978-1-4614-6968-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)