{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:08:06Z","timestamp":1789567686094,"version":"build-2803163510"},"reference-count":79,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460725"],"award-info":[{"award-number":["82460725"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovation Project of Guangxi Graduate Education","award":["YCBZ2025123"],"award-info":[{"award-number":["YCBZ2025123"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This research investigates how CVB modulates osteoclast development and functional activity, and elucidates its underlying molecular mechanisms. Osteoclasts are pivotal mediators of bone matrix degradation and reconstruction, and their overactivation is an important mechanism in diseases such as osteoporosis. By extracting bone marrow-derived macrophages (BMMs) from mouse bone marrow and inducing them to differentiate into osteoclasts under RANKL and M-CSF stimulation, we found that CVB dose-dependently inhibited osteoclast differentiation, pseudopod structure formation, acid secretion and bone resorption function at nontoxic concentrations; inhibited PI3K\/AKT pathway activation, enhanced the nuclear translocation and expression of FOXO1, and upregulated antioxidant enzymes such as CAT and SOD1, thereby suppressing intracellular ROS accumulation. Animal experiments further demonstrated that CVB exerted a protective effect against skeletal degradation in ovariectomized mice. These results suggest that CVB suppresses osteoclastogenesis and their resorptive function through modulation of MAPK and PI3K\/AKT\/FOXO1 pathways and by enhancing antioxidant defense, which has potential therapeutic value for antiosteoporosis treatment.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c01670","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:09:27Z","timestamp":1788451767000},"page":"28408-28424","source":"Crossref","is-referenced-by-count":0,"title":["Cyclovirobuxine\nPrevents Osteoclastogenesis and Estrogen\nDeficiency-Induced Bone Loss by Inhibiting ROS Generation via the\nPI3K\/AKT\/FOXO1 Pathway"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8676-0002","authenticated-orcid":true,"given":"Qiufei","family":"Li","sequence":"first","affiliation":[{"name":"Guangxi Medical University , , , ,","place":["Nanning, Guangxi, China, 530021"]},{"name":"The Eighth Affiliated Hospital of Guangxi Medical University , , , ,","place":["Guigang, Guangxi, China, 537100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Hai","sequence":"additional","affiliation":[{"name":"Guangxi Medical University , , , ,","place":["Nanning, Guangxi, China, 530021"]},{"name":"The First Affiliated Hospital of Guangxi Medical University , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jindeng","family":"Liao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University , , , ,","place":["Nanning, Guangxi, China, 530021"]},{"name":"The Eighth Affiliated Hospital of Guangxi Medical University , , , ,","place":["Guigang, Guangxi, China, 537100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Teng","sequence":"additional","affiliation":[{"name":"Henan University , , , ,","place":["Kaifeng, Henan, China, 475000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangxi Medical University , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zutuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Guangxi Medical University , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Sun","sequence":"additional","affiliation":[{"name":"Guangxi Medical University , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangxi Medical University , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmin","family":"Zhao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiake","family":"Xu","sequence":"additional","affiliation":[{"name":"The University of Western Australia , , , ,","place":["Perth, Western Australia, Australia, 6009"]},{"name":"Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences , , ,","place":["Shenzhen, China, 518000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangxi Medical University , , , ,","place":["Nanning, Guangxi, China, 530021"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"issue":"33","key":"2026091609100545100_cit1","doi-asserted-by":"publisher","first-page":"25103","DOI":"10.1074\/jbc.R109.041087","article-title":"Cellular\nand molecular mechanisms of bone remodeling","volume":"285","author":"Raggatt","year":"2010","journal-title":"J. Biol. Chem."},{"issue":"1","key":"2026091609100545100_cit2","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s11658-022-00371-3","article-title":"Osteoporosis pathogenesis\nand treatment: existing and emerging avenues","volume":"27","author":"Liang","year":"2022","journal-title":"Cell. Mol. Biol. Lett."},{"issue":"1","key":"2026091609100545100_cit3","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1186\/s12951-024-02466-9","article-title":"\u00c5ngstrom-scale gold particles loaded with alendronate via alpha-lipoic\nacid alleviate bone loss in osteoporotic mice","volume":"22","author":"Gao","year":"2024","journal-title":"J. Nanobiotechnol."},{"issue":"2","key":"2026091609100545100_cit4","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1002\/med.22081","article-title":"Estrogen deficiency-mediated\nosteoimmunity in postmenopausal osteoporosis","volume":"45","author":"Yao","year":"2025","journal-title":"Med. Res. Rev."},{"issue":"Pt C","key":"2026091609100545100_cit5","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.semcdb.2022.11.002","article-title":"Epigenetic regulation\nof bone remodeling and bone metastasis","volume":"154","author":"Sharma","year":"2024","journal-title":"Semin.\nCell Dev. Biol."},{"issue":"1","key":"2026091609100545100_cit6","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41423-022-00959-x","article-title":"RANKL-responsive epigenetic mechanism reprograms macrophages into\nbone-resorbing osteoclasts","volume":"20","author":"Bae","year":"2023","journal-title":"Cell. Mol. Immunol."},{"issue":"12","key":"2026091609100545100_cit7","doi-asserted-by":"publisher","first-page":"2094","DOI":"10.3390\/antiox12122094","article-title":"Nrf2Mitigates RANKL\nand M-CSF Induced Osteoclast Differentiation via ROS-Dependent Mechanisms","volume":"12","author":"Yang","year":"2023","journal-title":"Antioxidants"},{"issue":"2","key":"2026091609100545100_cit8","doi-asserted-by":"publisher","first-page":"197","DOI":"10.3390\/antiox14020197","article-title":"Divergent Requirements\nfor Glutathione Biosynthesis During Osteoclast Differentiation In\nVitro and In Vivo","volume":"14","author":"Hu","year":"2025","journal-title":"Antioxidants"},{"issue":"3","key":"2026091609100545100_cit9","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1182\/blood-2004-09-3662","article-title":"A crucial role for\nreactive oxygen species in RANKL-induced osteoclast differentiation","volume":"106","author":"Lee","year":"2005","journal-title":"Blood"},{"key":"2026091609100545100_cit10","doi-asserted-by":"publisher","first-page":"114834","DOI":"10.1016\/j.biopha.2023.114834","article-title":"Oxidative\nstress: A common pathological state in a high-risk population for\nosteoporosis","volume":"163","author":"Zhang","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"2026091609100545100_cit11","doi-asserted-by":"publisher","first-page":"155890","DOI":"10.1016\/j.phymed.2024.155890","article-title":"Active\nfraction of Polyrhachis vicina (Rogers) inhibits osteoclastogenesis\nby targeting Trim38 mediated proteasomal degradation of TRAF6","volume":"132","author":"Feng","year":"2024","journal-title":"Phytomedicine"},{"issue":"1","key":"2026091609100545100_cit12","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s12957-025-04139-9","article-title":"FOXO1 phosphorylation\nas a context-dependent molecular switch in cancer: from mechanisms\nto precision therapy","volume":"24","author":"Wang","year":"2026","journal-title":"World J. Surg. Oncol."},{"issue":"11","key":"2026091609100545100_cit13","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1016\/j.bbamcr.2011.01.007","article-title":"Regulation of FOXO\nprotein stability via ubiquitination\nand proteasome degradation","volume":"1813","author":"Huang","year":"2011","journal-title":"Biochim. Biophys.\nActa"},{"issue":"3","key":"2026091609100545100_cit14","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1093\/humupd\/dmaa060","article-title":"FOXO1 is a cell-specific core transcription\nfactor\nfor endometrial remodeling and homeostasis during menstrual cycle\nand early pregnancy","volume":"27","author":"Adiguzel","year":"2021","journal-title":"Hum. Reprod. Update"},{"key":"2026091609100545100_cit15","doi-asserted-by":"publisher","first-page":"3773","DOI":"10.1038\/ncomms4773","article-title":"FoxO proteins\nrestrain osteoclastogenesis and bone\nresorption by attenuating H2O2 accumulation","volume":"5","author":"Bartell","year":"2014","journal-title":"Nat. Commun."},{"issue":"1","key":"2026091609100545100_cit16","doi-asserted-by":"publisher","first-page":"202","DOI":"10.3892\/ijmm.2017.3208","article-title":"Resveratrol\nprevents osteoporosis by upregulating FOXO1 transcriptional activity","volume":"41","author":"Feng","year":"2017","journal-title":"Int. J. Mol. Med."},{"issue":"5","key":"2026091609100545100_cit17","doi-asserted-by":"publisher","first-page":"6681","DOI":"10.3892\/mmr.2018.8657","article-title":"Upregulation of SIRT1\ninhibits H2O2-induced osteoblast apoptosis via FOXO1\/\u03b2-catenin\npathway","volume":"17","author":"Yao","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"2026091609100545100_cit18a","doi-asserted-by":"publisher","first-page":"106493","DOI":"10.1016\/j.bioorg.2023.106493","article-title":"Structurally\nmodified\nCyclovirobuxine-D Buxus alkaloids as effective analgesic agents through\nCa(v)3.2 T-Type calcium channel inhibition","volume":"135","author":"Munikishore","year":"2023","journal-title":"Bioorg. Chem."},{"issue":"1","key":"2026091609100545100_cit18b","doi-asserted-by":"publisher","DOI":"10.1111\/eci.14085","article-title":"Heart rate variability\nand cardiovascular diseases: A Mendelian randomization study","volume":"54","author":"Zhao","year":"2024","journal-title":"Eur. J. Clin. Invest."},{"issue":"12","key":"2026091609100545100_cit18c","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.3390\/pharmaceutics16121600","article-title":"Unlocking the Stratum Corneum Barrier to Skin Penetration\nfor the Transdermal Delivery of Cyclovirobuxine D. Pharmaceutics","volume":"16","author":"Ren","year":"2024","journal-title":"Pharmaceutics"},{"issue":"6","key":"2026091609100545100_cit19","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1038\/aps.2014.16","article-title":"Cyclovirobuxinum\nD suppresses lipopolysaccharide-induced\ninflammatory responses in murine macrophages in vitro by blocking\nJAK-STAT signaling pathway","volume":"35","author":"Guo","year":"2014","journal-title":"Acta Pharmacol.\nSin."},{"issue":"1","key":"2026091609100545100_cit20","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1254\/jphs.14013FP","article-title":"Cyclovirobuxine\nD induces autophagy-associated cell death via the Akt\/mTOR pathway\nin MCF-7 human breast cancer cells","volume":"125","author":"Lu","year":"2014","journal-title":"J. Pharmacol.\nSci."},{"issue":"11","key":"2026091609100545100_cit21a","doi-asserted-by":"publisher","first-page":"5820","DOI":"10.3390\/ijms22115820","article-title":"Cyclovirobuxine D Induced-Mitophagy\nthrough the p65\/BNIP3\/LC3 Axis Potentiates Its Apoptosis-Inducing\nEffects in Lung Cancer Cells","volume":"22","author":"Zeng","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2026091609100545100_cit21b","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.brainresbull.2019.08.017","article-title":"Therapeutic effects of JLX-001 on ischemic stroke by inducing autophagy\nvia AMPK-ULK1 signaling pathway in rats","volume":"153","author":"Ao","year":"2019","journal-title":"Brain\nRes. Bull."},{"issue":"3","key":"2026091609100545100_cit21c","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.scib.2020.08.035","article-title":"Cyclovirobuxine\nD inhibits dengue virus replication by impeding the complete autophagy\nin a cholesterol-dependent manner","volume":"66","author":"Wang","year":"2021","journal-title":"Sci. Bull."},{"issue":"11","key":"2026091609100545100_cit22","doi-asserted-by":"publisher","first-page":"20659","DOI":"10.3390\/molecules201119729","article-title":"Cyclovirobuxine D Inhibits Cell Proliferation\nand Induces Mitochondria-Mediated Apoptosis in Human Gastric Cancer\nCells","volume":"20","author":"Wu","year":"2015","journal-title":"Molecules"},{"issue":"18","key":"2026091609100545100_cit23","doi-asserted-by":"publisher","first-page":"10444","DOI":"10.1111\/jcmm.15657","article-title":"Corilagin\nsuppresses RANKL-induced osteoclastogenesis and inhibits\noestrogen deficiency-induced bone loss via the NF-\u03baB and PI3K\/AKT\nsignalling pathways","volume":"24","author":"Lu","year":"2020","journal-title":"J. Cell. Mol. Med."},{"issue":"40","key":"2026091609100545100_cit24","doi-asserted-by":"publisher","first-page":"31055","DOI":"10.1074\/jbc.M109.079962","article-title":"Foxo1, a novel\nregulator of osteoblast differentiation and skeletogenesis","volume":"285","author":"Teixeira","year":"2010","journal-title":"J. Biol. Chem."},{"issue":"5","key":"2026091609100545100_cit25","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1007\/s00774-019-00997-y","article-title":"miR-142\u20135p promotes the osteoclast\ndifferentiation of bone\nmarrow-derived macrophages via PTEN\/PI3K\/AKT\/FOXO1 pathway","volume":"37","author":"Lou","year":"2019","journal-title":"J. Bone Miner. Metab."},{"issue":"1","key":"2026091609100545100_cit26","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41573-020-0088-2","article-title":"Therapeutic\nstrategies targeting\nFOXO transcription factors","volume":"20","author":"Calissi","year":"2021","journal-title":"Nat. Rev. Drug Discovery"},{"issue":"2","key":"2026091609100545100_cit27a","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/0014-4827(72)90064-X","article-title":"Catalase turnover\nin human diploid cell cultures","volume":"73","author":"Mellman","year":"1972","journal-title":"Exp. Cell Res."},{"issue":"3","key":"2026091609100545100_cit27b","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1161\/01.RES.67.3.636","article-title":"Evidence against\nthe \u201cearly protection-delayed death\u201d hypothesis of superoxide\ndismutase therapy in experimental myocardial infarction. Polyethylene\nglycol-superoxide dismutase plus catalase does not limit myocardial\ninfarct size in dogs","volume":"67","author":"Tanaka","year":"1990","journal-title":"Circ. Res."},{"issue":"1","key":"2026091609100545100_cit27c","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/BF02424575","article-title":"Stability of the anti-oxidative enzymes\nin aqueous and detergent solution","volume":"107","author":"Mailer","year":"1991","journal-title":"Mol. Cell.\nBiochem."},{"issue":"18","key":"2026091609100545100_cit28","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1101\/gad.1102703","article-title":"Transcriptional regulation\nby calcium, calcineurin, and NFAT","volume":"17","author":"Hogan","year":"2003","journal-title":"Genes Dev."},{"issue":"21","key":"2026091609100545100_cit29","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1056\/NEJMcp2307353","article-title":"Postmenopausal Osteoporosis","volume":"389","author":"Walker","year":"2023","journal-title":"N. Engl. J. Med."},{"issue":"5","key":"2026091609100545100_cit30","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3892\/ijmm.2023.5246","article-title":"Casticin suppresses RANKL-induced\nosteoclastogenesis and prevents ovariectomy-induced bone loss by regulating\nthe AKT\/ERK and NF-\u03baB signaling pathways","volume":"51","author":"Yang","year":"2023","journal-title":"Int. J. Mol. Med."},{"key":"2026091609100545100_cit31a","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1146\/annurev-med-052218-020620","article-title":"New Frontiers in Osteoporosis Therapy","volume":"71","author":"Cheng","year":"2020","journal-title":"Annu. Rev. Med."},{"issue":"2","key":"2026091609100545100_cit31b","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1210\/clinem\/dgad496","article-title":"Sequential Therapy for the Long-Term\nTreatment of Postmenopausal Osteoporosis","volume":"109","author":"Ramchand","year":"2024","journal-title":"J.\nClin. Endocrinol. Metab."},{"key":"2026091609100545100_cit32a","doi-asserted-by":"publisher","first-page":"3345","DOI":"10.2147\/IJGM.S416705","article-title":"Use of\nChinese Herbal Medicine Was Related to Lower Risk of Osteoporotic\nFracture in Sarcopenia Patients: Evidence from Population-Based Health\nClaims","volume":"16","author":"Chen","year":"2023","journal-title":"Int. J. Gen Med."},{"issue":"4","key":"2026091609100545100_cit32b","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1007\/s00198-018-4789-x","article-title":"Association\nof use of Chinese herbal medicines and the risk of fracture in patients\nwith osteoporosis: a population-based cohort study","volume":"30","author":"Chen","year":"2019","journal-title":"Osteoporos Int."},{"issue":"9","key":"2026091609100545100_cit33a","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.3109\/13880209.2014.884606","article-title":"Chinese herbal medicine for bone health","volume":"52","author":"Mukwaya","year":"2014","journal-title":"Pharm.\nBiol."},{"issue":"4","key":"2026091609100545100_cit33b","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1142\/S0192415X24500393","article-title":"The Role of Traditional Chinese Medicines in the Treatment\nof Osteoporosis","volume":"52","author":"Wang","year":"2024","journal-title":"Am. J. Chin Med."},{"issue":"4","key":"2026091609100545100_cit34a","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.joca.2020.02.027","article-title":"The PI3K\/AKT\/mTOR signaling pathway\nin osteoarthritis: a narrative review","volume":"28","author":"Sun","year":"2020","journal-title":"Osteoarthritis\nCartilage"},{"issue":"4","key":"2026091609100545100_cit34b","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1302\/2046-3758.104.BJR-2020-0255.R2","article-title":"LY3023414 inhibits both osteogenesis\nand osteoclastogenesis through the PI3K\/Akt\/GSK3 signalling pathway","volume":"10","author":"Chen","year":"2021","journal-title":"Bone Joint Res."},{"issue":"2","key":"2026091609100545100_cit35","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/s41419-024-06521-z","article-title":"Histone demethylase\nKDM7A regulates bone homeostasis\nthrough balancing osteoblast and osteoclast differentiation","volume":"15","author":"Shan","year":"2024","journal-title":"Cell Death Dis."},{"issue":"1","key":"2026091609100545100_cit36","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s11658-024-00614-5","article-title":"New mechanistic understanding\nof osteoclast differentiation\nand bone resorption mediated by P2 \u00d7 7 receptors and PI3K-Akt-GSK3\u03b2\nsignaling","volume":"29","author":"Lu","year":"2024","journal-title":"Cell. Mol. Biol. Lett."},{"issue":"8","key":"2026091609100545100_cit37","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1038\/s12276-022-00820-1","article-title":"Phospholipase D2 controls bone homeostasis\nby modulating\nM-CSF-dependent osteoclastic cell migration and microtubule stability","volume":"54","author":"Kim","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"2026091609100545100_cit38","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.jot.2023.12.007","article-title":"Therapeutic potential of a prominent\ndihydroxyflavanone pinocembrin for osteolytic bone disease: In vitro\nand in vivo evidence","volume":"45","author":"Hong","year":"2024","journal-title":"J. Orthop Translat"},{"issue":"14","key":"2026091609100545100_cit39","doi-asserted-by":"publisher","first-page":"3576","DOI":"10.3390\/ijms20143576","article-title":"Reactive Oxygen Species\nin Osteoclast Differentiation and Possible\nPharmaceutical Targets of ROS-Mediated Osteoclast Diseases","volume":"20","author":"Agidigbi","year":"2019","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"2026091609100545100_cit40","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1080\/15216540601156188","article-title":"Effects of\nreactive oxygen species (ROS) on antioxidant system and osteoblastic\ndifferentiation in MC3T3-E1 cells","volume":"59","author":"Arai","year":"2007","journal-title":"IUBMB Life"},{"issue":"3","key":"2026091609100545100_cit41","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/0304-4165(93)90116-P","article-title":"Participation of oxidative\nstress in the process of osteoclast differentiation","volume":"1157","author":"Suda","year":"1993","journal-title":"Biochim. Biophys. Acta"},{"issue":"4","key":"2026091609100545100_cit42a","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1002\/ptr.8141","article-title":"Cichoric acid targets RANKL to inhibit osteoclastogenesis\nand prevent ovariectomy-induced bone loss","volume":"38","author":"Xian","year":"2024","journal-title":"Phytother.\nRes."},{"key":"2026091609100545100_cit42b","doi-asserted-by":"publisher","first-page":"5982014","DOI":"10.1155\/2022\/5982014","article-title":"A Novel RANKL-Targeted Furoquinoline Alkaloid Ameliorates\nBone Loss in Ovariectomized Osteoporosis through Inhibiting the NF-\u03baB\nSignal Pathway and Reducing Reactive Oxygen Species","volume":"2022","author":"Wong","year":"2022","journal-title":"Oxid. Med. Cell. Longevity"},{"key":"2026091609100545100_cit42c","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.jare.2025.01.027","article-title":"Transcriptional regulation of Rankl by Txnip-Ecd in\naging and diabetic related osteoporosis","volume":"77","author":"Cao","year":"2025","journal-title":"J.\nAdv. Res."},{"issue":"4","key":"2026091609100545100_cit43","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1177\/1535370217746611","article-title":"MiR-145 regulates osteogenic differentiation\nof human adipose-derived mesenchymal stem cells through targeting\nFOXO1","volume":"243","author":"Hao","year":"2018","journal-title":"Exp. Biol. Med."},{"issue":"23","key":"2026091609100545100_cit44","doi-asserted-by":"publisher","first-page":"8969","DOI":"10.1128\/MCB.20.23.8969-8982.2000","article-title":"Forkhead\ntranscription factors are\ncritical effectors of cell death and cell cycle arrest downstream\nof PTEN","volume":"20","author":"Nakamura","year":"2000","journal-title":"Mol. Cell. Biol."},{"issue":"2","key":"2026091609100545100_cit45a","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.cell.2007.01.003","article-title":"FoxOs are critical mediators\nof hematopoietic stem cell resistance to physiologic oxidative stress","volume":"128","author":"Tothova","year":"2007","journal-title":"Cell"},{"issue":"6","key":"2026091609100545100_cit45b","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1089\/ars.2010.3403","article-title":"Forkhead Box O as\na Sensor, Mediator, and Regulator of Redox Signaling. Antioxidants\n& Redox Signaling","volume":"14","author":"de Keizer","year":"2011","journal-title":"Antioxid. Redox Signal"},{"issue":"8","key":"2026091609100545100_cit46","doi-asserted-by":"publisher","first-page":"3409","DOI":"10.1172\/JCI68049","article-title":"FOXOs attenuate bone\nformation by suppressing Wnt signaling","volume":"123","author":"Iyer","year":"2013","journal-title":"J. Clin.\nInvest."},{"key":"2026091609100545100_cit47a","doi-asserted-by":"publisher","first-page":"101309","DOI":"10.1016\/j.redox.2019.101309","article-title":"The Nrf2\nactivator RTA-408 attenuates osteoclastogenesis by inhibiting STING\ndependent NF-\u03bab signaling","volume":"28","author":"Sun","year":"2020","journal-title":"Redox Biol."},{"key":"2026091609100545100_cit47b","doi-asserted-by":"publisher","first-page":"104482","DOI":"10.1016\/j.fitote.2020.104482","article-title":"A review on\nosteoclast diseases and osteoclastogenesis inhibitors recently developed\nfrom natural resources","volume":"142","author":"Wang","year":"2020","journal-title":"Fitoterapia"},{"issue":"1","key":"2026091609100545100_cit47c","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00198-021-06095-y","article-title":"A systematic review\nand meta-analysis of efficacy and safety of Romosozumab in postmenopausal\nosteoporosis","volume":"33","author":"Singh","year":"2022","journal-title":"Osteoporos Int."},{"issue":"15","key":"2026091609100545100_cit47d","doi-asserted-by":"publisher","first-page":"4461","DOI":"10.7150\/thno.35219","article-title":"Vitamin C kills thyroid cancer cells through ROS-dependent inhibition\nof MAPK\/ERK and PI3K\/AKT pathways via distinct mechanisms","volume":"9","author":"Su","year":"2019","journal-title":"Theranostics"},{"issue":"7","key":"2026091609100545100_cit48a","doi-asserted-by":"publisher","first-page":"2530","DOI":"10.1172\/JCI94606","article-title":"The many ways of osteoclast activation","volume":"127","author":"Lorenzo","year":"2017","journal-title":"J. Clin. Invest."},{"issue":"26","key":"2026091609100545100_cit48b","doi-asserted-by":"publisher","first-page":"24233","DOI":"10.1074\/jbc.M212389200","article-title":"Hydrogen peroxide activates NF-kappa\nB through tyrosine phosphorylation of I kappa B alpha and serine phosphorylation\nof p65: evidence for the involvement of I kappa B alpha kinase and\nSyk protein-tyrosine kinase","volume":"278","author":"Takada","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2026091609100545100_cit49a","doi-asserted-by":"publisher","first-page":"925848","DOI":"10.3389\/fendo.2022.925848","article-title":"N-Butanol Extract of\nModified You-Gui-Yin Attenuates Osteoclastogenesis and Ameliorates\nOsteoporosis by Inhibiting RANKL-Mediated NF-\u03baB Signaling","volume":"13","author":"Zeng","year":"2022","journal-title":"Front. Endocrinol."},{"issue":"21","key":"2026091609100545100_cit49b","doi-asserted-by":"publisher","first-page":"10126","DOI":"10.1111\/jcmm.16949","article-title":"Bisphosphonate-enoxacin inhibit osteoclast formation\nand function by abrogating RANKL-induced JNK signalling pathways during\nosteoporosis treatment","volume":"25","author":"Xu","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"2026091609100545100_cit49c","doi-asserted-by":"publisher","first-page":"107459","DOI":"10.1016\/j.intimp.2021.107459","article-title":"Inhibitory effect of\nacetyl-11-keto-\u03b2-boswellic acid on titanium particle-induced\nbone loss by abrogating osteoclast formation and downregulating the\nERK signaling pathway","volume":"94","author":"Shi","year":"2021","journal-title":"Int. Immunopharmacol."},{"issue":"8","key":"2026091609100545100_cit49d","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1002\/jbmr.4095","article-title":"The Novel p38 Inhibitor, Pamapimod, Inhibits Osteoclastogenesis\nand Counteracts Estrogen-Dependent Bone Loss in Mice","volume":"35","author":"Zhao","year":"2020","journal-title":"J. Bone Miner. Res."},{"issue":"1","key":"2026091609100545100_cit49e","doi-asserted-by":"publisher","first-page":"34","DOI":"10.14348\/molcells.2019.0232","article-title":"Rev-erb\u03b1 Negatively Regulates Osteoclast and Osteoblast Differentiation\nthrough p38 MAPK Signaling Pathway","volume":"43","author":"Kim","year":"2020","journal-title":"Mol. Cells"},{"issue":"10","key":"2026091609100545100_cit50a","doi-asserted-by":"publisher","first-page":"3646","DOI":"10.3390\/ijms21103646","article-title":"The Role of Ca(2+)-NFATc1 Signaling\nand Its Modulation on Osteoclastogenesis","volume":"21","author":"Kang","year":"2020","journal-title":"Int.\nJ. Mol. Sci."},{"key":"2026091609100545100_cit50b","doi-asserted-by":"publisher","first-page":"110747","DOI":"10.1016\/j.biopha.2020.110747","article-title":"Beneficial effect of 2\u2019-acetylacteoside on ovariectomized\nmice via modulating the function of bone resorption","volume":"131","author":"Li","year":"2020","journal-title":"Biomed. Pharmacother."},{"issue":"4","key":"2026091609100545100_cit50c","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s00418-018-1636-2","article-title":"Recent advances\nin osteoclast biology","volume":"149","author":"Ono","year":"2018","journal-title":"Histochem. Cell Biol."},{"issue":"23","key":"2026091609100545100_cit50d","doi-asserted-by":"publisher","first-page":"8965","DOI":"10.3390\/ijms21238965","article-title":"Long-Lasting Activity of ERK Kinase\nDepends on NFATc1 Induction and Is Involved in Cell Migration-Fusion\nin Murine Macrophages RAW264.7","volume":"21","author":"Russo","year":"2020","journal-title":"Int. J. Mol.\nSci."},{"issue":"11","key":"2026091609100545100_cit51","doi-asserted-by":"publisher","first-page":"3775","DOI":"10.1172\/JCI35711","article-title":"NFATc1\nin mice represses osteoprotegerin during osteoclastogenesis and dissociates\nsystemic osteopenia from inflammation in cherubism","volume":"118","author":"Aliprantis","year":"2008","journal-title":"J. Clin. Invest."},{"issue":"9","key":"2026091609100545100_cit52","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1084\/jem.20051150","article-title":"Autoamplification\nof NFATc1 expression determines\nits essential role in bone homeostasis","volume":"202","author":"Asagiri","year":"2005","journal-title":"J. Exp.\nMed."},{"issue":"7","key":"2026091609100545100_cit53","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.3390\/ph18071029","article-title":"The Cellular and Mitochondrial Consequences of Mevalonate\nPathway Inhibition by Nitrogen-Containing Bisphosphonates: A Narrative\nReview","volume":"18","author":"Budzinska","year":"2025","journal-title":"Pharmaceuticals"},{"key":"2026091609100545100_cit54a","doi-asserted-by":"publisher","first-page":"1538472","DOI":"10.3389\/fmolb.2025.1538472","article-title":"FOXOs and their roles\nin acute and chronic neurological disorders","volume":"12","author":"Asadi","year":"2025","journal-title":"Front. Mol. Biosci."},{"issue":"15","key":"2026091609100545100_cit54b","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.3390\/cells14151183","article-title":"Specific Low\/Endogenous\nReplication Stress Response Protects Genomic Stability via Controlled\nROS Production in an Adaptive Way and Is Dysregulated in Transformed\nCells","volume":"14","author":"Lopez","year":"2025","journal-title":"Cells"}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c01670","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/36\/28408\/68188418\/acs.jafc.6c01670.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/36\/28408\/68188418\/acs.jafc.6c01670.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:33:48Z","timestamp":1789565628000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/36\/28408\/5404687\/Cyclovirobuxine-Prevents-Osteoclastogenesis-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":79,"journal-issue":{"issue":"36","published-online":{"date-parts":[[2026,9,2]]},"published-print":{"date-parts":[[2026,9,16]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c01670","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,2]]}}}