{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T23:41:03Z","timestamp":1781394063300,"version":"3.54.1"},"reference-count":34,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"crossref","award":["2018JJA140721"],"award-info":[{"award-number":["2018JJA140721"]}],"id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Osteoporosis is a disease associated with bone resorption, characterized primarily by the excessive activation of osteoclasts. Ginkgetin is a compound purified from natural ginkgo leaves which has various biological properties, including anti-inflammation, antioxidant, and anti-tumor effects. This study investigated the bone-protective effects of ginkgetin in ovariectomized (OVX) mice and explored their potential signaling pathway in inhibiting osteoclastogenesis in a mouse model of osteoporosis.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Biochemical assays were performed to assess the levels of Ca, ALP, and P in the blood. Micro CT scanning was used to evaluate the impact of ginkgetin on bone loss in mice. RT-PCR was employed to detect the expression of osteoclast-related genes (ctsk, c-fos, trap) in their femoral tissue. Hematoxylin and eosin (H&amp;E) staining was utilized to assess the histopathological changes in femoral tissue due to ginkgetin. The TRAP staining was used to evaluate the impact of ginkgetin osteoclast generation <jats:italic>in vivo<\/jats:italic>. Western blot analysis was conducted to investigate the effect of ginkgetin on the expression of p-NF-\u03baB p65 and I\u03baB\u03b1 proteins in mice.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Our findings indicate that ginkgetin may increase the serum levels of ALP and P, while decreasing the serum level of Ca in OVX mice. H&amp;E staining and micro CT scanning results suggest that ginkgetin can inhibit bone loss in OVX mice. The TRAP staining results showed ginkgetin suppresses the generation of osteoclasts in OVX mice. RT-PCR results demonstrate that ginkgetin downregulate the expression of osteoclast-related genes (ctsk, c-fos, trap) in the femoral tissue of mice, and this effect is dose-dependent. Western blot analysis results reveal that ginkgetin can inhibit the expression of p-NF-\u03baB p65 and I\u03baB\u03b1 proteins in mice.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Ginkgetin can impact osteoclast formation and activation in OVX mice by inhibiting the NF-\u03baB\/I\u03baB\u03b1 signaling pathway, thereby attenuating bone loss in mice.<\/jats:p>\n<\/jats:sec>","DOI":"10.7717\/peerj.17722","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T08:43:51Z","timestamp":1720601031000},"page":"e17722","source":"Crossref","is-referenced-by-count":8,"title":["Ginkgetin attenuates bone loss in OVX mice by inhibiting the NF-\u03baB\/I\u03baB\u03b1 signaling pathway"],"prefix":"10.7717","volume":"12","author":[{"given":"GeJin","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, 923rd Hospital of PLA, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongbo","family":"Liang","sequence":"additional","affiliation":[{"name":"Graduate School, Guilin Medical College, Guilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, 923rd Hospital of PLA, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changzhi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, 923rd Hospital of PLA, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, 923rd Hospital of PLA, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, 923rd Hospital of PLA, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"issue":"Suppl 3","key":"10.7717\/peerj.17722\/ref-1","doi-asserted-by":"publisher","first-page":"109568","DOI":"10.1016\/j.cbi.2021.109568","article-title":"Nuclear factor-kappa B and its role in inflammatory lung disease","volume":"345","author":"Alharbi","year":"2021","journal-title":"Chemico-Biological Interactions"},{"issue":"2","key":"10.7717\/peerj.17722\/ref-2","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.ecl.2021.03.009","article-title":"Postmenopausal osteoporosis: latest guidelines","volume":"50","author":"Arceo-Mendoza","year":"2021","journal-title":"Endocrinology and Metabolism Clinics of North America"},{"issue":"2","key":"10.7717\/peerj.17722\/ref-3","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1210\/er.2018-00001","article-title":"Atypical femur fractures: review of epidemiology, relationship to bisphosphonates, prevention, and clinical management","volume":"40","author":"Black","year":"2019","journal-title":"Endocrine Reviews"},{"issue":"5","key":"10.7717\/peerj.17722\/ref-4","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/ajh.2010.14","article-title":"Effect of ginkgo biloba on blood pressure and incidence of hypertension in elderly men and women","volume":"23","author":"Brinkley","year":"2010","journal-title":"American Journal of Hypertension"},{"issue":"4","key":"10.7717\/peerj.17722\/ref-5","doi-asserted-by":"publisher","first-page":"79","DOI":"10.14715\/cmb\/2019.65.4.13","article-title":"Ginkgetin inhibits proliferation of HeLa cells via activation of p38\/NF-\u03baB pathway","volume":"65","author":"Cheng","year":"2019","journal-title":"Cellular and Molecular Biology"},{"issue":"10169","key":"10.7717\/peerj.17722\/ref-6","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/S0140-6736(18)32112-3","article-title":"Osteoporosis","volume":"393","author":"Compston","year":"2019","journal-title":"The Lancet"},{"key":"10.7717\/peerj.17722\/ref-7","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3389\/fendo.2021.675385","article-title":"The role of osteoclast energy metabolism in the occurrence and development of osteoporosis","volume":"12","author":"Da","year":"2021","journal-title":"Frontiers in Endocrinology"},{"issue":"12","key":"10.7717\/peerj.17722\/ref-8","doi-asserted-by":"publisher","first-page":"9497","DOI":"10.1002\/jcp.29757","article-title":"miR-506-3p alleviates uncontrolled osteoclastogenesis via repression of RANKL\/NFATc1 signaling pathway","volume":"235","author":"Dinesh","year":"2020","journal-title":"Journal of Cellular Physiology"},{"key":"10.7717\/peerj.17722\/ref-9","doi-asserted-by":"publisher","first-page":"201","DOI":"10.3389\/fgene.2020.589326","article-title":"Temporospatial flavonoids metabolism variation in ginkgo biloba leaves","volume":"11","author":"Guo","year":"2020","journal-title":"Frontiers in Genetics"},{"issue":"7","key":"10.7717\/peerj.17722\/ref-10","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2017.03.002","article-title":"Writing group for the western osteoporosis alliance. Western osteoporosis alliance clinical practice series: evaluating the balance of benefits and risks of long-term osteoporosis therapies","volume":"130","author":"Hanley","year":"2017","journal-title":"American Journal of Medicine"},{"issue":"1\u20132","key":"10.7717\/peerj.17722\/ref-11","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1007\/s11657-013-0136-1","article-title":"Osteoporosis in the European Union: medical management, epidemiology and economic burden: a report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA)","volume":"8","author":"Hernlund","year":"2013","journal-title":"Archives of Osteoporosis"},{"issue":"12","key":"10.7717\/peerj.17722\/ref-12","doi-asserted-by":"publisher","first-page":"468","DOI":"10.3390\/ph13120468","article-title":"Eudebeiolide b inhibits osteoclastogenesis and prevents ovariectomy-induced bone loss by regulating rankl-induced nf-\u03bab, c-fos and calcium signaling","volume":"13","author":"Kim","year":"2020","journal-title":"Pharmaceuticals"},{"issue":"10","key":"10.7717\/peerj.17722\/ref-13","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1007\/s00198-021-05900-y","article-title":"The clinician\u2019s guide to prevention and treatment of osteoporosis","volume":"33","author":"LeBoff","year":"2022","journal-title":"Osteoporosis International"},{"issue":"5","key":"10.7717\/peerj.17722\/ref-14","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1248\/bpb.29.1046","article-title":"Effects of anti-inflammatory biflavonoid, ginkgetin, on chronic skin inflammation","volume":"29","author":"Lim","year":"2006","journal-title":"Biological and Pharmaceutical Bulletin"},{"issue":"1\u20132","key":"10.7717\/peerj.17722\/ref-15","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/bs.apcsb.2016.11.002","article-title":"NF-\u03baB as a therapeutic target in inflammatory-associated bone diseases","volume":"107","author":"Lin","year":"2017","journal-title":"Advances in Protein Chemistry and Structural Biology"},{"issue":"7","key":"10.7717\/peerj.17722\/ref-16","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.3390\/cells10071609","article-title":"Relb and neuroinflammation","volume":"10","author":"Mockenhaupt","year":"2021","journal-title":"Cells"},{"key":"10.7717\/peerj.17722\/ref-17","doi-asserted-by":"publisher","first-page":"7917309","DOI":"10.1155\/2020\/7917309","article-title":"Osteokines and bone markers at rest and following plyometric exercise in pre- and postmenopausal women","volume":"21","author":"Nelson","year":"2020","journal-title":"BioMed Research International"},{"issue":"1","key":"10.7717\/peerj.17722\/ref-18","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1146\/annurev.pathmechdis.3.121806.151431","article-title":"The osteoclast: friend or foe?","volume":"3","author":"Novack","year":"2008","journal-title":"Annual Review of Pathology: Mechanisms of Disease"},{"issue":"4","key":"10.7717\/peerj.17722\/ref-19","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s00418-018-1636-2","article-title":"Recent advances in osteoclast biology","volume":"149","author":"Ono","year":"2018","journal-title":"Histochemistry and Cell Biology"},{"issue":"9","key":"10.7717\/peerj.17722\/ref-20","doi-asserted-by":"publisher","first-page":"S85","DOI":"10.1042\/BSR20191452","article-title":"Ginkgetin attenuates cerebral ischemia\u2013reperfusion induced autophagy and cell death via modulation of the NF-\u03baB\/p53 signaling pathway","volume":"39","author":"Pan","year":"2019","journal-title":"Bioscience Reports"},{"issue":"10","key":"10.7717\/peerj.17722\/ref-21","doi-asserted-by":"publisher","first-page":"706","DOI":"10.14348\/molcells.2017.0225","article-title":"Current understanding of RANK signaling in osteoclast differentiation and maturation","volume":"40","author":"Park","year":"2017","journal-title":"Molecules and Cells"},{"issue":"2","key":"10.7717\/peerj.17722\/ref-22","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1023\/A:1007728729844","article-title":"Ginkgo biloba extract (EGb 761) pretreatment limits free radical-induced oxidative stress in patients undergoing coronary bypass surgery","volume":"11","author":"Pietri","year":"1997","journal-title":"Cardiovascular Drugs and Therapy"},{"issue":"17","key":"10.7717\/peerj.17722\/ref-23","doi-asserted-by":"publisher","first-page":"10112","DOI":"10.1111\/jcmm.15622","article-title":"Cytisine attenuates bone loss of ovariectomy mouse by preventing RANKL-induced osteoclastogenesis","volume":"24","author":"Qian","year":"2020","journal-title":"Journal of Cellular and Molecular Medicine"},{"issue":"2","key":"10.7717\/peerj.17722\/ref-24","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1620\/tjem.247.75","article-title":"Antiresorptive agent-related osteonecrosis of the jaw (ARONJ): a twist of fate in the bone","volume":"247","author":"Shibahara","year":"2019","journal-title":"Tohoku Journal of Experimental Medicine"},{"issue":"5","key":"10.7717\/peerj.17722\/ref-25","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.3390\/nu13051609","article-title":"Botanicals in postmenopausal osteoporosis","volume":"13","author":"S\u0142upski","year":"2021","journal-title":"Nutrients"},{"issue":"1","key":"10.7717\/peerj.17722\/ref-26","doi-asserted-by":"publisher","first-page":"46","DOI":"10.5152\/eurjrheum.2016.048","article-title":"An overview and management of osteoporosis","volume":"4","author":"Sozen","year":"2017","journal-title":"European Journal of Rheumatology"},{"issue":"8","key":"10.7717\/peerj.17722\/ref-27","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1111\/jcmm.17238","article-title":"Nur77 prevents osteoporosis by inhibiting the NF-\u03baB signalling pathway and osteoclast differentiation","volume":"26","author":"Tian","year":"2022","journal-title":"Journal of Cellular and Molecular Medicine"},{"issue":"3","key":"10.7717\/peerj.17722\/ref-28","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/jgs.12146","article-title":"Frailty and fracture, disability, and falls: a multiple country study from the global longitudinal study of osteoporosis in women","volume":"61","author":"Tom","year":"2013","journal-title":"Journal of the American Geriatrics Society"},{"issue":"4","key":"10.7717\/peerj.17722\/ref-29","doi-asserted-by":"publisher","first-page":"287","DOI":"10.3233\/jad-2003-5404","article-title":"Elevation of oxidative free radicals in Alzheimer\u2019s disease models can be attenuated by Ginkgo biloba extract EGb 761","volume":"5","author":"Vining Smith","year":"2003","journal-title":"Journal of Alzheimer\u2019s Disease"},{"issue":"11","key":"10.7717\/peerj.17722\/ref-30","doi-asserted-by":"publisher","first-page":"27470","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":"International Journal of Molecular Sciences"},{"issue":"1","key":"10.7717\/peerj.17722\/ref-31","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1080\/13880209.2021.1876100","article-title":"Guizhi-Shaoyao-Zhimu decoction attenuates bone erosion in rats that have collagen-induced arthritis via modulating NF-\u03baB signalling to suppress osteoclastogenesis","volume":"59","author":"Wei","year":"2021","journal-title":"Pharmaceutical Biology"},{"issue":"5","key":"10.7717\/peerj.17722\/ref-32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/5578088","article-title":"Inhibition effect of zoledronate on the osteoclast differentiation of RAW264.7 induced by titanium particles","volume":"2021","author":"Zhao","year":"2021","journal-title":"BioMed Research International"},{"issue":"7","key":"10.7717\/peerj.17722\/ref-33","doi-asserted-by":"publisher","first-page":"3060","DOI":"10.1021\/jf105017j","article-title":"Biflavonoids from caper (Capparis spinosa L.) fruits and their effects in inhibiting NF-kappa B activation","volume":"59","author":"Zhou","year":"2011","journal-title":"Journal of Agricultural and Food Chemistry"},{"issue":"5484","key":"10.7717\/peerj.17722\/ref-34","doi-asserted-by":"publisher","first-page":"109769","DOI":"10.1016\/j.biopha.2019.109769","article-title":"Huang Vinpocetine inhibits RANKL-induced osteoclastogenesis and attenuates ovariectomy-induced bone loss","volume":"123","author":"Zhu","year":"2020","journal-title":"Biomedicine and Pharmacotherapy"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/17722.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/17722.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/17722.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/17722.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T08:43:56Z","timestamp":1720601036000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/17722"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,10]]},"references-count":34,"alternative-id":["10.7717\/peerj.17722"],"URL":"https:\/\/doi.org\/10.7717\/peerj.17722","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,10]]},"article-number":"e17722"}}