{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T10:11:06Z","timestamp":1780913466694,"version":"3.54.1"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuropathic pain (NP) frequently co\u2010occurs with depression (DP), exhibiting complex pathogenesis and limited clinical treatment options. This study aims to investigate the efficacy of Eupalinolide B (EB) in alleviating NP co\u2010occurring with DP and its potential molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Combining network pharmacology, molecular docking, and molecular dynamics simulations to screen potential targets for EB, validated through transcriptomic data. Using a sciatic nerve branch\u2010preserving injury (SNI) mouse model, we assessed pain and depression\u2010like behaviors through von Frey testing, hot plate testing, tail suspension testing, forced swimming testing, and open field testing. Concurrently, Western blotting, immunofluorescence, and Nissl staining were employed to analyze relevant molecules and neuropathological alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Network pharmacology and bioinformatics analysis identified EGFR, PTGS2, and JUN as the key targets for EB in treating NP combined with DP. Behavioral studies showed that 20\u2009mg\/kg of EB significantly alleviated pain in SNI mice and improved depressive\u2010like behaviors. Mechanism research indicated that EB downregulated the expression of EGFR and PTGS2, inhibited the activation of microglia and astrocytes, and reduced neuronal damage. Additionally, EB could upregulate the expression of synaptic proteins (PSD95, SYN1, and BDNF) in the hippocampus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>EB alleviates neuroinflammation by reducing EGFR and PTGS2 protein expression, modulates synaptic plasticity, and improves pain\u2010depression comorbidity. EB may represent a promising therapeutic approach for pain\u2010related depression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70872","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T13:34:34Z","timestamp":1775828074000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Small Molecule Compound Eupalinolide B Ameliorates Depressive Behaviors and Neuropathic Pain in Mice With Spared Nerve Injury: Integrating Network Pharmacology, Molecular Docking, Bioinformatics, Molecular Dynamics Simulation and Experimental Verification"],"prefix":"10.1002","volume":"32","author":[{"given":"Xuesong","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Institute of Anesthesiology &amp; Pain (IAP), Department of Anesthesiology, Taihe Hospital Hubei University of Medicine  Shiyan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Department of Anesthesiology Wenchang People's Hospital  Wenchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7845-4190","authenticated-orcid":false,"given":"Hongbing","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.2"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.11.013"},{"issue":"3","key":"e_1_2_11_4_1","first-page":"249","article-title":"Neuropathic Pain and Chronic Pain as an Underestimated Interdisciplinary Problem","volume":"35","author":"Szewczyk A. 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