{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T13:07:55Z","timestamp":1794488875147,"version":"4.9.1"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":34,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-39082-6","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:03:58Z","timestamp":1771470238000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of the anti-inflammatory potential of atorvastatin targeting TNF-\u03b1, IL-6, and IL-1\u03b2 using integrated in vitro and in silico approaches"],"prefix":"10.1038","volume":"16","author":[{"given":"Krishna","family":"Swaroop","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renukaradhya","family":"M.","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadik","family":"Shaik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi Chander","family":"Thatipelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. V. Swathi","family":"Krishna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibghatullah Muhammad","family":"Ali Sangi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Monirul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girish","family":"Meravanige","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagaraja","family":"Sreeharsha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Shahzad","family":"Chohan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankar","family":"Thapa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinpelumi","family":"Akin-Adewumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayomide Victor","family":"Atoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"39082_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115764","volume":"168","author":"CLR Soares","year":"2023","unstructured":"Soares, C. L. R. et al. Biochemical aspects of the inflammatory process: A narrative review. Biomed. Pharmacother. 168, 115764 (2023).","journal-title":"Biomed. Pharmacother."},{"key":"39082_CR2","doi-asserted-by":"publisher","first-page":"2700","DOI":"10.19082\/2700","volume":"8","author":"Z Shariati Sarabi","year":"2016","unstructured":"Shariati Sarabi, Z. et al. Evaluation of the anti-inflammatory effects of atorvastatin on patients with rheumatoid arthritis: A randomized clinical trial. Electron. Physician 8, 2700\u20132706 (2016).","journal-title":"Electron. Physician"},{"key":"39082_CR3","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1016\/j.bcp.2012.08.004","volume":"84","author":"HN Lee","year":"2012","unstructured":"Lee, H. N. & Surh, Y. J. Therapeutic potential of resolvins in the prevention and treatment of inflammatory disorders. Biochem. Pharmacol. 84, 1340\u20131350 (2012).","journal-title":"Biochem. Pharmacol."},{"key":"39082_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms231810719","volume":"23","author":"S Alfaro","year":"2022","unstructured":"Alfaro, S. et al. Involvement of inflammation and its resolution in disease and therapeutics. Int. J. Mol. Sci. 23, 1\u201330 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"39082_CR5","doi-asserted-by":"publisher","first-page":"a016295","DOI":"10.1101\/cshperspect.a016295","volume":"6","author":"T Tanaka","year":"2014","unstructured":"Tanaka, T., Narazaki, M. & Kishimoto, T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb. Perspect. Biol. 6, a016295\u2013a016295 (2014).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"39082_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms20236008","volume":"20","author":"S Kany","year":"2019","unstructured":"Kany, S., Vollrath, J. T. & Relja, B. Cytokines in inflammatory disease. Int. J. Mol. Sci. 20, 1\u201331 (2019).","journal-title":"Int. J. Mol. Sci."},{"key":"39082_CR7","first-page":"1","volume":"9","author":"AA Al-Qahtani","year":"2024","unstructured":"Al-Qahtani, A. A., Alhamlan, F. S. & Al-Qahtani, A. A. Pro-inflammatory and anti-inflammatory interleukins in infectious diseases: A comprehensive review. Trop. Med. Infect. Dis. 9, 1\u201320 (2024).","journal-title":"Trop. Med. Infect. Dis."},{"key":"39082_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115942","volume":"263","author":"V Mehta","year":"2024","unstructured":"Mehta, V. et al. A decade of USFDA-approved small molecules as anti-inflammatory agents: Recent trends and Commentaries on the \u201cindustrial\u201d perspective. Eur. J. Med. Chem. 263, 115942 (2024).","journal-title":"Eur. J. Med. Chem."},{"key":"39082_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153712","volume":"91","author":"K Megha","year":"2021","unstructured":"Megha, K., Joseph, X., Akhil, V. & Mohanan, P. Cascade of immune mechanism and consequences of inflammatory disorders. Phytomedicine 91, 153712 (2021).","journal-title":"Phytomedicine"},{"key":"39082_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e38074","volume":"10","author":"KR Joshi","year":"2024","unstructured":"Joshi, K. R. et al. Therapeutic potential of Leea asiatica: Chemical isolation and validation of ethnomedicinal claims through in vitro and in silico assessment of antioxidant and anti-inflammatory properties. Heliyon 10, e38074 (2024).","journal-title":"Heliyon"},{"key":"39082_CR11","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/j.cell.2010.02.043","volume":"140","author":"CA Dinarello","year":"2010","unstructured":"Dinarello, C. A. Anti-inflammatory agents: Present and future. Cell 140, 935\u2013950 (2010).","journal-title":"Cell"},{"key":"39082_CR12","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.semarthrit.2008.08.001","volume":"39","author":"HE Vonkeman","year":"2010","unstructured":"Vonkeman, H. E. & van de Laar, M. A. F. J. Nonsteroidal anti-inflammatory drugs: Adverse effects and their prevention. Semin. Arthritis Rheum. 39, 294\u2013312 (2010).","journal-title":"Semin. Arthritis Rheum."},{"key":"39082_CR13","doi-asserted-by":"publisher","first-page":"3049","DOI":"10.1016\/j.apsb.2022.02.002","volume":"12","author":"D Sun","year":"2022","unstructured":"Sun, D., Gao, W., Hu, H. & Zhou, S. Why 90% of clinical drug development fails and how to improve it?. Acta Pharm. Sin. B 12, 3049\u20133062 (2022).","journal-title":"Acta Pharm. Sin. B"},{"key":"39082_CR14","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1134\/S1068162023020139","volume":"49","author":"VS Kulkarni","year":"2023","unstructured":"Kulkarni, V. S., Alagarsamy, V., Solomon, V. R., Jose, P. A. & Murugesan, S. Drug repurposing: An effective tool in modern drug discovery. Russ. J. Bioorgan. Chem. 49, 157\u2013166 (2023).","journal-title":"Russ. J. Bioorgan. Chem."},{"key":"39082_CR15","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.3390\/nu15061517","volume":"15","author":"S Zivkovic","year":"2023","unstructured":"Zivkovic, S., Maric, G., Cvetinovic, N., Lepojevic-Stefanovic, D. & Bozic Cvijan, B. Anti-inflammatory effects of lipid-lowering drugs and supplements\u2014A narrative review. Nutrients 15, 1517 (2023).","journal-title":"Nutrients"},{"key":"39082_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fphar.2022.819787","volume":"13","author":"J Xiang","year":"2022","unstructured":"Xiang, J. et al. Atorvastatin restores PPAR\u03b1 inhibition of lipid metabolism disorders by downregulating miR-21 expression to improve mitochondrial function and alleviate diabetic nephropathy progression. Front. Pharmacol. 13, 1\u201314 (2022).","journal-title":"Front. Pharmacol."},{"key":"39082_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fphar.2018.00438","volume":"9","author":"S Peng","year":"2018","unstructured":"Peng, S. et al. Atorvastatin inhibits inflammatory response, attenuates lipid deposition, and improves the stability of vulnerable atherosclerotic plaques by modulating autophagy. Front. Pharmacol. 9, 1\u201317 (2018).","journal-title":"Front. Pharmacol."},{"key":"39082_CR18","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1161\/CIRCRESAHA.116.308537","volume":"120","author":"A Oesterle","year":"2017","unstructured":"Oesterle, A., Laufs, U. & Liao, J. K. Pleiotropic effects of statins on the cardiovascular system. Circ. Res. 120, 229\u2013243 (2017).","journal-title":"Circ. Res."},{"key":"39082_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0323749","volume":"20","author":"S Sabeel","year":"2025","unstructured":"Sabeel, S. et al. Impact of statins as immune-modulatory agents on inflammatory markers in adults with chronic diseases: A systematic review and meta-analysis. PLoS ONE 20, 1\u201320 (2025).","journal-title":"PLoS ONE"},{"key":"39082_CR20","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1038\/nrd1901","volume":"4","author":"MK Jain","year":"2005","unstructured":"Jain, M. K. & Ridker, P. M. Anti-inflammatory effects of statins: Clinical evidence and basic mechanisms. Nat. Rev. Drug Discov. 4, 977\u2013987 (2005).","journal-title":"Nat. Rev. Drug Discov."},{"key":"39082_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ph17070883","volume":"17","author":"SK Kim","year":"2024","unstructured":"Kim, S. K., Choe, J. Y., Kim, J. W., Park, K. Y. & Kim, B. Anti-inflammatory effect of atorvastatin and rosuvastatin on monosodium urate-induced inflammation through IL-37\/Smad3-complex activation in an in vitro study using THP-1 macrophages. Pharmaceuticals 17, 1\u201313 (2024).","journal-title":"Pharmaceuticals"},{"key":"39082_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fpsyt.2019.00103","volume":"10","author":"SW Kim","year":"2019","unstructured":"Kim, S. W. et al. Statins and inflammation: New therapeutic opportunities in psychiatry. Front. Psychiatry 10, 1\u201316 (2019).","journal-title":"Front. Psychiatry"},{"key":"39082_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0280741","volume":"18","author":"E Wo\u017aniak","year":"2023","unstructured":"Wo\u017aniak, E., Broncel, M., Niedzielski, M., Wo\u017aniak, A. & Gorzelak-Pabi\u015b, P. The effect of lipid-lowering therapies on the pro-inflammatory and anti-inflammatory properties of vascular endothelial cells. PLoS ONE 18, 1\u201313 (2023).","journal-title":"PLoS ONE"},{"key":"39082_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms26178429","volume":"26","author":"S Khan","year":"2025","unstructured":"Khan, S., Huda, B., Bhurka, F., Patnaik, R. & Banerjee, Y. Molecular and immunomodulatory mechanisms of statins in inflammation and cancer therapeutics with emphasis on the NF-\u03baB, NLRP3 inflammasome, and cytokine regulatory axes. Int. J. Mol. Sci. 26, 1\u2013107 (2025).","journal-title":"Int. J. Mol. Sci."},{"key":"39082_CR25","doi-asserted-by":"publisher","first-page":"317","DOI":"10.3390\/immuno2020021","volume":"2","author":"A Sheridan","year":"2022","unstructured":"Sheridan, A., Wheeler-Jones, C. P. D. & Gage, M. C. The immunomodulatory effects of statins on macrophages. Immuno 2, 317\u2013343 (2022).","journal-title":"Immuno"},{"key":"39082_CR26","first-page":"1","volume":"9","author":"C Liu","year":"2022","unstructured":"Liu, C. et al. Biological actions, implications, and cautions of statins therapy in COVID-19. Front. Nutr. 9, 1\u201315 (2022).","journal-title":"Front. Nutr."},{"key":"39082_CR27","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.biopha.2016.04.043","volume":"82","author":"F Kong","year":"2016","unstructured":"Kong, F. et al. Atorvastatin suppresses NLRP3 inflammasome activation via TLR4\/MyD88\/NF-\u03baB signaling in PMA-stimulated THP-1 monocytes. Biomed. Pharmacother. 82, 167\u2013172 (2016).","journal-title":"Biomed. Pharmacother."},{"key":"39082_CR28","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1126\/science.1116304","volume":"310","author":"MM He","year":"2005","unstructured":"He, M. M. et al. Small-molecule inhibition of TNF-a. Science 310, 1022\u20131025 (2005).","journal-title":"Science"},{"key":"39082_CR29","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1093\/emboj\/16.5.989","volume":"16","author":"W Somers","year":"1997","unstructured":"Somers, W. 1.9 A crystal structure of interleukin 6: Implications for a novel mode of receptor dimerization and signaling. EMBO J. 16, 989\u2013997 (1997).","journal-title":"EMBO J."},{"key":"39082_CR30","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1073\/pnas.96.1.103","volume":"96","author":"B Yu","year":"1999","unstructured":"Yu, B., Blaber, M., Gronenborn, A. M., Clore, G. M. & Caspar, D. L. D. Disordered water within a hydrophobic protein cavity visualized by x-ray crystallography. Proc. Natl. Acad. Sci. U. S. A. 96, 103\u2013108 (1999).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"39082_CR31","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s44371-025-00128-9","volume":"2","author":"SPC Kurmi","year":"2025","unstructured":"Kurmi, S. P. C., Thapa, S. & Karati, D. Molecular docking and pharmacokinetic evaluations of curcumin-based scaffolds as MDM2-p53 inhibitors. Discov. Chem. 2, 53 (2025).","journal-title":"Discov. Chem."},{"key":"39082_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0309797","volume":"19","author":"B Pandey","year":"2024","unstructured":"Pandey, B. et al. LC-MS profiling and cytotoxic activity of Angiopteris helferiana against HepG2 cell line: Molecular insight to investigate anticancer agent. PLoS ONE 19, 1\u201324 (2024).","journal-title":"PLoS ONE"},{"key":"39082_CR33","first-page":"194","volume":"27","author":"S Thapa","year":"2023","unstructured":"Thapa, S., Biradar, M. S., Banerjee, J. & Karati, D. In-silico approach for predicting the inhibitory effect of home remedies on severe acute respiratory syndrome coronavirus-2. Makara J. Sci. 27, 194\u2013207 (2023).","journal-title":"Makara J. Sci."},{"key":"39082_CR34","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2009","unstructured":"Trott, O. & Olson, A. J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455\u2013461 (2009).","journal-title":"J. Comput. Chem."},{"key":"39082_CR35","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1007\/s44371-025-00165-4","volume":"2","author":"SPC Kurmi","year":"2025","unstructured":"Kurmi, S. P. C. et al. Medicinal chemistry insights of molecular docking and cell permeability mechanism of phytoconstituents present in Mimosa pudica as NS2B-NS3 protease inhibitors against dengue virus. Discov. Chem. 2, 78 (2025).","journal-title":"Discov. Chem."},{"key":"39082_CR36","first-page":"1","volume":"19","author":"C Pushpaveni","year":"2025","unstructured":"Pushpaveni, C. et al. Repurposing terfenadine and domperidone for inhibition of apoptotic gene association in colorectal cancer: A system pharmacology approach integrated with molecular docking, MD simulations, and post-MD simulation analysis. Bioinform. Biol. Insights 19, 1\u201321 (2025).","journal-title":"Bioinform. Biol. Insights"},{"key":"39082_CR37","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-025-04690-y","author":"Y Hs","year":"2025","unstructured":"Hs, Y. et al. Polyphenol-based therapeutics for glioblastoma: Validation from In-vitro cell viability assay and integrated onco-omics computational analysis. Naunyn. Schmiedebergs. Arch. Pharmacol. https:\/\/doi.org\/10.1007\/s00210-025-04690-y (2025).","journal-title":"Naunyn. Schmiedebergs. Arch. Pharmacol."},{"key":"39082_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.prmcm.2025.100636","volume":"16","author":"S Thapa","year":"2025","unstructured":"Thapa, S. et al. LC-MS profiling and multi-target mechanistic insights of Hibiscus rosa-sinensis in diabetes: Network pharmacology, molecular docking, MD simulation, PCA, and in-vitro \u03b1-amylase inhibition. Pharmacol. Res. Mod. Chin. Med. 16, 100636 (2025).","journal-title":"Pharmacol. Res. Mod. Chin. Med."},{"key":"39082_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.phyplu.2024.100533","volume":"4","author":"MB Oppong","year":"2024","unstructured":"Oppong, M. B. et al. In-vitro and in-vivo anti-inflammatory properties of extracts and isolates of Pangdahai. Phytomed. Plus 4, 100533 (2024).","journal-title":"Phytomed. Plus"},{"key":"39082_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.104981","volume":"113","author":"J Jin","year":"2021","unstructured":"Jin, J. et al. The in vitro and in vivo study of oleanolic acid indole derivatives as novel anti-inflammatory agents: Synthesis, biological evaluation, and mechanistic analysis. Bioorg. Chem. 113, 104981 (2021).","journal-title":"Bioorg. Chem."},{"key":"39082_CR41","doi-asserted-by":"publisher","first-page":"219","DOI":"10.3892\/etm.2014.1722","volume":"8","author":"MW Liu","year":"2014","unstructured":"Liu, M. W., Su, M. X., Zhang, W., Wang, L. & Qian, C. Y. Atorvastatin increases lipopolysaccharide-induced expression of tumour necrosis factor-\u03b1-induced protein 8-like 2 in RAW264.7 cells. Exp. Ther. Med. 8, 219\u2013228 (2014).","journal-title":"Exp. Ther. Med."},{"key":"39082_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.109940","volume":"117","author":"P Paramita Pal","year":"2023","unstructured":"Paramita Pal, P., Sajeli Begum, A., Ameer Basha, S., Araya, H. & Fujimoto, Y. New natural pro-inflammatory cytokines (TNF-\u03b1, IL-6 and IL-1\u03b2) and iNOS inhibitors identified from Penicillium polonicum through in vitro and in vivo studies. Int. Immunopharmacol. 117, 109940 (2023).","journal-title":"Int. Immunopharmacol."},{"key":"39082_CR43","doi-asserted-by":"publisher","first-page":"103","DOI":"10.2147\/CIA.S40405","volume":"8","author":"X-H Li","year":"2013","unstructured":"Li, X.-H., Li, X.-H., Zhang, Y.-Y., Wang, M. & Wang, D. Atorvastatin attenuates the production of IL-1β IL-6, and TNF-α in the hippocampus of an amyloid β1\u201342-induced rat model of Alzheimer\u2019s disease. Clin. Interv. Aging 8, 103 (2013).","journal-title":"Clin. Interv. Aging"},{"key":"39082_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/life15081184","volume":"15","author":"MA Maranduca","year":"2025","unstructured":"Maranduca, M. A. et al. Atorvastatin confers renoprotection and modulates inflammation in diabetic rats on a high-fat diet. Life 15, 1\u201322 (2025).","journal-title":"Life"},{"key":"39082_CR45","first-page":"1","volume":"9","author":"J Zhang","year":"2022","unstructured":"Zhang, J. et al. The effect of various types and doses of statins on C-reactive protein levels in patients with dyslipidemia or coronary heart disease: A systematic review and network meta-analysis. Front. Cardiovasc. Med. 9, 1\u201315 (2022).","journal-title":"Front. Cardiovasc. Med."},{"key":"39082_CR46","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1021\/acsomega.0c05054","volume":"6","author":"S Qasim","year":"2021","unstructured":"Qasim, S. et al. Rosuvastatin attenuates rheumatoid arthritis-associated manifestations via modulation of the pro-and anti-inflammatory cytokine network: A combination of in vitro and in vivo studies. ACS Omega 6, 2074\u20132084 (2021).","journal-title":"ACS Omega"},{"key":"39082_CR47","first-page":"483","volume":"23","author":"NA Gratsiansky","year":"2002","unstructured":"Gratsiansky, N. A. Statins as anti-inflammatory agents. Trends Pharmacol. Sci. 23, 483\u2013486 (2002).","journal-title":"Trends Pharmacol. Sci."},{"key":"39082_CR48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fphar.2021.690118","volume":"12","author":"LL Bai","year":"2021","unstructured":"Bai, L. L., Chen, H., Zhou, P. & Yu, J. Identification of tumor necrosis factor-alpha (TNF-\u03b1) inhibitor in rheumatoid arthritis using network pharmacology and molecular docking. Front. Pharmacol. 12, 1\u201312 (2021).","journal-title":"Front. Pharmacol."},{"key":"39082_CR49","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1615\/CritRevEukarGeneExpr.v20.i2.10","volume":"20","author":"N Parameswaran","year":"2010","unstructured":"Parameswaran, N. & Patial, S. Tumor necrosis factor-a signaling in macrophages. Crit. Rev. Eukaryot. Gene Expr. 20, 87\u2013103 (2010).","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"39082_CR50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms22052719","volume":"22","author":"DI Jang","year":"2021","unstructured":"Jang, D. I. et al. The role of tumor necrosis factor alpha (Tnf-\u03b1) in autoimmune disease and current tnf-\u03b1 inhibitors in therapeutics. Int. J. Mol. Sci. 22, 1\u201316 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"39082_CR51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-77750-3","volume":"10","author":"K Zia","year":"2020","unstructured":"Zia, K. et al. Identification of potential TNF-\u03b1 inhibitors: From in silico to in vitro studies. Sci. Rep. 10, 1\u20139 (2020).","journal-title":"Sci. Rep."},{"key":"39082_CR52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2022.872155","volume":"13","author":"D Boraschi","year":"2022","unstructured":"Boraschi, D. What is IL-1 for? The functions of interleukin-1 across evolution. Front. Immunol. 13, 1\u201312 (2022).","journal-title":"Front. Immunol."},{"key":"39082_CR53","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.brainresrev.2008.12.020","volume":"60","author":"K Ren","year":"2009","unstructured":"Ren, K. & Torres, R. Role of interleukin-1\u03b2 during pain and inflammation. Brain Res. Rev. 60, 57\u201364 (2009).","journal-title":"Brain Res. Rev."},{"key":"39082_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/ar1917","volume":"8","author":"C Gabay","year":"2006","unstructured":"Gabay, C. Interleukin-6 and chronic inflammation. Arthritis Res. Ther. 8, 1\u20136 (2006).","journal-title":"Arthritis Res. Ther."},{"key":"39082_CR55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2023.1255533","volume":"14","author":"E Grebenciucova","year":"2023","unstructured":"Grebenciucova, E. & VanHaerents, S. Interleukin 6: At the interface of human health and disease. Front. Immunol. 14, 1\u201310 (2023).","journal-title":"Front. Immunol."},{"key":"39082_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41419-024-07325-x","volume":"16","author":"J Wagner","year":"2025","unstructured":"Wagner, J. et al. TRAF2 and RIPK1 redundantly mediate classical NF\u03baB signaling by TNFR1 and CD95-type death receptors. Cell Death Dis. 16, 1\u201314 (2025).","journal-title":"Cell Death Dis."},{"key":"39082_CR57","doi-asserted-by":"publisher","first-page":"S464","DOI":"10.21037\/tcr.2017.04.01","volume":"6","author":"S Yamamoto","year":"2017","unstructured":"Yamamoto, S. & Iwakuma, T. RIPK1-TRAF2 interplay on the TNF\/NF-\u03baB signaling, cell death, and cancer development in the liver. Transl. Cancer Res. 6, S464\u2013S468 (2017).","journal-title":"Transl. Cancer Res."},{"key":"39082_CR58","doi-asserted-by":"publisher","first-page":"397","DOI":"10.3904\/kjim.2015.244","volume":"33","author":"WS Lee","year":"2018","unstructured":"Lee, W. S., Lee, E. G., Sung, M. S., Choi, Y. J. & Yoo, W. H. Atorvastatin inhibits osteoclast differentiation by suppressing NF-\u03baB and MAPK signaling during IL-1\u03b2-induced osteoclastogenesis. Korean J. Intern. Med. 33, 397\u2013406 (2018).","journal-title":"Korean J. Intern. Med."},{"key":"39082_CR59","doi-asserted-by":"publisher","first-page":"462","DOI":"10.18632\/aging.203824","volume":"14","author":"D Chen","year":"2022","unstructured":"Chen, D. et al. Atorvastatin suppresses NLRP3 inflammasome activation in intracerebral hemorrhage via TLR4- and MyD88-dependent pathways. Aging 14, 462\u2013476 (2022).","journal-title":"Aging"},{"key":"39082_CR60","first-page":"1","volume":"15","author":"KM Aldossary","year":"2024","unstructured":"Aldossary, K. M. et al. Effect of a high dose atorvastatin as added-on therapy on symptoms and serum AMPK\/NLRP3 inflammasome and IL-6\/STAT3 axes in patients with major depressive disorder: Randomized controlled clinical study. Front. Pharmacol. 15, 1\u201311 (2024).","journal-title":"Front. Pharmacol."},{"key":"39082_CR61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/molecules27155036","volume":"27","author":"I B\u00e2ldea","year":"2022","unstructured":"B\u00e2ldea, I. Why ortho- and para-hydroxy metabolites can scavenge free radicals that the parent atorvastatin cannot? Important pharmacologic insight from quantum chemistry. Molecules 27, 1\u201328 (2022).","journal-title":"Molecules"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-39082-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-39082-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-39082-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T10:10:42Z","timestamp":1774433442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-39082-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["39082"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-39082-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]},"assertion":[{"value":"16 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All authors give their consent for the publication of this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"9914"}}