{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T05:02:26Z","timestamp":1781067746305,"version":"3.54.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      To systematically evaluate the anti-osteoporotic efficacy and underlying mechanisms of\n                      <jats:italic>Semen Cuscutae<\/jats:italic>\n                      and to explore potential experimental factors associated with treatment efficacy using an integration of meta-analysis and machine learning (ML).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A comprehensive search of eight databases (from inception to December 1, 2025) was conducted to identify randomized controlled trials of\n                      <jats:italic>Semen Cuscutae<\/jats:italic>\n                      in osteoporotic animal models. Meta-analysis was performed to assess Bone Mineral Density (BMD), bone histomorphometry, and inflammatory\/metabolic markers. Additionally, an exploratory XGBoost model interpreted via SHapley Additive exPlanations (SHAP) was constructed to quantitatively rank ten experimental variables potentially associated with therapeutic efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifteen studies were included in the final analysis. Meta-analysis demonstrated that\n                      <jats:italic>Semen Cuscutae<\/jats:italic>\n                      intervention significantly increased femoral and lumbar spine BMD, improved trabecular micro-architecture (increased BV\/TV and Tb.Th; decreased Tb.Sp), and enhanced biomechanical strength. Mechanistically, Semen Cuscutae remodeled the osteoimmune microenvironment by suppressing pro-inflammatory cytokines (IL-6) and bone resorption markers (TRACP, CTX, RANKL), while ALP showed an increasing trend and osteogenic or reparative factors, including OPG, IGF, and TGF-\u03b2, were significantly upregulated. Exploratory ML analysis ranked \u201cSpecies,\u201d \u201cDose,\u201d and \u201cTreatment Duration\u201d as the variables most strongly associated with therapeutic efficacy within the current dataset. Specifically, rat models exhibited superior therapeutic responsiveness compared to mice, and gender showed minimal predictive weight.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Semen Cuscutae<\/jats:italic>\n                      exerts robust osteoprotective effects via coupled anti-inflammatory and osteogenic mechanisms. The exploratory ML-derived ranking suggests that species-specific dose scaling and treatment duration may be important considerations for future preclinical and translational studies of\n                      <jats:italic>Semen Cuscutae<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/<\/jats:ext-link>\n                      , identifier CRD420261397983.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1766283","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:30:05Z","timestamp":1781065805000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling the efficacy 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