An Organ System Approach to Explore the Antioxidative, Anti-Inflammatory, and Cytoprotective Actions of Resveratrol

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2015 Jul 17

PMID 26180596

Citations 51

Authors

Ashim Malhotra

Sundeep Bath

Fawzy Elbarbry

Affiliations

Soon will be listed here.

Abstract

Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson's and Alzheimer's disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratrol treatment. We summarize the known anti-inflammatory, antioxidative, and cytoprotective effects of resveratrol across disparate organ systems. Additionally, we analyze the available literature regarding the pharmacokinetics of resveratrol formulations used in these studies. Finally, we critically examine select clinical trials documenting a lack of effect following resveratrol treatment.

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References

Hong S, Lee H, Sohn E, Ko H, Shim B, Ahn K . Anti-nephrolithic potential of resveratrol via inhibition of ROS, MCP-1, hyaluronan and osteopontin in vitro and in vivo. Pharmacol Rep. 2013; 65(4):970-9. DOI: 10.1016/s1734-1140(13)71078-8. View

Tome-Carneiro J, Larrosa M, Gonzalez-Sarrias A, Tomas-Barberan F, Garcia-Conesa M, Espin J . Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence. Curr Pharm Des. 2013; 19(34):6064-93. PMC: 3782695. DOI: 10.2174/13816128113199990407. View

Toliopoulos I, Simos Y, Oikonomidis S, Karkabounas S . Resveratrol diminishes platelet aggregation and increases susceptibility of K562 tumor cells to natural killer cells. Indian J Biochem Biophys. 2013; 50(1):14-8. View

Brown V, Patel K, Viskaduraki M, Crowell J, Perloff M, Booth T . 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. 2010; 70(22):9003-11. PMC: 2982884. DOI: 10.1158/0008-5472.CAN-10-2364. View

Wang Z, Zou J, Huang Y, Cao K, Xu Y, Wu J . Effect of resveratrol on platelet aggregation in vivo and in vitro. Chin Med J (Engl). 2002; 115(3):378-80. View

Das S, Fraga C, Das D . Cardioprotective effect of resveratrol via HO-1 expression involves p38 map kinase and PI-3-kinase signaling, but does not involve NFkappaB. Free Radic Res. 2006; 40(10):1066-75. DOI: 10.1080/10715760600833085. View

Wang Z, Zou J, Cao K, Hsieh T, Huang Y, Wu J . Dealcoholized red wine containing known amounts of resveratrol suppresses atherosclerosis in hypercholesterolemic rabbits without affecting plasma lipid levels. Int J Mol Med. 2005; 16(4):533-40. View

Liu P, Liang H, Xia Q, Li P, Kong H, Lei P . Resveratrol induces apoptosis of pancreatic cancers cells by inhibiting miR-21 regulation of BCL-2 expression. Clin Transl Oncol. 2013; 15(9):741-6. DOI: 10.1007/s12094-012-0999-4. View

Ahn J, Cho I, Kim S, Kwon D, Ha T . Dietary resveratrol alters lipid metabolism-related gene expression of mice on an atherogenic diet. J Hepatol. 2008; 49(6):1019-28. DOI: 10.1016/j.jhep.2008.08.012. View

10.

Sharan S, Nagar S . Pulmonary metabolism of resveratrol: in vitro and in vivo evidence. Drug Metab Dispos. 2013; 41(5):1163-9. PMC: 3629805. DOI: 10.1124/dmd.113.051326. View

11.

Labbe A, Garand C, Cogger V, Paquet E, Desbiens M, Le Couteur D . Resveratrol improves insulin resistance hyperglycemia and hepatosteatosis but not hypertriglyceridemia, inflammation, and life span in a mouse model for Werner syndrome. J Gerontol A Biol Sci Med Sci. 2010; 66(3):264-78. DOI: 10.1093/gerona/glq184. View

12.

Uchiumi F, Watanabe T, Hasegawa S, Hoshi T, Higami Y, Tanuma S . The effect of resveratrol on the Werner syndrome RecQ helicase gene and telomerase activity. Curr Aging Sci. 2011; 4(1):1-7. DOI: 10.2174/1874609811104010001. View

13.

Dash S, Xiao C, Morgantini C, Szeto L, Lewis G . High-dose resveratrol treatment for 2 weeks inhibits intestinal and hepatic lipoprotein production in overweight/obese men. Arterioscler Thromb Vasc Biol. 2013; 33(12):2895-901. DOI: 10.1161/ATVBAHA.113.302342. View

14.

Oi N, Jeong C, Nadas J, Cho Y, Pugliese A, Bode A . Resveratrol, a red wine polyphenol, suppresses pancreatic cancer by inhibiting leukotriene A₄hydrolase. Cancer Res. 2010; 70(23):9755-64. PMC: 4872628. DOI: 10.1158/0008-5472.CAN-10-2858. View

15.

Lofrumento D, Nicolardi G, Cianciulli A, De Nuccio F, La Pesa V, Carofiglio V . Neuroprotective effects of resveratrol in an MPTP mouse model of Parkinson's-like disease: possible role of SOCS-1 in reducing pro-inflammatory responses. Innate Immun. 2013; 20(3):249-60. DOI: 10.1177/1753425913488429. View

16.

Wang Y, Xu H, Fu Q, Ma R, Xiang J . Protective effect of resveratrol derived from Polygonum cuspidatum and its liposomal form on nigral cells in parkinsonian rats. J Neurol Sci. 2011; 304(1-2):29-34. DOI: 10.1016/j.jns.2011.02.025. View

17.

Roy S, Chen Q, Fu J, Shankar S, Srivastava R . Resveratrol inhibits growth of orthotopic pancreatic tumors through activation of FOXO transcription factors. PLoS One. 2011; 6(9):e25166. PMC: 3181262. DOI: 10.1371/journal.pone.0025166. View

18.

Magyar K, Halmosi R, Palfi A, Feher G, Czopf L, Fulop A . Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease. Clin Hemorheol Microcirc. 2012; 50(3):179-87. DOI: 10.3233/CH-2011-1424. View

19.

Huang X, Wen D, Zhang M, Xie Q, Ma L, Guan Y . Sirt1 activation ameliorates renal fibrosis by inhibiting the TGF-β/Smad3 pathway. J Cell Biochem. 2013; 115(5):996-1005. DOI: 10.1002/jcb.24748. View

20.

Howitz K, Bitterman K, Cohen H, Lamming D, Lavu S, Wood J . Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003; 425(6954):191-6. DOI: 10.1038/nature01960. View