{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T21:00:02Z","timestamp":1783198802753,"version":"3.54.6"},"reference-count":72,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010804","name":"Faculty of Medicine, Prince of Songkla University","doi-asserted-by":"publisher","award":["MED65-023-3"],"award-info":[{"award-number":["MED65-023-3"]}],"id":[{"id":"10.13039\/501100010804","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010804","name":"Faculty of Medicine, Prince of Songkla University","doi-asserted-by":"publisher","award":["JRA-CO-2565-17575-TH"],"award-info":[{"award-number":["JRA-CO-2565-17575-TH"]}],"id":[{"id":"10.13039\/501100010804","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Coordinating Center for Thai Government Science and Technology Scholarship Students (CSTS), National Science and Technology Development Agency (NSTDA)","award":["MED65-023-3"],"award-info":[{"award-number":["MED65-023-3"]}]},{"name":"The Coordinating Center for Thai Government Science and Technology Scholarship Students (CSTS), National Science and Technology Development Agency (NSTDA)","award":["JRA-CO-2565-17575-TH"],"award-info":[{"award-number":["JRA-CO-2565-17575-TH"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of hematological malignancies, demonstrating high efficacy in targeting and eliminating cancer cells. However, its clinical application can be associated with the risk of acute adverse effects, including cytokine release syndrome (CRS), a severe inflammatory response caused by excessive cytokine production. While anti-cytokine therapies are available to manage CRS, additional strategies are needed to optimize CAR T-cell efficacy with reduced toxicities. Curcumin, a bioactive polyphenol known for its anti-inflammatory and antioxidant properties, represents a promising adjunct for CAR T-cell therapy. In this study, we investigated the effects of curcumin on anti-CD19 CAR T-cells in vitro. Our results show that curcumin enhances the cytotoxic activity of CAR T-cells against Nalm-6, a B-cell acute lymphoblastic leukemia model, while reducing the production of pro-inflammatory cytokines, including IL-2 and IFN-\u03b3. To explore its underlying mechanisms, network pharmacology and molecular docking analyses were performed, which revealed that curcumin interacts with key signaling pathways involved in T-cell activation and cytokine regulation. These findings support the potential of curcumin as a therapeutic adjunct to improve CAR T-cell efficacy while mitigating inflammatory toxicity.<\/jats:p>","DOI":"10.3390\/antiox14040454","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T11:26:41Z","timestamp":1744284401000},"page":"454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Immunomodulatory Effects of Curcumin on CAR T-Cell Therapy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7389-4533","authenticated-orcid":false,"given":"Praopim","family":"Limsakul","sequence":"first","affiliation":[{"name":"Division of Physical Science, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand"},{"name":"Center of Excellence for Trace Analysis and Biosensor (TAB-CoE), Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pemikar","family":"Srifa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziliang","family":"Huang","sequence":"additional","affiliation":[{"name":"Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linshan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6313-6015","authenticated-orcid":false,"given":"Yiqian","family":"Wu","sequence":"additional","affiliation":[{"name":"National Biomedical Imaging Center, College of Future Technology, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9803-2005","authenticated-orcid":false,"given":"Krit","family":"Charupanit","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hewlings, S.J., and Kalman, D.S. (2017). Curcumin: A Review of Its Effects on Human Health. Foods, 6.","DOI":"10.3390\/foods6100092"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1208\/s12248-012-9432-8","article-title":"Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials","volume":"15","author":"Gupta","year":"2013","journal-title":"AAPS J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"156144","DOI":"10.1016\/j.cyto.2023.156144","article-title":"Antioxidant and Anti-Inflammatory Effects of Curcumin\/Turmeric Supplementation in Adults: A GRADE-Assessed Systematic Review and Dose\u2013Response Meta-Analysis of Randomized Controlled Trials","volume":"164","author":"Dehzad","year":"2023","journal-title":"Cytokine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s10875-006-9066-7","article-title":"\u201cSpicing up\u201d of the Immune System by Curcumin","volume":"27","author":"Jagetia","year":"2007","journal-title":"J. Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1039\/c1np00051a","article-title":"Multitargeting by Curcumin as Revealed by Molecular Interaction Studies","volume":"28","author":"Gupta","year":"2011","journal-title":"Nat. Prod. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jss.2004.04.004","article-title":"Curcumin Inhibits Mitogen Stimulated Lymphocyte Proliferation, NF\u03baB Activation, and IL-2 Signaling","volume":"121","author":"Ranjan","year":"2004","journal-title":"J. Surg. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1080\/08923970500242244","article-title":"Immunomodulatory Effects of Curcumin","volume":"27","author":"Yadav","year":"2005","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kim, G., Jang, M.S., Son, Y.M., Seo, M.J., Ji, S.Y., Han, S.H., Jung, I.D., Park, Y.-M., Jung, H.J., and Yun, C.-H. (2013). Curcumin Inhibits CD4+ T Cell Activation, but Augments CD69 Expression and TGF-\u03921-Mediated Generation of Regulatory T Cells at Late Phase. PLoS ONE, 8.","DOI":"10.1371\/annotation\/631b0f02-bf10-4bac-88a3-c986f2b73284"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1006\/jsre.1998.5374","article-title":"Curcumin Blocks Cyclosporine A-Resistant CD28 Costimulatory Pathway of Human T-Cell Proliferation","volume":"77","author":"Ranjan","year":"1998","journal-title":"J. Surg. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13008-015-0012-z","article-title":"Curcumin and Tumor Immune-Editing: Resurrecting the Immune System","volume":"10","author":"Bose","year":"2015","journal-title":"Cell Div."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1126\/science.aar6711","article-title":"CAR T Cell Immunotherapy for Human Cancer","volume":"359","author":"June","year":"2018","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1056\/NEJMra1706169","article-title":"Chimeric Antigen Receptor Therapy","volume":"379","author":"June","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_13","first-page":"3321","article-title":"Toxicities of Chimeric Antigen Receptor T Cells: Recognition and Management","volume":"127","author":"Brudno","year":"2016","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nature22395","article-title":"Therapeutic T Cell Engineering","volume":"545","author":"Sadelain","year":"2017","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13045-018-0571-y","article-title":"Grading of Cytokine Release Syndrome Associated with the CAR T Cell Therapy Tisagenlecleucel","volume":"11","author":"Porter","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s40164-020-00166-2","article-title":"Interleukin-6-Knockdown of Chimeric Antigen Receptor-Modified T Cells Significantly Reduces IL-6 Release from Monocytes","volume":"9","author":"Kang","year":"2020","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41571-024-00903-0","article-title":"Current Understanding and Management of CAR T Cell-Associated Toxicities","volume":"21","author":"Brudno","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1158\/2159-8290.CD-17-0698","article-title":"Endothelial Activation and Blood\u2013Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells","volume":"7","author":"Gust","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s40425-018-0343-9","article-title":"Cytokine Release Syndrome","volume":"6","author":"Subklewe","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Su, M., Chen, L., Xie, L., Fleurie, A., Jonquieres, R., Cao, Q., Li, B., Liang, J., and Tang, Y. (2024). Identification of Early Predictive Biomarkers for Severe Cytokine Release Syndrome in Pediatric Patients with Chimeric Antigen Receptor T-Cell Therapy. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1450173"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1200\/JCO.19.02103","article-title":"Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity","volume":"38","author":"Jacobson","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_22","first-page":"3272","article-title":"Prognostic Impact of Corticosteroids on Efficacy of Chimeric Antigen Receptor T-Cell Therapy in Large B-Cell Lymphoma","volume":"137","author":"Strati","year":"2021","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1182\/blood.V130.Suppl_1.1547.1547","article-title":"Preliminary Results of Prophylactic Tocilizumab after Axicabtageneciloleucel (Axi-Cel; KTE-C19) Treatment for Patients with Refractory, Aggressive Non-Hodgkin Lymphoma (NHL)","volume":"130","author":"Locke","year":"2017","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"R141","DOI":"10.1186\/ar3455","article-title":"Integrated Safety in Tocilizumab Clinical Trials","volume":"13","author":"Schiff","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"978","DOI":"10.3324\/haematol.2019.238634","article-title":"Immune Reconstitution and Associated Infections Following Axicabtagene Ciloleucel in Relapsed or Refractory Large B-Cell Lymphoma","volume":"106","author":"Logue","year":"2020","journal-title":"Haematologica"},{"key":"ref_26","first-page":"137","article-title":"Tocilizumab Not Associated with Increased Infection Risk after CAR T-Cell Therapy: Implications for COVID-19?","volume":"136","author":"Frigault","year":"2020","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Martinez, M., and Moon, E.K. (2019). CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00128"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"759","DOI":"10.4049\/jimmunol.1401710","article-title":"Coexpressed Catalase Protects Chimeric Antigen Receptor\u2013Redirected T Cells as Well as Bystander Cells from Oxidative Stress\u2013Induced Loss of Antitumor Activity","volume":"196","author":"Ligtenberg","year":"2016","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Liu, R., Peng, L., Zhou, L., Huang, Z., Zhou, C., and Huang, C. (2022). Oxidative Stress in Cancer Immunotherapy: Molecular Mechanisms and Potential Applications. Antioxidants, 11.","DOI":"10.3390\/antiox11050853"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1172\/JCI89455","article-title":"Targeting the Adenosine 2A Receptor Enhances Chimeric Antigen Receptor T Cell Efficacy","volume":"127","author":"Beavis","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eaay9209","DOI":"10.1126\/sciadv.aay9209","article-title":"Engineering Light-Controllable CAR T Cells for Cancer Immunotherapy","volume":"6","author":"Huang","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1038\/s41551-021-00779-w","article-title":"Control of the Activity of CAR-T Cells within Tumours via Focused Ultrasound","volume":"5","author":"Wu","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"W357","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: Updated Data and New Features for Efficient Prediction of Protein Targets of Small Molecules","volume":"47","author":"Daina","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"W26","DOI":"10.1093\/nar\/gku477","article-title":"SuperPred: Update on Drug Classification and Target Prediction","volume":"42","author":"Nickel","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkad1025","article-title":"The Reactome Pathway Knowledgebase 2024","volume":"52","author":"Milacic","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Fabregat, A., Sidiropoulos, K., Viteri, G., Forner, O., Marin-Garcia, P., Arnau, V., D\u2019Eustachio, P., Stein, L., and Hermjakob, H. (2017). Reactome Pathway Analysis: A High-Performance in-Memory Approach. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1559-2"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1126\/science.abq0225","article-title":"Decoding CAR T Cell Phenotype Using Combinatorial Signaling Motif Libraries and Machine Learning","volume":"378","author":"Daniels","year":"2022","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Honikel, M.M., and Olejniczak, S.H. (2022). Co-Stimulatory Receptor Signaling in CAR-T Cells. Biomolecules, 12.","DOI":"10.3390\/biom12091303"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Alviano, A.M., Biondi, M., Grassenis, E., Biondi, A., Serafini, M., and Tettamanti, S. (2024). Fully Equipped CARs to Address Tumor Heterogeneity, Enhance Safety, and Improve the Functionality of Cellular Immunotherapies. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1407992"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING Database in 2023: Protein\u2013Protein Association Networks and Functional Enrichment Analyses for Any Sequenced Genome of Interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and Integrative Analysis of Large Gene Lists Using DAVID Bioinformatics Resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: A Web Server for Functional Enrichment Analysis and Functional Annotation of Gene Lists (2021 Update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1038\/s41596-020-0312-x","article-title":"The HDOCK Server for Integrated Protein\u2013Protein Docking","volume":"15","author":"Yan","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"W365","DOI":"10.1093\/nar\/gkx407","article-title":"HDOCK: A Web Server for Protein\u2013Protein and Protein\u2013DNA\/RNA Docking Based on a Hybrid Strategy","volume":"45","author":"Yan","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8155","DOI":"10.1073\/pnas.1806797115","article-title":"Ancient Drug Curcumin Impedes 26S Proteasome Activity by Direct Inhibition of Dual-Specificity Tyrosine-Regulated Kinase 2","volume":"115","author":"Banerjee","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"eabh2383","DOI":"10.1126\/sciimmunol.abh2383","article-title":"Targeting Monoamine Oxidase A for T Cell\u2013Based Cancer Immunotherapy","volume":"6","author":"Wang","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6506","DOI":"10.4049\/jimmunol.168.12.6506","article-title":"Curcumin Inhibits Experimental Allergic Encephalomyelitis by Blocking IL-12 Signaling through Janus Kinase-STAT Pathway in T Lymphocytes","volume":"168","author":"Natarajan","year":"2002","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1006\/phrs.1998.0404","article-title":"Curcumin Inhibition of Inflammatory Cytokine Production by Human Peripheral Blood Monocytes and Alveolar Macrophages","volume":"39","author":"Abe","year":"1999","journal-title":"Pharmacol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10200","DOI":"10.1074\/jbc.M111.318733","article-title":"Curcumin Suppresses T Cell Activation by Blocking Ca2+ Mobilization and Nuclear Factor of Activated T Cells (NFAT) Activation","volume":"287","author":"Kliem","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Benmebarek, M.-R., Karches, C.H., Cadilha, B.L., Lesch, S., Endres, S., and Kobold, S. (2019). Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061283"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/cmi.2010.11","article-title":"Curcumin Reverses T Cell-Mediated Adaptive Immune Dysfunctions in Tumor-Bearing Hosts","volume":"7","author":"Bhattacharyya","year":"2010","journal-title":"Cell Mol. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1038\/s41423-024-01198-y","article-title":"4-1BB-Encoding CAR Causes Cell Death via Sequestration of the Ubiquitin-Modifying Enzyme A20","volume":"21","author":"Dou","year":"2024","journal-title":"Cell Mol. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ccell.2019.12.014","article-title":"THEMIS-SHP1 Recruitment by 4-1BB Tunes LCK-Mediated Priming of Chimeric Antigen Receptor-Redirected T Cells","volume":"37","author":"Sun","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_54","first-page":"4472","article-title":"T-Cell Proliferation Involving the CD28 Pathway Is Associated with Cyclosporine-Resistant Interleukin 2 Gene Expression","volume":"7","author":"June","year":"1987","journal-title":"Mol. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1182\/blood-2004-04-1596","article-title":"The CD28 Family: A T-Cell Rheostat for Therapeutic Control of T-Cell Activation","volume":"105","author":"Riley","year":"2005","journal-title":"Blood"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"eaay8248","DOI":"10.1126\/scisignal.aay8248","article-title":"4-1BB Costimulation Promotes CAR T Cell Survival through Noncanonical NF-\u039aB Signaling","volume":"13","author":"Philipson","year":"2020","journal-title":"Sci. Signal"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Vafadari, R., Kraaijeveld, R., Weimar, W., and Baan, C.C. (2013). Tacrolimus Inhibits NF-\u039aB Activation in Peripheral Human T Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060784"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1054\/ceca.2001.0259","article-title":"Curcumin: A New Cell-Permeant Inhibitor of the Inositol 1, 4, 5-Trisphosphate Receptor","volume":"31","author":"Dyer","year":"2002","journal-title":"Cell Calcium"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e121322","DOI":"10.1172\/jci.insight.121322","article-title":"4-1BB Enhancement of CAR T Function Requires NF-\u039aB and TRAFs","volume":"3","author":"Li","year":"2018","journal-title":"JCI Insight"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.biocel.2008.06.010","article-title":"Potential Therapeutic Effects of Curcumin, the Anti-Inflammatory Agent, against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases","volume":"41","author":"Aggarwal","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"He, F., Ru, X., and Wen, T. (2020). NRF2, a Transcription Factor for Stress Response and Beyond. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134777"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of Nrf2 in Oxidative Stress and Toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41388-020-01501-x","article-title":"Counteracting CAR T Cell Dysfunction","volume":"40","author":"Poorebrahim","year":"2021","journal-title":"Oncogene"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e004458","DOI":"10.1136\/jitc-2021-004458","article-title":"Targeting of Nrf2 Improves Antitumoral Responses by Human NK Cells, TIL and CAR T Cells during Oxidative Stress","volume":"10","author":"Renken","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.bbrc.2022.01.075","article-title":"Curcumin Activates G Protein-Coupled Receptor 97 (GPR97) in a Manner Different from Glucocorticoid","volume":"595","author":"Harada","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1159\/000430126","article-title":"Curcumin Modulates Macrophage Polarization through the Inhibition of the Toll-like Receptor 4 Expression and Its Signaling Pathways","volume":"36","author":"Zhou","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.jff.2017.12.017","article-title":"Antiviral Potential of Curcumin","volume":"40","author":"Mathew","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_68","first-page":"e2900","article-title":"Phase I Clinical Trial of Curcumin, a Chemopreventive Agent, in Patients with High-Risk or Pre-Malignant Lesions","volume":"21","author":"Hsieh","year":"2001","journal-title":"Anticancer. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/S0090-9556(24)15211-7","article-title":"Biotransformation of Curcumin through Reduction and Glucuronidation in Mice","volume":"27","author":"Pan","year":"1999","journal-title":"Drug Metab. Dispos."},{"key":"ref_70","first-page":"1452","article-title":"Effects of Dietary Curcumin on Glutathione S-Transferase and Malondialdehyde-DNA Adducts in Rat Liver and Colon Mucosa: Relationship with Drug Levels1","volume":"7","author":"Sharma","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Bertoncini-Silva, C., Vlad, A., Ricciarelli, R., Giacomo Fassini, P., Suen, V.M.M., and Zingg, J.-M. (2024). Enhancing the Bioavailability and Bioactivity of Curcumin for Disease Prevention and Treatment. Antioxidants, 13.","DOI":"10.3390\/antiox13030331"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"10713","DOI":"10.1021\/acsomega.2c07326","article-title":"Curcumin Formulations for Better Bioavailability: What We Learned from Clinical Trials Thus Far?","volume":"8","author":"Hegde","year":"2023","journal-title":"ACS Omega"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/4\/454\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:12:30Z","timestamp":1760029950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/4\/454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,10]]},"references-count":72,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["antiox14040454"],"URL":"https:\/\/doi.org\/10.3390\/antiox14040454","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,10]]}}}