{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:58Z","timestamp":1790618278732,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Trial Design<\/jats:title>\n                    <jats:p>This study aimed to explore the antiepileptic effect of Ganoderic acid A (GA\u2010A) on pentylenetetrazol (PTZ)\u2010induced epilepsy in mice and clarify its underlying mechanism, focusing on the KCNQ2 channel.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>C57BL\/6 mice and hippocampal\u2010specific KCNQ2 knockout mice were used to establish PTZ\u2010induced acute epilepsy models. GA\u2010A was pretreated for 7\u2009days. Epileptic seizures were evaluated by the Racine score and electroencephalogram (EEG). Neuronal injury was detected by HE and TUNEL staining. Neuroinflammation and oxidative stress were assessed by measuring inflammatory factors and oxidative markers. The target interaction between GA\u2010A and KCNQ2 was verified by protein chip, molecular docking, surface plasmon resonance (SPR), and electrophysiological recording.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GA\u2010A dose\u2010dependently reduced seizure severity, shortened epileptiform discharge duration, alleviated hippocampal neuronal loss and apoptosis, and inhibited neuroinflammation and oxidative stress in PTZ\u2010treated mice. GA\u2010A directly bound to KCNQ2 and activated KCNQ2\/3 channels to generate M current. Hippocampal KCNQ2 knockout weakened the ameliorative effect of GA\u2010A on EEG abnormalities and epilepsy\u2010related anxiety\u2010 and depression\u2010like behaviors, but did not affect its anti\u2010inflammatory and antioxidant effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GA\u2010A attenuates PTZ\u2010induced epilepsy in mice via activating the KCNQ2 channel to suppress neuronal hyperexcitability and independently inhibiting neuroinflammation and oxidative stress. GA\u2010A is a promising KCNQ2 activator and lead compound for antiepileptic drug development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71152","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:16:20Z","timestamp":1790259380000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ganoderic Acid A Ameliorates Pentylenetetrazol\u2010Induced Epilepsy in Mice via Activating\n                    <scp>KCNQ2<\/scp>"],"prefix":"10.1002","volume":"32","author":[{"given":"Yang","family":"Yao","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area  Chongqing China"},{"name":"Department of Clinical Pharmacology, College of Pharmacy Dalian Medical University  Dalian China"},{"name":"Department of Pharmacology, College of Pharmacy Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhujun","family":"Liu","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area  Chongqing China"},{"name":"Department of Pharmacology, College of Pharmacy Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xujiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cunhao","family":"Bian","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6250-5202","authenticated-orcid":false,"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3557-0498","authenticated-orcid":false,"given":"Yukun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area  Chongqing China"},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences Peking University  Beijing China"},{"name":"Natural Drug Intervention in Aging Key Laboratory of Chongqing Education Commission  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi.70182"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/0118715273408076251118070427"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi.70153"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2025.1627517"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2025.117381"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70290"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58188-5"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.80250"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00669-6"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/14786419.2010.496367"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12010085"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1572771"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2025.111459"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2025.118060"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.31083\/ph.2016.5889"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102161"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061687"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/5940372"},{"issue":"1","key":"e_1_2_10_20_1","first-page":"847","article-title":"Effects of Ganoderic Acid A on Lipopolysaccharide\u2010Induced Proinflammatory Cytokine Release From Primary Mouse Microglia Cultures","volume":"15","author":"Chi B.","year":"2018","journal-title":"Experimental and Therapeutic Medicine"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.31083\/ph.2018.7108"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-024-02019-0"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103262"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/EXP.20240147"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2026.118879"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaim.2018.02.140"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2876350"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2026.151150"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00410-8"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2026.1754172"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.1c06304"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11418-025-01933-3"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2021.114561"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-021-03303-3"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2024.05.038"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S317207"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03365.x"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201110618"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmga.70044"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-025-01378-4"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X19857818"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062445"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030657"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2025.107126"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-026-03583-7"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117660"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.71152","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cns.71152","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.71152","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:13:11Z","timestamp":1790615591000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns.71152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":45,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/cns.71152"],"URL":"https:\/\/doi.org\/10.1002\/cns.71152","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71152"}}