{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T14:06:31Z","timestamp":1789221991193,"version":"build-2803163510"},"reference-count":42,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Shaanxi Province Key Industry Innovation Chain Project","award":["2023-ZDLSF-59"],"award-info":[{"award-number":["2023-ZDLSF-59"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic inflammatory pain has a high incidence, and existing drugs have side effects. The natural product Cimifugin has anti-inflammatory and analgesic potential, but its role and mechanism in treating chronic inflammatory pain remain unclear. This study aims to explore the potential targets, signaling pathways, and in vivo mechanism of Cimifugin in the treatment of chronic inflammatory pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Network pharmacology was used to predict the potential targets and related pathways of Cimifugin. A mouse model of chronic inflammatory pain induced by complete Freund\u2019s adjuvant (CFA) was established. Behavioral tests (mechanical\/thermal hyperalgesia, elevated plus maze) were conducted to evaluate pain sensation and anxiety-like behaviors. ELISA was used to detect inflammatory factors (IL-1\u03b2, IL-6, TNF-\u03b1). Western blot was employed to analyze synaptic functional proteins. HPLC-MS\/MS was used to verify Cimifugin\u2019s ability to cross the blood-brain barrier.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Network pharmacology analysis predicted that the 64 cross-targets of Cimifugin and chronic inflammatory pain are enriched in pathways such as MAPK and PI3K-Akt. Animal experiments showed that Cimifugin dose-dependently increased pain thresholds, reduced paw swelling, improved anxiety-like behaviors, decreased inflammatory factor levels, reversed abnormal expression of synaptic functional proteins, and could cross the blood-brain barrier.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cimifugin alleviates chronic inflammatory pain and related behavioral abnormalities, an effect associated with inhibition of inflammatory responses and restoration of synaptic protein expression. These findings suggest a multi-target, multi-pathway mechanism of action.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17448069261488527","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T16:55:45Z","timestamp":1789059345000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cimifugin alleviates chronic inflammatory pain by inhibiting neuroinflammation and restoring synaptic function: A network pharmacology and in vivo study"],"prefix":"10.1177","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4813-9597","authenticated-orcid":false,"given":"Hanyu","family":"Lei","sequence":"first","affiliation":[{"name":"The Fourth Military Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Rong","sequence":"additional","affiliation":[{"name":"The Fourth Military Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan","family":"Liu","sequence":"additional","affiliation":[{"name":"The Fourth Military Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1706-5241","authenticated-orcid":false,"given":"Le","family":"Yang","sequence":"additional","affiliation":[{"name":"The Fourth Military Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7539-3887","authenticated-orcid":false,"given":"Minggao","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Fourth Military Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2024.01.045"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00392-5"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/imj.15711"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/aas.13380"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j3221"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112958"},{"issue":"4","key":"e_1_3_8_8_2","first-page":"CD007400","article-title":"Topical NSAIDs for chronic musculoskeletal pain in adults","volume":"4","author":"Derry S","year":"2016","unstructured":"Derry S, Conaghan P, Da Silva JA, et al. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev 2016; 4(4): CD007400. https:\/\/doi.org\/10.1002\/14651858.CD007400.pub3","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2017.05.008"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0661-4"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnad016"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12178"},{"issue":"8","key":"e_1_3_8_13_2","first-page":"1107","article-title":"Development of an Efficient Protocol for Cimifugin Isolation from Peucedanum schottii and Evaluation of Enzyme Inhibitory Activity","volume":"11","author":"Koziol E","year":"2016","unstructured":"Koziol E, Orhan IE, Senol FS, et al. Development of an Efficient Protocol for Cimifugin Isolation from Peucedanum schottii and Evaluation of Enzyme Inhibitory Activity. Nat Prod Commun 2016; 11(8): 1107\u20131110.","journal-title":"Nat Prod Commun"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13204"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.3c09697"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.5603\/fm.106197"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.912042"},{"key":"e_1_3_8_18_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132612"},{"key":"e_1_3_8_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-013-0633-0"},{"key":"e_1_3_8_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2026.109016"},{"key":"e_1_3_8_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2021.11.004"},{"key":"e_1_3_8_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116306"},{"key":"e_1_3_8_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12111"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/6.1.1"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.1214\/aoms\/1177704711"},{"key":"e_1_3_8_26_2","doi-asserted-by":"publisher","DOI":"10.2307\/3001913"},{"key":"e_1_3_8_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_3_8_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-01001-2"},{"key":"e_1_3_8_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13275"},{"key":"e_1_3_8_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7704"},{"key":"e_1_3_8_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1551892"},{"key":"e_1_3_8_32_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26199591"},{"key":"e_1_3_8_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e34870"},{"key":"e_1_3_8_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.113338"},{"key":"e_1_3_8_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-022-00616-y"},{"key":"e_1_3_8_36_2","doi-asserted-by":"publisher","DOI":"10.15586\/aei.v52i4.1107"},{"key":"e_1_3_8_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-024-01513-4"},{"key":"e_1_3_8_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-023-04121-9"},{"key":"e_1_3_8_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr350"},{"key":"e_1_3_8_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15284"},{"key":"e_1_3_8_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2023.148375"},{"key":"e_1_3_8_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.3c00254"},{"key":"e_1_3_8_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202512375"}],"container-title":["Molecular Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17448069261488527","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17448069261488527","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17448069261488527","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T13:16:57Z","timestamp":1789219017000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17448069261488527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":42,"alternative-id":["10.1177\/17448069261488527"],"URL":"https:\/\/doi.org\/10.1177\/17448069261488527","relation":{},"ISSN":["1744-8069","1744-8069"],"issn-type":[{"value":"1744-8069","type":"print"},{"value":"1744-8069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"article-number":"17448069261488527"}}