{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T11:04:08Z","timestamp":1789902248205,"version":"4.0.1"},"reference-count":87,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973404"],"award-info":[{"award-number":["81973404"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.phrs.2026.108416","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T23:15:42Z","timestamp":1788045342000},"page":"108416","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Targeted structural destabilization of flavonoids: A novel paradigm for metabolic reprogramming and anti-senescence to repair the alveolar-capillary barrier"],"prefix":"10.1016","volume":"232","author":[{"given":"Miao","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao-Sen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Qing","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chen","family":"Man","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Lu","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Ying","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7146-8290","authenticated-orcid":false,"given":"Yun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phrs.2026.108416_bib1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s00418-018-1747-9","article-title":"The micromechanics of lung alveoli: structure and function of surfactant and tissue components","volume":"150","author":"Knudsen","year":"2018","journal-title":"Histochem. Cell Biol."},{"key":"10.1016\/j.phrs.2026.108416_bib2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13054-019-2339-3","article-title":"Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury","volume":"23","author":"Zhou","year":"2019","journal-title":"Crit. Care"},{"key":"10.1016\/j.phrs.2026.108416_bib3","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.02978-2020","article-title":"Mesenchymal stromal cell extracellular vesicles rescue mitochondrial dysfunction and improve barrier integrity in clinically relevant models of ARDS","volume":"58","author":"Dutra Silva","year":"2021","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.phrs.2026.108416_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2024.116547","article-title":"Human placental mesenchymal stem cells transplantation repairs the alveolar epithelial barrier to alleviate lipopolysaccharides-induced acute lung injury","volume":"229","author":"Yu","year":"2024","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.phrs.2026.108416_bib5","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.freeradbiomed.2025.05.400","article-title":"SIRT1 and its SUMOylation attenuate hyperoxia-induced lung injury by improving mitochondrial biogenesis and fusion","volume":"236","author":"Yang","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.phrs.2026.108416_bib6","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2025.1738713","article-title":"From \"metabolic storm\" to \"immune paralysis\": the dynamic evolution of macrophages and metabolism reprogramming in ARDS","volume":"16","author":"Tang","year":"2025","journal-title":"Front. Immunol."},{"key":"10.1016\/j.phrs.2026.108416_bib7","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1164\/rccm.202004-1274OC","article-title":"Senescence of alveolar type 2 cells drives progressive pulmonary fibrosis","volume":"203","author":"Yao","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.phrs.2026.108416_bib8","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/s41556-020-0542-8","article-title":"Persistence of a regeneration-associated, transitional alveolar epithelial cell state in pulmonary fibrosis","volume":"22","author":"Kobayashi","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.phrs.2026.108416_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155807","article-title":"Therapeutic effects of flavonoids on pulmonary fibrosis: a preclinical meta-analysis","volume":"132","author":"Geng","year":"2024","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phrs.2026.108416_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155757","article-title":"Baicalein alleviates cisplatin-induced acute kidney injury by inhibiting ALOX12-dependent ferroptosis","volume":"130","author":"Guo","year":"2024","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phrs.2026.108416_bib11","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.jconrel.2022.12.026","article-title":"Resveratrol-loaded macrophage exosomes alleviate multiple sclerosis through targeting microglia","volume":"353","author":"Zheng","year":"2023","journal-title":"J. Control. Release"},{"key":"10.1016\/j.phrs.2026.108416_bib12","doi-asserted-by":"crossref","DOI":"10.3390\/molecules29051000","article-title":"Quercetin, a flavonoid with great pharmacological capacity","volume":"29","author":"Carrillo-Martinez","year":"2024","journal-title":"Molecules"},{"key":"10.1016\/j.phrs.2026.108416_bib13","article-title":"Kaempferol suppresses carbon tetrachloride-induced liver damage in rats via the MAPKs\/NF-\u03baB and AMPK\/Nrf2 signaling pathways","volume":"24","author":"Lee","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phrs.2026.108416_bib14","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1002\/ptr.8217","article-title":"Luteolin: a promising multifunctional natural flavonoid for human diseases","volume":"38","author":"Zhu","year":"2024","journal-title":"Phytother. Res."},{"key":"10.1016\/j.phrs.2026.108416_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2023.154646","article-title":"Apigenin ameliorates non-eosinophilic inflammation, dysregulated immune homeostasis and mitochondria-mediated airway epithelial cell apoptosis in chronic obese asthma via the ROS-ASK1-MAPK pathway","volume":"111","author":"Yu","year":"2023","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phrs.2026.108416_bib16","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.ejphar.2015.11.038","article-title":"Hesperetin attenuates ventilator-induced acute lung injury through inhibition of NF-\u03baB-mediated inflammation","volume":"769","author":"Ma","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.phrs.2026.108416_bib17","doi-asserted-by":"crossref","DOI":"10.3390\/ijms232012605","article-title":"Flavonoids as antidiabetic and anti-inflammatory agents: a review on structural activity relationship-based studies and meta-analysis","volume":"23","author":"Shamsudin","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phrs.2026.108416_bib18","doi-asserted-by":"crossref","first-page":"D564","DOI":"10.1093\/nar\/gkae1091","article-title":"Updated resources for exploring experimentally-determined PDB structures and computed structure models at the RCSB protein data bank","volume":"53","author":"Burley","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.phrs.2026.108416_bib19","article-title":"Mitochondrial dysfunction and alveolar type II epithelial cell senescence: the destroyer and rescuer of idiopathic pulmonary fibrosis","volume":"13","author":"Liu","year":"2025","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.phrs.2026.108416_bib20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev-immunol-081619-104850","article-title":"Krebs cycle reborn in macrophage immunometabolism","volume":"38","author":"Ryan","year":"2020","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.phrs.2026.108416_bib21","doi-asserted-by":"crossref","DOI":"10.1126\/science.1250684","article-title":"mTOR- and HIF-1\u03b1-mediated aerobic glycolysis as metabolic basis for trained immunity","volume":"345","author":"Cheng","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.phrs.2026.108416_bib22","doi-asserted-by":"crossref","DOI":"10.1038\/emm.2015.8","article-title":"MyD88-BLT2-dependent cascade contributes to LPS-induced interleukin-6 production in mouse macrophage","volume":"47","author":"Lee","year":"2015","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.phrs.2026.108416_bib23","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1160719","article-title":"Advances in the role of STAT3 in macrophage polarization","volume":"14","author":"Xia","year":"2023","journal-title":"Front. Immunol."},{"key":"10.1016\/j.phrs.2026.108416_bib24","doi-asserted-by":"crossref","first-page":"3816","DOI":"10.1038\/s41467-020-17669-5","article-title":"STAT3 serine phosphorylation is required for TLR4 metabolic reprogramming and IL-1\u03b2 expression","volume":"11","author":"Balic","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.phrs.2026.108416_bib25","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nature11986","article-title":"Succinate is an inflammatory signal that induces IL-1\u03b2 through HIF-1\u03b1","volume":"496","author":"Tannahill","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.phrs.2026.108416_bib26","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.cell.2016.08.064","article-title":"Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages","volume":"167","author":"Mills","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.phrs.2026.108416_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.labinv.2023.100266","article-title":"Melatonin alleviates acute respiratory distress syndrome by inhibiting alveolar macrophage NLRP3 inflammasomes through the ROS\/HIF-1\u03b1\/GLUT1 pathway","volume":"103","author":"Zheng","year":"2023","journal-title":"Lab. Invest."},{"key":"10.1016\/j.phrs.2026.108416_bib28","doi-asserted-by":"crossref","DOI":"10.1172\/JCI165612","article-title":"Regulation of epithelial transitional states in murine and human pulmonary fibrosis","volume":"133","author":"Wang","year":"2023","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.phrs.2026.108416_bib29","doi-asserted-by":"crossref","first-page":"87","DOI":"10.4049\/jimmunol.1500054","article-title":"Unexpected role for adaptive \u03b1\u03b2Th17 cells in acute respiratory distress syndrome","volume":"195","author":"Li","year":"2015","journal-title":"J. Immunol."},{"key":"10.1016\/j.phrs.2026.108416_bib30","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.ccell.2024.04.009","article-title":"Understanding the complexity of p53 in a new era of tumor suppression","volume":"42","author":"Liu","year":"2024","journal-title":"Cancer Cell"},{"key":"10.1016\/j.phrs.2026.108416_bib31","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/s42255-020-00305-3","article-title":"Senescent cells promote tissue NAD(+) decline during ageing via the activation of CD38(+) macrophages","volume":"2","author":"Covarrubias","year":"2020","journal-title":"Nat. Metab."},{"key":"10.1016\/j.phrs.2026.108416_bib32","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/s41588-025-02080-x","article-title":"Spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis","volume":"57","author":"Vannan","year":"2025","journal-title":"Nat. Genet."},{"key":"10.1016\/j.phrs.2026.108416_bib33","doi-asserted-by":"crossref","first-page":"7150","DOI":"10.1038\/s41467-025-61880-1","article-title":"Temporo-spatial cellular atlas of the regenerating alveolar niche in idiopathic pulmonary fibrosis","volume":"16","author":"Weeratunga","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.phrs.2026.108416_bib34","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/nyas.13384","article-title":"Flavonoids as modulators of metabolic enzymes and drug transporters","volume":"1398","author":"Miron","year":"2017","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.phrs.2026.108416_bib35","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25137124","article-title":"Binding affinity determination in drug design: insights from lock and key, induced fit, conformational selection, and inhibitor trapping models","volume":"25","author":"Spassov","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phrs.2026.108416_bib36","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.ccm.2024.08.014","article-title":"Future directions in therapies for acute respiratory distress syndrome","volume":"45","author":"Millar","year":"2024","journal-title":"Clin. Chest Med."},{"key":"10.1016\/j.phrs.2026.108416_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2025.178159","article-title":"Molecular mechanisms and emerging therapeutics in pulmonary fibrosis: a recent update","volume":"1006","author":"Sharma","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.phrs.2026.108416_bib38","doi-asserted-by":"crossref","first-page":"7129","DOI":"10.1073\/pnas.1820799116","article-title":"From single drug targets to synergistic network pharmacology in ischemic stroke","volume":"116","author":"Casas","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.phrs.2026.108416_bib39","doi-asserted-by":"crossref","DOI":"10.3390\/ph18111648","article-title":"Unveiling the therapeutic mechanisms of Chinese herbs in heart failure: integrating network pharmacology, molecular docking, and simulation analysis","volume":"18","author":"Ahmad","year":"2025","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.phrs.2026.108416_bib40","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbapap.2023.140951","article-title":"Effect of flavonoids on the destabilization of \u03b1-synuclein fibrils and their conversion to amorphous aggregate: a molecular dynamics simulation and experimental study","volume":"1871","author":"Jahan","year":"2023","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"10.1016\/j.phrs.2026.108416_bib41","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21176339","article-title":"Advances in molecular dynamics simulations and enhanced sampling methods for the study of protein systems","volume":"21","author":"Lazim","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phrs.2026.108416_bib42","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1002\/bip.360221211","article-title":"Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features","volume":"22","author":"Kabsch","year":"1983","journal-title":"Biopolymers"},{"key":"10.1016\/j.phrs.2026.108416_bib43","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24032424","article-title":"Pre-molten, wet, and dry molten globules en route to the functional state of proteins","volume":"24","author":"Gupta","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phrs.2026.108416_bib44","doi-asserted-by":"crossref","DOI":"10.3390\/molecules27144361","article-title":"The molten globule state of a globular protein in a cell is more or less frequent case rather than an exception","volume":"27","author":"Bychkova","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.phrs.2026.108416_bib45","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nsmb.2045","article-title":"The client protein p53 adopts a molten globule-like state in the presence of Hsp90","volume":"18","author":"Park","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.phrs.2026.108416_bib46","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.836724","article-title":"Novel STAT3 inhibitors targeting STAT3 dimerization by binding to the STAT3 SH2 domain","volume":"13","author":"Hua","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.phrs.2026.108416_bib47","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1073\/pnas.012458999","article-title":"Conformational landscape of cytochrome c folding studied by microsecond-resolved small-angle x-ray scattering","volume":"99","author":"Akiyama","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.phrs.2026.108416_bib48","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1007\/s11030-024-11001-9","article-title":"Destabilisation of Alzheimer's amyloid-\u03b2 protofibrils by baicalein: mechanistic insights from all-atom molecular dynamics simulations","volume":"29","author":"Choudhury","year":"2025","journal-title":"Mol. Divers."},{"key":"10.1016\/j.phrs.2026.108416_bib49","doi-asserted-by":"crossref","first-page":"15690","DOI":"10.1021\/ja0560682","article-title":"The burial of solvent-accessible surface area is a predictor of polypeptide folding and misfolding as a function of chain elongation","volume":"127","author":"Kurt","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.phrs.2026.108416_bib50","doi-asserted-by":"crossref","DOI":"10.3390\/plants12142732","article-title":"Flavonoids: overview of biosynthesis, biological activity, and current extraction techniques","volume":"12","author":"Liga","year":"2023","journal-title":"Plants"},{"key":"10.1016\/j.phrs.2026.108416_bib51","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24054666","article-title":"Role of plant-derived compounds in the molecular pathways related to inflammation","volume":"24","author":"Ol\u0119dzka","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phrs.2026.108416_bib52","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41580-023-00645-4","article-title":"Understanding mechanisms of antioxidant action in health and disease","volume":"25","author":"Halliwell","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.phrs.2026.108416_bib53","doi-asserted-by":"crossref","DOI":"10.1016\/j.tips.2026.02.002","article-title":"Macrophage heterogeneity and plasticity: mechanism and therapeutics","author":"Li","year":"2026","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.phrs.2026.108416_bib54","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1172\/JCI84431","article-title":"HIF1\u03b1 and metabolic reprogramming in inflammation","volume":"126","author":"Corcoran","year":"2016","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.phrs.2026.108416_bib55","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2021.112408","article-title":"Baicalein suppresses lipopolysaccharide-induced acute lung injury by regulating Drp1-dependent mitochondrial fission of macrophages","volume":"145","author":"Jiang","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.phrs.2026.108416_bib56","doi-asserted-by":"crossref","DOI":"10.1016\/j.gene.2026.150143","article-title":"Quercetin-driven M2 polarization of macrophages via ALOX5 inhibition in kupffer cells: a strategy for mouse liver fibrosis treatment","volume":"996","author":"Chen","year":"2026","journal-title":"Gene"},{"key":"10.1016\/j.phrs.2026.108416_bib57","article-title":"Fatty acid oxidation-glycolysis metabolic transition affects ECM homeostasis in silica-induced pulmonary fibrosis","volume":"12","author":"Sun","year":"2025","journal-title":"Adv. Sci."},{"key":"10.1016\/j.phrs.2026.108416_bib58","article-title":"Baicalein suppresses inflammation and attenuates acute lung injury by inhibiting glycolysis via HIF\u20111\u03b1 signaling","volume":"31","author":"Liu","year":"2025","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.phrs.2026.108416_bib59","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellsig.2022.110363","article-title":"Quercetin attenuates sepsis-induced acute lung injury via suppressing oxidative stress-mediated ER stress through activation of SIRT1\/AMPK pathways","volume":"96","author":"Sang","year":"2022","journal-title":"Cell Signal."},{"key":"10.1016\/j.phrs.2026.108416_bib60","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s10020-024-00929-1","article-title":"Metabolic effects of quercetin on inflammatory and autoimmune responses in rheumatoid arthritis are mediated through the inhibition of JAK1\/STAT3\/HIF-1\u03b1 signaling","volume":"30","author":"Zhang","year":"2024","journal-title":"Mol. Med."},{"key":"10.1016\/j.phrs.2026.108416_bib61","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.biopha.2016.09.020","article-title":"Resveratrol ameliorates LPS-induced acute lung injury via NLRP3 inflammasome modulation","volume":"84","author":"Jiang","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.phrs.2026.108416_bib62","first-page":"54","article-title":"STAT3 and NF-\u03baB are common targets for kaempferol-mediated attenuation of COX-2 expression in IL-6-induced macrophages and carrageenan-induced mouse paw edema","volume":"12","author":"Basu","year":"2017","journal-title":"Biochem. Biophys. Rep."},{"key":"10.1016\/j.phrs.2026.108416_bib63","doi-asserted-by":"crossref","DOI":"10.1016\/j.biomaterials.2026.124063","article-title":"Macrophages: redefining extracellular matrix architecture through phenotypic switches as therapeutic targets","volume":"330","author":"Dai","year":"2026","journal-title":"Biomaterials"},{"key":"10.1016\/j.phrs.2026.108416_bib64","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2022.108208","article-title":"Mitochondrial metabolism mediated macrophage polarization in chronic lung diseases","volume":"239","author":"Dong","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.phrs.2026.108416_bib65","article-title":"The multifaceted roles of natural products in mitochondrial dysfunction","volume":"14","author":"Chen","year":"2023","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.phrs.2026.108416_bib66","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202509998","article-title":"Interfacial coordination-engineered emulgel modulates the osteo-immune microenvironment in periodontitis treatment via HIF1 signaling pathway-induced metabolic reprogramming","volume":"12","author":"Zhang","year":"2025","journal-title":"Adv. Sci."},{"key":"10.1016\/j.phrs.2026.108416_bib67","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2022.175407","article-title":"Quercetin alleviates ferroptosis accompanied by reducing M1 macrophage polarization during neutrophilic airway inflammation","volume":"938","author":"Wang","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.phrs.2026.108416_bib68","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.freeradbiomed.2024.12.036","article-title":"Baicalein disrupts the KEAP1-NRF2 interaction to alleviate oxidative stress injury by inhibiting M1 macrophage polarization","volume":"227","author":"Chi","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.phrs.2026.108416_bib69","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41420-019-0147-9","article-title":"Alveolar type 2 progenitor cells for lung injury repair","volume":"5","author":"Olajuyin","year":"2019","journal-title":"Cell Death Discov."},{"key":"10.1016\/j.phrs.2026.108416_bib70","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/s41586-023-06253-8","article-title":"p53 governs an AT1 differentiation programme in lung cancer suppression","volume":"619","author":"Kaiser","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.phrs.2026.108416_bib71","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1165\/rcmb.2023-0453OC","article-title":"CSP7 protects alveolar epithelial cells by targeting p53-fibrinolytic pathways during lung injuries","volume":"72","author":"Puthusseri","year":"2025","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"10.1016\/j.phrs.2026.108416_bib72","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155659","article-title":"JinLiDa granules alleviates cardiac hypertrophy and inflammation in diabetic cardiomyopathy by regulating TP53","volume":"130","author":"Fang","year":"2024","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phrs.2026.108416_bib73","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1038\/s12276-024-01277-0","article-title":"YAP1 inhibits the senescence of alveolar epithelial cells by targeting Prdx3 to alleviate pulmonary fibrosis","volume":"56","author":"Su","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.phrs.2026.108416_bib74","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1165\/rcmb.2019-0071OC","article-title":"PAI-1 regulation of TGF-\u03b21-induced alveolar type II cell senescence, SASP secretion, and SASP-mediated activation of alveolar macrophages","volume":"62","author":"Rana","year":"2020","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.phrs.2026.108416_bib75","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/s41418-024-01326-1","article-title":"Determinants of p53 DNA binding, gene regulation, and cell fate decisions","volume":"31","author":"Fischer","year":"2024","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.phrs.2026.108416_bib76","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1080\/13880209.2022.2160767","article-title":"Baicalein attenuates bleomycin-induced lung fibroblast senescence and lung fibrosis through restoration of Sirt3 expression","volume":"61","author":"Ji-Hong","year":"2023","journal-title":"Pharm. Biol."},{"key":"10.1016\/j.phrs.2026.108416_bib77","doi-asserted-by":"crossref","first-page":"4809","DOI":"10.1007\/s00210-023-02913-8","article-title":"Quercetin influences intestinal dysbacteriosis and delays alveolar epithelial cell senescence by regulating PTEN\/PI3K\/AKT signaling in pulmonary fibrosis","volume":"397","author":"Wu","year":"2024","journal-title":"Naunyn Schmiede Arch. Pharmacol."},{"key":"10.1016\/j.phrs.2026.108416_bib78","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/MOL.0000000000000987","article-title":"Alveolar macrophages: guardians of the alveolar lipid galaxy","volume":"36","author":"Little","year":"2025","journal-title":"Curr. Opin. Lipidol."},{"key":"10.1016\/j.phrs.2026.108416_bib79","doi-asserted-by":"crossref","first-page":"186","DOI":"10.21037\/jtd-22-886","article-title":"Molecular mechanisms of alveolar epithelial cell senescence and idiopathic pulmonary fibrosis: a narrative review","volume":"15","author":"Tu","year":"2023","journal-title":"J. Thorac Dis."},{"key":"10.1016\/j.phrs.2026.108416_bib80","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1038\/nature06522","article-title":"Dynamic personalities of proteins","volume":"450","author":"Henzler-Wildman","year":"2007","journal-title":"Nature"},{"key":"10.1016\/j.phrs.2026.108416_bib81","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.cell.2013.03.034","article-title":"Allostery in disease and in drug discovery","volume":"153","author":"Nussinov","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.phrs.2026.108416_bib82","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1002\/pro.2539","article-title":"Conformational selection in protein binding and function","volume":"23","author":"Weikl","year":"2014","journal-title":"Protein Sci."},{"key":"10.1016\/j.phrs.2026.108416_bib83","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2022.892426","article-title":"Inhibition of dipeptidyl peptidase-4 by flavonoids: structure-activity relationship, kinetics and interaction mechanism","volume":"9","author":"Pan","year":"2022","journal-title":"Front. Nutr."},{"key":"10.1016\/j.phrs.2026.108416_bib84","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1425466","article-title":"Spatial and phenotypic heterogeneity of resident and monocyte-derived macrophages during inflammatory exacerbations leading to pulmonary fibrosis","volume":"15","author":"Moos","year":"2024","journal-title":"Front. Immunol."},{"key":"10.1016\/j.phrs.2026.108416_bib85","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115774","article-title":"Discovery of novel flavonoid-based CDK9 degraders for prostate cancer treatment via a PROTAC strategy","volume":"260","author":"Wu","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.phrs.2026.108416_bib86","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1080\/17568919.2024.2347067","article-title":"Exploring the current advancements of quercetin nanoformulations alleviating respiratory diseases","volume":"16","author":"Yeung","year":"2024","journal-title":"Future Med. Chem."},{"key":"10.1016\/j.phrs.2026.108416_bib87","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1097\/CCM.0000000000005704","article-title":"Alveolar biomarker profiles in subphenotypes of the acute respiratory distress syndrome","volume":"51","author":"Sathe","year":"2023","journal-title":"Crit. Care Med."}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661826003312?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661826003312?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T10:54:58Z","timestamp":1789901698000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661826003312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":87,"alternative-id":["S1043661826003312"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2026.108416","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeted structural destabilization of flavonoids: A novel paradigm for metabolic reprogramming and anti-senescence to repair the alveolar-capillary barrier","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2026.108416","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"108416"}}