{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:00:24Z","timestamp":1790089224218,"version":"4.0.1"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"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":["82171216"],"award-info":[{"award-number":["82171216"]}],"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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Bone cancer pain (BCP) is a chronic and debilitating condition often accompanied by neuroinflammation, microglial activation, and neuronal damage, which are difficult to manage with current therapies. Cycloastragenol (CAG), a bioactive compound from Astragalus membranaceus, exhibits anti\u2010inflammatory and neuroprotective activities, yet its potential in BCP remains unclear. This study aimed to investigate the analgesic effects and underlying mechanisms of CAG in a rat model of BCP. In this study, we induced BCP in rats and administered CAG to evaluate its therapeutic effects. Behavioral testing, Western blotting, immunofluorescence, and molecular docking were employed to assess pain behaviors, inflammation, microglial polarization, and ferroptosis markers. CAG treatment significantly attenuated BCP\u2010related pain and suppressed inflammation, promoting a shift from pro\u2010inflammatory M1 to anti\u2010inflammatory M2 microglial phenotypes, while inhibiting ferroptosis in spinal cord neurons through activation of the Sirt1\u2013Nrf2 pathway. Sirt1 knockdown via siRNA abolished these beneficial effects, and cellular thermal shift assays confirmed a direct interaction between CAG and Sirt1. These findings demonstrate that CAG alleviates BCP by modulating microglial polarization and inhibiting neuronal ferroptosis via Sirt1 activation, suggesting its promise as a multi\u2010targeted therapeutic strategy for BCP and other neuroinflammatory pain disorders.<\/jats:p>","DOI":"10.1002\/ptr.70217","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T07:22:55Z","timestamp":1769584975000},"page":"1626-1641","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cycloastragenol Alleviates Bone Cancer Pain by Targeting Sirt1 to Inhibit Neuronal Ferroptosis and Promote\n                    <scp>M2<\/scp>\n                    Microglial Polarization in the Spinal Dorsal Horn of Rats"],"prefix":"10.1002","volume":"40","author":[{"given":"Chengfei","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Bengbu Third People's Hospital Affiliated to Bengbu Medical University  Bengbu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6957-2136","authenticated-orcid":false,"given":"Kan","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Pain Medicine The First Affiliated Hospital of Bengbu Medical University  Bengbu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pain Medicine The First Affiliated Hospital of Bengbu Medical University  Bengbu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengwei","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Bengbu Third People's Hospital Affiliated to Bengbu Medical University  Bengbu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Bengbu Third People's Hospital Affiliated to Bengbu Medical University  Bengbu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Bengbu Third People's Hospital Affiliated to Bengbu Medical University  Bengbu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Xiao","sequence":"additional","affiliation":[{"name":"Bengbu Hospital of Traditional Chinese Medicine  Bengbu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pain Medicine The First Affiliated Hospital of Bengbu Medical University  Bengbu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinsheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Bengbu Third People's Hospital Affiliated to Bengbu Medical University  Bengbu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pain Medicine The First Affiliated Hospital of Bengbu Medical University  Bengbu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Bengbu Third People's Hospital Affiliated to Bengbu Medical University  Bengbu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Bengbu Third People's Hospital Affiliated to Bengbu Medical University  Bengbu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huadong","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Research Center The Affiliated Hospital of Jiaxing University  Jiaxing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21823"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.156097"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.11.016"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2024.110284"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109290"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103030"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102022\u2010004874"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565\u2010024\u201009970\u20106"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102700"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/17448069241239231"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177305"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12394"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2013.51.7219"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.134120"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112912"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112230"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2025.101123"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2019.01.024"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102615"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102745"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.156165"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.09.016"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202304521"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.2147\/cmar.S263177"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12948"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44319-025-00634-y"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2024.110164"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2024.1424137"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2023.05.001"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154862"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2024.01.009"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17300"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14764"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.156502"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s44254\u2010025\u201000113\u20106"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.156462"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44319\u2010024\u201000292\u20106"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/17448069221135743"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.49426"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2022.109254"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114591"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70067"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2023.12.003"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202403818"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.157000"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.06.006"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2023.110698"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153910"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70217","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.70217","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70217","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T04:21:02Z","timestamp":1775622062000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":48,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/ptr.70217"],"URL":"https:\/\/doi.org\/10.1002\/ptr.70217","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]},"assertion":[{"value":"2025-08-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}