{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:20:26Z","timestamp":1777695626215,"version":"3.51.4"},"reference-count":47,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Youth Talent Support Project of the China Association of Chinese Medicine","award":["2024-QNRC2-B12"],"award-info":[{"award-number":["2024-QNRC2-B12"]}]},{"DOI":"10.13039\/501100001809","name":"national natural science foundation of china","doi-asserted-by":"publisher","award":["81904134,82474291"],"award-info":[{"award-number":["81904134,82474291"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Integr Cancer Ther"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Chemotherapy-induced peripheral neuropathy (CIPN) is a serious clinical problem with no widely applicable solutions. Modified Wen Luo Tong (mWLT) was designed specifically for paclitaxel-related CIPN, yet its efficacy and mechanisms remain unclear. This study aimed to investigate its therapeutic effects and potential mechanisms via network pharmacology and animal experimental validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Paclitaxel-induced CIPN rat models were treated with mWLT pediluvium. The effect of mWLT was estimated by behavior test. The components and targets of 5 herbs in mWLT were screened from TCMSP and TCMIP databases. CIPN-related targets were retrieved from Genecards and DisGeNET. Networks of gene ontology and pathway associations related to intersection targets were constructed and visualized. A pharmacological network encompassing the intersecting genes and active components was mapped out. A protein-protein interaction network was established for these intersecting targets and visualized using Cytoscape software. Finally, the findings derived from network pharmacology were validated through a series of in vivo experiments, including ELISA, Western Blot, immunohistochemistry and RT-qPCR. Molecular docking was used to predict binding sites between small molecules of mWLT and CX3CR1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      mWLT ameliorates mechanical withdrawal threshold of CIPN model rats. Three hundred and three targets of mWLT against CIPN were identified through intersection analysis, and 8\u2009hub targets such as\n                      <jats:italic toggle=\"yes\">IL6<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">TNF<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">STAT3<\/jats:italic>\n                      were pinpointed. Enrichment analysis of intersection targets highlighted cellular response to cytokine stimulus, JAK-STAT3 pathway and NF-\u03baB pathway. Thus, we speculated that mWLT may exert its effects by acting on\n                      <jats:italic toggle=\"yes\">IL6<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">TNF<\/jats:italic>\n                      , subsequently regulating IL6-JAK-STAT3 and TNF\u03b1-NF-\u03baB signaling pathway, ultimately mitigating CIPN. Experimental validation demonstrated that mWLT significantly decreased the levels of IL-6, IL-1\u03b2 and TNF-\u03b1 in both spinal cord and plasma. Additionally, mWLT downregulated the phosphorylation of JAK, STAT3 and NF-\u03baB in spinal cord. Further analyses using Immunohistochemistry, Western Blot and ELISA confirmed that mWLT reduced the protein expression of CX3CL1. RT-qPCR results revealed downregulation of\n                      <jats:italic toggle=\"yes\">Cx3cl1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Cx3cr1<\/jats:italic>\n                      mRNA level in spinal cord and dorsal root ganglia. Molecular docking predicts 4 potential of compounds derived from mWLT to treat CIPN targeting CX3CR1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>mWLT exerts therapeutic effects in the treatment of CIPN by inhibiting CX3CL1\/CX3CR1 axis and modulating JAK-STAT3 and NF-\u03baB pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15347354251408836","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T11:28:03Z","timestamp":1767612483000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Modified Wen Luo Tong Alleviated Chemotherapy-Induced Peripheral Neuropathy via Regulating the CX3CL1\/CX3CR1 Axis Through Inhibiting NF-\u03baB and STAT3 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Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanjing","family":"Ling","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine School of Traditional Chinese Medicine, Beijing, China"},{"name":"Beijing Key Laboratory of TCM Syndrome and Formula, Beijing, China"},{"name":"Ministry of Education Key Laboratory of Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yilin","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine School of Traditional Chinese Medicine, Beijing, China"},{"name":"Beijing Key Laboratory of TCM Syndrome and Formula, Beijing, China"},{"name":"Ministry of Education Key Laboratory of Beijing University of Chinese Medicine, Beijing, 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