{"id":"https://openalex.org/W7225328530","doi":"https://doi.org/10.1038/s41598-026-78599-8","title":"Puerarin alleviates cerebral ischemic injury by modulating PINK1-mediated mitophagy and NLRP3/GSDMD-dependent pyroptosis: an integrated in silico and in vitro study","display_name":"Puerarin alleviates cerebral ischemic injury by modulating PINK1-mediated mitophagy and NLRP3/GSDMD-dependent pyroptosis: an integrated in silico and in vitro study","publication_year":2026,"publication_date":"2026-11-05","ids":{"openalex":"https://openalex.org/W7225328530","doi":"https://doi.org/10.1038/s41598-026-78599-8"},"language":"en","primary_location":{"id":"doi:10.1038/s41598-026-78599-8","doi":"https://doi.org/10.1038/s41598-026-78599-8","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41598-026-78599-8","pdf_url":"https://www.nature.com/articles/s41598-026-78599-8_reference.pdf","source":{"id":"https://openalex.org/S196734849","display_name":"Scientific Reports","issn_l":"2045-2322","issn":["2045-2322"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319908","host_organization_name":"Nature Portfolio","host_organization_lineage":["https://openalex.org/P4310319908","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Nature Portfolio","Springer Nature"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Scientific Reports","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.nature.com/articles/s41598-026-78599-8_reference.pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5160758590","display_name":"Qiang Wu","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Qiang Wu","raw_affiliation_strings":["Department of Neurosurgery, Department of Neurosurgery, Hebei, Shijiazhuang, Shijiazhuang, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurosurgery, Department of Neurosurgery, Hebei, Shijiazhuang, Shijiazhuang, China","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102355591","display_name":"Pengfei Dong","orcid":"https://orcid.org/0000-0002-5103-4687","observed_orcids":["https://orcid.org/0000-0002-5103-4687"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Pengfei Dong","raw_affiliation_strings":["Department of Neurosurgery, Department of Neurosurgery, Hebei, Shijiazhuang, Shijiazhuang, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurosurgery, Department of Neurosurgery, Hebei, Shijiazhuang, Shijiazhuang, China","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160877127","display_name":"Xin Zhao","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Xin Zhao","raw_affiliation_strings":["Laboratory of Medicine, Datong Second People\u2019s Hospital (Datong Tumor Hospital), Datong, 037000, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Laboratory of Medicine, Datong Second People\u2019s Hospital (Datong Tumor Hospital), Datong, 037000, China","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5121767961","display_name":"Wenpeng Lu","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Wenpeng Lu","raw_affiliation_strings":["Department of Neurosurgery, Department of Neurosurgery, Hebei, Shijiazhuang, Shijiazhuang, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurosurgery, Department of Neurosurgery, Hebei, Shijiazhuang, Shijiazhuang, China","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5160974747","display_name":"Xin Liu","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Xin Liu","raw_affiliation_strings":["Department of Neurosurgery, Department of Neurosurgery, Hebei, Shijiazhuang, Shijiazhuang, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurosurgery, Department of Neurosurgery, Hebei, Shijiazhuang, Shijiazhuang, China","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5121767961","https://openalex.org/A5160877127","https://openalex.org/A5160974747"],"corresponding_institution_ids":[],"apc_list":{"value":2690,"currency":"USD","value_usd":2690},"apc_paid":{"value":2690,"currency":"USD","value_usd":2690},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11078","display_name":"Inflammasome and immune disorders","score":0.7304999828338623,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11078","display_name":"Inflammasome and immune disorders","score":0.7304999828338623,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12582","display_name":"Flavonoids in Medical Research","score":0.048700001090765,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.02539999969303608,"subfield":{"id":"https://openalex.org/subfields/3002","display_name":"Drug Discovery"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/puerarin","display_name":"puerarin","score":1.0},{"id":"https://openalex.org/keywords/ischemic-brain-injury","display_name":"ischemic brain injury","score":0.8700000047683716},{"id":"https://openalex.org/keywords/pyroptosis","display_name":"pyroptosis","score":0.8619999885559082},{"id":"https://openalex.org/keywords/nlrp3-inflammasome","display_name":"NLRP3 inflammasome","score":0.9990000128746033},{"id":"https://openalex.org/keywords/gsdmd-cleavage","display_name":"GSDMD cleavage","score":0.9070000052452087},{"id":"https://openalex.org/keywords/neuroprotection","display_name":"neuroprotection","score":0.6010000109672546},{"id":"https://openalex.org/keywords/oxidative-stress","display_name":"oxidative stress","score":0.8349999785423279},{"id":"https://openalex.org/keywords/neuroinflammation","display_name":"neuroinflammation","score":0.9279999732971191},{"id":"https://openalex.org/keywords/protein-ligand-binding","display_name":"protein-ligand binding","score":0.6869999766349792},{"id":"https://openalex.org/keywords/molecular-dynamics-simulation","display_name":"molecular dynamics simulation","score":0.5019999742507935},{"id":"https://openalex.org/keywords/mm-gbsa-binding-free-energy","display_name":"MM-GBSA binding free energy","score":0.9139999747276306},{"id":"https://openalex.org/keywords/ros-scavenging","display_name":"reactive oxygen species scavenging","score":0.9010000228881836},{"id":"https://openalex.org/keywords/parkin","display_name":"Parkin","score":0.5170000195503235},{"id":"https://openalex.org/keywords/caspase-3","display_name":"caspase-3","score":0.7200000286102295},{"id":"https://openalex.org/keywords/ht22-cells","display_name":"HT22 cells","score":0.7860000133514404}],"concepts":[{"id":"https://openalex.org/C2778356392","wikidata":"https://www.wikidata.org/wiki/Q4392082","display_name":"Puerarin","level":3,"score":0.9610000252723694},{"id":"https://openalex.org/C2779324830","wikidata":"https://www.wikidata.org/wiki/Q1806192","display_name":"Mitophagy","level":4,"score":0.90829998254776},{"id":"https://openalex.org/C203522944","wikidata":"https://www.wikidata.org/wiki/Q288322","display_name":"Autophagy","level":3,"score":0.6754000186920166},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5756000280380249},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.5503000020980835},{"id":"https://openalex.org/C2776151105","wikidata":"https://www.wikidata.org/wiki/Q898814","display_name":"Oxidative stress","level":2,"score":0.5109999775886536},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.5041000247001648},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.5015000104904175},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.4916999936103821},{"id":"https://openalex.org/C48349386","wikidata":"https://www.wikidata.org/wiki/Q424361","display_name":"Reactive oxygen species","level":2,"score":0.4551999866962433},{"id":"https://openalex.org/C25498285","wikidata":"https://www.wikidata.org/wiki/Q1981368","display_name":"Neuroprotection","level":2,"score":0.3400000035762787},{"id":"https://openalex.org/C41685203","wikidata":"https://www.wikidata.org/wiki/Q1974042","display_name":"Docking (animal)","level":2,"score":0.3287999927997589},{"id":"https://openalex.org/C2780216420","wikidata":"https://www.wikidata.org/wiki/Q83330","display_name":"Lysosome","level":3,"score":0.3240000009536743},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.3183000087738037},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.31209999322891235},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3050000071525574},{"id":"https://openalex.org/C57600042","wikidata":"https://www.wikidata.org/wiki/Q227564","display_name":"Oxidative phosphorylation","level":2,"score":0.2831000089645386},{"id":"https://openalex.org/C28859421","wikidata":"https://www.wikidata.org/wiki/Q39572","display_name":"Mitochondrion","level":2,"score":0.2815999984741211},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.2800000011920929},{"id":"https://openalex.org/C88045685","wikidata":"https://www.wikidata.org/wiki/Q174576","display_name":"Activator (genetics)","level":3,"score":0.27469998598098755},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.2702000141143799},{"id":"https://openalex.org/C169822122","wikidata":"https://www.wikidata.org/wiki/Q230187","display_name":"Crosstalk","level":2,"score":0.26649999618530273}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1038/s41598-026-78599-8","doi":"https://doi.org/10.1038/s41598-026-78599-8","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41598-026-78599-8","pdf_url":"https://www.nature.com/articles/s41598-026-78599-8_reference.pdf","source":{"id":"https://openalex.org/S196734849","display_name":"Scientific Reports","issn_l":"2045-2322","issn":["2045-2322"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319908","host_organization_name":"Nature Portfolio","host_organization_lineage":["https://openalex.org/P4310319908","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Nature Portfolio","Springer Nature"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Scientific Reports","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.1038/s41598-026-78599-8","doi":"https://doi.org/10.1038/s41598-026-78599-8","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41598-026-78599-8","pdf_url":"https://www.nature.com/articles/s41598-026-78599-8_reference.pdf","source":{"id":"https://openalex.org/S196734849","display_name":"Scientific Reports","issn_l":"2045-2322","issn":["2045-2322"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319908","host_organization_name":"Nature Portfolio","host_organization_lineage":["https://openalex.org/P4310319908","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Nature Portfolio","Springer Nature"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Scientific Reports","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9391000270843506,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225328530.pdf","grobid_xml":"https://content.openalex.org/works/W7225328530.grobid-xml"},"referenced_works_count":1,"referenced_works":["https://openalex.org/W4407941159"],"related_works":["https://openalex.org/W4200134927","https://openalex.org/W4408257095","https://openalex.org/W4377292461","https://openalex.org/W4412548818","https://openalex.org/W2155415498","https://openalex.org/W4411190470","https://openalex.org/W2039624339","https://openalex.org/W2000067823","https://openalex.org/W2127642000","https://openalex.org/W4206335012"],"abstract_inverted_index":{"CIRI":[0,220],"is":[1],"characterized":[2],"by":[3,11,57,151],"severe":[4],"oxidative":[5,246],"stress":[6],"and":[7,18,48,63,68,76,95,122,125,141,184,210],"neuroinflammation,":[8],"fundamentally":[9],"driven":[10],"the":[12,22,54,115,119,133,138,168,189,192,203,225,235],"pathological":[13],"interplay":[14],"between":[15,207],"defective":[16,208],"mitophagy":[17,62,177,209],"robust":[19],"pyroptosis.":[20,65,211],"While":[21],"natural":[23],"isoflavonoid":[24],"puerarin":[25,59,100,171,217],"exhibits":[26],"neuroprotective":[27],"potential,":[28],"its":[29],"precise":[30],"atomistic":[31],"interactions":[32],"with":[33,160,234],"targeted":[34],"biological":[35,205],"macromolecules":[36],"remain":[37],"elusive.":[38],"In":[39],"this":[40],"study,":[41],"we":[42],"employed":[43],"an":[44,152],"integrated":[45],"computational":[46],"biophysics":[47],"in":[49,153,236],"vitro":[50,154,237],"approach":[51],"to":[52,111,242],"explore":[53],"multiscale":[55],"mechanisms":[56],"which":[58],"modulates":[60],"PINK1-mediated":[61],"NLRP3/GSDMD-dependent":[64],"ADMET":[66],"profiling":[67],"DFT":[69],"calculations":[70],"initially":[71],"confirmed":[72],"puerarin\u2019s":[73],"favorable":[74],"pharmacokinetics":[75],"intrinsic":[77,204],"reactive":[78],"oxygen":[79],"species":[80],"(ROS)":[81],"scavenging":[82],"capacity":[83],"(Bond":[84],"Dissociation":[85],"Energy":[86],"=":[87],"89.68":[88],"kcal/mol).":[89],"Extensive":[90],"100":[91],"ns":[92],"MD":[93],"simulations":[94],"MM/GBSA":[96],"analyses":[97],"suggested":[98],"that":[99,216],"could":[101],"act":[102,126],"as":[103,127,163],"a":[104,128,164,222],"structural":[105],"modulator.":[106],"It":[107],"was":[108],"computationally":[109,226],"predicted":[110,227],"anchor":[112],"stably":[113],"within":[114],"functional":[116],"cavities":[117],"of":[118,137,175,191,230,239],"PINK1,":[120],"NLRP3,":[121],"GSDMD":[123,186],"monomers":[124],"steric":[129],"hindrance,":[130],"theoretically":[131],"attenuating":[132],"binding":[134],"free":[135],"energies":[136],"native":[139],"NLRP3-ASC":[140],"Caspase-3-GSDMD":[142],"macromolecular":[143],"assemblies.":[144],"These":[145],"thermodynamic":[146,228],"predictions":[147],"were":[148],"empirically":[149],"supported":[150],"OGD/R":[155],"model":[156],"using":[157],"HT22":[158],"cells,":[159],"nimodipine":[161],"included":[162],"reference":[165],"comparator.":[166],"At":[167],"protein":[169],"level,":[170],"significantly":[172],"upregulated":[173],"markers":[174],"PINK1/Parkin-mediated":[176],"while":[178],"profoundly":[179],"suppressing":[180],"NLRP3":[181],"inflammasome":[182],"activation":[183],"subsequent":[185],"cleavage.":[187],"Furthermore,":[188],"application":[190],"autophagy":[193],"inhibitor":[194],"3-MA":[195],"exacerbated":[196],"OGD/R-induced":[197],"pyroptotic":[198,231],"marker":[199],"expression,":[200],"experimentally":[201],"validating":[202],"crosstalk":[206],"Collectively,":[212],"our":[213],"findings":[214],"propose":[215],"may":[218],"mitigate":[219],"through":[221],"dual-pronged":[223],"mechanism:":[224],"destabilization":[229],"machineries,":[232],"coupled":[233],"modulation":[238],"mitophagy-related":[240],"proteins":[241],"potentially":[243],"clear":[244],"upstream":[245],"triggers.":[247]},"counts_by_year":[],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2026-11-06T00:00:00"}
