{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:53:01Z","timestamp":1789584781473,"version":"build-2803163510"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"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. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Postmenopausal osteoporosis (PMOP) is characterized by high-turnover bone loss and oxidative stress. Astragaloside IV (AS-IV) exhibits antioxidant and immunomodulatory activities, yet its skeletal effects and mechanistic basis in ovariectomized (OVX) models remain incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Female Sprague\u2013Dawley rats underwent bilateral ovariectomy. Six weeks after surgery, OVX rats were randomized to model, positive control, or AS-IV treatment (20\/40\/80\u202fmg\/kg, gavage, 8\u202fweeks), with sham-operated controls. Serum bone-turnover markers (CTX-I, OCN, PTH) and oxidative stress markers (SOD, MDA) were measured by ELISA. Femora were assessed by micro-CT (BMD, BV\/TV, Tb.N, Tb.Sp) and H&amp;amp;E staining. RNA sequencing was performed followed by GO\/KEGG enrichment and WGCNA to identify hub genes, and molecular docking was used to evaluate AS-IV\u2013target interactions. Multiplex immunofluorescence in the femoral trabecular bone quantified Lep, Ptgs2, Gfap, Igfbp2, Wnt1,\n                      <jats:italic>\u03b2<\/jats:italic>\n                      -catenin, and NF-\u03baB p65 region (mean fluorescence intensity, normalized to Sham).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      OVX rats developed a clear high-turnover phenotype with trabecular rarefaction, reflected by higher CTX-I and MDA and lower SOD. AS-IV produced a dose-related improvement in these readouts\u2014CTX-I fell, oxidative stress was eased (SOD increased and MDA decreased), and OCN and PTH moved back toward control levels. Histological analysis showed AS-IV treatment partially mitigated the trabecular deterioration observed in OVX rats. However, micro-CT analysis showed no statistically significant differences in trabecular bone structure between AS-IV-treated groups and OVX controls (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;gt;\u202f0.05). RNA-seq identified osteoimmune and Wnt-centered programs and nominated hub genes including Lep, Ptgs2, Gfap, Igfbp2, Il22ra2, Wnt10a, and Wnt1. In femoral trabecular bone, multiplex immunofluorescence revealed increased NF-\u03baB p65 and decreased Wnt1 and Gfap signals in OVX rats compared to Sham. High-dose AS-IV significantly reduced NF-\u03baB p65 and partly restored Wnt1 and Gfap. However, Ptgs2 showed no significant differences across groups, and Igfbp2 and\n                      <jats:italic>\u03b2<\/jats:italic>\n                      -catenin were not significantly rescued within this sampling window. Molecular docking suggested favorable binding between AS-IV and selected targets, supporting its multitarget profile.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>AS-IV modulates oxidative stress and osteoimmune\u2013Wnt signaling in OVX rats, with directional improvements in bone turnover markers but without significant micro-CT structural changes. This work provides a foundation for hypothesis-driven investigation of AS-IV in PMOP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1785452","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:48:15Z","timestamp":1776059295000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Astragaloside IV modulates oxidative stress and osteoimmune\u2013Wnt signaling in ovariectomized rats: an integrated study of RNA sequencing, molecular docking, and experimental validation"],"prefix":"10.3389","volume":"13","author":[{"given":"Ya-Qing","family":"Li","sequence":"first","affiliation":[{"name":"First Clinical College, Shanxi University of Traditional Chinese Medicine","place":["Jinzhong, China"]},{"name":"Clinical Research Laboratory, Shanxi Province Key Laboratory Cultivation Base Jointly Established by the Department and City of Hormone Metabolic Diseases During Perimenopause, The First People's Hospital of Datong","place":["Datong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-Ying","family":"Yao","sequence":"additional","affiliation":[{"name":"First Clinical College, Shanxi University of Traditional Chinese Medicine","place":["Jinzhong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jing","sequence":"additional","affiliation":[{"name":"Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Datong Key Laboratory of Smart Medicine and Health Care for Elderly Chronic Diseases, Shanxi Datong University","place":["Datong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Wang","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Research Laboratory, Shanxi Province Key Laboratory Cultivation Base Jointly Established by the Department and City of Hormone Metabolic Diseases During Perimenopause, The First People's Hospital of Datong","place":["Datong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liang","sequence":"additional","affiliation":[{"name":"Clinical Research Laboratory, Shanxi Province Key Laboratory Cultivation Base Jointly Established by the Department and City of Hormone Metabolic Diseases During Perimenopause, The First People's Hospital of Datong","place":["Datong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai-Yu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Yueyang Clinical Medical College, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Lu","sequence":"additional","affiliation":[{"name":"Datong Key Laboratory of Smart Medicine and Health Care for Elderly Chronic Diseases, Shanxi Datong University","place":["Datong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Datong Key Laboratory of Smart Medicine and Health Care for Elderly Chronic Diseases, Shanxi Datong University","place":["Datong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Ping","family":"Gao","sequence":"additional","affiliation":[{"name":"First Clinical College, Shanxi University of Traditional Chinese Medicine","place":["Jinzhong, China"]},{"name":"Clinical Research Laboratory, Shanxi Province Key Laboratory Cultivation Base Jointly Established by the Department and City of Hormone Metabolic Diseases During Perimenopause, The First People's Hospital of Datong","place":["Datong, 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