Resveratrol: Molecular Mechanisms, Health Benefits, and Potential Adverse Effects

Abstract

Resveratrol (RES), a naturally occurring polyphenolic compound, has garnered significant attention due to its diverse biological activities, which include anti-inflammatory, antioxidant, and antiaging properties. This review synthesizes current evidence concerning the molecular mechanisms, therapeutic efficacy, and safety profile of RES across a variety of pathologies, with an emphasis on the latest research conducted in recent years. Mechanistically, RES is known to modulate critical signaling pathways such as the activation of sirtuin 1. These actions collectively contribute to the attenuation of oxidative stress, regulation of apoptosis, and promotion of autophagy. Preclinical studies have demonstrated the potential of RES in the mitigation of degenerative musculoskeletal disorders, cardiovascular diseases, cancer progression, and neurological diseases. Given the low bioavailability of RES and the potential for adverse reactions in clinical applications, we summarize and discuss its safety profile while outlining future research directions. This review underscores the therapeutic versatility of RES while advocating for rigorous pharmacokinetic optimization, standardized dosing protocols, and large-scale randomized controlled trials to validate its efficacy and safety in human populations.

Keywords

aging / cancer / pathogenesis / potential adverse effects / resveratrol / therapeutic mechanisms

References

[1] H. I. Rocha-González, M. Ambriz-Tututi, and G.-S. V. Resveratrol, “A Natural Compound With Pharmacological Potential in Neurodegenerative Diseases,” CNS Neuroscience & Therapeutics 14, no. 3 (2008): 234-247.

[2] S. Weiskirchen and W. R. Resveratrol, “How Much Wine Do You Have to Drink to Stay Healthy?,” Advances in Nutrition 7, no. 4 (2016): 706-718.

[3] M. TAKAOKA, “The Phenolic Substances of White Hellebore (Veratrum Grandiflorum Loes fil.) II,” Nippon Kagaku Kaishi 60, no. 12 (1939): 1261-1264.

[4] D. D. Zhou, M. Luo, S. Y. Huang, et al., “Effects and Mechanisms of Resveratrol on Aging and Age-Related Diseases,” Oxid Med Cell Longev 2021 (2021): 9932218.

[5] B. Paul, I. Masih, J. Deopujari, and C. Charpentier, “Occurrence of Resveratrol and Pterostilbene in Age-old Darakchasava, an Ayurvedic Medicine From India,” Journal of Ethnopharmacology 68, no. 1-3 (1999): 71-76.

[6] S. Renaud and M. de Lorgeril, “Wine, Alcohol, Platelets, and the French Paradox for Coronary Heart Disease,” The Lancet 339, no. 8808 (1992): 1523-1526.

[7] C. Wang, J. Yang, X. Gu, et al., “Nitrogen-doped Waste Biomass-derived Carbon Dots as Fluorescent Sensors for Economical, Green, Rapid and Sensitive Detection of Resveratrol in Foods,” Food Chemistry 472 (2025): 142886.

[8] I. Szymkowiak, M. Kucinska, and M. Murias, “Between the Devil and the Deep Blue Sea-Resveratrol, Sulfotransferases and Sulfatases-A Long and Turbulent Journey From Intestinal Absorption to Target Cells,” Molecules (Basel, Switzerland) 28, no. 8 (2023): 3297.

[9] S. V. Luca, I. Macovei, A. Bujor, et al., “Bioactivity of Dietary Polyphenols: The Role of Metabolites,” Critical Reviews in Food Science and Nutrition 60, no. 4 (2020): 626-659.

[10] L. Perico, G. Remuzzi, and A. Benigni, “Sirtuins in Kidney Health and Disease,” Nature Reviews Nephrology 20, no. 5 (2024): 313-329.

[11] Q. J. Wu, T. N. Zhang, H. H. Chen, et al., “The sirtuin family in Health and Disease,” Signal Transduct Target Ther 7, no. 1 (2022): 402.

[12] A. Dasgupta, S. K. Shukla, E. Vernucci, et al., “SIRT1-NOX4 signaling Axis Regulates Cancer Cachexia,” Journal of Experimental Medicine 217, no. 7 (2020): e20190745.

[13] M. Liao, X. Sun, W. Zheng, et al., “LINC00922 decoys SIRT3 to Facilitate the Metastasis of Colorectal Cancer Through Up-regulation the H3K27 Crotonylation of ETS1 Promoter,” Molecular cancer 22, no. 1 (2023): 163-163.

[14] D. S. Buglio, L. T. Marton, L. F. Laurindo, et al., “The Role of Resveratrol in Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review,” Journal of Medicinal Food 25, no. 8 (2022): 797-806.

[15] X. Meng, J. Zhou, C. N. Zhao, R. Y. Gan, and H. B. Li, “Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review,” Foods 9, no. 3 (2020): 340.

[16] Y. Zhuang, H. Wu, X. Wang, J. He, S. He, and Y. Yin, “Resveratrol Attenuates Oxidative Stress-Induced Intestinal Barrier Injury Through PI3K/Akt-Mediated Nrf2 Signaling Pathway,” Oxidative Medicine and Cellular Longevity 2019 (2019): 1-14.

[17] S. Mirzaei, A. T. Mohammadi, M. H. Gholami, et al., “Nrf2 signaling Pathway in Cisplatin Chemotherapy: Potential Involvement in Organ Protection and Chemoresistance,” Pharmacological Research 167 (2021): 105575.

[18] X. Yu, X. Li, Y. Xu, et al., “Resveratrol Ameliorates Ulcerative Colitis by Upregulating Nrf2/HO‑1 Pathway Activity: Integrating Animal Experiments and Network Pharmacology,” Mol Med Rep 29, no. 5 (2024): 77.

[19] H. H. Gaballah, S. S. Zakaria, M. M. Elbatsh, and N. M. Tahoon, “Modulatory Effects of Resveratrol On Endoplasmic Reticulum Stress-associated Apoptosis and Oxido-inflammatory Markers in a Rat Model of Rotenone-induced Parkinson's Disease,” Chemico-Biological Interactions 251 (2016): 10-16.

[20] X. Li, F. Li, F. Wang, J. Li, C. Lin, and J. Du, “Resveratrol Inhibits the Proliferation of A549 Cells by Inhibiting the Expression of COX-2,” Onco Targets Ther 11 (2018): 2981-2989.

[21] S. H. Eo and S. J. Kim, “Resveratrol-mediated Inhibition of Cyclooxygenase-2 in Melanocytes Suppresses Melanogenesis Through Extracellular Signal-regulated Kinase 1/2 and Phosphoinositide 3-kinase/Akt Signalling,” European Journal of Pharmacology 860 (2019): 172586.

[22] M. Xin, H. Wu, Y. Du, S. Liu, F. Zhao, and X. Mou, “Synthesis and Biological Evaluation of Resveratrol Amide Derivatives as Selective COX-2 Inhibitors,” Chemico-Biological Interactions 380 (2023): 110522.

[23] N. M. Hartung, J. Fischer, A. I. Ostermann, et al., “Impact of Food Polyphenols on Oxylipin Biosynthesis in human Neutrophils,” Biochimica Et Biophysica Acta (BBA)—Molecular and Cell Biology of Lipids 1864, no. 10 (2019): 1536-1544.

[24] Q. Yang, B. Han, S. Li, et al., “The Link Between Deacetylation and Hepatotoxicity Induced by Exposure to Hexavalent Chromium,” Journal of Advanced Research 35 (2021): 129-140.

[25] W. Zhou, Z. Zhu, X. Xiao, et al., “Jiangzhi Granule Attenuates Non-alcoholic Steatohepatitis by Suppressing TNF/NFκB Signaling Pathway-a Study Based on Network Pharmacology,” Biomedicine & Pharmacotherapy 143 (2021): 112181.

[26] I. T. Lee, H. C. Lin, T. H. Huang, et al., “Anti-Inflammatory Effect of Resveratrol Derivatives via the Downregulation of Oxidative-Stress-Dependent and c-Src Transactivation EGFR Pathways on Rat Mesangial Cells,” Antioxidants (Basel) 11, no. 5 (2022): 835.

[27] J. P. Jhou, S. J. Chen, H. Y. Huang, W. W. Lin, D. Y. Huang, and S. J. Tzeng, “Upregulation of FcγRIIB by Resveratrol via NF-κB Activation Reduces B-cell Numbers and Ameliorates Lupus,” Experimental & Molecular Medicine 49, no. 9 (2017): e381-e381.

[28] X. Fan, X. Li, J. Li, et al., “Polystyrene Nanoplastics Induce Glycolipid Metabolism Disorder via NF-κB and MAPK Signaling Pathway in Mice,” Journal of Environmental Sciences 137 (2024): 553-566.

[29] L. Cao, X. Chen, X. Xiao, Q. Ma, and W. Li, “Resveratrol Inhibits Hyperglycemia-driven ROS-induced Invasion and Migration of Pancreatic Cancer Cells Via Suppression of the ERK and p38 MAPK Signaling Pathways,” International Journal of Oncology 49, no. 2 (2016): 735-743.

[30] A. Ungurianu, A. Zanfirescu, and D. Margină, “Sirtuins, Resveratrol and the Intertwining Cellular Pathways Connecting Them,” Ageing Research Reviews 88 (2023): 101936.

[31] Q. J. Wu, T. N. Zhang, H. H. Chen, et al., “The sirtuin family in Health and Disease,” Signal Transduct Target Ther 7, no. 1 (2022): 402-402.

[32] J. A. Baur, Z. Ungvari, and R. K. Minor, “Le Couteur DG, de Cabo R. Are Sirtuins Viable Targets for Improving Healthspan and Lifespan?,” Nat Rev Drug Discovery 11, no. 6 (2012): 443-461.

[33] L. Chen, B. Z. Wang, J. Xie, et al., “Therapeutic Effect of SIRT3 On Glucocorticoid-induced Osteonecrosis of the Femoral Head via Intracellular Oxidative Suppression,” Free Radic Biol Med 176 (2021): 228-240.

[34] M. M. Cao, X. Lu, G. D. Liu, Y. Su, Y. B. Li, and J. Zhou, “Resveratrol Attenuates Type 2 Diabetes Mellitus by Mediating Mitochondrial Biogenesis and Lipid Metabolism via Sirtuin Type 1,” Exp Ther Med 15, no. 1 (2018): 576-584.

[35] H. Yang, F. Wang, P. Zhao, et al., “Black Soybean Peptide Mediates the AMPK/SIRT1/NF-κB Signaling Pathway to Alleviate Alzheimer's-related Neuroinflammation in Lead-exposed HT22 Cells,” International Journal of Biological Macromolecules 286 (2025): 138404.

[36] A. A. Mamun, C. Shao, P. Geng, S. Wang, and J. Xiao, “Polyphenols Targeting NF-κB Pathway in Neurological Disorders: What We Know So Far?,” Int J Biol Sci 20, no. 4 (2024): 1332-1355.

[37] W. Dong, K. Zhang, X. Wang, et al., “SIRT1 alleviates Cd Nephrotoxicity Through NF-κB/p65 Deacetylation-mediated Pyroptosis in Rat Renal Tubular Epithelial Cells,” Science of the Total Environment 929 (2024): 172392.

[38] H. S. Ghosh, M. McBurney, and P. D. Robbins, “SIRT1 negatively Regulates the Mammalian Target of Rapamycin,” PLoS ONE 5, no. 2 (2010): e9199.

[39] H. Qin, H. Zhang, X. Zhang, S. Zhang, S. Zhu, and H. Wang, “Resveratrol Protects Intestinal Epithelial Cells Against Radiation-induced Damage by Promoting Autophagy and Inhibiting Apoptosis Through SIRT1 Activation,” J Radiat Res 62, no. 4 (2021): 574-581.

[40] X. Liao, J. Lu, Z. Huang, et al., “Aminophylline Suppresses Chronic Renal Failure Progression by Activating SIRT1/AMPK/mTOR-dependent Autophagy,” Acta Biochim Biophys Sin (Shanghai) 56, no. 9 (2024): 1311-1322.

[41] Y. Jiang, W. Luo, B. Wang, X. Wang, P. Gong, and Y. Xiong, “Resveratrol Promotes Osteogenesis via Activating SIRT1/FoxO1 Pathway in Osteoporosis Mice,” Life Sciences 246 (2020): 117422.

[42] X. Wang, T. Shen, J. Lian, et al., “Resveratrol Reduces ROS-induced Ferroptosis by Activating SIRT3 and Compensating the GSH/GPX4 Pathway,” Molecular Medicine 29, no. 1 (2023): 137.

[43] Z. Li, Z. Zhang, L. Ke, et al., “Resveratrol Promotes White Adipocytes Browning and Improves Metabolic Disorders in Sirt1-dependent Manner in Mice,” Faseb Journal 34, no. 3 (2020): 4527-4539.

[44] Z. Q. Wen, J. Lin, W. Q. Xie, Y. H. Shan, G. H. Zhen, and Y. S. Li, “Insights Into the Underlying Pathogenesis and Therapeutic Potential of Endoplasmic Reticulum Stress in Degenerative Musculoskeletal Diseases,” Mil Med Res 10, no. 1 (2023): 54.

[45] H. Zhu, X. Li, M. Qiao, X. Sun, and G. Li, “Resveratrol Alleviates Inflammation and ER Stress through SIRT1/NRF2 to Delay Ovarian Aging in a Short-Lived Fish,” Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 78, no. 4 (2023): 596-602.

[46] Y. Yin, G. Lv, W. Zhang, et al., “Resveratrol Glycoside Mediates Microglial Endoplasmic Reticulum Stress to Mitigate LPS-induced Sepsis-associated Cognitive Dysfunction,” Behavioural Brain Research 443 (2023): 114326.

[47] X. Yu, M. Chen, J. Wu, and R. Song, “Research Progress of SIRTs Activator Resveratrol and Its Derivatives in Autoimmune Diseases,” Frontiers in immunology 15 (2024): 1390907.

[48] A. C. N. de Moraes, C. B. V. de Andrade, I. P. R. Ramos, et al., “Resveratrol Promotes Liver Regeneration in Drug-induced Liver Disease in Mice,” Food Research International 142 (2021): 110185.

[49] D. G. Le Couteur, S. M. Solon-Biet, and B. L. Parker, e, “Nutritional Reprogramming of Mouse Liver Proteome Is Dampened by Metformin, Resveratrol, and Rapamycin,” Cell metabolism 33, no. 12 (2021): 2367-2379. e4.

[50] I. Ramli, T. Cheriet, A. M. Posadino, et al., “Potential Therapeutic Targets of Resveratrol in the Prevention and Treatment of Pulmonary Fibrosis,” Front Biosci (Landmark Ed) 28, no. 9 (2023): 198.

[51] J. Feng, K. Ji, Y. Pan, P. Huang, T. He, and Y. Xing, “Resveratrol Ameliorates Retinal Ischemia-Reperfusion Injury by Modulating the NLRP3 Inflammasome and Keap1/Nrf2/HO-1 Signaling Pathway,” Molecular Neurobiology 61, no. 10 (2024): 8454-8466.

[52] Y. Wei, J. Jia, X. Jin, W. Tong, and H. Tian, “Resveratrol Ameliorates Inflammatory Damage and Protects Against Osteoarthritis in a Rat Model of Osteoarthritis,” Mol Med Rep 17, no. 1 (2018): 1493-1498.

[53] X. Xu, X. Liu, Y. Yang, et al., “Resveratrol Inhibits the Development of Obesity-related Osteoarthritis via the TLR4 and PI3K/Akt Signaling Pathways,” Connective Tissue Research 60, no. 6 (2019): 571-582.

[54] C. Buhrmann, B. Popper, B. B. Aggarwal, and M. Shakibaei, “Resveratrol Downregulates Inflammatory Pathway Activated by Lymphotoxin α (TNF-β) in Articular Chondrocytes: Comparison With TNF-α,” PLoS ONE 12, no. 11 (2017): e0186993-e0186993.

[55] M. Dave, M. Attur, G. Palmer, et al., “The Antioxidant Resveratrol Protects Against Chondrocyte Apoptosis via Effects on Mitochondrial Polarization and ATP Production,” Arthritis and Rheumatism 58, no. 9 (2008): 2786-2797.

[56] W. Zhao, Y. Zhu, S. K. Wong, N. Muhammad, K. L. Pang, and K. Y. Chin, “Effects of Resveratrol on Biochemical and Structural Outcomes in Osteoarthritis: A Systematic Review and Meta-analysis of Preclinical Studies,” Heliyon 10, no. 13 (2024): e34064.

[57] N. Qin, L. Wei, W. Li, et al., “Local Intra-articular Injection of Resveratrol Delays Cartilage Degeneration in C57BL/6 Mice by Inducing Autophagy via AMPK/mTOR Pathway,” Journal of Pharmacological Sciences 134, no. 3 (2017): 166-174.

[58] F. C. Liu, L. F. Hung, W. L. Wu, et al., “Chondroprotective Effects and Mechanisms of Resveratrol in Advanced Glycation End Products-stimulated Chondrocytes,” Arthritis Research & Therapy 12, no. 5 (2010): R167.

[59] D. G. Kang, H. J. Lee, C. J. Lee, and J. S. Park, “Inhibition of the Expression of Matrix Metalloproteinases in Articular Chondrocytes by Resveratrol Through Affecting Nuclear Factor-Kappa B Signaling Pathway,” Biomol Ther (Seoul) 26, no. 6 (2018): 560-567.

[60] G. Wang, X. Xie, L. Yuan, et al., “Resveratrol Ameliorates Rheumatoid Arthritis via Activation of SIRT1-Nrf2 Signaling Pathway,” Biofactors 46, no. 3 (2020): 441-453.

[61] M. N. Valcárcel-Ares, R. R. Riveiro-Naveira, C. Vaamonde-García, et al., “Mitochondrial Dysfunction Promotes and Aggravates the Inflammatory Response in Normal human Synoviocytes,” Rheumatology 53, no. 7 (2014): 1332-1343.

[62] X. Gao, X. Kang, H. Lu, et al., “Piceatannol Suppresses Inflammation and Promotes Apoptosis in Rheumatoid Arthritis‑Fibroblast‑Like Synoviocytes by Inhibiting the NF‑κB and MAPK Signaling Pathways,” Mol Med Rep 25, no. 5 (2022): 180.

[63] G. Yang, C. C. Chang, Y. Yang, et al., “Resveratrol Alleviates Rheumatoid Arthritis via Reducing ROS and Inflammation, Inhibiting MAPK Signaling Pathways, and Suppressing Angiogenesis,” Journal of Agricultural and Food Chemistry 66, no. 49 (2018): 12953-12960.

[64] G. Zaychenko, I. Belenichev, V. Hnatiuk, et al., “Protective Effect of Vaginal Resveratrol Administration On Joint Tissues in Ovariectomized Rats: Targeting mTOR and Сaspase 3,” Biomedicine & Pharmacotherapy 165 (2023): 115176.

[65] L. Loundagin and D. Cooper, “Towards Novel Measurements of Remodeling Activity in Cortical Bone: Implications for Osteoporosis and Related Pharmaceutical Treatments,” European Cells and Materials 43 (2022): 202-227.

[66] M. Shakibaei, C. Buhrmann, and A. Mobasheri, “Resveratrol-mediated SIRT-1 Interactions With p300 Modulate Receptor Activator of NF-kappaB Ligand (RANKL) Activation of NF-kappaB Signaling and Inhibit Osteoclastogenesis in Bone-derived Cells,” Journal of Biological Chemistry 286, no. 13 (2011): 11492-11505.

[67] J. W. Liu, D. Chandra, M. D. Rudd, et al., “Induction of Prosurvival Molecules by Apoptotic Stimuli: Involvement of FOXO3a and ROS,” Oncogene 24, no. 12 (2005): 2020-2031.

[68] H. Chen, X. Hu, R. Yang, et al., “SIRT1/FOXO3a axis Plays an Important Role in the Prevention of Mandibular Bone Loss Induced by 1,25(OH)(2)D Deficiency,” Int J Biol Sci 16, no. 14 (2020): 2712-2726.

[69] M. M. Elseweidy, S. E. El-Swefy, M. A. Shaheen, N. M. Baraka, and S. K. Hammad, “Effect of Resveratrol and Mesenchymal Stem Cell Monotherapy and Combined Treatment in Management of Osteoporosis in Ovariectomized Rats: Role of SIRT1/FOXO3a and Wnt/β-catenin Pathways,” Archives of Biochemistry and Biophysics 703 (2021): 108856.

[70] A. Ratz-Łyko and J. Arct, “Resveratrol as an Active Ingredient for Cosmetic and Dermatological Applications: A Review,” Journal of Cosmetic and Laser Therapy 21, no. 2 (2018): 84-90.

[71] U. Zehra, M. Tryfonidou, J. C. Iatridis, S. Illien-Jünger, F. Mwale, and D. Samartzis, “Mechanisms and Clinical Implications of Intervertebral Disc Calcification,” Nat Rev Rheumatol 18, no. 6 (2022): 352-362.

[72] P. P. A. Vergroesen, I. Kingma, K. S. Emanuel, et al., “Mechanics and Biology in Intervertebral Disc Degeneration: A Vicious Circle,” Osteoarthritis and Cartilage 23, no. 7 (2015): 1057-1070.

[73] W. Jiang, X. Zhang, J. Hao, et al., “SIRT1 protects Against Apoptosis by Promoting Autophagy in Degenerative human Disc Nucleus Pulposus Cells,” Scientific Reports 4 (2014): 7456.

[74] X. H. Wang, L. Zhu, X. Hong, et al., “Resveratrol Attenuated TNF-α-induced MMP-3 Expression in human Nucleus Pulposus Cells by Activating Autophagy via AMPK/SIRT1 Signaling Pathway,” Experimental Biology and Medicine (Maywood, N.J.) 241, no. 8 (2016): 848-853.

[75] F. He, Q. Li, B. Sheng, H. Yang, and W. Jiang, “SIRT1 Inhibits Apoptosis by Promoting Autophagic Flux in Human Nucleus Pulposus Cells in the Key Stage of Degeneration via ERK Signal Pathway,” BioMed research international 2021 (2021): 8818713-8818713.

[76] K. Li, Y. Li, J. Mi, L. Mao, X. Han, and J. Zhao, “Resveratrol Protects Against Sodium Nitroprusside Induced Nucleus Pulposus Cell Apoptosis by Scavenging ROS,” International Journal of Molecular Medicine 41, no. 5 (2018): 2485-2492.

[77] W. Wang, P. Li, J. Xu, et al., “Resveratrol Attenuates High Glucose-induced Nucleus Pulposus Cell Apoptosis and Senescence Through Activating the ROS-mediated PI3K/Akt Pathway,” Bioscience Reports 38, no. 2 (2018): BSR20171454.

[78] Z. Zhang, F. Wen, C. He, and J. Yu, “Resveratrol Attenuates Mechanical Compression-induced Nucleus Pulposus Cell Apoptosis Through Regulating the ERK1/2 Signaling Pathway in a Disc Organ Culture,” Bioscience Reports 38, no. 2 (2018): BSR20171703.

[79] Q. Shan, N. Li, F. Zhang, P. Yu, and Q. Meng, “Resveratrol Suppresses Annulus Fibrosus Cell Apoptosis Through Regulating Oxidative Stress Reaction in an Inflammatory Environment,” BioMed research international 2021 (2021): 9100444-9100444.

[80] H. Hu, L. Li, Y. Liu, S. Wang, S. Xie, and J. Sun, “Effect of Resveratrol On High Mobility Group Box-1 Protein Signaling Pathway in Cartilage Endplate Degeneration Caused by Inflammation],” Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi = Zhongguo Xiufu Chongjian Waike Zazhi = Chinese Journal of Reparative and Reconstructive Surgery 36, no. 4 (2022): 461-469.

[81] A. A. Damluji, M. Alfaraidhy, N. AlHajri, et al., “Sarcopenia and Cardiovascular Diseases,” Circulation 147, no. 20 (2023): 1534-1553.

[82] K. Tuntevski, A. Hajira, A. Nichols, S. E. Alway, and J. S. Mohamed, “Muscle-specific sirtuin1 Gain-of-function Ameliorates Skeletal Muscle Atrophy in a Pre-clinical Mouse Model of Cerebral Ischemic Stroke,” FASEB Bioadv 2, no. 7 (2020): 387-397.

[83] Y. Huang, X. Zhu, K. Chen, et al., “Resveratrol Prevents Sarcopenic Obesity by Reversing Mitochondrial Dysfunction and Oxidative Stress via the PKA/LKB1/AMPK Pathway,” Aging (Albany NY) 11, no. 8 (2019): 2217-2240.

[84] G. Sirago, L. Toniolo, E. Crea, and E. Giacomello, “A Short-term Treatment With Resveratrol Improves the Inflammatory Conditions of Middle-aged Mice Skeletal Muscles,” International Journal of Food Science and Nutrition 73, no. 5 (2022): 630-637.

[85] J. R. Jackson, M. J. Ryan, and S. E. Alway, “Long-term Supplementation With Resveratrol Alleviates Oxidative Stress but Does Not Attenuate Sarcopenia in Aged Mice,” Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 66, no. 7 (2011): 751-764.

[86] B. T. Bennett, J. S. Mohamed, and S. E. Alway, “Effects of Resveratrol on the Recovery of Muscle Mass Following Disuse in the Plantaris Muscle of Aged Rats,” PLoS ONE 8, no. 12 (2013): e83518.

[87] S. B. Ballak, R. T. Jaspers, L. Deldicque, et al., “Blunted Hypertrophic Response in Old Mouse Muscle Is Associated With a Lower Satellite Cell Density and Is Not Alleviated by Resveratrol,” Experimental Gerontology 62 (2015): 23-31.

[88] D. Zhao, J. Liu, M. Wang, X. Zhang, and M. Zhou, “Epidemiology of Cardiovascular Disease in China: Current Features and Implications,” Nature Reviews Cardiology 16, no. 4 (2019): 203-212.

[89] P. Libby, “The Changing Landscape of Atherosclerosis,” Nature 592, no. 7855 (2021): 524-533.

[90] Y. Peng, X. Zheng, S. Zhang, et al., “Advances in the Activity of Resveratrol and Its Derivatives in Cardiovascular Diseases,” Arch Pharm (Weinheim) 358, no. 2 (2025): e2400865.

[91] A. K. Vidanapathirana, P. J. Psaltis, C. A. Bursill, A. D. Abell, and S. J. Nicholls, “Cardiovascular Bioimaging of Nitric Oxide: Achievements, Challenges, and the Future,” Medicinal Research Reviews 41, no. 1 (2021): 435-463.

[92] T. Li, Y. Chen, C. Gua, and X. Li, “Elevated Circulating Trimethylamine N-Oxide Levels Contribute to Endothelial Dysfunction in Aged Rats Through Vascular Inflammation and Oxidative Stress,” Front Physiol 8 (2017): 350.

[93] D. W. Park, K. Baek, J. R. Kim, et al., “Resveratrol Inhibits Foam Cell Formation via NADPH Oxidase 1- mediated Reactive Oxygen Species and Monocyte Chemotactic Protein-1,” Experimental & Molecular Medicine 41, no. 3 (2009): 171-179.

[94] Y. Huang, J. Lu, L. Zhan, et al., “Resveratrol-induced Sirt1 Phosphorylation by LKB1 Mediates Mitochondrial Metabolism,” Journal of Biological Chemistry 297, no. 2 (2021): 100929.

[95] S. J. Park, F. Ahmad, A. Philp, et al., “Resveratrol Ameliorates Aging-related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases,” Cell 148, no. 3 (2012): 421-433.

[96] C. M. Klinge, N. S. Wickramasinghe, M. M. Ivanova, and S. M. Dougherty, “Resveratrol Stimulates Nitric Oxide Production by Increasing Estrogen Receptor Alpha-Src-caveolin-1 Interaction and Phosphorylation in human Umbilical Vein Endothelial Cells,” Faseb Journal 22, no. 7 (2008): 2185-2197.

[97] H. Li, N. Xia, S. Hasselwander, and A. Daiber, “Resveratrol and Vascular Function,” International Journal of Molecular Sciences 20, no. 9 (2019): 2155.

[98] N. Xia, S. Strand, F. Schlufter, et al., “Role of SIRT1 and FOXO Factors in eNOS Transcriptional Activation by Resveratrol,” Nitric Oxide 32 (2013): 29-35.

[99] Y. Xu, P. Liu, S. Xu, et al., “Tannic Acid as a Plant-derived Polyphenol Exerts Vasoprotection via Enhancing KLF2 Expression in Endothelial Cells,” Scientific Reports 7, no. 1 (2017): 6686.

[100] T. Zhang, W. Deng, Y. Deng, et al., “Mechanisms of Ferroptosis Regulating Oxidative Stress and Energy Metabolism in Myocardial Ischemia-reperfusion Injury and a Novel Perspective of Natural Plant Active Ingredients for Its Treatment,” Biomedicine & Pharmacotherapy 165 (2023): 114706.

[101] D. Wang, P. Uhrin, A. Mocan, et al., “Vascular Smooth Muscle Cell Proliferation as a Therapeutic Target. Part 1: Molecular Targets and Pathways,” Biotechnology Advances 36, no. 6 (2018): 1586-1607.

[102] G. Wang, X. Song, L. Zhao, Z. Li, and B. Liu, “Resveratrol Prevents Diabetic Cardiomyopathy by Increasing Nrf2 Expression and Transcriptional Activity,” BioMed research international 2018 (2018): 2150218.

[103] K. A. Ibrahim, H. A. Abdelgaid, M. Eleyan, R. A. Mohamed, and N. M. Gamil, “Resveratrol Alleviates Cardiac Apoptosis Following Exposure to Fenitrothion by Modulating the sirtuin1/c-Jun N-terminal Kinases/p53 Pathway Through Pro-oxidant and Inflammatory Response Improvements: In Vivo and in Silico Studies,” Life Sciences 290 (2022): 120265.

[104] Y. Chen, T. He, Z. Zhang, and J. Zhang, “Activation of SIRT1 by Resveratrol Alleviates Pressure Overload-Induced Cardiac Hypertrophy via Suppression of TGF-β1 Signaling,” Pharmacology 106, no. 11-12 (2021): 667-681.

[105] M. Su, W. Zhao, S. Xu, and J. Weng, “Resveratrol in Treating Diabetes and Its Cardiovascular Complications: A Review of Its Mechanisms of Action,” Antioxidants (Basel) 11, no. 6 (2022): 1085.

[106] J. Bernal-Ramírez, C. Silva-Platas, C. Jerjes-Sánchez, et al., “Resveratrol Prevents Right Ventricle Dysfunction, Calcium Mishandling, and Energetic Failure via SIRT3 Stimulation in Pulmonary Arterial Hypertension,” Oxid Med Cell Longev 2021 (2021): 9912434.

[107] K. Liu, Y. Zhu, W. Gao, et al., “Resveratrol Alleviates Heart Failure by Activating foxo3a to Counteract Oxidative Stress and Apoptosis,” Biomedicine & Pharmacotherapy 181 (2024): 117716.

[108] H. Chu, H. Li, X. Guan, et al., “Resveratrol Protects Late Endothelial Progenitor Cells From TNF-α-induced Inflammatory Damage by Upregulating Krüppel-Like Factor-2,” Mol Med Rep 17, no. 4 (2018): 5708-5715.

[109] X. Zheng, S. Zhu, S. Chang, et al., “Protective Effects of Chronic Resveratrol Treatment On Vascular Inflammatory Injury in Steptozotocin-induced Type 2 Diabetic Rats: Role of NF-kappa B Signaling,” European Journal of Pharmacology 720, no. 1-3 (2013): 147-157.

[110] W. Dong, R. Yang, J. Yang, et al., “Resveratrol Pretreatment Protects Rat Hearts From Ischemia/Reperfusion Injury Partly via a NALP3 Inflammasome Pathway,” Int J Clin Exp Pathol 8, no. 8 (2015): 8731-8741.

[111] P. Mohapatra, R. Preet, M. Choudhuri, T. Choudhuri, and C. N. Kundu, “5-fluorouracil Increases the Chemopreventive Potentials of Resveratrol Through DNA Damage and MAPK Signaling Pathway in human Colorectal Cancer Cells,” Oncology Research 19, no. 7 (2011): 311-321.

[112] V. Singh, R. Singh, P. K. Kujur, and R. P. Singh, “Combination of Resveratrol and Quercetin Causes Cell Growth Inhibition, DNA Damage, Cell Cycle Arrest, and Apoptosis in Oral Cancer Cells,” Assay and Drug Development Technologies 18, no. 5 (2020): 226-238.

[113] J. Lucas, T. C. Hsieh, H. D. Halicka, Z. Darzynkiewicz, and J. M. Wu, “Upregulation of PD‑L1 Expression by Resveratrol and Piceatannol in Breast and Colorectal Cancer Cells Occurs via HDAC3/p300‑Mediated NF‑κB Signaling,” International Journal of Oncology 53, no. 4 (2018): 1469-1480.

[114] H. Wu, L. Chen, F. Zhu, X. Han, L. Sun, and K. Chen, “The Cytotoxicity Effect of Resveratrol: Cell Cycle Arrest and Induced Apoptosis of Breast Cancer 4T1 Cells,” Toxins (Basel) 11, no. 12 (2019): 731.

[115] S. K. Singh, S. Banerjee, E. P. Acosta, J. W. Lillard, and R. Singh, “Resveratrol Induces Cell Cycle Arrest and Apoptosis With Docetaxel in Prostate Cancer Cells via a p53/p21WAF1/CIP1 and p27KIP1 Pathway,” Oncotarget 8, no. 10 (2017): 17216-17228.

[116] R. Florio, B. De Filippis, S. Veschi, et al., “Resveratrol Derivative Exhibits Marked Antiproliferative Actions, Affecting Stemness in Pancreatic Cancer Cells,” International Journal of Molecular Sciences 24, no. 3 (2023): 1977.

[117] S. Thongchot, A. Ferraresi, C. Vidoni, et al., “Preclinical Evidence for Preventive and Curative Effects of Resveratrol on Xenograft Cholangiocarcinogenesis,” Cancer Letters 582 (2024): 216589.

[118] A. Brockmueller, A. L. Mueller, P. Shayan, and M. Shakibaei, “β1-Integrin Plays a Major Role in Resveratrol-mediated Anti-invasion Effects in the CRC Microenvironment,” Frontiers in pharmacology 13 (2022): 978625.

[119] T. Yang, J. Zhang, J. Zhou, M. Zhu, L. Wang, and L. Yan, “Resveratrol Inhibits Interleukin-6 Induced Invasion of human Gastric Cancer Cells,” Biomedicine & Pharmacotherapy 99 (2018): 766-773.

[120] Z. Yang, Q. Xie, Z. Chen, et al., “Resveratrol Suppresses the Invasion and Migration of human Gastric Cancer Cells via Inhibition of MALAT1-mediated Epithelial-to-mesenchymal Transition,” Exp Ther Med 17, no. 3 (2019): 1569-1578.

[121] M. A. Lacerda-Abreu, T. Russo-Abrahão, and M.-F. JR, “Resveratrol Is an Inhibitor of Sodium-dependent Inorganic Phosphate Transport in Triple-negative MDA-MB-231 Breast Cancer Cells,” Cell Biology International 45, no. 8 (2021): 1768-1775.

[122] Y. Sun, Q. M. Zhou, Y. Y. Lu, et al., “Resveratrol Inhibits the Migration and Metastasis of MDA-MB-231 Human Breast Cancer by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition,” Molecules (Basel, Switzerland) 24, no. 6 (2019): 1131.

[123] H. Jiang, G. Wang, J. Gu, et al., “Resveratrol Inhibits the Expression of RYR2 and Is a Potential Treatment for Pancreatic Cancer,” Naunyn-Schmiedebergs Archives of Pharmacology 395, no. 3 (2022): 315-324.

[124] T. C. Hsieh and J. M. Wu, “Resveratrol Suppresses Prostate Cancer Epithelial Cell Scatter/Invasion by Targeting Inhibition of Hepatocyte Growth Factor (HGF) Secretion by Prostate Stromal Cells and Upregulation of E-cadherin by Prostate Cancer Epithelial Cells,” International Journal of Molecular Sciences 21, no. 5 (2020): 1760.

[125] Y. Fu, Y. Ye, G. Zhu, et al., “Resveratrol Induces human Colorectal Cancer Cell Apoptosis by Activating the Mitochondrial Pathway via Increasing Reactive Oxygen Species,” Mol Med Rep 23, no. 3 (2021): 170.

[126] C. daI. C. Araldi, F. P. R. Bordin, et al, “The in Vitro Radiosensitizer Potential of Resveratrol on MCF-7 Breast Cancer Cells,” Chemico-Biological Interactions 282 (2018): 85-92.

[127] C. Liang, K. Yi, X. Zhou, et al., “Destruction of the Cellular Antioxidant Pool Contributes to Resveratrol-induced Senescence and Apoptosis in Lung Cancer,” Phytotherapy Research 37, no. 7 (2023): 2995-3008.

[128] A. Brockmueller, C. Buhrmann, P. Shayan, and M. Shakibaei, “Resveratrol Induces Apoptosis by Modulating the Reciprocal Crosstalk Between p53 and Sirt-1 in the CRC Tumor Microenvironment,” Frontiers in immunology 14 (2023): 1225530.

[129] J. Li, Y. Fan, Y. Zhang, Y. Liu, Y. Yu, and M. Ma, “Resveratrol Induces Autophagy and Apoptosis in Non-Small-Cell Lung Cancer Cells by Activating the NGFR-AMPK-mTOR Pathway,” Nutrients 14, no. 12 (2022): 2413.

[130] J. Wang, P. Huang, X. Pan, et al., “Resveratrol Reverses TGF-β1-mediated Invasion and Metastasis of Breast Cancer Cells via the SIRT3/AMPK/Autophagy Signal Axis,” Phytotherapy Research 37, no. 1 (2023): 211-230.

[131] C. H. Chang, C. Y. Lee, C. C. Lu, et al., “Resveratrol-induced Autophagy and Apoptosis in Cisplatin-resistant human Oral Cancer CAR Cells: A Key Role of AMPK and Akt/mTOR Signaling,” International Journal of Oncology 50, no. 3 (2017): 873-882.

[132] Z. J. Liang, Y. Wan, D. D. Zhu, et al., “Resveratrol Mediates the Apoptosis of Triple Negative Breast Cancer Cells by Reducing POLD1 Expression,” Frontiers in oncology 11 (2021): 569295.

[133] M. Yang, Z. Li, J. Tao, et al., “Resveratrol Induces PD-L1 Expression Through Snail-driven Activation of Wnt Pathway in Lung Cancer Cells,” Journal of Cancer Research and Clinical Oncology 147, no. 4 (2021): 1101-1113.

[134] H. R. Alrafas, P. B. Busbee, K. N. Chitrala, M. Nagarkatti, and P. Nagarkatti, “Alterations in the Gut Microbiome and Suppression of Histone Deacetylases by Resveratrol Are Associated With Attenuation of Colonic Inflammation and Protection against Colorectal Cancer,” Journal of Clinical Medicine 9, no. 6 (2020): 1796.

[135] L. Yang, J. Yin, J. Wu, et al., “Engineering genetic devices for in vivo control of therapeutic T cell activity triggered by the dietary molecule resveratrol,” Proceedings of the National Academy of Sciences of the United States of America (2021): e2106612118.

[136] M. M. Islam, N. Sultana, C. Liu, A. Mao, T. Katsube, and B. Wang, “Impact of Dietary Ingredients on Radioprotection and Radiosensitization: A Comprehensive Review,” Annals of Medicine 56, no. 1 (2024): 2396558.

[137] G. Pai Bellare and B. Sankar Patro, “Resveratrol Sensitizes Breast Cancer to PARP Inhibitor, Talazoparib Through Dual Inhibition of AKT and Autophagy Flux,” Biochemical Pharmacology 199 (2022): 115024.

[138] A. Brockmueller, S. Girisa, A. B. Kunnumakkara, and M. Shakibaei, “Resveratrol Modulates Chemosensitisation to 5-FU via β1-Integrin/HIF-1α Axis in CRC Tumor Microenvironment,” International Journal of Molecular Sciences 24, no. 5 (2023): 4988.

[139] Y. Wang, W. Wang, X. Wu, et al., “Resveratrol Sensitizes Colorectal Cancer Cells to Cetuximab by Connexin 43 Upregulation-Induced Akt Inhibition,” Frontiers in oncology 10 (2020): 383.

[140] S. Amintas, C. Dupin, M. A. Derieppe, et al., “Resveratrol and Capsaicin as Safer Radiosensitizers for Colorectal Cancer Compared to 5-fluorouracil,” Biomedicine & Pharmacotherapy 183 (2025): 117799.

[141] N. Wang, E. Gao, C. Cui, et al., “The Combined Anticancer of Peanut Skin Procyanidins and Resveratrol to CACO-2 Colorectal Cancer Cells,” Food Sci Nutr 11, no. 10 (2023): 6483-6497.

[142] K. Makk-Merczel, D. Varga, P. Hajdinák, and A. Szarka, “The Interlacing Anticancer Effect of Pharmacologic Ascorbate, Chloroquine, and Resveratrol,” Biofactors 50, no. 5 (2024): 980-996.

[143] N. Gupta, B. Zhang, Y. Zhou, et al., “Safety and Efficacy of Combined Resveratrol and Sirolimus in Lymphangioleiomyomatosis,” Chest 163, no. 5 (2023): 1144-1155.

[144] D. Taheri, H. A. Ghajar, A. Mirzaei, et al., “Resveratrol Enhances Sensitivity of Renal Cell Carcinoma to Tivozanib: An in-vitro Study,” Tissue & Cell 91 (2024): 102584.

[145] L. R. Dos Reis, M. T. Luiz, R. M. Sábio, et al., “Design of Rapamycin and Resveratrol Coloaded Liposomal Formulation for Breast Cancer Therapy,” Nanomedicine (Lond) 18, no. 10 (2023): 789-801.

[146] A. M. Radwan, H. A. Abosharaf, M. Sharaky, R. Abdelmonem, and H. Effat, “Functional Combination of Resveratrol and Tamoxifen to Overcome Tamoxifen-resistance in Breast Cancer Cells,” Arch Pharm (Weinheim) 357, no. 10 (2024): e2400261.

[147] S. Sinha, S. Paul, S. S. Acharya, et al., “Combination of Resveratrol and PARP Inhibitor Olaparib Efficiently Deregulates Homologous Recombination Repair Pathway in Breast Cancer Cells Through Inhibition of TIP60-mediated Chromatin Relaxation,” Medical Oncology 41, no. 2 (2024): 49.

[148] A. N. Sharma, P. K. Upadhyay, and H. K. Dewangan, “Dual Combination of Resveratrol and Pterostilbene Aqueous Core Nanocapsules for Integrated Prostate Cancer Targeting,” Ther Deliv 15, no. 9 (2024): 685-698.

[149] B. K. Utpal, F. Z. Mokhfi, M. Zehravi, et al., “Resveratrol: A Natural Compound Targeting the PI3K/Akt/mTOR Pathway in Neurological Diseases,” Molecular Neurobiology (2024). Published online November 23.

[150] S. Y. Wong and B. L. Tang, “SIRT1 as a Therapeutic Target for Alzheimer's Disease,” Reviews in the Neurosciences 27, no. 8 (2016): 813-825.

[151] K. Surya, N. Manickam, K. S. Jayachandran, M. Kandasamy, and M. Anusuyadevi, “Resveratrol Mediated Regulation of Hippocampal Neuroregenerative Plasticity via SIRT1 Pathway in Synergy With Wnt Signaling: Neurotherapeutic Implications to Mitigate Memory Loss in Alzheimer's Disease,” Journal of Alzheimer's Disease 94, no. s1 (2023): S125-S140.

[152] L. Zhu, M. Yang, L. Fan, et al., “Interaction Between Resveratrol and SIRT1: Role in Neurodegenerative Diseases,” Naunyn-Schmiedebergs Archives of Pharmacology 398, no. 1 (2025): 89-101.

[153] Y. Zhang, H. Chen, R. Li, K. Sterling, and W. Song, “Amyloid β-based Therapy for Alzheimer's Disease: Challenges, Successes and Future,” Signal Transduct Target Ther 8, no. 1 (2023): 248.

[154] T. Ahmed, S. Javed, S. Javed, et al., “Resveratrol and Alzheimer's Disease: Mechanistic Insights,” Molecular Neurobiology 54, no. 4 (2017): 2622-2635.

[155] H. R. Lee, H. K. Shin, S. Y. Park, et al., “Cilostazol Upregulates Autophagy via SIRT1 Activation: Reducing Amyloid-β Peptide and APP-CTFβ Levels in Neuronal Cells,” PLoS ONE 10, no. 8 (2015): e0134486.

[156] N. Zhao, X. Zhang, B. Li, J. Wang, C. Zhang, and B. Xu, “Treadmill Exercise Improves PINK1/Parkin-Mediated Mitophagy Activity against Alzheimer's Disease Pathologies by Upregulated SIRT1-FOXO1/3 Axis in APP/PS1 Mice,” Molecular Neurobiology 60, no. 1 (2023): 277-291.

[157] O. a. R. Abozaid, M. W. Sallam, and E. S. A. Ahmed, “Mesenchymal Stem Cells Modulate SIRT1/MiR-134/GSK3β Signaling Pathway in a Rat Model of Alzheimer's Disease,” J Prev Alzheimers Dis 9, no. 3 (2022): 458-468.

[158] R. M. Wei, Y. M. Zhang, Y. Z. Feng, et al., “Resveratrol Ameliorates Maternal Separation-induced Anxiety- and Depression-Like Behaviors and Reduces Sirt1-NF-kB Signaling-mediated Neuroinflammation,” Frontiers in Behavioral Neuroscience 17 (2023): 1172091.

[159] Y. Zhang, S. Anoopkumar-Dukie, D. Arora, and A. K. Davey, “Review of the Anti-inflammatory Effect of SIRT1 and SIRT2 Modulators on Neurodegenerative Diseases,” European Journal of Pharmacology 867 (2020): 172847.

[160] Q. Zheng, P. Ma, P. Yang, et al., “Alpha Lipoic Acid Ameliorates Motor Deficits by Inhibiting Ferroptosis in Parkinson's Disease,” Neuroscience Letters 810 (2023): 137346.

[161] X. S. Zhang, Y. Lu, W. Li, et al., “Cerebroprotection by Dioscin After Experimental Subarachnoid Haemorrhage via Inhibiting NLRP3 Inflammasome Through SIRT1-dependent Pathway,” British Journal of Pharmacology 178, no. 18 (2021): 3648-3666.

[162] Y. Wu, X. Li, J. X. Zhu, et al., “Resveratrol-activated AMPK/SIRT1/Autophagy in Cellular Models of Parkinson's Disease,” Neuro-Signals 19, no. 3 (2011): 163-174.

[163] J. Xu, C. W. Jackson, N. Khoury, I. Escobar, and M. A. Perez-Pinzon, “Brain SIRT1 Mediates Metabolic Homeostasis and Neuroprotection,” Front Endocrinol (Lausanne) 9 (2018): 702.

[164] N. Salimian, M. Peymani, K. Ghaedi, and M. H. Nasr Esfahani, “Modulation in miR-200a/SIRT1axis Is Associated With Apoptosis in MPP+-induced SH-SY5Y Cells,” Gene 674 (2018): 25-30.

[165] C. C. Chang, S. H. Tsou, W. J. Chen, et al., “miR-302 Attenuates Mutant Huntingtin-Induced Cytotoxicity Through Restoration of Autophagy and Insulin Sensitivity,” International Journal of Molecular Sciences 22, no. 16 (2021): 8424.

[166] J. Yoon, D. Ku, M. Lee, N. Lee, S. G. Im, and Y. Kim, “Resveratrol Attenuates the Mitochondrial RNA-Mediated Cellular Response to Immunogenic Stress,” International Journal of Molecular Sciences 24, no. 8 (2023): 7403.

[167] M. Jiang, J. Wang, J. Fu, et al., “Neuroprotective Role of Sirt1 in Mammalian Models of Huntington's Disease Through Activation of Multiple Sirt1 Targets,” Nature Medicine 18, no. 1 (2011): 153-158.

[168] G. A. Abdel-Aleem, E. F. Khaleel, D. G. Mostafa, and L. K. Elberier, “Neuroprotective Effect of Resveratrol Against Brain Ischemia Reperfusion Injury in Rats Entails Reduction of DJ-1 Protein Expression and Activation of PI3K/Akt/GSK3b Survival Pathway,” Archives of Physiology and Biochemistry 122, no. 4 (2016): 200-213.

[169] J. Lei and Q. Chen, “Resveratrol Attenuates Brain Damage in Permanent Focal Cerebral Ischemia Via Activation of PI3K/Akt Signaling Pathway in Rats,” Neurological Research 40, no. 12 (2018): 1014-1020.

[170] Y. K. Gupta, S. Briyal, and G. Chaudhary, “Protective Effect of Trans-resveratrol Against Kainic Acid-induced Seizures and Oxidative Stress in Rats,” Pharmacology Biochemistry and Behavior 71, no. 1-2 (2002): 245-249.

[171] X. Chen, J. Xue, J. Zou, et al., “Resveratrol Alleviated Neuroinflammation Induced by Pseudorabies Virus Infection Through Regulating Microglial M1/M2 Polarization,” Biomedicine & Pharmacotherapy 160 (2023): 114271.

[172] M. Amontree, M. Nelson, L. Stefansson, et al., “Resveratrol Differentially Affects MMP-9 Release From Neurons and Glia; Implications for Therapeutic Efficacy,” Journal of Neurochemistry 168, no. 9 (2024): 1895-1908.

[173] M. Jhanji, C. N. Rao, J. C. Massey, et al., “Cis- and Trans-resveratrol Have Opposite Effects on Histone Serine-ADP-ribosylation and Tyrosine Induced Neurodegeneration,” Nature Communications 13, no. 1 (2022): 3244-3244.

[174] J. P. de Magalhães, “Cellular Senescence in Normal Physiology,” Science 384, no. 6702 (2024): 1300-1301.

[175] L. Grosse, N. Wagner, A. Emelyanov, et al., “Defined p16High Senescent Cell Types Are Indispensable for Mouse Healthspan,” Cell Metabolism 32, no. 1 (2020): 87-99.

[176] C. Moussa, M. Hebron, X. Huang, et al., “Resveratrol Regulates Neuro-inflammation and Induces Adaptive Immunity in Alzheimer's Disease,” J Neuroinflammation 14, no. 1 (2017): 1-1.

[177] R. S. Turner, R. G. Thomas, S. Craft, et al., “A Randomized, Double-blind, Placebo-controlled Trial of Resveratrol for Alzheimer Disease,” Neurology 85, no. 16 (2015): 1383-1391.

[178] G. Corbi, V. Nobile, V. Conti, et al., “Equol and Resveratrol Improve Bone Turnover Biomarkers in Postmenopausal Women: A Clinical Trial,” International Journal of Molecular Sciences 24, no. 15 (2023): 12063.

[179] R. H. Wong, J. J. Thaung Zaw, C. J. Xian, and P. R. Howe, “Regular Supplementation with Resveratrol Improves Bone Mineral Density in Postmenopausal Women: A Randomized, Placebo-Controlled Trial,” Journal of Bone and Mineral Research 35, no. 11 (2020): 2121-2131.

[180] J. Li, L. Li, T. Wu, et al., “An Injectable Thermosensitive Hydrogel Containing Resveratrol and Dexamethasone-Loaded Carbonated Hydroxyapatite Microspheres for the Regeneration of Osteoporotic Bone Defects,” Small Methods 8, no. 1 (2024): e2300843.

[181] O. Toupchian, S. Abdollahi, A. Salehi-Abargouei, et al., “The Effects of Resveratrol Supplementation on PPARα, p16, p53, p21 Gene Expressions, and sCD163/sTWEAK Ratio in Patients With Type 2 Diabetes Mellitus: A Double-blind Controlled Randomized Trial,” Phytotherapy Research 35, no. 6 (2021): 3205-3213.

[182] F. M. Delpino and L. M. Figueiredo, “Resveratrol Supplementation and Type 2 Diabetes: A Systematic Review and Meta-analysis,” Critical Reviews in Food Science and Nutrition 62, no. 16 (2021): 4465-4480.

[183] K. Szkudelska, M. Okulicz, I. Hertig, and T. Szkudelski, “Resveratrol Ameliorates Inflammatory and Oxidative Stress in Type 2 Diabetic Goto-Kakizaki Rats,” Biomedicine & Pharmacotherapy 125 (2020): 110026.

[184] M. Liu, Y. Yin, X. Ye, et al., “Resveratrol Protects Against Age-associated Infertility in Mice,” Human Reproduction 28, no. 3 (2013): 707-717.

[185] R. Gonçalves, Á. C. C. Maciel, Y. Rolland, B. Vellas, S. de, and P. Barreto, “Frailty Biomarkers Under the Perspective of Geroscience: A Narrative Review,” Ageing Research Reviews 81 (2022): 101737.

[186] V. S. Dhillon, M. Shahid, P. Deo, and M. Fenech, “Reduced SIRT1 and SIRT3 and Lower Antioxidant Capacity of Seminal Plasma Is Associated With Shorter Sperm Telomere Length in Oligospermic Men,” International Journal of Molecular Sciences 25, no. 2 (2024): 718.

[187] D. Hernández-Silva, M. D. López-Abellán, F. J. Martínez-Navarro, J. García-Castillo, M. L. Cayuela, and F. Alcaraz-Pérez, “Development of a Short Telomere Zebrafish Model for Accelerated Aging Research and Antiaging Drug Screening,” Aging Cell (2025): e70007. Published online February 8.

[188] A. Shaito, M. Al-Mansoob, S. M. S. Ahmad, et al., “Resveratrol-Mediated Regulation of Mitochondria Biogenesis-associated Pathways in Neurodegenerative Diseases: Molecular Insights and Potential Therapeutic Applications,” Current Neuropharmacology 21, no. 5 (2023): 1184-1201.

[189] N. Hart, L. Sarga, Z. Csende, et al., “Resveratrol Enhances Exercise Training Responses in Rats Selectively Bred for High Running Performance,” Food and Chemical Toxicology 61 (2013): 53-59.

[190] G. Gherardi, G. Corbioli, F. Ruzza, and R. Rizzuto, “CoQ₁₀ and Resveratrol Effects to Ameliorate Aged-Related Mitochondrial Dysfunctions,” Nutrients 14, no. 20 (2022): 4326.

[191] D. R. Valenzano, E. Terzibasi, T. Genade, A. Cattaneo, L. Domenici, and A. Cellerino, “Resveratrol Prolongs Lifespan and Retards the Onset of Age-Related Markers in a Short-Lived Vertebrate,” Current Biology 16, no. 3 (2006): 296-300.

[192] K. T. Howitz, K. J. Bitterman, H. Y. Cohen, et al., “Small Molecule Activators of Sirtuins Extend Saccharomyces Cerevisiae Lifespan,” Nature 425, no. 6954 (2003): 191-196.

[193] I. S. Pyo, S. Yun, Y. E. Yoon, J. W. Choi, and S. J. Lee, “Mechanisms of Aging and the Preventive Effects of Resveratrol on Age-Related Diseases,” Molecules (Basel, Switzerland) 25, no. 20 (2020): 4649.

[194] C. T. Madreiter-Sokolowski, M. Waldeck-Weiermair, M. P. Bourguignon, et al., “Enhanced Inter-compartmental Ca²⁺ Flux Modulates Mitochondrial Metabolism and Apoptotic Threshold During Aging,” Redox Biology 20 (2019): 458-466.

[195] P. Wang, Y. Yang, J. Guo, et al., “Resveratrol Inhibits Zinc Deficiency-Induced Mitophagy and Exerts Cardiac Cytoprotective Effects,” Biological Trace Element Research 202, no. 4 (2024): 1669-1682.

[196] X. Ren, L. Chen, J. Xie, et al., “Resveratrol Ameliorates Mitochondrial Elongation via Drp1/Parkin/PINK1 Signaling in Senescent-Like Cardiomyocytes,” Oxid Med Cell Longev 2017 (2017): 4175353.

[197] S. Yadegar, F. Mohammadi, A. Yadegar, et al., “Effects and Safety of Resveratrol Supplementation in Older Adults: A Comprehensive Systematic Review,” Phytotherapy Research 38, no. 5 (2024): 2448-2461.

[198] B. Chatterjee, K. Ghosh, and S. R. Kanade, “Resveratrol Modulates Epigenetic Regulators of Promoter Histone Methylation and Acetylation That Restores BRCA1, p53, p21CIP1 in human Breast Cancer Cell Lines,” Biofactors 45, no. 5 (2019): 818-829.

[199] V. Izquierdo, V. Palomera-Ávalos, S. López-Ruiz, A. M. Canudas, M. Pallàs, and C. Griñán-Ferré, “Maternal Resveratrol Supplementation Prevents Cognitive Decline in Senescent Mice Offspring,” International Journal of Molecular Sciences 20, no. 5 (2019): 1134.

[200] J. A. McCubrey, K. Lertpiriyapong, L. S. Steelman, et al., “Effects of Resveratrol, Curcumin, Berberine and Other Nutraceuticals on Aging, Cancer Development, Cancer Stem Cells and microRNAs,” Aging 9, no. 6 (2017): 1477-1536.

[201] I. Pérez-Torres, V. Castrejón-Téllez, M. E. Soto, M. E. Rubio-Ruiz, L. Manzano-Pech, and V. Guarner-Lans, “Oxidative Stress, Plant Natural Antioxidants, and Obesity,” International Journal of Molecular Sciences 22, no. 4 (2021): 1786.

[202] Y. Liu, X. Wu, X. Hu, et al., “Multiple Repair Pathways Mediate Cellular Tolerance to Resveratrol-induced DNA Damage,” Toxicology in Vitro 42 (2017): 130-138.

[203] G. A. Locatelli, M. Savio, L. Forti, et al., “Inhibition of Mammalian DNA Polymerases by Resveratrol: Mechanism and Structural Determinants,” Biochemical Journal 389, no. Pt 2 (2005): 259-268.

[204] M. Fontecave, M. Lepoivre, E. Elleingand, C. Gerez, and O. Guittet, “Resveratrol, a Remarkable Inhibitor of Ribonucleotide Reductase,” Febs Letters 421, no. 3 (1998): 277-279.

[205] B. Li, D. Hou, H. Guo, et al., “Resveratrol Sequentially Induces Replication and Oxidative Stresses to Drive p53-CXCR2 Mediated Cellular Senescence in Cancer Cells,” Scientific Reports 7, no. 1 (2017): 208.

[206] A. M. Posadino, A. Cossu, R. Giordo, et al., “Resveratrol Alters human Endothelial Cells Redox state and Causes Mitochondrial-dependent Cell Death,” Food and Chemical Toxicology 78 (2015): 10-16.

[207] S. Khanvilkar and I. Mittra, “Copper Imparts a New Therapeutic Property to Resveratrol by Generating ROS to Deactivate Cell-Free Chromatin,” Pharmaceuticals (Basel) 18, no. 1 (2025): 132.

[208] R. Podgrajsek, H. Ban Frangez, and M. Stimpfel, “Molecular Mechanism of Resveratrol and Its Therapeutic Potential on Female Infertility,” International Journal of Molecular Sciences 25, no. 7 (2024): 3613.

[209] R. T. Mankowski, L. You, T. W. Buford, et al., “Higher Dose of Resveratrol Elevated Cardiovascular Disease Risk Biomarker Levels in Overweight Older Adults—A Pilot Study,” Experimental Gerontology 131 (2020): 110821.

[210] P. Detampel, M. Beck, S. Krähenbühl, and J. Huwyler, “Drug Interaction Potential of Resveratrol,” Drug Metabolism Reviews 44, no. 3 (2012): 253-265.

[211] S. M. Hadi, M. F. Ullah, A. S. Azmi, et al., “Resveratrol Mobilizes Endogenous Copper in human Peripheral Lymphocytes Leading to Oxidative DNA Breakage: A Putative Mechanism for Chemoprevention of Cancer,” Pharmaceutical Research 27, no. 6 (2010): 979-988.

[212] A. Brockmueller, A. Sajeev, L. Koklesova, et al., “Resveratrol as Sensitizer in Colorectal Cancer Plasticity,” Cancer and Metastasis Reviews 43, no. 1 (2024): 55-85.

[213] V. Mohos, T. Bencsik, G. Boda, et al., “Interactions of Casticin, Ipriflavone, and Resveratrol With Serum Albumin and Their Inhibitory Effects on CYP2C9 and CYP3A4 Enzymes,” Biomedicine & Pharmacotherapy 107 (2018): 777-784.

[214] J. S. Choi, B. C. Choi, and K. W. Kang, “Effect of Resveratrol on the Pharmacokinetics of Oral and Intravenous Nicardipine in Rats: Possible Role of P-glycoprotein Inhibition by Resveratrol,” Die Pharmazie 64, no. 1 (2009): 49-52.

[215] S. B. Ji, S. Y. Park, S. Bae, et al., “Comprehensive Investigation of Stereoselective Food Drug Interaction Potential of Resveratrol on Nine P450 and Six UGT Isoforms in Human Liver Microsomes,” Pharmaceutics 13, no. 9 (2021): 1419.

[216] A. Zayed, J. Al Hroot, A. Mayyas, and B. Al-Husein, “Rapid High Performance Liquid Chromatography Method for Erlotinib Quantification in Vitro: Application to Study the Effect of Resveratrol on Metabolism and Cellular Uptake of erlotinib,” Fundamental and Clinical Pharmacology 37, no. 5 (2023): 983-993.

[217] Y. Ye, Z. Chen, Y. Shen, H. Wu, R. A. Xu, and C. J. Zhou, “Analyzing the Effect of Resveratrol on Pharmacokinetics of Antituberculosis Drug Bedaquiline in Rats by a Novel UPLC-MS/MS Approach,” ACS Omega 9, no. 49 (2024): 48650-48656.

[218] Y. Jia, Z. Liu, C. Wang, et al., “P-gp, MRP2 and OAT1/OAT3 Mediate the Drug-drug Interaction Between Resveratrol and Methotrexate,” Toxicology and Applied Pharmacology 306 (2016): 27-35.

[219] R. J. Qasem, “The Estrogenic Activity of Resveratrol: A Comprehensive Review of in Vitro and in Vivo Evidence and the Potential for Endocrine Disruption,” Critical Reviews in Toxicology 50, no. 5 (2020): 439-462.

[220] R. T. Turner, G. L. Evans, M. Zhang, A. Maran, and J. D. Sibonga, “Is Resveratrol an Estrogen Agonist in Growing Rats?,” Endocrinology 140, no. 1 (1999): 50-54.

[221] L. Li, X. Chen, Q. Zhu, et al., “Disrupting Androgen Production of Leydig Cells by Resveratrol Via Direct Inhibition of human and Rat 3β-hydroxysteroid Dehydrogenase,” Toxicology Letters 226, no. 1 (2014): 14-19.

[222] Y. C. Chen, M. L. Nagpal, D. M. Stocco, and T. Lin, “Effects of Genistein, Resveratrol, and Quercetin on Steroidogenesis and Proliferation of MA-10 Mouse Leydig Tumor Cells,” Journal of Endocrinology 192, no. 3 (2007): 527-537.

[223] S. K. Banu, J. A. Stanley, K. K. Sivakumar, J. A. Arosh, and R. C. Burghardt, “Resveratrol Protects the Ovary Against Chromium-toxicity by Enhancing Endogenous Antioxidant Enzymes and Inhibiting Metabolic Clearance of Estradiol,” Toxicology and Applied Pharmacology 303 (2016): 65-78.

[224] N. Tagawa, S. Kubota, I. Kato, and Y. Kobayashi, “Resveratrol Inhibits 11β-hydroxysteroid Dehydrogenase Type 1 Activity in Rat Adipose Microsomes,” Journal of Endocrinology 218, no. 3 (2013): 311-320.

[225] C. Andreani, C. Bartolacci, K. Wijnant, et al., “Resveratrol Fuels HER2 and ERα-positive Breast Cancer Behaving as Proteasome Inhibitor,” Aging (Albany NY) 9, no. 2 (2017): 508-523.

[226] M. D. Walker and E. Shane, “Postmenopausal Osteoporosis,” New England Journal of Medicine 389, no. 21 (2023): 1979-1991.

[227] J. K. Bird, D. Raederstorff, P. Weber, and R. E. Steinert, “Cardiovascular and Antiobesity Effects of Resveratrol Mediated Through the Gut Microbiota,” Advances in nutrition 8, no. 6 (2017): 839-849.

[228] F. Chen, L. Zhang, Y. Liu, A. Zhang, and W. Wang, “Resveratrol Alleviates Perinatal Methylmercury-induced Neurobehavioral Impairments by Modulating the Gut Microbiota Composition and Neurotransmitter Disturbances,” Environmental Toxicology 39, no. 1 (2024): 329-340.

[229] V. A. Brown, K. R. Patel, M. Viskaduraki, et al., “Repeat Dose Study of the Cancer Chemopreventive Agent Resveratrol in Healthy Volunteers: Safety, Pharmacokinetics, and Effect on the Insulin-Like Growth Factor Axis,” Cancer Research 70, no. 22 (2010): 9003-9011.

[230] H. H. S. Chow, L. L. Garland, B. M. Heckman-Stoddard, et al., “A Pilot Clinical Study of Resveratrol in Postmenopausal Women With High Body Mass Index: Effects on Systemic Sex Steroid Hormones,” Journal of translational medicine 12, no. 1 (2014): 223.

[231] C. la Porte, N. Voduc, G. Zhang, et al., “Steady-State Pharmacokinetics and Tolerability of Trans-resveratrol 2000 mg Twice Daily With Food, Quercetin and Alcohol (ethanol) in Healthy human Subjects,” Clinical Pharmacokinetics 49, no. 7 (2010): 449-454.

[232] V. S. Chachay, G. A. Macdonald, J. H. Martin, et al., “Resveratrol Does Not Benefit Patients With Nonalcoholic Fatty Liver Disease,” Clinical Gastroenterology and Hepatology 12, no. 12 (2014): 2092-2103. e1-6.

[233] A. Agarwal, A. Khandelwal, K. Pal, et al., “A Novel Pro-oxidant Combination of Resveratrol and Copper Reduces Transplant Related Toxicities in Patients Receiving High Dose Melphalan for Multiple Myeloma (RESCU 001),” PLoS ONE 17, no. 2 (2022): e0262212.

[234] J. H. Chung, J. S. Lee, and H. G. Lee, “Resveratrol-loaded Chitosan-γ-poly(glutamic acid) Nanoparticles: Optimization, Solubility, UV Stability, and Cellular Antioxidant Activity,” Colloids and Surfaces. B, Biointerfaces 186 (2020): 110702.

[235] T. Walle, F. Hsieh, M. H. DeLegge, J. E. Oatis, and W. Uk, “High Absorption but Very Low Bioavailability of Oral Resveratrol in Humans,” Drug Metabolism and Disposition: the Biological Fate of Chemicals 32, no. 12 (2004).

[236] M. Pantusa, R. Bartucci, and B. Rizzuti, “Stability of Trans-resveratrol Associated With Transport Proteins,” Journal of Agricultural and Food Chemistry 62, no. 19 (2014): 4384-4391.

[237] D. J. Boocock, G. E. S. Faust, K. R. Patel, et al., “Phase I Dose Escalation Pharmacokinetic Study in Healthy Volunteers of Resveratrol, a Potential Cancer Chemopreventive Agent,” Cancer Epidemiology and Prevention Biomarkers 16, no. 6 (2007): 1246-1252.

[238] M. Springer and S. Moco, “Resveratrol and Its Human Metabolites-Effects on Metabolic Health and Obesity,” Nutrients 11, no. 1 (2019): 143.

[239] G. Luo, L. Xiao, D. Wang, et al., “Resveratrol Protects Against Ethanol-induced Impairment of Insulin Secretion in INS-1 Cells Through SIRT1-UCP2 Axis,” Toxicology in Vitro 65 (2020): 104808.

[240] P. Wang and S. Sang, “Metabolism and Pharmacokinetics of Resveratrol and Pterostilbene,” Biofactors 44, no. 1 (2018): 16-25.

[241] Š. Zupančič, Z. Lavrič, and J. Kristl, “Stability and Solubility of Trans-resveratrol Are Strongly Influenced by pH and Temperature,” European Journal of Pharmaceutics and Biopharmaceutics 93 (2015): 196-204.

[242] L. Radeva and K. Yoncheva, “Resveratrol-A Promising Therapeutic Agent With Problematic Properties,” Pharmaceutics 17, no. 1 (2025): 134.

[243] R. Battaglia, A. Caponnetto, A. M. Caringella, et al., “Resveratrol Treatment Induces Mito-miRNome Modification in Follicular Fluid From Aged Women With a Poor Prognosis for in Vitro Fertilization Cycles,” Antioxidants (Basel) 11, no. 5 (2022): 1019.

[244] K. M. Jardon, G. H. Goossens, J. Most, et al., “Examination of Sex-specific Interactions Between Gut Microbiota and Host Metabolism After 12-week Combined Polyphenol Supplementation in Individuals With Overweight or Obesity,” Gut Microbes 16, no. 1 (2024): 2392875.

[245] C. Nguyen, E. Coudeyre, I. Boutron, et al., “Oral Resveratrol in Adults With Knee Osteoarthritis: A Randomized Placebo-controlled Trial (ARTHROL),” Plos Medicine 21, no. 8 (2024): e1004440.

[246] C. J. Gimblet, N. T. Kruse, K. Geasland, et al., “Effect of Resveratrol on Endothelial Function in Patients With CKD and Diabetes: A Randomized Controlled Trial,” Clin J Am Soc Nephrol 19, no. 2 (2024): 161-168.

[247] M. M. Van Andel, D. Bosshardt, E. M. Schrauben, et al., “Effects of Resveratrol on Aortic Growth in Patients With Marfan Syndrome: A Single-arm Open-label Multicentre Trial,” Heart (2024): 324343. Published online September 24. heartjnl-2024.

[248] B. I. García-Martínez, M. Ruiz-Ramos, J. Pedraza-Chaverri, E. Santiago-Osorio, and M.-N. VM, “Effect of Resveratrol on Markers of Oxidative Stress and Sirtuin 1 in Elderly Adults With Type 2 Diabetes,” International Journal of Molecular Sciences 24, no. 8 (2023): 7422.

[249] F. N. Reis, J. V. F. Câmara, G. Abuna, et al., “Resveratrol Alters Oral Biofilm in Vitro and in Vivo,” Journal of Dentistry 152 (2025): 105466.

[250] M. Ławiński, K. Zadka, N. Ksepka, et al., “Does Resveratrol Impact Oxidative Stress Markers in Patients With Head and Neck Cancer Receiving Home Enteral Nutrition?,” Nutrients 17, no. 3 (2025): 504.

[251] L. A. Gonzaga, A. A. Porto, C. Takahashi, R. L. Gomes, L. C. M. Vanderlei, and V. E. Valenti, “Acute Effects of Beetroot Extract and Resveratrol Ingestion On Cardiovascular and Cardiac Autonomic Modulation Recovery After Moderate-intensity Aerobic Exercise in Individuals With Coronary Artery Disease: A Triple-blinded, Randomized, Placebo-controlled Trial,” European Journal of Nutrition 64, no. 2 (2025): 67.

[252] X. Zheng, J. Hai, Y. Yang, et al., “Effects of Resveratrol Supplementation on Cardiac Remodeling in Hypertensive Patients: A Randomized Controlled Clinical Trial,” Hypertension Research 46, no. 6 (2023): 1493-1503.

[253] E. D. Ö, K. Ç.e. KE, M. Baş, E. H. Alan, and Y. F. Çağın, “Effects of Mediterranean Diet, Curcumin, and Resveratrol on Mild-to-Moderate Active Ulcerative Colitis: A Multicenter Randomized Clinical Trial,” Nutrients 16, no. 10 (2024): 1504.

[254] A. Montoya-Estrada, A. Y. García-Cortés, J. Romo-Yañez, et al., “The Administration of Resveratrol and Vitamin C Reduces Oxidative Stress in Postmenopausal Women-A Pilot Randomized Clinical Trial,” Nutrients 16, no. 21 (2024): 3775.

RIGHTS & PERMISSIONS

2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.