{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:07:48Z","timestamp":1782281268967,"version":"3.54.5"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pain Res."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Orientin is a bioactive agent isolated from natural resources successfully applied for pain control. This study was to explore candidate hub gene of orientin to intervertebral disc degeneration (IDD) -associated low back pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study integrated the network pharmacology analysis using orientin and IDD-associated pain, machine learning and immune infiltration analysis using GSE70362 as prediction analysis. The validation was performed via molecular docking, molecular dynamics simulation, single-cell RNA sequencing (scRNA-seq) analysis and cell experiment using human annulus fibrosus cells under IL-1\u03b2 stimulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Network pharmacology analysis showed that there were 368 overlapped genes between orientin and IDD-associated low back pain. Machine learning demonstrated that Cytochrome P450 1B1 (CYP1B1) was candidate hub genes with excellent diagnostic performance (AUC\u2009=\u20090.95). Immune infiltration analysis showed that CYP1B1 had no correlation with infiltration levels of any immune cell subset cells after Benjamini-Hochberg false discovery rate correction. Molecular Docking showed docking energies of orientin to CYP1B1 were all smaller than \u22129.5 kcal\/mol. The molecular dynamics simulation showed a system of orientin-CYP1B1 showed a relatively stable conformational ensemble. scRNA-seq analysis revealed tissue- and cell-type specific expression of CYP1B1, with significant upregulation in annulus fibrosus fibroblasts from diseased samples. In cell experiments, orientin alleviated the decrease in cell viability induced by IL-1\u03b2 stimulation, and down-regulated CYP1B1 gene expression and CYP1B1 protein levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study showed that CYP1B1 is a potential candidate hub gene for orientin to IDD-associated low back pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpain.2026.1870398","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:45:44Z","timestamp":1782279944000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated machine learning and multi-omics analysis identifies CYP1B1 as a candidate target of orientin in intervertebral disc degeneration-associated low back 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