{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T09:48:59Z","timestamp":1774950539177,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China\n              https:\/\/ror.org\/01h0zpd94","doi-asserted-by":"publisher","award":["82270991"],"award-info":[{"award-number":["82270991"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China\n              https:\/\/ror.org\/01h0zpd94","doi-asserted-by":"publisher","award":["82571101"],"award-info":[{"award-number":["82571101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China\n              https:\/\/ror.org\/01h0zpd94","doi-asserted-by":"publisher","award":["82501220"],"award-info":[{"award-number":["82501220"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zhejiang Provincial Natural Science Foundation of China\/Outstanding Youth Science Foundation","award":["LR21H140002"],"award-info":[{"award-number":["LR21H140002"]}]},{"name":"Zhejiang Provincial Medical and Health Science and Technology Program General Project","award":["2023KY916"],"award-info":[{"award-number":["2023KY916"]}]},{"name":"State Key Laboratory of Oral Diseases Open Fund","award":["SKLOD2024OF08"],"award-info":[{"award-number":["SKLOD2024OF08"]}]},{"name":"Medical Health Science and Technology Major Project of Zhejiang Provincial Health Commission","award":["WKJ-ZJ-2311"],"award-info":[{"award-number":["WKJ-ZJ-2311"]}]},{"name":"Wenzhou Science and Technology Bureau Public Welfare Social Development (Medical and Health) Science and Technology Project","award":["ZY2021015"],"award-info":[{"award-number":["ZY2021015"]}]},{"name":"Opening Research Fund from Shanghai Key Laboratory of Stomatology, Shanghai Ninth People\u2019s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine","award":["2022SKLS-KFKT011"],"award-info":[{"award-number":["2022SKLS-KFKT011"]}]},{"name":"Guangxi Key Laboratory of the Rehabilitation and Reconstruction for Oral and Maxillofacial Research","award":["GXKLRROM2106"],"award-info":[{"award-number":["GXKLRROM2106"]}]},{"name":"Zhejiang Provincial College Students\u2019 Science and Technology Innovation Project and Fresh Talent Program","award":["2021R413083"],"award-info":[{"award-number":["2021R413083"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The global prevalence of osteoporosis is rising, particularly among the elderly and post-menopausal population. Although natural flavonoids can inhibit osteoclast overactivation, their low abundance and extraction challenges limit clinical translation. In this study, we synthesized a flavonoid derivative, SZQ-4, and evaluated its therapeutic potential for post-menopausal osteoporosis (PMO). Using an RANKL-induced osteoclastogenesis model in vitro, we demonstrated through TRAP staining, RT-qPCR, and bone resorption assays that SZQ-4 significantly suppresses osteoclast formation and activity. Mechanistically, RNA-seq, Western blot, siRNA knockdown, and plasmid-based overexpression experiments revealed that SZQ-4 reduces RANKL-induced reactive oxygen species (ROS) production, regulates SIRT3 expression, and improves mitochondrial function, thereby attenuating osteoclast differentiation. In an ovariectomy-induced bone loss mouse model, SZQ-4 treatment markedly alleviated femoral bone loss, decreased osteoclast numbers, and lowered ROS levels in the bone marrow microenvironment. Collectively, our findings indicate that SZQ-4 inhibits osteoclast-driven bone resorption by modulating the ROS-SIRT3\u2013mitochondrial function axis, highlighting its potential as a candidate for preventing pathological bone loss.<\/jats:p>","DOI":"10.3390\/antiox15040426","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:41:03Z","timestamp":1774878063000},"page":"426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthetic Novel Flavonoids SZQ-4 Suppress Osteoclastogenesis and Ameliorate Osteoporosis via Inhibiting Reactive Oxygen Species and Regulating SIRT3"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3462-0534","authenticated-orcid":false,"given":"Runqi","family":"Zhou","sequence":"first","affiliation":[{"name":"Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, 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School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xian","family":"Tong","sequence":"additional","affiliation":[{"name":"Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4522-2769","authenticated-orcid":false,"given":"Shengbin","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shufan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, 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