{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T23:00:41Z","timestamp":1778886041503,"version":"3.51.4"},"reference-count":67,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation (FAPESP)","doi-asserted-by":"publisher","award":["2019\/18886-1"],"award-info":[{"award-number":["2019\/18886-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation (FAPESP)","doi-asserted-by":"publisher","award":["2017\/08122-9"],"award-info":[{"award-number":["2017\/08122-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Priapism is a frequent and debilitating complication in patients with sickle cell disease (SCD), characterized by recurrent ischemic episodes that can culminate in fibrosis of the erectile tissue and irreversible erectile dysfunction. Despite significant advancements in the management of acute episodes, current therapies remain largely ineffective in preventing recurrences, emphasizing the need for novel strategies that target the underlying pathophysiology. This narrative review describes the mechanistic links between oxidative stress and nitric oxide (NO) dysregulation in the pathogenesis of SCD-associated priapism, with a particular focus on the NO\u2013cyclic guanosine monophosphate (cGMP)\u2013phosphodiesterase type 5 (PDE5) signaling axis. We analyze preclinical evidence supporting resveratrol, a natural polyphenolic compound, as well as its NO-donor hybrid derivatives, as emerging therapeutic candidates. Additionally, we discuss the potential of combining resveratrol with current treatment approaches, and address the translational challenges that must be overcome to move from preclinical data to clinical application. Taken together, the evidence presented in this review supports resveratrol-based therapies as a promising approach for oxidative-stress-driven priapism in SCD and delineates critical perspectives for their further investigation.<\/jats:p>","DOI":"10.3390\/antiox14101213","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T08:22:08Z","timestamp":1759911728000},"page":"1213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Resveratrol and Its Nitric Oxide\u2013Donor Hybrid as an Emerging Therapy for Oxidative-Stress-Driven Priapism in Sickle Cell Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Carolina Oliveira","family":"Splendore","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology, S\u00e3o Francisco University Medical School, Bragan\u00e7a Paulista 12916-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2226-2530","authenticated-orcid":false,"given":"Mariana G.","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, S\u00e3o Francisco University Medical School, Bragan\u00e7a Paulista 12916-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando Ferreira","family":"Costa","sequence":"additional","affiliation":[{"name":"Hematology and Hemotherapy Center, University of Campinas, Campinas 13083-878, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3374-5570","authenticated-orcid":false,"given":"F\u00e1bio Henrique","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, S\u00e3o Francisco University Medical School, Bragan\u00e7a Paulista 12916-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18010","DOI":"10.1038\/nrdp.2018.10","article-title":"Sickle Cell Disease","volume":"4","author":"Kato","year":"2018","journal-title":"Nat. Rev. Dis. Primer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/03630269.2018.1452760","article-title":"Prevalence and Characteristics of Priapism in Sickle Cell Disease","volume":"42","author":"Arduini","year":"2018","journal-title":"Hemoglobin"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/JU.0000000000002767","article-title":"The Diagnosis and Management of Recurrent Ischemic Priapism, Priapism in Sickle Cell Patients, and Non-Ischemic Priapism: An AUA\/SMSNA Guideline","volume":"208","author":"Bivalacqua","year":"2022","journal-title":"J. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Silveira, T.H.R., Pereira, D.A., Calmasini, F.B., Costa, F.F., Burnett, A.L., and Silva, F.H. (2024). Sympathetic Hypoactivity Leads to Hypocontractility of the Corpus Cavernosum in Sickle Cell Mice: A Mechanism Contributing to Priapism. Int. J. Impot. Res., 1\u20136.","DOI":"10.1038\/s41443-024-00997-1"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1080\/14728222.2020.1745188","article-title":"Mechanisms Underlying Priapism in Sickle Cell Disease: Targeting and Key Innovations on the Preclinical Landscape","volume":"24","author":"Musicki","year":"2020","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1124\/jpet.123.001962","article-title":"Nitric Oxide Resistance in Priapism Associated with Sickle Cell Disease: Mechanisms, Therapeutic Challenges, and Future Directions","volume":"390","author":"Pereira","year":"2024","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1111\/j.1743-6109.2012.02798.x","article-title":"Targeting NADPH Oxidase Decreases Oxidative Stress in the Transgenic Sickle Cell Mouse Penis","volume":"9","author":"Musicki","year":"2012","journal-title":"J. Sex. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bivalacqua, T.J., Musicki, B., Hsu, L.L., Berkowitz, D.E., Champion, H.C., and Burnett, A.L. (2013). Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism via Control of Oxidative\/Nitrosative Stress. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068028"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Silva, F.H., Claudino, M.A., Calmasini, F.B., Alexandre, E.C., Franco-Penteado, C., Burnett, A.L., Antunes, E., and Costa, F.F. (2016). Sympathetic Hyperactivity, Increased Tyrosine Hydroxylase and Exaggerated Corpus Cavernosum Relaxations Associated with Oxidative Stress Plays a Major Role in the Penis Dysfunction in Townes Sickle Cell Mouse. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166291"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pereira, P.d.S., Pereira, D.A., Calmasini, F.B., Reis, L.O., Brinkman, N., Burnett, A.L., Costa, F.F., and Silva, F.H. (2022). Haptoglobin Treatment Contributes to Regulating Nitric Oxide Signal and Reduces Oxidative Stress in the Penis: A Preventive Treatment for Priapism in Sickle Cell Disease. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.961534"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1124\/jpet.116.235473","article-title":"Beneficial Effect of the Nitric Oxide Donor Compound 3-(1,3-Dioxoisoindolin-2-Yl)Benzyl Nitrate on Dysregulated Phosphodiesterase 5, NADPH Oxidase, and Nitrosative Stress in the Sickle Cell Mouse Penis: Implication for Priapism Treatment","volume":"359","author":"Silva","year":"2016","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/andr.12442","article-title":"Testosterone Replacement in Transgenic Sickle Cell Mice Controls Priapic Activity and Upregulates PDE5 Expression and eNOS Activity in the Penis","volume":"6","author":"Musicki","year":"2018","journal-title":"Andrology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.1002\/jcp.30075","article-title":"TSPO Ligand FGIN-1-27 Controls Priapism in Sickle Cell Mice via Endogenous Testosterone Production","volume":"236","author":"Musicki","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1111\/j.1743-6109.2010.02193.x","article-title":"Vardenafil and Resveratrol Synergistically Enhance the Nitric Oxide\/Cyclic Guanosine Monophosphate Pathway in Corpus Cavernosal Smooth Muscle Cells and Its Therapeutic Potential for Erectile Dysfunction in the Streptozotocin-Induced Diabetic Rat: Preliminary Findings","volume":"8","author":"Fukuhara","year":"2011","journal-title":"J. Sex. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bonnefont-Rousselot, D. (2016). Resveratrol and Cardiovascular Diseases. Nutrients, 8.","DOI":"10.3390\/nu8050250"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/s41443-018-0042-6","article-title":"Resveratrol Treatment May Preserve the Erectile Function after Radiotherapy by Restoring Antioxidant Defence Mechanisms, SIRT1 and NOS Protein Expressions","volume":"30","author":"Sener","year":"2018","journal-title":"Int. J. Impot. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/s41443-018-0048-0","article-title":"Restorative Effect of Resveratrol on Expression of Endothelial and Neuronal Nitric Oxide Synthase in Cavernous Tissues of Chronic Unpredictable Mild Stress-Exposed Rats: An Impact of Inflammation","volume":"30","author":"Yazir","year":"2018","journal-title":"Int. J. Impot. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"666","DOI":"10.4103\/aja202199","article-title":"Modulation of SIRT1 Expression Improves Erectile Function in Aged Rats","volume":"24","author":"Yu","year":"2022","journal-title":"Asian J. Androl."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Splendore, C.O., Silveira, T.H.R., Pereira, D.A., Bossarino, B.P., de Oliveira, M.G., Calmasini, F.B., Burnett, A.L., Costa, F.F., and Silva, F.H. (2025). Resveratrol Attenuates the Priapism Phenotype in Sickle Cell Mice by Restoring NO-cGMP-PDE5 Signaling and Reducing NADPH Oxidase 2 Expression. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1551533"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Bosquesi, P.L., Melchior, A.C.B., Pavan, A.R., Lanaro, C., de Souza, C.M., Rusinova, R., Chelucci, R.C., Barbieri, K.P., Fernandes, G.F.d.S., and Carlos, I.Z. (2020). Synthesis and Evaluation of Resveratrol Derivatives as Fetal Hemoglobin Inducers. Bioorg. Chem., 100.","DOI":"10.1016\/j.bioorg.2020.103948"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pinheiro, A.K., Pereira, D.A., Dos Santos, J.L., Calmasini, F.B., Alexandre, E.C., Reis, L.O., Burnett, A.L., Costa, F.F., and Silva, F.H. (2022). Resveratrol-Nitric Oxide Donor Hybrid Effect on Priapism in Sickle Cell and Nitric Oxide-Deficient Mouse. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0269310"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.ucl.2021.06.009","article-title":"Physiology of Erection and Pathophysiology of Erectile Dysfunction","volume":"48","author":"MacDonald","year":"2021","journal-title":"Urol. Clin. N. Am."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1124\/pr.111.004515","article-title":"Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction","volume":"63","author":"Andersson","year":"2011","journal-title":"Pharmacol. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1073\/pnas.0407183102","article-title":"Phosphodiesterase-5A Dysregulation in Penile Erectile Tissue Is a Mechanism of Priapism","volume":"102","author":"Champion","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.juro.2012.08.198","article-title":"Molecular Analysis of Erection Regulatory Factors in Sickle Cell Disease-Associated Priapism in Human Penis","volume":"189","author":"Lagoda","year":"2013","journal-title":"J. Urol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/sj.ijir.3900802","article-title":"Human PDE5A Gene Encodes Three PDE5 Isoforms from Two Alternate Promoters","volume":"14","author":"Lin","year":"2002","journal-title":"Int. J. Impot. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pereira, D.A., Pereira, D.A., Pereira, P.d.S., Silveira, T.H.R., Calmasini, F.B., Reis, L.O., Costa, F.F., and Silva, F.H. (2023). Hydroxyurea Does Not Reverse Functional Alterations of the Nitric Oxide-cGMP Pathway Associated with Priapism Phenotype in Corpus Cavernosum from Sickle Cell Mouse. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0292706"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1096\/fj.13-228817","article-title":"Sustained Nitric Oxide (NO)-Releasing Compound Reverses Dysregulated NO Signal Transduction in Priapism","volume":"28","author":"Lagoda","year":"2014","journal-title":"FASEB J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1038\/nm1202-799","article-title":"Cell-Free Hemoglobin Limits Nitric Oxide Bioavailability in Sickle-Cell Disease","volume":"8","author":"Reiter","year":"2002","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Iacopucci, A.P.M., da Silva Pereira, P., Pereira, D.A., Calmasini, F.B., Pittal\u00e0, V., Reis, L.O., Burnett, A.L., Costa, F.F., and Silva, F.H. (2022). Intravascular Hemolysis Leads to Exaggerated Corpus Cavernosum Relaxation: Implication for Priapism in Sickle Cell Disease. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol., 36.","DOI":"10.1096\/fj.202200867R"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Schmidt, H.M., Kelley, E.E., and Straub, A.C. (2019). The Impact of Xanthine Oxidase (XO) on Hemolytic Diseases. Redox Biol., 21.","DOI":"10.1016\/j.redox.2018.101072"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1152\/physrev.00029.2006","article-title":"Nitric Oxide and Peroxynitrite in Health and Disease","volume":"87","author":"Pacher","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/jsm.12391","article-title":"Sildenafil Promotes eNOS Activation and Inhibits NADPH Oxidase in the Transgenic Sickle Cell Mouse Penis","volume":"11","author":"Musicki","year":"2014","journal-title":"J. Sex. Med."},{"key":"ref_34","first-page":"3633","article-title":"Opiorphin Is a Master Regulator of the Hypoxic Response in Corporal Smooth Muscle Cells","volume":"28","author":"Fu","year":"2014","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_35","first-page":"2725","article-title":"Excess Adenosine A2B Receptor Signaling Contributes to Priapism through HIF-1\u03b1 Mediated Reduction of PDE5 Gene Expression","volume":"28","author":"Ning","year":"2014","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1016\/j.urology.2010.02.050","article-title":"Attenuated RhoA\/Rho-Kinase Signaling in Penis of Transgenic Sickle Cell Mice","volume":"76","author":"Bivalacqua","year":"2010","journal-title":"Urology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1111\/bph.13492","article-title":"Antioxidant Effects of Resveratrol in the Cardiovascular System","volume":"174","author":"Xia","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.bbrc.2003.08.105","article-title":"Resveratrol Scavenges Reactive Oxygen Species and Effects Radical-Induced Cellular Responses","volume":"309","author":"Leonard","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1007\/s00204-023-03562-9","article-title":"Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging","volume":"97","author":"Jomova","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.bbrc.2005.03.237","article-title":"Resveratrol Upregulates Heme Oxygenase-1 Expression via Activation of NF-E2-Related Factor 2 in PC12 Cells","volume":"331","author":"Chen","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ejphar.2008.06.067","article-title":"Resveratrol Protects Primary Rat Hepatocytes against Oxidative Stress Damage: Activation of the Nrf2 Transcription Factor and Augmented Activities of Antioxidant Enzymes","volume":"591","author":"Rubiolo","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"R840","DOI":"10.1152\/ajpregu.00308.2014","article-title":"Resveratrol Restored Nrf2 Function, Reduced Renal Inflammation, and Mitigated Hypertension in Spontaneously Hypertensive Rats","volume":"308","author":"Javkhedkar","year":"2015","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.mce.2015.05.034","article-title":"Resveratrol Attenuates High Glucose-Induced Oxidative Stress and Cardiomyocyte Apoptosis through AMPK","volume":"412","author":"Guo","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6133","DOI":"10.3892\/mmr.2015.4199","article-title":"Resveratrol Inhibits Oligomeric A\u03b2-Induced Microglial Activation via NADPH Oxidase","volume":"12","author":"Yao","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.lfs.2017.07.018","article-title":"Resveratrol Efficiently Improves Pulmonary Function via Stabilizing Mast Cells in a Rat Intestinal Injury Model","volume":"185","author":"Huang","year":"2017","journal-title":"Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"H2721","DOI":"10.1152\/ajpheart.00235.2008","article-title":"Vasoprotective Effects of Resveratrol and SIRT1: Attenuation of Cigarette Smoke-Induced Oxidative Stress and Proinflammatory Phenotypic Alterations","volume":"294","author":"Csiszar","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1161\/HYPERTENSIONAHA.111.01009","article-title":"Resveratrol Improves Vascular Function in Patients with Hypertension and Dyslipidemia by Modulating NO Metabolism","volume":"62","author":"Carrizzo","year":"2013","journal-title":"Hypertension"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.phrs.2018.11.041","article-title":"Resveratrol Ameliorates Endothelial Dysfunction in Diabetic and Obese Mice through Sirtuin 1 and Peroxisome Proliferator-Activated Receptor \u03b4","volume":"139","author":"Cheang","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Li, J., Feng, Z., Lu, B., Fang, X., Huang, D., and Wang, B. (2023). Resveratrol Alleviates High Glucose-Induced Oxidative Stress and Apoptosis in Rat Cardiac Microvascular Endothelial Cell through AMPK\/Sirt1 Activation. Biochem. Biophys. Rep., 34.","DOI":"10.1016\/j.bbrep.2023.101444"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bbrc.2010.01.080","article-title":"SIRT1 Regulates Oxidant- and Cigarette Smoke-Induced eNOS Acetylation in Endothelial Cells: Role of Resveratrol","volume":"393","author":"Arunachalam","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Pan, W., Yu, H., Huang, S., and Zhu, P. (2016). Resveratrol Protects against TNF-\u03b1-Induced Injury in Human Umbilical Endothelial Cells through Promoting Sirtuin-1-Induced Repression of NF-KB and P38 MAPK. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147034"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Liu, C.-W., Sung, H.-C., Lin, S.-R., Wu, C.-W., Lee, C.-W., Lee, I.-T., Yang, Y.-F., Yu, I.-S., Lin, S.-W., and Chiang, M.-H. (2017). Resveratrol Attenuates ICAM-1 Expression and Monocyte Adhesiveness to TNF-\u03b1-Treated Endothelial Cells: Evidence for an Anti-Inflammatory Cascade Mediated by the miR-221\/222\/AMPK\/P38\/NF-\u03baB Pathway. Sci. Rep., 7.","DOI":"10.1038\/srep44689"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Nallasamy, P., Kang, Z.Y., Sun, X., Anandh Babu, P.V., Liu, D., and Jia, Z. (2021). Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-\u03baB Signaling Pathway. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212486"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"L317","DOI":"10.1152\/ajplung.00285.2013","article-title":"Resveratrol Prevents Hypoxia-Induced Arginase II Expression and Proliferation of Human Pulmonary Artery Smooth Muscle Cells via Akt-Dependent Signaling","volume":"307","author":"Chen","year":"2014","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.vph.2017.12.064","article-title":"Resveratrol Attenuates Hyperproliferation of Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats: Role of ROS and ROS-Mediated Cell Signaling","volume":"101","author":"Almajdoob","year":"2018","journal-title":"Vascul. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1265\/ehpm.23-00020","article-title":"Resveratrol Inhibits TGF-\u03921-Induced Fibrotic Effects in Human Pterygium Fibroblasts","volume":"28","author":"Fan","year":"2023","journal-title":"Environ. Health Prev. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1182\/blood.2024027898","article-title":"A Controlled Trial for Preventing Priapism in Sickle Cell Anemia: Hydroxyurea plus Placebo vs Hydroxyurea plus Tadalafil","volume":"145","author":"Idris","year":"2025","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1056\/NEJMoa1715971","article-title":"A Phase 3 Trial of L-Glutamine in Sickle Cell Disease","volume":"379","author":"Niihara","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1056\/NEJMoa1611770","article-title":"Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease","volume":"376","author":"Ataga","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e248","DOI":"10.1016\/S2352-3026(24)00384-3","article-title":"Crizanlizumab with or without Hydroxyurea in Patients with Sickle Cell Disease (STAND): Primary Analyses from a Placebo-Controlled, Randomised, Double-Blind, Phase 3 Trial","volume":"12","author":"Abboud","year":"2025","journal-title":"Lancet Haematol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Godos, J., Romano, G.L., Gozzo, L., Laudani, S., Paladino, N., Dominguez Azp\u00edroz, I., Mart\u00ednez L\u00f3pez, N.M., Giampieri, F., Quiles, J.L., and Battino, M. (2024). Resveratrol and Vascular Health: Evidence from Clinical Studies and Mechanisms of Actions Related to Its Metabolites Produced by Gut Microbiota. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1368949"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1158\/1055-9965.EPI-07-0022","article-title":"Phase I Dose Escalation Pharmacokinetic Study in Healthy Volunteers of Resveratrol, a Potential Cancer Chemopreventive Agent","volume":"16","author":"Boocock","year":"2007","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2165\/11531820-000000000-00000","article-title":"Steady-State Pharmacokinetics and Tolerability of Trans-Resveratrol 2000 Mg Twice Daily with Food, Quercetin and Alcohol (Ethanol) in Healthy Human Subjects","volume":"49","author":"Voduc","year":"2010","journal-title":"Clin. Pharmacokinet."},{"key":"ref_64","first-page":"e1","article-title":"Resveratrol Does Not Benefit Patients with Nonalcoholic Fatty Liver Disease","volume":"12","author":"Chachay","year":"2014","journal-title":"Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1124\/dmd.104.000885","article-title":"High Absorption but Very Low Bioavailability of Oral Resveratrol in Humans","volume":"32","author":"Walle","year":"2004","journal-title":"Drug Metab. Dispos. Biol. Fate Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1002\/mnfr.200800177","article-title":"Pharmacokinetic and Safety Profile of Trans-Resveratrol in a Rising Multiple-Dose Study in Healthy Volunteers","volume":"53","author":"Almeida","year":"2009","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.numecd.2013.09.008","article-title":"Bioaccumulation of Resveratrol Metabolites in Myocardial Tissue Is Dose-Time Dependent and Related to Cardiac Hemodynamics in Diabetic Rats","volume":"24","author":"Bresciani","year":"2014","journal-title":"Nutr. Metab. Cardiovasc. Dis. 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