{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:22:26Z","timestamp":1792232546120,"version":"4.4.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study investigates osimertinib-induced cardiac adverse reactions (CAR) using real-world FDA Adverse Event Reporting System (FAERS) data and explores molecular mechanisms via network pharmacology, molecular docking, and dynamics simulations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed osimertinib-related adverse events from Q4 2015 to Q4 2024 using FAERS data, applying reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) methods. Potential CAR targets were identified via PharmMapper, Swiss Target Prediction, and GeneCards. Protein-protein interaction (PPI) networks, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, molecular docking, and dynamics simulations were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 15,382 reports, 274 were CAR-related, including pericardial effusion, cardiomyopathy, and cardiac dysfunction (25.00% mortality). Key targets (AKT1, ESR1, EGFR, SRC, ALB, CASP3) and pathways (PI3K-Akt, Ras, MAPK, calcium, JAK-STAT, TNF) were identified. Molecular docking confirmed strong binding affinity with binding energies below \u22127.5\u00a0kJ\/mol for key targets (AKT1: -9.9\u00a0kJ\/mol; ALB: \u22128.4\u00a0kJ\/mol). Molecular dynamics simulations (100\u00a0ns) demonstrated stable binding of osimertinib-AKT1\/ALB complexes, with average RMSD values of 0.52\u00a0nm and 0.50\u00a0nm, respectively, and binding free energies of \u221244.63\u00a0kJ\/mol (AKT1) and \u221242.92\u00a0kJ\/mol (ALB).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study clarifies osimertinib-induced CAR mechanisms involving multi-target interactions and pathway dysregulation, aiding clinical safety and future research.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1619517","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T05:23:51Z","timestamp":1749446631000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["An integrated approach based on FDA adverse event reporting system, network pharmacology, molecular docking, and molecular dynamics simulation analysis to study the cardiac adverse reactions and mechanism of action of osimertinib"],"prefix":"10.3389","volume":"16","author":[{"given":"Wenjuan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"B2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1109\/iccabs.2011.5729867","article-title":"bcl::Cluster: a method for clustering biological molecules coupled with visualization in the Pymol Molecular Graphics System","volume":"2011","author":"Alexander","year":"2011","journal-title":"IEEE Int. Conf. Comput. Adv. Bio Med. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1021\/acs.chemrestox.0c00005","article-title":"EGFR inhibitor gefitinib induces cardiotoxicity through the modulation of cardiac PTEN\/Akt\/FoxO3a pathway and reactive metabolites formation: in vivo and in vitro rat studies","volume":"33","author":"Alhoshani","year":"2020","journal-title":"Chem. Res. Toxicol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s43088-021-00138-3","article-title":"Interaction of SARS-CoV-2 spike protein with angiotensin converting enzyme inhibitors and selected compounds from the chemical entities of biological interest","volume":"10","author":"Aminu","year":"2021","journal-title":"Beni Suef Univ. J. Basic Appl. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.jaccao.2019.10.006","article-title":"Osimertinib-induced cardiotoxicity: a retrospective review of the FDA adverse events reporting system (FAERS)","volume":"1","author":"Anand","year":"2019","journal-title":"JACC CardioOncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1002\/bab.2233","article-title":"Caspase-3: structure, function, and biotechnological aspects","volume":"69","author":"Asadi","year":"2022","journal-title":"Biotechnol. Appl. Biochem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s002280050466","article-title":"A Bayesian neural network method for adverse drug reaction signal generation","volume":"54","author":"Bate","year":"1998","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"7322","DOI":"10.3390\/ijms23137322","article-title":"Acquired resistance to osimertinib in EGFR-mutated non-small cell lung cancer: how do we overcome it?","volume":"23","author":"Bertoli","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4421","DOI":"10.1111\/bcp.14868","article-title":"Pharmacovigilance-based drug repurposing: the search for inverse signals via OpenVigil identifies putative drugs against viral respiratory infections","volume":"87","author":"B\u00f6hm","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"273","DOI":"10.3892\/etm.2024.12561","article-title":"Osimertinib-induced erythromelalgia: a case report","volume":"28","author":"Bolzon","year":"2024","journal-title":"Exp. Ther. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"014101","DOI":"10.1063\/1.2408420","article-title":"Canonical sampling through velocity rescaling","volume":"126","author":"Bussi","year":"2007","journal-title":"J. Chem. Phys."},{"key":"B12","doi-asserted-by":"publisher","first-page":"110797","DOI":"10.1016\/j.intimp.2023.110797","article-title":"Ruxolitinib ameliorated coxsackievirus B3-induced acute viral myocarditis by suppressing the JAK-STAT pathway","volume":"124","author":"Chen","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e3607","DOI":"10.1002\/jgm.3607","article-title":"Network pharmacology prediction and molecular docking analysis reveal the mechanism of modified Bushen Yiqi formulas on chronic obstructive pulmonary disease","volume":"26","author":"Choi","year":"2024","journal-title":"J. Gene Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1097\/JTO.0b013e3181f38816","article-title":"Association between age at diagnosis and the presence of EGFR mutations in female patients with resected non-small cell lung cancer","volume":"5","author":"Choi","year":"2010","journal-title":"J. Thorac. Oncol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1093\/cid\/ciac128","article-title":"Association between statin use and daptomycin-related musculoskeletal adverse events: a mixed approach combining a meta-analysis and a disproportionality analysis","volume":"75","author":"Chuma","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1158\/2159-8290.CD-14-0337","article-title":"AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer","volume":"4","author":"Cross","year":"2014","journal-title":"Cancer Discov."},{"key":"B17","doi-asserted-by":"publisher","first-page":"113097","DOI":"10.1016\/j.jep.2020.113097","article-title":"Systematically characterized mechanism of treatment for lumbar disc herniation based on Yaobitong capsule ingredient analysis in rat plasma and its network pharmacology strategy by UPLC-MS\/MS","volume":"260","author":"Deng","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"111279","DOI":"10.1016\/j.biopha.2021.111279","article-title":"The emerging role of non-coding RNAs in the regulation of PI3K\/AKT pathway in the carcinogenesis process","volume":"137","author":"Ghafouri-Fard","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"B19","doi-asserted-by":"publisher","first-page":"9767","DOI":"10.1007\/s11033-022-07468-0","article-title":"Interplay between PI3K\/AKT pathway and heart disorders","volume":"49","author":"Ghafouri-Fard","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"892503","DOI":"10.3389\/fphar.2022.892503","article-title":"Development of a drug risk analysis and assessment system and its application in signal excavation and analysis of 263 cases of fluoroquinolone-induced adverse reactions","volume":"13","author":"Guan","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/nrm1983","article-title":"Regulation of cardiac hypertrophy by intracellular signalling pathways","volume":"7","author":"Heineke","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2905","DOI":"10.2217\/fon-2019-0346","article-title":"Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: updated analysis of the observational GioTag study","volume":"15","author":"Hochmair","year":"2019","journal-title":"Future Oncol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1002\/prot.21123","article-title":"Comparison of multiple Amber force fields and development of improved protein backbone parameters","volume":"65","author":"Hornak","year":"2006","journal-title":"Proteins"},{"key":"B24","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.ahj.2007.11.043","article-title":"Albumin levels predict survival in patients with systolic heart failure","volume":"155","author":"Horwich","year":"2008","journal-title":"Am. Heart J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"108804","DOI":"10.1016\/j.compbiomed.2024.108804","article-title":"Molecular insights into chronic atrophic gastritis treatment: coptis chinensis Franch studied via network pharmacology, molecular dynamics simulation and experimental analysis","volume":"178","author":"Hu","year":"2024","journal-title":"Comput. Biol. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"154843","DOI":"10.1016\/j.phymed.2023.154843","article-title":"Identification of the active compounds in the Yi-Fei-San-Jie formula using a comprehensive strategy based on cell extraction\/UPLC-MS\/MS, network pharmacology, and molecular biology techniques","volume":"115","author":"Hu","year":"2023","journal-title":"Phytomedicine"},{"key":"B27","doi-asserted-by":"publisher","first-page":"9516726","DOI":"10.1155\/2021\/9516726","article-title":"Mechanism prediction of Astragalus membranaceus against cisplatin-induced kidney damage by network pharmacology and molecular docking","volume":"2021","author":"Jia","year":"2021","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"150702","DOI":"10.1016\/j.bbrc.2024.150702","article-title":"Puerarin inhibits macrophage M1 polarization by combining STAT1 to reduce myocardial damage in EAM model mice","volume":"733","author":"Jia","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B29","doi-asserted-by":"publisher","first-page":"107402","DOI":"10.1016\/j.compbiolchem.2020.107402","article-title":"A comprehensive application: molecular docking and network pharmacology for the prediction of bioactive constituents and elucidation of mechanisms of action in component-based Chinese medicine","volume":"90","author":"Jiao","year":"2021","journal-title":"Comput. Biol. Chem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1161\/01.HYP.0000047104.42047.9B","article-title":"Antisense to epidermal growth factor receptor prevents the development of left ventricular hypertrophy","volume":"41","author":"Kagiyama","year":"2003","journal-title":"Hypertension"},{"key":"B31","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.lungcan.2020.10.021","article-title":"Osimertinib is associated with reversible and dose-independent cancer therapy-related cardiac dysfunction","volume":"153","author":"Kunimasa","year":"2021","journal-title":"Lung Cancer"},{"key":"B32","doi-asserted-by":"publisher","first-page":"155941","DOI":"10.1016\/j.phymed.2024.155941","article-title":"p-Hydroxy benzaldehyde, a phenolic compound from Nostoc commune, ameliorates DSS-induced colitis against oxidative stress via the Nrf2\/HO-1\/NQO-1\/NF-\u03baB\/AP-1 pathway","volume":"133","author":"Liu","year":"2024","journal-title":"Phytomedicine"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e27591","DOI":"10.1016\/j.heliyon.2024.e27591","article-title":"Targeted next-generation sequencing of 491 lung cancers in clinical practice: implications for future detection strategy and targeted therapy","volume":"10","author":"Liu","year":"2024","journal-title":"Heliyon"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2913","DOI":"10.26355\/eurrev_202407_36516","article-title":"Fas\/FasL induces myocardial cell apoptosis in myocardial ischemia-reperfusion rat model","volume":"21","author":"Liu","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1498204","DOI":"10.3389\/fpsyt.2024.1498204","article-title":"Safety assessment of disulfiram: real-world adverse event analysis based on FAERS database","volume":"15","author":"Luo","year":"2024","journal-title":"Front. Psychiatry"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1056\/NEJMoa040938","article-title":"Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib","volume":"350","author":"Lynch","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"109629","DOI":"10.1016\/j.cellsig.2020.109629","article-title":"Exogenous dihydrosphingosine 1 phosphate mediates collagen synthesis in cardiac fibroblasts through JAK\/STAT signalling and regulation of TIMP1","volume":"72","author":"Magaye","year":"2020","journal-title":"Cell Signal"},{"key":"B38","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s40291-021-00563-1","article-title":"Worldwide prevalence of epidermal growth factor receptor mutations in non-small cell lung cancer: a meta-analysis","volume":"26","author":"Melosky","year":"2022","journal-title":"Mol. Diagn Ther."},{"key":"B39","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s43044-020-00099-5","article-title":"Effect of carvedilol versus nebivolol on insulin resistance among non-diabetic, non-ischemic cardiomyopathy with heart failure","volume":"72","author":"Metwally","year":"2020","journal-title":"Egypt Heart J."},{"key":"B40","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s10741-012-9313-3","article-title":"Diabetic cardiomyopathy: pathophysiology and clinical features","volume":"18","author":"Miki","year":"2013","journal-title":"Heart Fail Rev."},{"key":"B41","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1056\/NEJMoa1612674","article-title":"Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer","volume":"376","author":"Mok","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e004713","DOI":"10.1161\/CIRCOUTCOMES.118.004713","article-title":"Evolution of age and female representation in the most-cited randomized controlled trials of cardiology of the last 20 years","volume":"11","author":"Nguyen","year":"2018","journal-title":"Circ. Cardiovasc Qual. Outcomes"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1126\/science.1099314","article-title":"EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy","volume":"304","author":"Paez","year":"2004","journal-title":"Science"},{"key":"B44","doi-asserted-by":"publisher","first-page":"13306","DOI":"10.1073\/pnas.0405220101","article-title":"EGF receptor gene mutations are common in lung cancers from never smokers and are associated with sensitivity of tumors to gefitinib and erlotinib","volume":"101","author":"Pao","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera--a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.cca.2011.10.028","article-title":"ESR1 in myocardial infarction","volume":"413","author":"Puzianowska-Ku\u017anicka","year":"2012","journal-title":"Clin. Chim. Acta"},{"key":"B47","doi-asserted-by":"publisher","first-page":"103527","DOI":"10.1016\/j.sjbs.2022.103527","article-title":"Molecular mechanism of Ferula asafoetida for the treatment of asthma: network pharmacology and molecular docking approach","volume":"30","author":"Qasim","year":"2023","journal-title":"Saudi J. Biol. Sci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2595","DOI":"10.1042\/CS20200302","article-title":"Cardiovascular toxicity of PI3K\u03b1 inhibitors","volume":"134","author":"Sadasivan","year":"2020","journal-title":"Clin. Sci. (Lond)"},{"key":"B49","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1056\/NEJMoa1713137","article-title":"Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer","volume":"378","author":"Soria","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1186\/1756-0500-5-367","article-title":"ACPYPE - AnteChamber PYthon parser interfacE","volume":"5","author":"Sousa Da Silva","year":"2012","journal-title":"BMC Res. Notes"},{"key":"B52","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1200\/JCO.21.01626","article-title":"Targeted therapies for lung cancer patients with oncogenic driver molecular alterations","volume":"40","author":"Tan","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: fast, flexible, and free","volume":"26","author":"Van Der Spoel","year":"2005","journal-title":"J. Comput. Chem."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.3390\/cells11091553","article-title":"Insight into the role of the PI3K\/Akt pathway in ischemic injury and post-infarct left ventricular remodeling in normal and diabetic heart","volume":"11","author":"Walkowski","year":"2022","journal-title":"Cells"},{"key":"B55","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s00408-017-0014-5","article-title":"Plasma MMP2\/TIMP4 ratio at follow-up assessment predicts disease progression of idiopathic pulmonary arterial hypertension","volume":"195","author":"Wetzl","year":"2017","journal-title":"Lung"},{"key":"B56","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s12012-021-09718-2","article-title":"Indoxyl sulfate activates NLRP3 inflammasome to induce cardiac contractile dysfunction accompanied by myocardial fibrosis and hypertrophy","volume":"22","author":"Yamaguchi","year":"2022","journal-title":"Cardiovasc Toxicol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1517\/14728222.2013.745513","article-title":"Caspase-3 as a therapeutic target for heart failure","volume":"17","author":"Yang","year":"2013","journal-title":"Expert Opin. Ther. Targets"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.3390\/jcm9051268","article-title":"Cardiovascular complications of systemic therapy in non-small-cell lung cancer","volume":"9","author":"Zaborowska-Szmit","year":"2020","journal-title":"J. Clin. Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"175622","DOI":"10.1016\/j.ejphar.2023.175622","article-title":"Integrated network pharmacology and molecular docking analyses of the mechanisms underlying the antihypertensive effects of lotusine","volume":"945","author":"Zhan","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"e14316","DOI":"10.1111\/jfbc.14316","article-title":"Integrated LC-MS\/MS method and network pharmacology for exploring the characterization and mechanism of neuroprotective effect of Vitis amurensis Rupr. wine polyphenol","volume":"46","author":"Zhang","year":"2022","journal-title":"J. Food Biochem."},{"key":"B61","doi-asserted-by":"publisher","first-page":"104347","DOI":"10.1016\/j.mvr.2022.104347","article-title":"Inhibition of Src improves cardiac fibrosis in AngII-induced hypertrophy by regulating the expression of galectin-3","volume":"142","author":"Zhong","year":"2022","journal-title":"Microvasc. Res."},{"key":"B62","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.chmed.2022.07.001","article-title":"Assessment of pulmonary infectious disease treatment with Mongolian medicine formulae based on data mining, network pharmacology and molecular docking","volume":"14","author":"Zhou","year":"2022","journal-title":"Chin. Herb. Med."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1619517\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T05:23:53Z","timestamp":1749446633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1619517\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":62,"alternative-id":["10.3389\/fphar.2025.1619517"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1619517","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,9]]},"article-number":"1619517"}}