The Sirtuin System: The Holy Grail of Resveratrol?
Open accessAbstract
The oxidative stress theory has been associated with atherosclerosis and has prompted a multitude of studies to evaluate the effects of antioxidants on cardiovascular disease prevention. Resveratrol, a relatively new antioxidant has gained considerable curiosity. This polyphenol stilbene identified in grape skin, is believed to be the main component contributing to the anti-atherosclerotic benefits linked to red wine consumption. It has demonstrated the ability to protect endothelial cells from lipid damage, promote vasodilation via modulation of nitric oxide synthesis, and inhibit platelet aggregation and smooth muscle proliferation. Although the complete mechanism of Resveratrol has yet to be fully elucidated, the Sirtuin system, consisting of 7 highly conserved families of regulator genes, are thought to be instrumental in establishing the various health benefits. In this article we assess the current applications, mechanism, pharmacokinetics, bioavailability, and safety profile of the novel antioxidant Resveratrol and provide an in-depth review of the influence of the Sirtuin system on the Resveratrol mechanism of action. We resolve that while early data on Resveratrol are promising, the anti-oxidative and ultimately, anti-atherosclerotic potential depends on further clarification of the intricate and complex relationship between Resveratrol and the Sirtruin system.
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Resveratrol reduces blood pressure.
“It reduces blood pressure, has antiapoptotic effects on cardiomyocytes and prevents thrombus formation [64].”
From Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing (2021) · cites this paper as [64]
Resveratrol has protective effects on the cardiovascular system.
“Resveratrol, a polyphenoid that is present in berries, grapes, and grape products such as red wine, has also been proven to have protective effects on the cardiovascular system. It reduces blood pressure, has antiapoptotic effects on cardiomyocytes and prevents thrombus formation [64].”
From Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing (2021) · cites this paper as [64]
Resveratrol prevents thrombus formation.
“It reduces blood pressure, has antiapoptotic effects on cardiomyocytes and prevents thrombus formation [64].”
From Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing (2021) · cites this paper as [64]
Resveratrol has antiapoptotic effects on cardiomyocytes.
“It reduces blood pressure, has antiapoptotic effects on cardiomyocytes and prevents thrombus formation [64].”
From Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing (2021) · cites this paper as [64]
Low oral bioavailability can be the reason scientists cannot replicate the beneficial effects of resveratrol against Alzheimer's disease in humans.
“The reason that scientists cannot replicate the beneficial effects of resveratrol against AD in humans can be its low oral bioavailability [222,223].”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [222]
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“Notably, FADS1 induction possibly occurs via a PPARα activation mediated by R, as previously postulated [52,76,78].”
BackgroundHigh throughput drug screening identifies resveratrol as suppressor of hepatic SELENOP expression
Hackler, J., Demircan, K., Chillon, T. S., Sun, Q., Geisler, N., Schupp, M., Renko, K., & Schomburg, L. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102592 · Cited by 21 · see citing works
“The additional metabolic benefits are ascribed mainly to a positive modulation of the family of sirtuins [79,80], and by reducing intracellular H2O2 concentration [81].”
BackgroundUV Protection in the Cornea: Failure and Rescue
Volatier, T. L. A., Schumacher, B., Cursiefen, C., & Notara, M. (2022) · Biology · doi:10.3390/biology11020278 · Cited by 22 · see citing works
Méndez-Durazno, C., Cisneros‐Pérez, P. A., Loja-Ojeda, B. A., Monge-Sevilla, R., Romero‐Estévez, D., Fernández, L., & Espinoza-Montero, P. J. (2023) · Antioxidants · doi:10.3390/antiox12020318 · Cited by 20 · see citing works
Targeting Neurological Disorders with Stilbenes: Bridging the Preclinical-Clinical Gap
Begh, M. Z. A., Khan, J., Zehravi, M., Sweilam, S. H., Raja, A. D., Muthukumar, A., Haque, M. A., Kar, N. R., Singh, L. P., Priya, B. D., et al. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.102032 · Cited by 18 · see citing works
“Its ability to activate sirtuins, a family of enzymes known to regulate cellular stress responses and longevity pathways, has placed it at the forefront of research investigating its potential benefits against aging-related diseases, including neurodegeneration (6,7).”
BackgroundResveratrol and Extra Virgin Olive Oil: Protective Agents Against Age-Related Disease
Morkovin, E. I., Litvinov, R., Koushner, A., & Babkov, D. A. (2024) · Nutrients · doi:10.3390/nu16244258 · Cited by 18 · see citing works
Benalaya, I., Alves, G., Lopes, J. A., & Silva, L. R. (2024) · Macromol—A Journal of Macromolecular Research · doi:10.3390/macromol4040048 · Cited by 17 · see citing works
Aziz, N. A. W. A., Iezhitsa, I. N., Agarwal, R., Kadir, R. F. A., Latiff, A. A., & Ismail, N. M. (2020) · Neurological Research · doi:10.1080/01616412.2020.1716470 · Cited by 16 · see citing works
“tem [86] and peroxisome proliferator-activated receptor (PPAR) [87].”
BackgroundPhenolic Profiles of Red Wine Relate to Vascular Endothelial Benefits Mediated by SIRT1 and SIRT6
D’Onofrio, N., Martino, E., Chianese, G., Coppola, F., Picariello, L., Luigi Moio, B., Balestrieri, M. L., Angelita Gambuti, B., & Forino, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115677 · Cited by 15 · see citing works
Mlakić, M., Rajič, L., Ljubić, A., Vušak, V., Zelić, B., Gojun, M., Odak, I., Čule, I., Šagud, I., Šalić, A., et al. (2022) · Journal of Flow Chemistry · doi:10.1007/s41981-022-00239-9 · Cited by 15 · see citing works
Atoki, A. V., Aja, P. M., Ondari, E. N., & Shinkafi, T. S. (2023) · International Journal of Food Properties · doi:10.1080/10942912.2023.2243050 · Cited by 19 · see citing works
“[315,316] These examples from scientific investigations demonstrated how limited bioavailability is a barrier to phytochemicals’ beneficial effect.”
BackgroundPhillips, M., Arnold, K. R., Vue, Z., Beasley, H. K., Lopez, E. G., Marshall, A. G., Morton, D. J., McReynolds, M. R., Barter, T. T., & Hinton, A. O., Jr. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031067 · Cited by 13 · see citing works
Baek, S. J., Hammock, B. D., Hwang, I. K., Li, Q. X., Moustaïd‐Moussa, N., Park, Y., Safe, S. H., Suh, N., Yi, S.-S., Zeldin, D. C., et al. (2021) · Nutrients · doi:10.3390/nu13061881 · Cited by 13 · see citing works
Promising drug discovery strategies for sirtuin modulators: what lessons have we learnt?
Garg, G., Singh, A. K., Singh, S., & Rizvi, S. I. (2021) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2021.1915980 · Cited by 11 · see citing works
“associated with multiple health benefits [108].”
Trade-Offs Between Anti-Aging Dietary Supplementation and Exercise
Mendelsohn, A. R., & Larrick, J. W. (2013) · Rejuvenation Research · doi:10.1089/rej.2013.1484 · Cited by 11 · see citing works
“11 However, recent data suggest that SIRT1 may not increase longevity in Caenorhabditis elegans and Drosophila melanogaster.”
Rakhra, G., Malhotra, R., Prasad, P., Sahu, J. K., Rakhra, G., Khan, T. U., Khan, M. U., & Rastogi, S. (2026) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.70360 · Cited by 10 · see citing works
The Potential Role of Dietary Polyphenols in the Prevention and Treatment of Acute Leukemia
Fakhar, F., Mohammadian, K., Keramat, S., & Stanek, A. (2024) · Nutrients · doi:10.3390/nu16234100 · Cited by 10 · see citing works
Arcaro, A., Lepore, A., Cetrangolo, G. P., Paventi, G., Ames, P. R. J., & Gentile, F. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26167787 · Cited by 10 · see citing works
Cardiometabolic Risk: Characteristics of the Intestinal Microbiome and the Role of Polyphenols
Haș, I. M., Ţiţ, D. M., BUNGAU, S. G., Pavel, F. M., Teleky, B., Vodnar, D. C., & Vesa, C. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813757 · Cited by 7 · see citing works
Resveratrol improves high-fructose-induced vascular dysfunction in rats
Develi-İş, S., Özen, G., Bekpınar, S., Topal, G., Ünlüçerçi, Y., Doğan, B. S. U., & Uysal, M. (2014) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2014-0245 · Cited by 7 · see citing works
Nicotinamide riboside alleviates cisplatin-induced peripheral neuropathy via SIRT2 activation
Acklin, S., Sadhukhan, R., Du, W., Patra, M., Cholia, R. P., & Xia, F. (2022) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdac101 · Cited by 6 · see citing works
We Are What We Eat: Ubiquitin–Proteasome System (UPS) Modulation Through Dietary Products
Panagiotidou, E., & Chondrogianni, N. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-38266-7_15 · Cited by 5 · see citing works
Identification of pulmonary comorbid diseases network based repurposing effective drugs for COVID-19Preprint
Patel, J. C., Tulswani, R., Khurana, P., Sharma, Y. K., Ganju, L., Kumar, B., & Sugadev, R. (2020) · doi:10.21203/rs.3.rs-28148/v1 · Cited by 4 · see citing works
Kwok, A., Chaqour, B., Khan, R. S., Aravand, P., Dine, K. E., Ross, A. G., & Shindler, K. S. (2024) · Translational Vision Science & Technology · doi:10.1167/tvst.13.9.27 · Cited by 3 · see citing works
“42 There is experimental evidence to suggest that although RSV has multiple targets, 43,44 its neuroprotective effects are mediated by SIRT1.”
BackgroundRen, O. Y., Siddiqui, Y., Ansari, M. T., & Ali, A. (2025) · Journal of Asian Natural Products Research · doi:10.1080/10286020.2025.2459597 · Cited by 3 · see citing works
Identification of NQO2 As a Protein Target in Small Molecule Modulation of Hepatocellular Function
Schepers, A. G., Shan, J., Cox, A. G., Huang, A. J., Evans, H. L., Walesky, C. M., Fleming, H. E., Goessling, W., & Bhatia, S. N. (2021) · ACS Chemical Biology · doi:10.1021/acschembio.1c00503 · Cited by 3 · see citing works
Tvrdá, E., Ďuračka, M., & Ivanišová, E. (2024) · Advances in biochemistry in health and disease · doi:10.1007/978-3-031-47375-3_21 · Cited by 2 · see citing works
Novel Classification Perspective of Geroprotective and Senolytic Drugs as an Antiaging Strategy
Yanar, K. (2018) · Springer eBooks · doi:10.1007/978-981-13-1699-9_6 · Cited by 2 · see citing works
Medicinal plants containing resveratrol. a mini review
de Chile, U. D. S., Martinez, J. L., Yumrutaş, Ö., Muñoz-Acevedo, A., del Norte, U., Jaimes, L., de Chile, U. D. S., & Parlar, A. (2020) · Medicinal Plant Communications · doi:10.37360/mpc.20.3.3.11 · Cited by 2 · see citing works
Mass spectrometric investigations of caloric restriction mimetics
Bibyk, M. J., Campbell, M. J., & Hummon, A. B. (2021) · PROTEOMICS · doi:10.1002/pmic.202000121 · Cited by 1 · see citing works
“Resveratrol has been recognized for its potent anti-oxidant properties and its impact on glucose homeostasis and sirtuin protein family upregulation [31].”
BackgroundCiocoiu, M., Diaconescu, B. M., & Badescu, C. M. (2018) · InTech eBooks · doi:10.5772/intechopen.71689
FQAD and Neurotoxicity/Peripheral Neuropathy (PN)/Autonomic Neuropathy/Small Fibre Neuropathy
Pieper, S. (2021) · Springer eBooks · doi:10.1007/978-3-030-74173-0_4
Health-promoting activities and bioavailability of bioactive compounds from functional foods
Socaci, S., Fărcaș, A. C., Dulf, F. V., Pop, O. L., Diaconeasa, Z. M., & Fogarasi, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823482-2.00002-9
Chaithep, C., & Jomduang, S. (2022) · Journal Of Agrobiotechnology · doi:10.37231/jab.2022.13.1.297
“…benefits such as antioxidant activities (Gustavo et al., 2015), tumor inhibition (Jeong et al., 2017), heart and blood vessel diseases protection (Dilbahar & Shaista, 2012), decreasing and prevention of retinal cell deterioration (Thimmappa & Grazyna, 2008) and decreasing of blood sugar level…”
BackgroundD’Ascenzio, M. (2022) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9789815079098122010015
Rizwan, A., Aqeel, A., Choudhary, F., Nizam, A., Khan, A., & Farooqi, H. (2025) · Nutrition · doi:10.1016/j.nut.2025.112955
FQAD: Pathogenesis, Diagnosis, and Therapy
Pieper, S. (2025) · Springer eBooks · doi:10.1007/978-3-662-72123-0_3
Computational approaches to pleiotropic drug design for intestinal ischemia-reperfusion injury
Hezekiah, O. S., Afolabi, O. A., Ajike, R. A., Oyekunle, O. S., Ezekiel Oladele, O. J. O., & KOMOLAFE, A. I. (2026) · In Silico Research in Biomedicine · doi:10.1016/j.insi.2026.100511
- Authors
- S. Mohar, D.
- Venue
- Journal of Clinical & Experimental Cardiology
- Publisher
- OMICS Publishing Group
- Published
- 2012
- Volume
- 03
- Issue
- 11
- ISSN
- 2155-9880 (ISSN-L)
- PMC
- PMC3613783
- OpenAlex
- W2171553079
- Cited by
- 67
- References
- 51
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 3 · 2022: 11 · 2021: 12 · 2020: 12 · 2019: 4 · 2018: 4 · 2016: 1 · 2014: 4 · 2013: 4
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Clinical & Experimental Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (K23HL097158)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- resveratrol, sirtuins, SIRT1, oxidative stress, atherosclerosis, antioxidants, red wine, polyphenols, nitric oxide, endothelial cells, platelet aggregation, smooth muscle cell proliferation, pharmacokinetics, bioavailability, safety profile
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