{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T15:20:07Z","timestamp":1775229607959,"version":"3.50.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"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><jats:title>Introduction<\/jats:title><jats:p>Ferroptosis plays a crucial role in the progression of postmenopausal osteoporosis. <jats:italic>Anemarrhena asphodeloides<\/jats:italic> Bunge\/<jats:italic>Phellodendron chinense<\/jats:italic> C.K. Schneid (AA\/PC) is the core herb pair in traditional Chinese medicines formulae for postmenopausal osteoporosis treatment. However, the synergistic effects, and mechanisms, of AA\/PC on alleviating ferroptosis and postmenopausal osteoporosis remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The goal herein was to analyze the effective ingredients and molecular mechanisms of AA\/PC in the treatment of osteoporosis through serum pharmacochemistry, network pharmacology, metabolomics analysis, and pharmacodynamics evaluation. A bilateral ovariectomized (OVX) mouse model was established.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Discussion<\/jats:title><jats:p>Micron-scale computed tomography analysis showed that AA\/PC increased bone mineral density in OVX mice. The effects of AA\/PC were better than AA or PC alone on inhibiting the bone resorption marker nuclear factor of activated T-cells 1. Furthermore, five absorbable compounds were detected in serum: mangiferin, magnoflorine, berberine, timosaponin BIII, and timosaponin AIII. Network pharmacology showed these compounds had close relationship with seven ferroptosis targets. Importantly, compared with AA or PC alone, the AA\/PC herb pair exerted better effects on regulating crucial ferroptosis pathways, including the system xc-\/glutathione\/glutathione peroxidase 4, transferrin receptor\/ferritin, and acyl-CoA synthetase long chain family member 4\/polyunsaturated fatty acids signaling pathways. These results indicate that AA\/PC exerts synergistic effects on regulating glutathione synthesis, iron homeostasis, and lipid metabolism in ferroptosis. This work lays the foundation for further development and use of AA\/PC herb pair for preventing and treating postmenopausal osteoporosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1378634","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T04:53:24Z","timestamp":1729745604000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Synergistic anti-osteoporosis effects of Anemarrhena asphodeloides bunge\u2013Phellodendron chinense C.K. Schneid herb pair via ferroptosis suppression in ovariectomized mice"],"prefix":"10.3389","volume":"15","author":[{"given":"Xuehui","family":"Deng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenlong","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingfeng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nani","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"672054","DOI":"10.3389\/fphar.2021.672054","article-title":"Therapeutic effects of naringin in rheumatoid arthritis: network pharmacology and experimental validation","volume":"12","author":"Aihaiti","year":"2021","journal-title":"Front. 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