{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:51:27Z","timestamp":1793742687644,"version":"4.6.1"},"reference-count":91,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013827","name":"INTI International University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013827","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007401","name":"Sri Ramachandra Institute of Higher Education and Research","doi-asserted-by":"publisher","award":["14\/PROVC\/2024"],"award-info":[{"award-number":["14\/PROVC\/2024"]}],"id":[{"id":"10.13039\/501100007401","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology Reports"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.toxrep.2026.102248","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T03:26:24Z","timestamp":1775100384000},"page":"102248","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Unravelling the multi-target mechanism of methoxylated flavonoids in Parkinson's disease: Insights from network pharmacology and molecular dynamics"],"prefix":"10.1016","volume":"16","author":[{"given":"Chetan","family":"Ashok","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srikanth","family":"Jeyabalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parasuraman","family":"Pavadai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vignesh","family":"M","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devaraja Dravida Pandiyan","family":"S","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Durga","family":"Mohan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Revathi","family":"Sugumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramya","family":"Sugumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sugin Lal","family":"Jabaris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vetriselvan","family":"Subramaniyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling Shing","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahendran","family":"Sekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.toxrep.2026.102248_bib1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1159\/000369933","article-title":"Role of immunity and inflammation in the pathophysiology of neurodegenerative diseases","volume":"15","author":"Fakhoury","year":"2015","journal-title":"Neurodegener. Dis."},{"key":"10.1016\/j.toxrep.2026.102248_bib2","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nrd1330","article-title":"Neurodegenerative diseases and oxidative stress","volume":"3","author":"Barnham","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.toxrep.2026.102248_bib3","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.neuroscience.2006.10.056","article-title":"Oxidative stress and mitochondrial dysfunction in neurodegenerative diseases","volume":"145","author":"Trushina","year":"2007","journal-title":"Neuroscience"},{"key":"10.1016\/j.toxrep.2026.102248_bib4","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.pathol.2024.10.006","article-title":"Current concepts and molecular pathology of neurodegenerative diseases","volume":"57","author":"Forrest","year":"2025","journal-title":"Pathology"},{"key":"10.1016\/j.toxrep.2026.102248_bib5","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/1752570","article-title":"Network pharmacology-based and molecular docking-based analysis of suanzaoren decoction for the treatment of Parkinson\u2019s disease with sleep disorder","volume":"2021","author":"Liu","year":"2021","journal-title":"Biomed. Res Int"},{"key":"10.1016\/j.toxrep.2026.102248_bib6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0140-6736(14)61682-2","article-title":"Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the global burden of disease study 2013","volume":"385","author":"GBD 2013 Mortality and Causes of Death Collaborators","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.toxrep.2026.102248_bib7","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1136\/jnnp-2015-311890","article-title":"The prediagnostic phase of Parkinson\u2019s disease","volume":"87","author":"Noyce","year":"2016","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"10.1016\/j.toxrep.2026.102248_bib8","series-title":"Advances in Neurotoxicology, Environmental Factors in Neurodegenerative Diseases","first-page":"185","article-title":"Chapter seven - roles of microglia in inflammation-mediated neurodegeneration: models, mechanisms, and therapeutic interventions for Parkinson\u2019s disease","author":"Gao","year":"2017"},{"key":"10.1016\/j.toxrep.2026.102248_bib9","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.toxrep.2026.102248_bib10","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1146\/annurev-pathol-011110-130242","article-title":"Parkinson\u2019s disease: genetics and pathogenesis","volume":"6","author":"Shulman","year":"2011","journal-title":"Annu Rev. Pathol."},{"issue":"1","key":"10.1016\/j.toxrep.2026.102248_bib11","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/jnc.13691","article-title":"The clinical symptoms of Parkinson\u2019s disease","volume":"139","author":"Sveinbjornsdottir","year":"2016","journal-title":"J. Neurochem."},{"key":"10.1016\/j.toxrep.2026.102248_bib12","article-title":"Research progress on natural product ingredients\u2019 therapeutic effects on Parkinson\u2019s disease by regulating autophagy","volume":"2021","author":"Li","year":"2021","journal-title":"Evid. Based Complement Altern. Med"},{"key":"10.1016\/j.toxrep.2026.102248_bib13","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1586\/ern.09.117","article-title":"Current strategies in the treatment of Parkinson\u2019s disease and a personalized approach to management","volume":"9","author":"Diaz","year":"2009","journal-title":"Expert Rev. Neurother."},{"key":"10.1016\/j.toxrep.2026.102248_bib14","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1017\/S1092852920001510","article-title":"Dopamine D3 partial agonists in the treatment of psychosis and substance use disorder comorbidity: a pharmacological alternative to consider?","volume":"26","author":"Hern\u00e1ndez-Huerta","year":"2021","journal-title":"CNS Spectr."},{"issue":"6","key":"10.1016\/j.toxrep.2026.102248_bib15","article-title":"Is levodopa toxic?","volume":"251","author":"M\u00fcller","year":"2004","journal-title":"J. Neurol."},{"key":"10.1016\/j.toxrep.2026.102248_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.109624","article-title":"Molecular targeted study in tumors: from western medicine to active ingredients of traditional Chinese medicine","volume":"121","author":"Li","year":"2020","journal-title":"Biomed. & Pharmacother."},{"key":"10.1016\/j.toxrep.2026.102248_bib17","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s11101-020-09730-4","article-title":"Molecular combination networks in medicinal plants: understanding synergy by network pharmacology in Indian traditional medicine","volume":"20","author":"Mukherjee","year":"2021","journal-title":"Phytochem Rev."},{"key":"10.1016\/j.toxrep.2026.102248_bib18","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.3390\/molecules22071135","article-title":"How can synergism of traditional medicines benefit from network pharmacology?","volume":"22","author":"Yuan","year":"2017","journal-title":"Molecules"},{"key":"10.1016\/j.toxrep.2026.102248_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiolchem.2025.108427","article-title":"Discovery of natural MCL1 inhibitors using pharmacophore modelling, QSAR, docking, ADMET, molecular dynamics, and DFT analysis","volume":"117","author":"Das","year":"2025","journal-title":"Comput. Biol. Chem."},{"key":"10.1016\/j.toxrep.2026.102248_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiolchem.2024.108211","article-title":"Unveiling therapeutic biomarkers and druggable targets in ALS: an integrative microarray analysis, molecular docking, and structural dynamic studies","volume":"113","author":"Eshak","year":"2024","journal-title":"Comput. Biol. Chem."},{"key":"10.1016\/j.toxrep.2026.102248_bib21","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1080\/17460441.2024.2387856","article-title":"Molecular dynamics simulations for the structure-based drug design: targeting small-GTPases proteins","volume":"19","author":"Parise","year":"2024","journal-title":"Expert Opin. Drug Discov."},{"key":"10.1016\/j.toxrep.2026.102248_bib22","article-title":"Establishing network pharmacology between natural polyphenols and Alzheimer\u2019s disease using bioinformatic tools \u2013 an advancement in Alzheimer\u2019s research","volume":"13","author":"Subramanian","year":"2024","journal-title":"Toxicol. Rep."},{"key":"10.1016\/j.toxrep.2026.102248_bib23","doi-asserted-by":"crossref","first-page":"73","DOI":"10.5607\/en20051","article-title":"Nobiletin exhibits neuroprotective effects against mitochondrial complex i inhibition via regulating apoptotic signaling","volume":"30","author":"Amarsanaa","year":"2021","journal-title":"Exp. Neurobiol."},{"key":"10.1016\/j.toxrep.2026.102248_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.brainresbull.2025.111202","article-title":"Protective effects of wogonin in the treatment of central nervous system and degenerative diseases","volume":"221","author":"Fu","year":"2025","journal-title":"Brain Res. Bull."},{"key":"10.1016\/j.toxrep.2026.102248_bib25","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.3390\/biology11121820","article-title":"Anti-inflammatory property of 5-demethylnobiletin (5-hydroxy-6, 7, 8, 3\u2032, 4\u2032-pentamethoxyflavone) and its metabolites in lipopolysaccharide (LPS)-induced RAW 264.7 cells","volume":"11","author":"Guo","year":"2022","journal-title":"Biology"},{"key":"10.1016\/j.toxrep.2026.102248_bib26","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.3390\/molecules25215087","article-title":"Neuroprotective effects of baicalein, wogonin, and oroxylin A on amyloid beta-induced toxicity via NF-\u03baB\/MAPK pathway modulation","volume":"25","author":"Ji","year":"2020","journal-title":"Molecules"},{"key":"10.1016\/j.toxrep.2026.102248_bib27","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1111\/bph.13569","article-title":"Butein provides neuroprotective and anti-neuroinflammatory effects through Nrf2\/ARE-dependent haem oxygenase 1 expression by activating the PI3K\/Akt pathway","volume":"173","author":"Lee","year":"2016","journal-title":"Br. J. Pharm."},{"key":"10.1016\/j.toxrep.2026.102248_bib28","article-title":"Inhibitory effect of chemical constituents isolated from artemisia iwayomogi on polyol pathway and simultaneous quantification of major bioactive compounds","volume":"2017","author":"Lee","year":"2017","journal-title":"Biomed. Res Int"},{"key":"10.1016\/j.toxrep.2026.102248_bib29","series-title":"Studies in Natural Products Chemistry","first-page":"509","article-title":"Chapter 15 - citrus polymethoxyflavones: biofunctional molecules of therapeutic interest","author":"Owis","year":"2018"},{"key":"10.1016\/j.toxrep.2026.102248_bib30","doi-asserted-by":"crossref","DOI":"10.3892\/etm.2018.6699","article-title":"Eupatilin inhibits microglia activation and attenuates brain injury in intracerebral hemorrhage","author":"Qiao","year":"2018","journal-title":"Exp. Ther. Med 16 40054009"},{"key":"10.1016\/j.toxrep.2026.102248_bib31","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/s11357-020-00229-6","article-title":"5\u2032-Hydroxy-6, 7, 8, 3\u2032, 4\u2032-pentamethoxyflavone extends longevity mediated by DR-induced autophagy and oxidative stress resistance in C. elegans","volume":"43","author":"Trivedi","year":"2020","journal-title":"GeroScience"},{"key":"10.1016\/j.toxrep.2026.102248_bib32","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3390\/ijms21010341","article-title":"Nobiletin delays aging and enhances stress resistance of caenorhabditis elegans","volume":"21","author":"Yang","year":"2020","journal-title":"Int J. Mol. Sci."},{"key":"10.1016\/j.toxrep.2026.102248_bib33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2008.07.029","article-title":"Anti-inflammatory and immunosuppressive effect of flavones isolated from Artemisia vestita","volume":"120","author":"Yin","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.toxrep.2026.102248_bib34","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.ejphar.2012.05.042","article-title":"The neuroprotective effect of eupatilin against ischemia\/reperfusion-induced delayed neuronal damage in mice","volume":"689","author":"Cai","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.toxrep.2026.102248_bib35","doi-asserted-by":"crossref","first-page":"10246","DOI":"10.1021\/acs.jafc.4c12619","article-title":"Tricin delays aging and enhances muscle function via activating AMPK-mediated autophagy in diverse model organisms","volume":"73","author":"Zhu","year":"2025","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.toxrep.2026.102248_bib36","doi-asserted-by":"crossref","DOI":"10.1038\/srep42717","article-title":"SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.toxrep.2026.102248_bib37","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1021\/jm000942e","article-title":"Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties","volume":"43","author":"Ertl","year":"2000","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.toxrep.2026.102248_bib38","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ddtec.2004.11.007","article-title":"Lead- and drug-like compounds: the rule-of-five revolution","volume":"1","author":"Lipinski","year":"2004","journal-title":"Drug Discov. Today. Technol."},{"key":"10.1016\/j.toxrep.2026.102248_bib39","doi-asserted-by":"crossref","DOI":"10.1155\/2022\/4758189","article-title":"Network pharmacology and molecular docking analyses unveil the mechanisms of Yiguanjian decoction against Parkinson\u2019s disease from inner\/outer brain perspective","volume":"2022","author":"Shen","year":"2022","journal-title":"Biomed. Res Int"},{"key":"10.1016\/j.toxrep.2026.102248_bib40","doi-asserted-by":"crossref","first-page":"W257","DOI":"10.1093\/nar\/gky318","article-title":"ProTox-II: a webserver for the prediction of toxicity of chemicals","volume":"46","author":"Banerjee","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.toxrep.2026.102248_bib41","doi-asserted-by":"crossref","first-page":"W513","DOI":"10.1093\/nar\/gkae303","article-title":"ProTox 3.0: a webserver for the prediction of toxicity of chemicals","volume":"52","author":"Banerjee","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.toxrep.2026.102248_bib42","series-title":"Drug Discovery and Development - New Advances","article-title":"ADME profiling in drug discovery and a new path paved on silica","author":"Kr\u00fcger","year":"2019"},{"key":"10.1016\/j.toxrep.2026.102248_bib43","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.toxrep.2026.102248_bib44","doi-asserted-by":"crossref","first-page":"W32","DOI":"10.1093\/nar\/gku293","article-title":"SwissTargetPrediction: a web server for target prediction of bioactive small molecules","volume":"42","author":"Gfeller","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.toxrep.2026.102248_bib45","doi-asserted-by":"crossref","DOI":"10.1155\/2022\/9214589","article-title":"Potential molecular mechanisms of ephedra herb in the treatment of nephrotic syndrome based on network pharmacology and molecular docking","volume":"2022","author":"Yao","year":"2022","journal-title":"Biomed. Res Int"},{"key":"10.1016\/j.toxrep.2026.102248_bib46","doi-asserted-by":"crossref","first-page":"4780","DOI":"10.3390\/molecules27154780","article-title":"Identification of potential parkinson\u2019s disease drugs based on multi-source data fusion and convolutional neural network","volume":"27","author":"Liu","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.toxrep.2026.102248_bib47","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1186\/s13018-023-03948-6","article-title":"Network pharmacology prediction and molecular docking-based strategy to discover the potential pharmacological mechanism of Huang\u2013Qi\u2013Gui\u2013Zhi\u2013Wu\u2013Wu decoction against deep vein thrombosis","volume":"18","author":"Fan","year":"2023","journal-title":"J. Orthop. Surg. Res"},{"key":"10.1016\/j.toxrep.2026.102248_bib48","article-title":"Potential active compounds and molecular mechanism of Xuefu Zhuyu decoction for atherosclerosis, based on network pharmacology and molecular docking","volume":"101","author":"Li","year":"2022","journal-title":"Med. (Baltim. )"},{"key":"10.1016\/j.toxrep.2026.102248_bib49","doi-asserted-by":"crossref","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":"10.1016\/j.toxrep.2026.102248_bib50","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1002\/pro.3715","article-title":"Toward understanding the origin and evolution of cellular organisms","volume":"28","author":"Kanehisa","year":"2019","journal-title":"Protein Sci."},{"key":"10.1016\/j.toxrep.2026.102248_bib51","doi-asserted-by":"crossref","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","article-title":"KEGG: integrating viruses and cellular organisms","volume":"49","author":"Kanehisa","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.toxrep.2026.102248_bib52","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkae909","article-title":"KEGG: biological systems database as a model of the real world","volume":"53","author":"Kanehisa","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.toxrep.2026.102248_bib53","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s40643-024-00764-6","article-title":"Network pharmacology and molecular docking: combined computational approaches to explore the antihypertensive potential of Fabaceae species","volume":"11","author":"Shahzadi","year":"2024","journal-title":"Bioresour. Bioprocess."},{"key":"10.1016\/j.toxrep.2026.102248_bib54","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-75603-x","article-title":"System biology-based assessment of the molecular mechanism of IMPHY000797 in Parkinson\u2019s disease: a network pharmacology and in-silico evaluation","volume":"14","author":"Subramanian","year":"2024","journal-title":"Sci. Rep."},{"key":"10.1016\/j.toxrep.2026.102248_bib55","doi-asserted-by":"crossref","first-page":"7893","DOI":"10.1007\/s00289-023-05087-8","article-title":"Pharmacophore modelling and molecular dynamics simulation to identify novel molecules targeting catechol-O-methyltransferase and dopamine D3 receptor to combat Parkinson\u2019s disease","volume":"81","author":"Joy","year":"2024","journal-title":"Polym. Bull."},{"key":"10.1016\/j.toxrep.2026.102248_bib56","series-title":"Presented at the conference BioSangam 2022: Emerging trends in Biotechnology (BIOSANGAM 2022)","first-page":"205","article-title":"Docking and molecular dynamics simulation studies for the evaluation of laccase mediated biodegradation of triclosan","author":"Ranimol","year":"2022"},{"key":"10.1016\/j.toxrep.2026.102248_bib57","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1002\/cmdc.201600182","article-title":"A BOILED-egg to predict gastrointestinal absorption and brain penetration of small molecules","volume":"11","author":"Daina","year":"2016","journal-title":"ChemMedChem"},{"key":"10.1016\/j.toxrep.2026.102248_bib58","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.1007\/s12325-021-01747-1","article-title":"The long-term impact of levodopa\/carbidopa intestinal gel on \u2018off\u2019-time in patients with advanced parkinson\u2019s disease: a systematic review","volume":"38","author":"Antonini","year":"2021","journal-title":"Adv. Ther."},{"key":"10.1016\/j.toxrep.2026.102248_bib59","series-title":"Parkinson\u2019s Disease: Pathogenesis and Clinical Aspects. Codon","article-title":"Pharmacological treatment of Parkinson\u2019s disease","author":"Zahoor","year":"2018"},{"key":"10.1016\/j.toxrep.2026.102248_bib60","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiolchem.2025.108488","article-title":"A virtual screening of Withaniasomnifera compounds using ADMET predictions, molecular docking, MD simulation and DFT calculations: withasomniferol C an effective drug and potent inhibitor of anti-inflammatory targets","volume":"118","author":"Khushboo","year":"2025","journal-title":"Comput. Biol. Chem."},{"key":"10.1016\/j.toxrep.2026.102248_bib61","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiolchem.2025.108371","article-title":"Design of BBB permeable BACE-1 inhibitor as potential drug candidate for Alzheimer disease: 2D-QSAR, molecular docking, ADMET, molecular dynamics, MMGBSA","volume":"116","author":"Kaur","year":"2025","journal-title":"Comput. Biol. Chem."},{"key":"10.1016\/j.toxrep.2026.102248_bib62","doi-asserted-by":"crossref","DOI":"10.1016\/j.cscee.2024.100992","article-title":"Chemical profiles, in silico pharmacokinetic and toxicity prediction of bioactive compounds from Boesenbergia rotunda","volume":"10","author":"Muharrami","year":"2024","journal-title":"Case Stud. Chem. Environ. Eng."},{"key":"10.1016\/j.toxrep.2026.102248_bib63","article-title":"Establishing network pharmacology between natural polyphenols and Alzheimer\u2019s disease using bioinformatic tools \u2013 an advancement in Alzheimer\u2019s research","volume":"13","author":"Subramanian","year":"2024","journal-title":"Toxicol. Rep."},{"key":"10.1016\/j.toxrep.2026.102248_bib64","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiolchem.2025.108370","article-title":"Computational phytochemical screening for Parkinson\u2019s disease therapeutics: c-Abl and beyond","volume":"116","author":"Yasmine","year":"2025","journal-title":"Comput. Biol. Chem."},{"key":"10.1016\/j.toxrep.2026.102248_bib65","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3390\/biomedicines9020158","article-title":"IGF1R deficiency modulates brain signaling pathways and disturbs mitochondria and redox homeostasis","volume":"9","author":"Cardoso","year":"2021","journal-title":"Biomedicines"},{"key":"10.1016\/j.toxrep.2026.102248_bib66","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s10863-024-10044-9","article-title":"Effects of MMP2 and its inhibitor TIMP2 on DNA damage, apoptosis and senescence of human lens epithelial cells induced by oxidative stress","volume":"56","author":"Deng","year":"2024","journal-title":"J. Bioenerg. Biomembr."},{"key":"10.1016\/j.toxrep.2026.102248_bib67","doi-asserted-by":"crossref","first-page":"442","DOI":"10.37349\/ent.2024.00093","article-title":"Potentialities of IGF-1 for regulating oxidative stress in neuroinflammation and neurodegeneration: theoretical review","volume":"4","author":"Herrera","year":"2024","journal-title":"Explor Neuroprot Ther."},{"key":"10.1016\/j.toxrep.2026.102248_bib68","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3390\/antiox13010005","article-title":"Identification and validation of PTGS2 gene as an oxidative stress-related biomarker for arteriovenous fistula failure","volume":"13","author":"Hu","year":"2023","journal-title":"Antioxid. (Basel)"},{"key":"10.1016\/j.toxrep.2026.102248_bib69","doi-asserted-by":"crossref","first-page":"6068","DOI":"10.1523\/JNEUROSCI.4940-07.2008","article-title":"Mcl-1 Is a key regulator of apoptosis during CNS development and after DNA damage","volume":"28","author":"Arbour","year":"2008","journal-title":"J. Neurosci."},{"key":"10.1016\/j.toxrep.2026.102248_bib70","article-title":"Neurodegenerative diseases and neuroinflammation-induced apoptosis","volume":"20","author":"Huang","year":"2025","journal-title":"Open Life Sci."},{"key":"10.1016\/j.toxrep.2026.102248_bib71","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejcb.2023.151376","article-title":"Oxidative stress and signaling through EGFR and PKA pathways converge on the nuclear transport factor RanBP1","volume":"103","author":"Kodiha","year":"2024","journal-title":"Eur. J. Cell Biol."},{"key":"10.1016\/j.toxrep.2026.102248_bib72","doi-asserted-by":"crossref","first-page":"8595","DOI":"10.18632\/aging.204359","article-title":"ESR1 dysfunction triggers neuroinflammation as a critical upstream causative factor of the Alzheimer\u2019s disease process","volume":"14","author":"Liu","year":"2022","journal-title":"Aging (Albany NY)"},{"key":"10.1016\/j.toxrep.2026.102248_bib73","doi-asserted-by":"crossref","first-page":"6209","DOI":"10.1111\/febs.16136","article-title":"Understanding MCL1: from cellular function and regulation to pharmacological inhibition","volume":"289","author":"Sancho","year":"2022","journal-title":"FEBS J."},{"key":"10.1016\/j.toxrep.2026.102248_bib74","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/7369020","article-title":"Matrix metalloproteinase 9 in epilepsy: the role of neuroinflammation in seizure development","volume":"2016","author":"Bronisz","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"10.1016\/j.toxrep.2026.102248_bib75","doi-asserted-by":"crossref","DOI":"10.1016\/j.dscb.2020.100001","article-title":"Hsp90 inhibition protects the brain microvascular endothelium against oxidative stress","volume":"1","author":"Uddin","year":"2021","journal-title":"Brain Disord."},{"issue":"2020","key":"10.1016\/j.toxrep.2026.102248_bib76","article-title":"Heat shock protein 90: biological functions, diseases, and therapeutic targets","volume":"5","author":"Wei","year":"2024","journal-title":"MedComm"},{"key":"10.1016\/j.toxrep.2026.102248_bib77","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3389\/fnmol.2020.00081","article-title":"GSK-3\u03b2 contributes to Parkinsonian dopaminergic neuron death: evidence from conditional knockout mice and tideglusib","volume":"13","author":"Li","year":"2020","journal-title":"Front Mol. Neurosci."},{"key":"10.1016\/j.toxrep.2026.102248_bib78","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13024-021-00428-5","article-title":"Mammalian\/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration","volume":"16","author":"Querfurth","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.toxrep.2026.102248_bib79","doi-asserted-by":"crossref","first-page":"7092","DOI":"10.1007\/s12035-024-04003-z","article-title":"Therapeutic potential effect of glycogen synthase kinase 3 beta (GSK-3\u03b2) inhibitors in Parkinson disease: exploring an overlooked avenue","volume":"61","author":"Turkistani","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.toxrep.2026.102248_bib80","doi-asserted-by":"crossref","first-page":"630","DOI":"10.3390\/biom14060630","article-title":"Network pharmacology analysis of the potential pharmacological mechanism of a sleep cocktail","volume":"14","author":"Liang","year":"2024","journal-title":"Biomolecules"},{"key":"10.1016\/j.toxrep.2026.102248_bib81","doi-asserted-by":"crossref","DOI":"10.1155\/jare\/7062203","article-title":"Identification of therapeutic potential of hydroxychavicol against Alzheimer\u2019s disease: an integrated network pharmacology, molecular docking, and dynamic simulation study","volume":"2025","author":"Upadhayay","year":"2025","journal-title":"J. Aging Res."},{"key":"10.1016\/j.toxrep.2026.102248_bib82","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1177\/1756285613493469","article-title":"Targeting heat shock proteins to modulate \u03b1-synuclein toxicity","volume":"7","author":"Jones","year":"2014","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"10.1016\/j.toxrep.2026.102248_bib83","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.neuroscience.2023.11.031","article-title":"Heat shock protein 90 in Parkinson\u2019s disease: profile of a serial killer","volume":"537","author":"Mansour","year":"2024","journal-title":"Neuroscience"},{"key":"10.1016\/j.toxrep.2026.102248_bib84","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1177\/0271678X16655551","article-title":"Matrix metalloproteinases in the brain and blood\u2013brain barrier: versatile breakers and makers","volume":"36","author":"Rempe","year":"2016","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"10.1016\/j.toxrep.2026.102248_bib85","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.3390\/ijms22031413","article-title":"Multifaceted role of matrix metalloproteinases in neurodegenerative diseases: pathophysiological and therapeutic perspectives","volume":"22","author":"Behl","year":"2021","journal-title":"Int J. Mol. Sci."},{"key":"10.1016\/j.toxrep.2026.102248_bib86","doi-asserted-by":"crossref","first-page":"5206","DOI":"10.3390\/molecules25215206","article-title":"Neuroprotective effects of safflower flavonoid extract in 6-hydroxydopamine-induced model of Parkinson\u2019s disease may be related to its anti-inflammatory action","volume":"25","author":"Lei","year":"2020","journal-title":"Molecules"},{"key":"10.1016\/j.toxrep.2026.102248_bib87","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2020.549037","article-title":"Fisetin regulates gut microbiota and exerts neuroprotective effect on mouse model of Parkinson\u2019s disease","volume":"14","author":"Chen","year":"2020","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.toxrep.2026.102248_bib88","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1080\/00207454.2022.2089136","article-title":"Apigenin alleviates neuroinflammation in a mouse model of Parkinson\u2019s disease","volume":"135","author":"Yarim","year":"2025","journal-title":"Int. J. Neurosci."},{"key":"10.1016\/j.toxrep.2026.102248_bib89","doi-asserted-by":"crossref","first-page":"13406","DOI":"10.3390\/ijms232113406","article-title":"Inhibition of synaptic glutamate exocytosis and prevention of glutamate neurotoxicity by eupatilin from artemisia argyi in the rat cortex","volume":"23","author":"Lu","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.toxrep.2026.102248_bib90","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0171479","article-title":"Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation","volume":"12","author":"Sapkota","year":"2017","journal-title":"PLOS ONE"},{"key":"10.1016\/j.toxrep.2026.102248_bib91","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/03602532.2020.1714646","article-title":"Toward a better understanding of metabolic and pharmacokinetic characteristics of low-solubility, low-permeability natural medicines","volume":"52","author":"Yang","year":"2020","journal-title":"Drug Metab. Rev."}],"container-title":["Toxicology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2214750026000508?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2214750026000508?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:22:56Z","timestamp":1786533776000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2214750026000508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":91,"alternative-id":["S2214750026000508"],"URL":"https:\/\/doi.org\/10.1016\/j.toxrep.2026.102248","relation":{},"ISSN":["2214-7500"],"issn-type":[{"value":"2214-7500","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Unravelling the multi-target mechanism of methoxylated flavonoids in Parkinson's disease: Insights from network pharmacology and molecular dynamics","name":"articletitle","label":"Article Title"},{"value":"Toxicology Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.toxrep.2026.102248","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"102248"}}