{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:06:03Z","timestamp":1789049163595,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":["Brain and Behavior"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Ethnopharmacological relevance<\/jats:title>\n                    <jats:p>The Xuanshi Choudong Recipe (CDR), a classic traditional Chinese medicine (TCM) formula, has long been clinically prescribed to relieve tic disorder (TD). However, its underlying in\u2010depth mechanism remains largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim of the study<\/jats:title>\n                    <jats:p>To elucidate the mechanism by which CDR exerts therapeutic effects in the treatment of TD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Four\u2010week\u2010old SD rats were injected intraperitoneally with apomorphine at 2 mg\/kg per day to establish the model. After successful modeling, the rats were randomly divided into the model, CDR low\u2010dose (CDRL, 6.84 g\/kg), CDR medium\u2010dose (CDRM, 13.67 g\/kg), CDR high\u2010dose (CDRH, 27.34 g\/kg), and haloperidol (1 mg\/kg) groups. Age\u2010matched SD rats served as the control group. Therapeutic efficacy was evaluated using the open field test, hematoxylin and eosin (H&amp;E) staining, and biochemical analysis. The potential mechanisms of CDR were explored using network pharmacology and transcriptomic analyses and validated by western blotting, immunofluorescence, biochemical analysis, and terminal deoxynucleotidyl transferase dUTP nick\u2010end labeling (TUNEL) staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In this study, a total of 126 compounds were identified in CDR using liquid chromatography\u2010mass spectrometry, with phenylpropanoids, polyketides, benzenoids, and lipids being the main components. Network pharmacology prediction revealed 265 overlapping targets between CDR and TD, with core targets including AKT1, BCL2, and IL6, and the phosphoinositide 3\u2010kinase\/protein kinase B (PI3K\u2010AKT) signaling pathway being significantly enriched. Transcriptomic analysis showed that CDR reversed the expression of 111 genes in the striatum of TD rats, and these genes were significantly enriched in pathways related to apoptosis and the PI3K\u2010Akt signaling pathway. Behavioral assessment demonstrated that CDR dose\u2010dependently reduced apo\u2010induced stereotypic behavior scores and spontaneous locomotor activity in TD rats. H&amp;E staining indicated that CDR attenuated striatal neuronal damage. High dose CDR treatment significantly decreased the elevated levels of dopamine, 5\u2010HT, norepinephrine, glutamate, and gamma\u2010aminobutyric acid in the striatum (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01 or\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). Furthermore, High\u2010dose CDR alleviated oxidative stress\u2010induced injury by reducing reactive oxygen species and oxidized glutathione (GSSG) levels and increasing superoxide dismutase (SOD) activity, reduced glutathione (GSH) levels, and the GSH\/GSSG ratio (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01 or\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). TUNEL staining and immunofluorescence results showed that CDR inhibited neuronal apoptosis in the striatum. Western blotting confirmed that CDR upregulated the phosphorylation levels of PI3K and AKT, increased the Bcl\u20102\/Bax ratio, and downregulated caspase\u20103 expression, with high\u2010dose CDR exerting the most significant effect.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71687","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:30:12Z","timestamp":1787031012000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Network Pharmacology and Transcriptomics Reveal the Mechanism of XuanShi Choudong Recipe in the Treatment of Tic Disorder"],"prefix":"10.1002","volume":"16","author":[{"given":"Hu","family":"Jue","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma","family":"Jingying","sequence":"additional","affiliation":[{"name":"Department of Clinical Psychology Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yaqin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Yulu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yanhong","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center Zhejiang University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Jiaye","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Danfei","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Jian","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Xiao\u2010bo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2006.01.001"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.13129"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1205"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.5334\/tohm.459"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201600182"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.08.038"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.16840\/j.issn1673\u20104297.2021.05.01"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.220206"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000356"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.21037\/tp.2019.09.11"},{"key":"e_1_2_12_13_1","volume-title":"Insights Into Medicine","author":"Guopeng C.","year":"1959"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011\u2010023\u201001211\u20109"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedneo.2020.03.007"},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","unstructured":"Jin Y. 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