{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:55:50Z","timestamp":1785412550103,"version":"3.56.0"},"reference-count":74,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301535"],"award-info":[{"award-number":["82301535"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Neuroinflammation caused by neuroimmune dysfunction is important for the pathogenesis of major depressive disorders; new antidepressant treatments are urgently needed. Artemisinin (ART) has anti\u2010inflammatory and neuroprotective effects; it can alleviate the inflammatory response in the central nervous system. This study investigated the antidepressant effects and potential mechanisms of action of ART in mice with depression. Mice with chronic social defeat stress (CSDS) and lipopolysaccharide (LPS)\u2010induced depression were used to investigate the antidepressant effects and mechanisms of ART. Mice were treated with ART for 60\u2009min or 5\u2009days. Behavioral tests, RNA sequence analysis, molecular docking, immunofluorescence, and Western blotting were used to evaluate the antidepressant effects of ART as well as its potential therapeutic targets and signaling pathways. Additionally, LPS\u2010 and ATP\u2010treated BV2 microglia were analyzed\n                    <jats:italic>in vitro<\/jats:italic>\n                    to confirm the effect of ART on the NLRP3 signaling pathway. After 60\u2009min or 5\u2009days of treatment, ART alleviated depression\u2010like behavior in CSDS\u2010induced mice. RNA sequence analysis and molecular docking revealed that ART inhibited the TLR4\/NLRP3 signaling pathway. After 5\u2009days of treatment, ART suppressed CSDS\u2010induced microglia, astrocytes, and NLRP3 inflammasome activation as well as the expression of IL\u201017A in the hippocampus. Mechanistically, ART markedly inhibited TLR4, MyD88, p\u2010NF\u2010\u03baB, and NLRP3 inflammasome\u2010associated proteins in the hippocampus of CSDS\u2010induced mice. Furthermore, ART improved LPS\u2010induced depression\u2010like behavior by inhibiting the TLR4\/NLRP3 signaling pathway. ART, a novel antidepressant with clinical potential, inhibits neuroinflammation by downregulating the TLR4\/MyD88\/NF\u2010\u03baB\/NLRP3 signaling pathway in the mouse hippocampus.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70106","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T04:15:48Z","timestamp":1759810548000},"page":"5263-5281","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Artemisinin Alleviates Chronic Social Defeat Stress\u2010Induced Depressive\u2010Like Behavior by Inhibiting Neuroinflammation via the\n                    <scp>TLR4<\/scp>\n                    \/\n                    <scp>MyD88<\/scp>\n                    \/\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    \/\n                    <scp>NLRP3<\/scp>\n                    Signaling Pathway"],"prefix":"10.1002","volume":"39","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"School of Medicine, Yunnan International Joint Laboratory of Virology &amp; Immunology Yunnan University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Li","sequence":"additional","affiliation":[{"name":"Medical School Kunming University of Science and Technology  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjie","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Medicine, Yunnan International Joint Laboratory of Virology &amp; Immunology Yunnan University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingzong","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Medicine, Yunnan International Joint Laboratory of Virology &amp; Immunology Yunnan University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghan","family":"Qian","sequence":"additional","affiliation":[{"name":"School of Medicine, Yunnan International Joint Laboratory of Virology &amp; Immunology Yunnan University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faling","family":"Shao","sequence":"additional","affiliation":[{"name":"School of Medicine, Yunnan International Joint Laboratory of Virology &amp; Immunology Yunnan University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, Yunnan International Joint Laboratory of Virology &amp; Immunology Yunnan University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Medicine, Yunnan International Joint Laboratory of Virology &amp; Immunology Yunnan University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Dai","sequence":"additional","affiliation":[{"name":"School of Agronomy and Life Sciences Kunming University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7563-0520","authenticated-orcid":false,"given":"Hongkun","family":"Bao","sequence":"additional","affiliation":[{"name":"School of Medicine, Yunnan International Joint Laboratory of Virology &amp; Immunology Yunnan University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.13337"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-022-02227-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-023-02866-y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110985"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2017.08.001"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.06.002"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-022-01095-1"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1515\/jbcpp-2016-0083"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2015.12.012"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.04.040"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2015.04.004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00056"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.114692"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00039.2016"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.07.015"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2021.07.004"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2015.06.009"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2011.361"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-020-0263-9"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.1982311"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527315666160527163526"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180200"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2021.09.009"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.707"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1458143"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-020-1815-6"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20041170"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1374"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.12.016"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2021.05.028"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.13965"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.010"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111532"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.11.008"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2006.03.004"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.06.006"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.255960"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14063"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107658"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/02698811211069110"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00746-9"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7551"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40968-6"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4002148"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9543-1"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13139"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.09.024"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.06.033"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010617-052823"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00521"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2297"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09611"},{"issue":"11","key":"e_1_2_9_54_1","first-page":"1905","article-title":"Acute and Longer\u2010Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report","volume":"163","author":"Rush A. J.","year":"2015","journal-title":"Psychiatry"},{"issue":"10","key":"e_1_2_9_55_1","article-title":"Lipopolysaccharide\u2010Induced Depressive\u2010Like Behavior Is Associated With \u03b11\u2010Adrenoceptor Dependent Downregulation of the Membrane GluR1 Subunit in the Mouse Medial Prefrontal Cortex and Ventral Tegmental Area","volume":"19","author":"Sekio M.","year":"2014","journal-title":"International Journal of Neuropsychopharmacology"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12066"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2010.06.020"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2022_369"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1134\/S1062359018010107"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1159\/000490866"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules20033758"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4158-11.2011"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201601967"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-012-2754-5"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02492-0"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.11"},{"key":"e_1_2_9_67_1","first-page":"15","article-title":"Microglial Activation Mediates Chronic Mild Stress\u2010Induced Depressive\u2010 and Anxiety\u2010Like Behavior in Adult Rats","volume":"2018","author":"Wang Y.\u2010L.","year":"2018","journal-title":"Journal of Neuroinflammation"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.08.018"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2016.08.001"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.02.022"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-020-0484-5"},{"issue":"17","key":"e_1_2_9_72_1","first-page":"2618","article-title":"Anti\u2010Inflammatory Effect and Mechanism of Artemisinin and Dihydroartemisinin","volume":"37","author":"Yu W.\u2010y.","year":"2012","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23116354"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035125"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1148258"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70106","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.70106","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T11:05:42Z","timestamp":1769857542000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,6]]},"references-count":74,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/ptr.70106"],"URL":"https:\/\/doi.org\/10.1002\/ptr.70106","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,6]]},"assertion":[{"value":"2023-12-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}