{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T09:38:39Z","timestamp":1784885919145,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp;amp; Nutrition"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Osteoporosis is a disorder of decreased bone mass, microarchitectural deterioration, and fragility fractures. Ganoderma lucidum has been reported to have a variety of pharmacological activities, including immune regulation, anti\u2010inflammation, antioxidation, sedative hypnosis, blood sugar and lipid regulation, and so on. However, the effective ingredients and the underlying mechanism of Ganoderma lucidum against osteoporosis are rarely clarified. Ganoderic acid A (GA\u2010A), a triterpenoid, is one of the main components of Ganoderma lucidum. Our previous preliminary bioinformatic study found that it may affect bone metabolism, and it has been reported that GA\u2010A has anti\u2010osteoporosis potential via regulating MC3T3\u2010E1 cells' osteogenic differentiation activity. Therefore, the aim of this study is to investigate the effects of Ganoderic acid A in preventing osteoporosis and uncover the potential mechanisms. In\u00a0vivo, the 8\u2010week\u2010old C57BL\/6J female mice were used to establish the osteoporosis model by ovariectomy (OVX). Two cell lines, MC3T3\u2010E1 cells and primary osteoblasts, were used and induced with hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) to the state of oxidative stress in osteoporosis in\u00a0vitro. We showed that Ganoderic acid A could inhibit OVX\u2010induced bone loss in a dose\u2010dependent manner and promote H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010induced osteogenic differentiation of primary osteoblasts and MC3T3\u2010E1 cells. The mechanism\u2010related signaling pathways were identified by network pharmacology screening and verified by bioinformatics. Results predicted that the target of Ganoderic acid A might be PIK3CA. Mechanistically, we found that PIK3CA activated the Akt receptor, then inhibited the expression of TWIST1 in the osteoblasts to up\u2010regulate the protein expression of the osteogenic\u2010related markers. Our results suggested that Ganoderic acid A could prevent OVX\u2010induced osteoporosis and promote H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010induced osteogenic differentiation of primary osteoblasts and MC3T3\u2010E1 cells. Ganoderic acid A might play an important role in the prevention of osteoporosis by modulating the PIK3CA\/p\u2010Akt\/TWIST1 signaling pathway.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.70177","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T04:54:16Z","timestamp":1744692856000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ganoderic Acid A Prevented Osteoporosis by Modulating the\n                    <scp>PIK3CA<\/scp>\n                    \/p\u2010Akt\/\n                    <scp>TWIST1<\/scp>\n                    Signaling Pathway"],"prefix":"10.1002","volume":"13","author":[{"given":"Jianyu","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, the First Affiliated Hospital Dalian Medical University  Dalian 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