{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T09:12:02Z","timestamp":1778231522230,"version":"3.51.4"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Postmenopausal osteoporosis (PMO) is driven by estrogen deficiency, enhanced osteoclastic activity, impaired osteoblast function, and persistent inflammatory signaling. Eucommia ulmoides extract (EUE) and soy isoflavones (Isf) are known to possess phytoestrogenic and anti\u2014inflammatory properties, but their combined molecular effects on PMO remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An ovariectomy\u2014induced PMO rat model was used to assess the therapeutic efficacy of EUE, Isf, and their combination. Bone strength and mineral content were evaluated together with serum indicators of bone turnover, including type I procollagen N\u2014terminal propeptide, alkaline phosphatase, C\u2014terminal telopeptide of type I collagen, and tartrate\u2014resistant acid phosphatase. Serum calcium, phosphorus, superoxide dismutase, and malondialdehyde levels were also measured. Trabecular microarchitecture was assessed histologically.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , osteoblast differentiation was examined by Alizarin Red staining and proliferative activity by EdU incorporation, while osteoclast formation and apoptosis were analyzed by tartrate\u2014resistant acid phosphatase staining and flow cytometry. Mechanistic evaluation focused on bone\u2014related transcriptional regulators such as Runx2 and alkaline phosphatase, key mediators of osteoclastogenesis including RANKL, RANK, OPG, and TRAP, and inflammatory cytokines including tumor necrosis factor\u2014\u03b1, interleukin\u20146, interleukin\u20141\u03b2, and interleukin\u201410.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The combined EUE and Isf treatment significantly improved biomechanical performance of the femur and restored bone mineral content in ovariectomized rats. Levels of bone formation markers were elevated, whereas indices of bone resorption were reduced. Serum calcium\u2013phosphorus homeostasis and oxidative stress were markedly corrected, accompanied by substantial improvement in trabecular structure.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , the combination enhanced osteoblast mineralization and proliferation, suppressed osteoclast formation, and increased osteoclast apoptosis. Mechanistically, the combined treatment increased the expression of osteogenic regulators Runx2, alkaline phosphatase, and osteoprotegerin, while reducing the expression of RANKL, RANK, and TRAP. Pro\u2014inflammatory cytokines were lowered, whereas interleukin\u201410 was upregulated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>EUE combined with soy isoflavones effectively attenuates postmenopausal osteoporosis by enhancing osteoblast function, suppressing osteoclastogenesis, and rebalancing bone\u2014related transcriptional and inflammatory pathways. This botanical combination represents a promising therapeutic strategy for the management of PMO.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1753846","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T08:46:40Z","timestamp":1778230000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Eucommia ulmoides extract and soy isoflavones attenuate postmenopausal osteoporosis by modulating bone\u2014specific transcription factors and inflammatory signaling pathways"],"prefix":"10.3389","volume":"17","author":[{"given":"Ruihong","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Food and Biological Engineering, Henan University of Animal Husbandry and Economy","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhuan","family":"He","sequence":"additional","affiliation":[{"name":"College of Food and Biological Engineering, Henan University of Animal Husbandry and Economy","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengdi","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food and Biological Engineering, Henan University of Animal Husbandry and Economy","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiming","family":"Li","sequence":"additional","affiliation":[{"name":"College of Food and Biological Engineering, Henan University of Animal Husbandry and Economy","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyu","family":"Hao","sequence":"additional","affiliation":[{"name":"College of Food and Biological Engineering, Henan University of Animal Husbandry and Economy","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiying","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Food and Biological Engineering, Henan University of Animal Husbandry and Economy","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yabo","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Food and Biological Engineering, Henan University of Animal Husbandry and Economy","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1097\/00042192-200211000-00007","article-title":"Effects of tibolone and hormone replacement therapy on the breast of cynomolgus monkeys","volume":"9","author":"Cline","year":"2002","journal-title":"Menopause"},{"key":"B2","doi-asserted-by":"publisher","first-page":"107052","DOI":"10.1016\/j.bioorg.2023.107052","article-title":"Characterization of the metabolites of Eucommiae Cortex in rats provides a further insight into its estrogen-like effective substances","volume":"143","author":"Ding","year":"2024","journal-title":"Bioorg Chem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"177","DOI":"10.3389\/fphar.2013.00177","article-title":"The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety","volume":"4","author":"Ekor","year":"2014","journal-title":"Front. 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