{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:13:47Z","timestamp":1793056427181,"version":"4.5.0"},"reference-count":132,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"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","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017956","name":"Health Commission of Gansu Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017956","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Osteoporosis (OP) is a chronic metabolic bone disorder marked by reduced bone mass, damaged microarchitecture, and increased skeletal fragility. Its pathogenesis is complicated, and the central mechanism involves an imbalance between osteoblastic bone formation and osteoclastic bone resorption, together with several pathological processes, including excessive oxidative stress, persistent inflammatory infiltration, and abnormal apoptosis. The Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), Nuclear Factor-\u03baB (NF-\u03baB), and Mitogen-Activated Protein Kinase (MAPK) pathways are important signaling networks controlling bone metabolism, oxidative stress, and inflammation. These pathways interact through upstream and downstream regulatory molecules. They establish complex regulatory networks through molecular interactions and crosstalk, collectively promoting the initiation and progression of OP. Traditional Chinese medicine (TCM), based on the holistic concept and \u201csyndrome differentiation and treatment,\u201d shows promising clinical value in OP prevention and therapy because of its characteristic multi-target, multi-pathway actions and low toxicity. Extensive pharmacological evidence has confirmed that individual TCM compounds can specifically regulate the Nrf2\/NF-\u03baB pathways. By modulating redox homeostasis, inhibiting inflammatory responses, and regulating osteocyte proliferation, differentiation, and apoptosis, these compounds restore bone metabolic equilibrium and produce anti-OP effects. Current reviews mostly focus on individual signaling pathway or single herbal component, lacking systematic sorting of the cross-talk among Nrf2, NF-\u03baB and MAPK networks. This article systematically reviews the major roles of the Nrf2, NF-\u03baB, and MAPK pathways in osteoporosis and discusses the anti-osteoporotic mechanisms of Chinese herbal monomers, thereby providing a theoretical foundation for TCM intervention. Furthermore, it highlights syndrome differentiation and personalized treatment to overcome the limitations of basic research and clarify future clinical translation.<\/jats:p>","DOI":"10.3389\/fendo.2026.1789264","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:49:37Z","timestamp":1782276577000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Research progress on the intervention of osteoporosis by Chinese herbal monomers based on the Nrf2\/NF-\u03baB\/MAPK pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Wenjie","family":"Kou","sequence":"first","affiliation":[{"name":"Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglong","family":"Guo","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Lu","sequence":"additional","affiliation":[{"name":"Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiwen","family":"Liu","sequence":"additional","affiliation":[{"name":"Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxiang","family":"Ma","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jishu","family":"Li","sequence":"additional","affiliation":[{"name":"Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiandong","family":"Gao","sequence":"additional","affiliation":[{"name":"Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linzhong","family":"Cao","sequence":"additional","affiliation":[{"name":"Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]},{"name":"Affiliated Hospital of Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Gansu University of Traditional Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"B1","article-title":"Public guidelines for osteoporosis risk management in Chinese population, (2024)","volume":"17","author":"Yuan","year":"2024","journal-title":"Chin J Osteoporosis. Bone Mineral. Res"},{"key":"B2","first-page":"92","article-title":"Osteoporosis: A review of treatment options","volume":"43","author":"Tu","year":"2018","journal-title":"P. T. A. Peer-Review. J For. Formul. Manage"},{"key":"B3","first-page":"985","article-title":"Expert consensus on rational application of anti-osteoporosis drugs, (2023)","volume":"44","author":"Zhang","year":"2024","journal-title":"Chin J Osteoporosis. Bone Mineral. Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1142\/9789812701220_0019","article-title":"Expert consensus on traditional Chinese medicine prevention and treatment of primary osteoporosis, (2025)","volume":"26","author":"Ge","year":"","journal-title":"Chin J Osteoporosis. Bone Mineral. Res"},{"key":"B5","article-title":"Research progress on kidney-tonifying traditional Chinese medicine for articular cartilage injury based on theory of kidney governing bone and generating marrow","volume":"60","author":"Song","year":"2025","journal-title":"Chin Pharm J"},{"key":"B6","article-title":"Research progress on traditional Chinese medicine regulating oxidative stress to prevent and treat osteoporosis","volume":"31","author":"Yang","year":"2025","journal-title":"Exp Trad. Med Formulae"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-025-01985-7","article-title":"Nrf2 signaling in bone health: Unlocking new avenues for osteoporosis management","volume":"33","author":"Lavhale","year":"2025","journal-title":"Inflammopharmacology"},{"key":"B8","article-title":"Research progress of traditional Chinese medicine in regulating Nrf2 signaling pathway to intervene ulcerative colitis","volume":"31","author":"Deng","year":"2025","journal-title":"Chin J Exp Trad. Med Formulae"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.24.16.7130-7139.2004","article-title":"Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2","volume":"24","author":"Kobayashi","year":"2004","journal-title":"Mol Cell Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.113820","article-title":"Curcumin induces stabilization of Nrf2 protein through Keap1 cysteine modification","volume":"173","author":"Shin","year":"2020","journal-title":"Biochem Pharmacol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.120111","article-title":"Nrf2\/Keap1\/ARE signaling: Towards specific regulation","volume":"291","author":"Ulasov","year":"2022","journal-title":"Life Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/cells10030515","article-title":"Heme Oxgenase-1, a cardinal modulator of regulated cell death and inflammation","volume":"10","author":"Ryter","year":"2021","journal-title":"Cells"},{"key":"B13","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41413-020-00128-8","article-title":"Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis","volume":"9","author":"Chen","year":"2021","journal-title":"Bone Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41419-023-05595-5","article-title":"PINK1\/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products","volume":"14","author":"Li","year":"2023","journal-title":"Cell Death Dis"},{"key":"B15","article-title":"Effect of reactive oxygen species (ROS) on bone destruction in rheumatoid arthritis","volume":"37","author":"Guo","year":"2021","journal-title":"Chin J Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222413458","article-title":"Conditioned medium from bone marrow mesenchymal stem cells restored oxidative stress-related impaired osteogenic differentiation","volume":"22","author":"Saleem","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B17","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1186\/s13018-023-04125-5","article-title":"Geniposide suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2\/NF-\u03baB signaling pathway","volume":"18","author":"Xiao","year":"2023","journal-title":"J Orthopaedic. Surg Res"},{"key":"B18","article-title":"Curculigoside phenol gentian glycoside from Curculigo orchioides regulates NF-\u03baB\/Nrf2 pathway to inhibit osteoclast oxidative stress and bone resorption","volume":"55","author":"Li","year":"2024","journal-title":"Chin Trad. Herbal. Drugs"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e25601","article-title":"Garcinone C attenuates RANKL-induced osteoclast differentiation and oxidative stress by activating Nrf2\/HO-1 and inhibiting the NF-kB signaling pathway","volume":"10","author":"Ji","year":"2024","journal-title":"Heliyon"},{"key":"B20","article-title":"Mechanism of total flavonoids of Drynaria fortunei in regulating ferroptosis and osteogenic differentiation of BMSCs via Nrf2 signaling pathway","volume":"31","author":"Li","year":"2025","journal-title":"Chin J Osteoporosis"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.028266","article-title":"Nuclear factor (NF)-kappaB proteins: Therapeutic targets","author":"Verma","year":"2004","journal-title":"Ann Rheumatic. Dis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1134661","article-title":"NF-\u03baB in monocytes and macrophages - an inflammatory master regulator in multitalented immune cells","volume":"14","author":"Mussbacher","year":"2023","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2016.01.001","article-title":"Binding of NF\u03baB appears to twist the ankyrin repeat domain of I\u03baB\u03b1","volume":"110","author":"Trelle","year":"2016","journal-title":"Biophys J"},{"key":"B24","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/bs.ircmb.2020.10.006","article-title":"The many-sided contributions of NF-\u03baB to T-cell biology in health and disease","volume":"361","author":"Voisin","year":"2021","journal-title":"Int Rev Cell Mol Biol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1646","article-title":"The noncanonical NF\u03baB pathway: Regulatory mechanisms in health and disease","volume":"16","author":"Rodriguez","year":"2024","journal-title":"WIREs. Mech Dis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.171962","article-title":"Anti-NF-\u03baB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice","volume":"8","author":"Takami","year":"2023","journal-title":"JCI Insight"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1172\/jci90527","article-title":"RANKL coordinates multiple osteoclastogenic pathways by regulating expression of ubiquitin ligase RNF146","volume":"127","author":"Matsumoto","year":"2017","journal-title":"J Clin Invest"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3803\/enm.2023.501","article-title":"Nuclear factor-kappa B regulation of osteoclastogenesis and osteoblastogenesis","volume":"38","author":"Boyce","year":"2023","journal-title":"Endocrinol Metab (Seoul. Kor)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13535","article-title":"IKK\/NF-\u03baB and ROS signal axes are involved in Tenacissoside H mediated inhibitory effects on LPS-induced inflammatory osteolysis","volume":"57","author":"Xie","year":"2024","journal-title":"Cell Proliferat"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2108","article-title":"NF-\u03baB RelB negatively regulates osteoblast differentiation and bone formation","volume":"29","author":"Yao","year":"2014","journal-title":"J Bone Mineral. Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091421","article-title":"Constitutive activation of IKK2\/NF-\u03baB impairs osteogenesis and skeletal development","volume":"9","author":"Swarnkar","year":"2014","journal-title":"PloS One"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.5483\/bmbrep.2023-0054","article-title":"Boeravinone B, a natural rotenoid, inhibits osteoclast differentiation through modulating NF-\u03baB, MAPK and PI3K\/Akt signaling pathways","volume":"56","author":"Piao","year":"2023","journal-title":"BMB. Rep"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1109296","article-title":"Effect of Bifidobacterium on osteoclasts: TNF-\u03b1\/NF-\u03baB inflammatory signal pathway-mediated mechanism","volume":"14","author":"Wu","year":"2023","journal-title":"Front Endocrinol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.581545","article-title":"Extracellular vesicle-encapsulated miR-29b-3p released from bone marrow-derived mesenchymal stem cells underpins osteogenic differentiation","volume":"8","author":"Zhang","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B35","article-title":"Activation of ROS\/MAPKs\/NF-\u03baB\/NLRP3 and inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis","volume":"33","author":"An","year":"2019","journal-title":"FASEB J Off Publ Fed Am Societ. For. Exp Biol"},{"key":"B36","article-title":"MAPK signaling pathway: A new therapeutic target for hepatic echinococcosis","volume":"38","author":"Dong","year":"2022","journal-title":"J Clin Hepatol"},{"key":"B37","first-page":"16","article-title":"Research progress on the mechanism of Nemo-like kinase in development and diseases","volume":"38","author":"Wang","year":"2025","journal-title":"Acta Med. Sin"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109541","article-title":"The road to ERK activation: Do neurons take alternate routes","volume":"68","author":"Miningou","year":"2020","journal-title":"Cell Signall"},{"key":"B39","article-title":"Osteogenic response of mesenchymal stem cells to continuous mechanical strain is dependent on ERK1\/2-Runx2 signaling","volume":"29","author":"Zhang","year":"2012","journal-title":"Int J Mol Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2017.1397177","article-title":"Sika pilose antler type I collagen promotes BMSC differentiation via the ERK1\/2 and p38-MAPK signal pathways","volume":"55","author":"Wang","year":"2017","journal-title":"Pharm Biol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.7.1198","article-title":"Role of osteoclast extracellular signal-regulated kinase (ERK) in cell survival and maintenance of cell polarity","volume":"18","author":"Nakamura","year":"2003","journal-title":"J Bone Mineral. Res"},{"key":"B42","doi-asserted-by":"publisher","first-page":"4594","DOI":"10.1038\/s41598-025-88658-1","article-title":"FoxA1 knockdown promotes BMSC osteogenesis in part by activating the ERK1\/2 signaling pathway and preventing ovariectomy-induced bone loss","volume":"15","author":"Li","year":"2025","journal-title":"Sci Rep"},{"key":"B43","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.pep.2012.10.010","article-title":"High yield purification of JNK1\u03b21 and activation by in vitro reconstitution of the MEKK1\u2192MKK4\u2192JNK MAPK phosphorylation cascade","volume":"87","author":"Owen","year":"2013","journal-title":"Protein Expression Purif"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.1002\/hep.28486","article-title":"c-Jun N-terminal kinase mediates mouse liver injury through a novel Sab (SH3BP5)-dependent pathway leading to inactivation of intramitochondrial Src","volume":"63","author":"Win","year":"2016","journal-title":"Hepatol (Balt. Md)"},{"key":"B45","doi-asserted-by":"publisher","first-page":"61","DOI":"10.2147\/dddt.s283694","article-title":"Pristimerin protects against OVX-mediated bone loss by attenuating osteoclast formation and activity via inhibition of RANKL-mediated activation of NF-\u03baB and ERK signaling pathways","volume":"15","author":"Li","year":"2021","journal-title":"Drug Des Dev Ther"},{"key":"B46","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3892\/mmr.2021.12575","article-title":"Zoledronic acid inhibits osteoclastogenesis and bone resorptive function by suppressing RANKL-mediated NF-\u03baB and JNK and their downstream signalling pathways","volume":"25","author":"Huang","year":"2022","journal-title":"Mol Med Rep"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-019-01035-6","article-title":"MAPKAP kinase 2-mediated phosphorylation of HspA1L protects male germ cells from heat stress-induced apoptosis","volume":"24","author":"Williams","year":"2019","journal-title":"Cell Stress Chaperones"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-0983-8","article-title":"The p38\u03b1 MAPK positively regulates osteoblast function and postnatal bone acquisition","volume":"69","author":"Thouverey","year":"2012","journal-title":"Cell Mol Life Sci.: CMLS"},{"key":"B49","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1186\/s13018-022-03349-1","article-title":"ENPP1 deletion causes mouse osteoporosis via the MKK3\/p38 MAPK\/PCNA signaling pathway","volume":"17","author":"Wang","year":"2022","journal-title":"J Orthopaedic. Surg Res"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116571","article-title":"Restoring bone-fat equilibrium: Baicalin's impact on P38 MAPK pathway for treating diabetic osteoporosis","volume":"175","author":"Qin","year":"2024","journal-title":"Biomed. Pharmacother. = Biomed. Pharmacother"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e09-03-0211","article-title":"REDOX reaction at ASK1-Cys250 is essential for activation of JNK and induction of apoptosis","volume":"20","author":"Nadeau","year":"2009","journal-title":"Mol Biol Cell"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12020274","article-title":"Stress activated MAP kinases and cyclin-dependent kinase 5 mediate nuclear translocation of Nrf2 via Hsp90\u03b1-Pin1-dynein motor transport machinery","volume":"12","author":"Ishii","year":"2023","journal-title":"Antioxid. (Basel. Switzerl)"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11091765","article-title":"The activation of Nrf2\/HO-1 by 8-Epi-7-deoxyloganic acid attenuates inflammatory symptoms through the suppression of the MAPK\/NF-\u03baB signaling cascade in in vitro and in vivo models","volume":"11","author":"Simu","year":"2022","journal-title":"Antioxid. (Basel. Switzerl)"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1155\/sci\/7214250","article-title":"Imbalance of bone homeostasis caused by Nrf2 deficiency leads to bone loss in OVX rats","volume":"2025","author":"Sun","year":"2025","journal-title":"Stem Cells Int"},{"key":"B55","doi-asserted-by":"publisher","first-page":"502","DOI":"10.3892\/etm.2021.9933","article-title":"Increased sensitivity to TNF-\u03b1 promotes keloid fibroblast hyperproliferation by activating the NF-\u03baB, JNK and p38 MAPK pathways","volume":"21","author":"Li","year":"2021","journal-title":"Exp Ther Med"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.03.013","article-title":"Regulation of Nrf2 signaling pathway in heart failure: Role of extracellular vesicles and non-coding RNAs","volume":"167","author":"Tian","year":"2021","journal-title":"Free Radical Biol Med"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27773","article-title":"Biogenic nanoselenium particles activate Nrf2-ARE pathway by phosphorylating p38, ERK1\/2, and AKT on IPEC-J2 cells","volume":"234","author":"Xiao","year":"2019","journal-title":"J Cell Physiol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.809952","article-title":"Dissecting the crosstalk between Nrf2 and NF-\u03baB response pathways in drug-induced toxicity","volume":"9","author":"Gao","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"B59","first-page":"25","article-title":"Lignans and flavonoids from Drynaria fortunei","volume":"42","author":"Liang","year":"2011","journal-title":"Trad. Herbal. Drugs"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1443235","article-title":"Effects of total flavonoids of Rhizoma Drynariae on biochemical indicators of bone metabolism: A systematic review and meta-analysis","volume":"15","author":"Li","year":"2024","journal-title":"Front Pharmacol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1017\/s0007114512005405","article-title":"Drynaria fortunei-derived total flavonoid fraction and isolated compounds exert oestrogen-like protective effects in bone","volume":"110","author":"Wong","year":"2013","journal-title":"Br J Nutr"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22071033","article-title":"Total flavonoids of Drynariae rhizoma prevent bone loss induced by hindlimb unloading in rats","volume":"22","author":"Song","year":"2017","journal-title":"Molecule. (Basel. Switzerl)"},{"key":"B63","article-title":"Research progress of quercetin in organ ischemia-reperfusion injury","volume":"29","author":"Yu","year":"2025","journal-title":"Front Pharm Sci"},{"key":"B64","first-page":"78","article-title":"Mechanism of quercetin in regulating Nrf2\/HO-1 signaling pathway to antagonize oxidative stress","volume":"35","author":"Yu","year":"2023","journal-title":"J Jiangxi. Univ Trad. Chin Med"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1080\/14786419.2014.980252","article-title":"Protection by the flavonoids quercetin and luteolin against peroxide- or menadione-induced oxidative stress in MC3T3-E1 osteoblast cells","volume":"29","author":"Fatokun","year":"2015","journal-title":"Nat Prod. Res"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176448","article-title":"Quercetin as an agent for protecting the bone: A review of the current evidence","volume":"21","author":"Wong","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B67","article-title":"Quercetin alleviates estrogen deficiency-induced osteoporosis through anti-senescence effect on bone cells","volume":"40","author":"Gu","year":"2019","journal-title":"J Tongji. Univ (Med. Sci)"},{"key":"B68","article-title":"Research progress on the mechanism and signaling pathway of active components of Epimedium in preventing and treating osteoporotic fracture","volume":"22","author":"Wang","year":"2025","journal-title":"China Med Herald"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2025.1675160","article-title":"The efficacy and safety of Epimedium in the treatment of primary osteoporosis: a systematic review and meta-analysis","volume":"12","author":"Zhang","year":"2025","journal-title":"Front Med"},{"key":"B70","first-page":"915","article-title":"Protective effect of icariin on osteoporosis in ovariectomized rats and its mechanism","volume":"42","author":"Zhu","year":"2016","journal-title":"J Jilin. Univ (Med. Ed)"},{"key":"B71","article-title":"Icariin attenuates DNA damage of testicular germ cells in natural aging rats by activating Nrf2\/HO-1 signaling pathway","volume":"50","author":"You","year":"2019","journal-title":"Chin Trad. Herbal. Drugs"},{"key":"B72","article-title":"Dioscin stimulates differentiation of mesenchymal stem cells towards hypertrophic chondrocytes in vitro and endochondral ossification in vivo","volume":"8","author":"You","year":"2016","journal-title":"Am J Trans Res"},{"key":"B73","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1186\/s13018-024-04933-3","article-title":"The SPI1\/SMAD5 cascade in the promoting effect of icariin on osteogenic differentiation of MC3T3-E1 cells: a mechanism study","volume":"19","author":"Zhang","year":"2024","journal-title":"J Orthopaedic. Surg Res"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.176244","article-title":"Icariin inhibits osteoblast ferroptosis via Nrf2\/HO-1 signaling and enhances healing of osteoporotic fractures","volume":"965","author":"Xiang","year":"2024","journal-title":"Eur J Pharmacol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.5c08170","article-title":"A comprehensive review of medicarpin: A phytoalexin with therapeutic potential","volume":"10","author":"Tanimoto","year":"2025","journal-title":"ACS Omega"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.05.016","article-title":"Medicarpin inhibits osteoclastogenesis and has nonestrogenic bone conserving effect in ovariectomized mice","volume":"325","author":"Tyagi","year":"2010","journal-title":"Mol Cell Endocrinol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2015.04.023","article-title":"9-demethoxy-medicarpin promotes peak bone mass achievement and has bone conserving effect in ovariectomized mice: Positively regulates osteoblast functions and suppresses osteoclastogenesis","volume":"411","author":"Goel","year":"2015","journal-title":"Mol Cell Endocrinol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.s227738","article-title":"The osteoprotective effects of kaempferol: The evidence from in vivo and in vitro studies","volume":"13","author":"Wong","year":"2019","journal-title":"Drug Des Dev Ther"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2011.04.031","article-title":"Kaempferol protects MC3T3-E1 cells through antioxidant effect and regulation of mitochondrial function","volume":"49","author":"Choi","year":"2011","journal-title":"Food Chem Toxicol Int J Publish. For. Br Ind Biol Res Assoc"},{"key":"B80","doi-asserted-by":"publisher","first-page":"6269","DOI":"10.1038\/s41598-026-37688-4","article-title":"Kaempferol inhibits osteoclast differentiation and bone resorption by targeting the TNF-\u03b1\/NF-\u03baB and SRC\/PI3K\/AKT signaling pathways","volume":"16","author":"Yu","year":"2026","journal-title":"Sci Rep"},{"key":"B81","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1186\/s13018-024-05174-0","article-title":"Kaempferol promotes osteogenic differentiation in bone marrow mesenchymal stem cells by inhibiting CAV-1","volume":"19","author":"Li","year":"2024","journal-title":"J Orthopaedic. Surg Res"},{"key":"B82","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.mce.2008.02.027","article-title":"Kaempferol has osteogenic effect in ovariectomized adult Sprague-Dawley rats","volume":"289","author":"Trivedi","year":"2008","journal-title":"Mol Cell Endocrinol"},{"key":"B83","article-title":"Mechanism by which terpenoid herbal monomers prevent osteoporosis by regulating nuclear factor-kappaB signaling pathway","volume":"28","author":"Pan","year":"2024","journal-title":"Chin J Tissue Eng Res"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.3390\/nu10020247","article-title":"Oleanolic acid exerts osteoprotective effects and modulates vitamin D metabolism","volume":"10","author":"Cao","year":"2018","journal-title":"Nutrients"},{"key":"B85","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jphs.2018.03.007","article-title":"Oleanolic acid exerts bone protective effects in ovariectomized mice by inhibiting osteoclastogenesis","volume":"137","author":"Zhao","year":"2018","journal-title":"J Pharmacol Sci"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24214002","article-title":"Oleanolic acid acetate exerts anti-inflammatory activity via IKK\u03b1\/\u03b2 suppression in TLR3-mediated NF-\u03baB activation","volume":"24","author":"Lim","year":"2019","journal-title":"Molecule. (Basel. Switzerl)"},{"key":"B87","article-title":"Role and mechanism of oleanolic acid in inhibiting bone loss of ovariectomized mice via gut microbiot","volume":"34","author":"Ma","year":"2023","journal-title":"Hainan. Med J"},{"key":"B88","article-title":"Effect of local administration of oleanolic acid on fracture healing in ovariectomized mice","volume":"27","author":"Chen","year":"2021","journal-title":"Chin J Osteoporosis"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109752","article-title":"Oleanolic acid inhibits mouse spinal cord injury through suppressing inflammation and apoptosis via the blockage of p38 and JNK MAPKs","volume":"123","author":"Wang","year":"2020","journal-title":"Biomed. Pharmacother. = Biomed. Pharmacother"},{"key":"B90","article-title":"Research progress on pharmacological effects and mechanism of dioscin","volume":"42","author":"Tan","year":"2024","journal-title":"Chin Arch Trad. Chin Med"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110342","article-title":"Effects of diosgenin on the skeletal system in rats with experimental type 1 diabetes","volume":"129","author":"Londzin","year":"2020","journal-title":"Biomed. Pharmacother. = Biomed. Pharmacother"},{"key":"B92","first-page":"46","article-title":"Research progress on anti-inflammatory mechanism of dioscin","volume":"22","author":"Lai","year":"2025","journal-title":"China Med Herald"},{"key":"B93","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.phrs.2016.05.003","article-title":"Dioscin reduces ovariectomy-induced bone loss by enhancing osteoblastogenesis and inhibiting osteoclastogenesis","volume":"108","author":"Tao","year":"2016","journal-title":"Pharmacol Res"},{"key":"B94","article-title":"Effect and mechanism of dioscin on apoptosis of human colon cancer cells","volume":"28","author":"Guang","year":"2022","journal-title":"J Tianjin. Med Univ"},{"key":"B95","article-title":"Research progress on pharmacological effects of ginsenoside Rg1 in recent 5 years","volume":"23","author":"Wang","year":"2025","journal-title":"Chin Med Mod. Dist. Educ China"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1411354","article-title":"Ginsenoside Rg1 reduces oxidative stress via Nrf2 activation to regulate age-related mesenchymal stem cells fate switch between osteoblasts and adipocytes","volume":"2022","author":"Hou","year":"2022","journal-title":"Evidence-Based Complement. Altern Med ECAM"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/2365814","article-title":"Ginsenoside Rg1 improves differentiation by inhibiting senescence of human bone marrow mesenchymal stem cell via GSK-3\u03b2 and \u03b2-catenin","volume":"2020","author":"Wang","year":"2020","journal-title":"Stem Cells Int"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/305071","article-title":"The study of mechanisms of protective effect of Rg1 against arthritis by inhibiting osteoclast differentiation and maturation in CIA mice","volume":"2014","author":"Gu","year":"2014","journal-title":"Mediators Inflammation"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1483431","article-title":"Salvia miltiorrhiza in osteoporosis: A review of its phytochemistry, traditional clinical uses and preclinical studies, (2014-2024)","volume":"15","author":"Wang","year":"2024","journal-title":"Front Pharmacol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3390\/dj13070309","article-title":"Therapeutic potential of tanshinones in osteolytic diseases: From molecular and cellular pathways to preclinical models","volume":"13","author":"de Molon","year":"2025","journal-title":"Dentistry. J"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2015.08.003","article-title":"Blockade of TNF-\u03b1-induced NF-\u03baB signaling pathway and anti-cancer therapeutic response of dihydrotanshinone I","volume":"28","author":"Wang","year":"2015","journal-title":"Int Immunopharmacol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110572","article-title":"Dihydrotanshinone I attenuates estrogen-deficiency bone loss through RANKL-stimulated NF-\u03baB, ERK and NFATc1 signaling pathways","volume":"123","author":"Ma","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.920435","article-title":"Andrographolide, a natural anti-inflammatory agent: An update","volume":"13","author":"Li","year":"2022","journal-title":"Front Pharmacol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12463","article-title":"Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo","volume":"171","author":"Zhai","year":"2014","journal-title":"Br J Pharmacol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1159\/000430196","article-title":"Andrographolide exerts pro-osteogenic effect by activation of Wnt\/\u03b2-catenin signaling pathway in vitro","volume":"36","author":"Jiang","year":"2015","journal-title":"Cell Physiol Biochem Int J Exp Cell Physiol. Biochem. Pharmacol"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161126039","article-title":"Andrographolide inhibits ovariectomy-induced bone loss via the suppression of RANKL signaling pathways","volume":"16","author":"Wang","year":"2015","journal-title":"Int J Mol Sci"},{"key":"B107","article-title":"Research progress on mechanism of anti-osteoporosis effective components of Astragalus membranaceus","volume":"54","author":"Liu","year":"2023","journal-title":"Chin Trad. Herbal. Drugs"},{"key":"B108","article-title":"Mechanism of astragalus polysaccharide in protecting osteoblast function in ovariectomized rats","volume":"50","author":"Zuo","year":"2022","journal-title":"Tianjin. Med J"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16683","article-title":"Astragalus polysaccharide attenuates LPS-related inflammatory osteolysis by suppressing osteoclastogenesis by reducing the MAPK signalling pathway","volume":"25","author":"Yang","year":"2021","journal-title":"J Cell Mol Med"},{"key":"B110","first-page":"35","article-title":"Astragalus polysaccharide promotes osteoblast proliferation in rats with glucocorticoid-induced osteoporosis through PI3K\/AKT\/mTOR pathway","volume":"29","author":"Kong","year":"2023","journal-title":"Chin J Osteoporosis"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26882","article-title":"Cistanche deserticola polysaccharide attenuates osteoclastogenesis and bone resorption via inhibiting RANKL signaling and reactive oxygen species production","volume":"233","author":"Song","year":"2018","journal-title":"J Cell Physiol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.113899","article-title":"Total glycosides and polysaccharides of Cistanche deserticola prevent osteoporosis by activating Wnt\/\u03b2-catenin signaling pathway in SAMP6 mice","volume":"271","author":"Wang","year":"2021","journal-title":"J Ethnopharmacol"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.b2200213","article-title":"Lyciumbarbarum polysaccharides ameliorate canine acute liver injury by reducing oxidative stress, protecting mitochondrial function, and regulating metabolic pathways","volume":"24","author":"Huang","year":"2023","journal-title":"J Zhejiang. Univ Sci B"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/4615745","article-title":"A systematic review of potential therapeutic use of Lycium barbarum polysaccharides in disease","volume":"2019","author":"Kwok","year":"2019","journal-title":"BioMed Res Int"},{"key":"B115","doi-asserted-by":"publisher","first-page":"20241104","DOI":"10.1515\/med-2024-1104","article-title":"Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis","volume":"20","author":"Wang","year":"2025","journal-title":"Open Med (Warsaw. Poland)"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.29219\/fnr.v64.4208","article-title":"Lycium barbarum polysaccharide (LBP) inhibits palmitic acid (PA)-induced MC3T3-E1 cell apoptosis by regulating miR-200b-3p\/Chrdl1\/PPAR\u03b3","volume":"64","author":"Jing","year":"2020","journal-title":"Food Nutr Res"},{"key":"B117","article-title":"Research status of pharmacological effects and mechanism of berberine","volume":"37","author":"Yu","year":"2020","journal-title":"Chin J Mod. Appl Pharm"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-009-0141-z","article-title":"Hop rho iso-alpha acids, berberine, vitamin D3 and vitamin K1 favorably impact biomarkers of bone turnover in postmenopausal women in a 14-week trial","volume":"28","author":"Holick","year":"2010","journal-title":"J Bone Miner. Metab"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1177\/0022034518797275","article-title":"Berberine ameliorates periodontal bone loss by regulating gut microbiota","volume":"98","author":"Jia","year":"2019","journal-title":"J Dent Res"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1080\/13813455.2025.2465360","article-title":"Role of berberine in metabolic and bone changes in ovariectomized rats","volume":"131","author":"Eid","year":"2025","journal-title":"Arch Physiol Biochem"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076364","article-title":"Role of berberine thermosensitive hydrogel in periodontitis via PI3K\/AKT pathway in vitro","volume":"24","author":"Wang","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2023.1187718","article-title":"Berberine influences multiple diseases by modifying gut microbiota","volume":"10","author":"Yang","year":"2023","journal-title":"Front Nutr"},{"key":"B123","article-title":"Research progress on Sophora flavescens","volume":"43","author":"Liu","year":"2025","journal-title":"J Pharm Pract Serv"},{"key":"B124","article-title":"Effect of oxymatrine on stemness marker expression and osteogenic differentiation of periodontal ligament stem cells","volume":"29","author":"Luo","year":"2025","journal-title":"Chin J Tissue Eng Res"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.977374","article-title":"Research progress on the pharmacological effects of matrine","volume":"16","author":"Sun","year":"2022","journal-title":"Front Neurosci"},{"key":"B126","first-page":"10","article-title":"Research progress of natural products in regulating osteogenic differentiation","volume":"56","author":"Cai","year":"2025","journal-title":"J China Pharm Univ"},{"key":"B127","article-title":"Atrine, an active component of Cuscuta chinensis, in treatment of postmenopausal osteoporosis: a network pharmacology analysis and experimental verification","volume":"30","author":"Xu","year":"2026","journal-title":"Chin J Tissue Eng Res"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b12-00445","article-title":"Tetrandrine prevents bone loss in sciatic-neurectomized mice and inhibits receptor activator of nuclear factor \u03baB ligand-induced osteoclast differentiation","volume":"35","author":"Takahashi","year":"2012","journal-title":"Biol Pharm Bull"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.13339","article-title":"Tetrandrine: A review of its anticancer potentials, clinical settings, pharmacokinetics and drug delivery systems","volume":"72","author":"Luan","year":"2020","journal-title":"J Pharm Pharmacol"},{"key":"B130","doi-asserted-by":"publisher","first-page":"990","DOI":"10.21037\/atm-20-5548","article-title":"Tetrandrine mediates renal function and redox homeostasis in a streptozotocin-induced diabetic nephropathy rat model through Nrf2\/HO-1 reactivation","volume":"8","author":"Su","year":"2020","journal-title":"Ann Trans Med"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01530","article-title":"Tetrandrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis","volume":"10","author":"Zhong","year":"2020","journal-title":"Front Pharmacol"},{"key":"B132","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/s10020-022-00568-4","article-title":"Tetrandrine inhibits RANKL-induced osteoclastogenesis by promoting the degradation of TRAIL","volume":"28","author":"Li","year":"2022","journal-title":"Mol Med (Cambrid. Mass)"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1789264\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:49:47Z","timestamp":1782276587000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1789264\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":132,"alternative-id":["10.3389\/fendo.2026.1789264"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1789264","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]},"article-number":"1789264"}}