{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:03:06Z","timestamp":1792454586608,"version":"4.5.0"},"reference-count":129,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"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","award":["81973447"],"award-info":[{"award-number":["81973447"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY21H280001"],"award-info":[{"award-number":["LY21H280001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017599","name":"Science and Technology Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2021C02047 2021ZQ018 2021ZYYFC8"],"award-info":[{"award-number":["2021C02047 2021ZQ018 2021ZYYFC8"]}],"id":[{"id":"10.13039\/501100017599","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2020M681364"],"award-info":[{"award-number":["2020M681364"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Natural alkaloids are polycyclic, nitrogen-containing, and basic compounds obtained from plants. In this review, the advances in bioactive alkaloids with respect to their chemical structures, herbal sources, and effects for the prevention and treatment of osteoporosis are discussed. Anti-osteoporosis alkaloids are classified into six categories based on the chemical structure, namely, isoquinoline alkaloids, quinolizidine alkaloids, piperidine alkaloids, indole alkaloids, pyrrolizidine alkaloids and steroidal alkaloids. They promote mesenchymal stem cells differentiation, improve osteoblast proliferation, stimulate osteoblast autophagy and suppress osteoclast formation. These natural alkaloids can regulate multiple signaling pathways, including interrupting the tumor necrosis factor receptor associated factor 6- receptor activator of nuclear factor kappa B interaction, inhibiting the nuclear factor kappa B pathway in osteoclasts, activating the p38 mitogen-activated protein kinases pathway in osteoblasts, and triggering the wingless and int-1 pathway in mesenchymal stem cells. This review provides evidence and support for novel drug and clinical treatment of osteoporosis using natural alkaloids.<\/jats:p>","DOI":"10.3389\/fphar.2022.1014173","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T12:13:47Z","timestamp":1663935227000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Effects and mechanisms of natural alkaloids for prevention and treatment of osteoporosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Bingfeng","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingcui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehui","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qitao","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nani","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1007\/s11926-019-0836-7","article-title":"Osteoporosis pathophysiology, epidemiology, and screening in rheumatoid arthritis","volume":"21","author":"Adami","year":"2019","journal-title":"Curr. Rheumatol. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1016\/j.biopha.2017.08.001","article-title":"Pioglitazone-induced bone loss in diabetic rats and its amelioration by berberine: A portrait of molecular crosstalk","volume":"94","author":"Adil","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"B3","doi-asserted-by":"publisher","first-page":"111","DOI":"10.2174\/1871530320666200821124817","article-title":"Natural alkaloids and diabetes mellitus: A review","volume":"21","author":"Ajebli","year":"2021","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"B4","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.lfs.2016.01.024","article-title":"Natural products for treatment of osteoporosis: The effects and mechanisms on promoting osteoblast-mediated bone formation","volume":"147","author":"An","year":"2016","journal-title":"Life Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.lfs.2018.02.032","article-title":"Pharmacological benefits of neferine - a comprehensive review","volume":"199","author":"Asokan","year":"2018","journal-title":"Life Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1080\/14786419.2019.1682575","article-title":"Pyrroloquinolone a, a new alkaloid and other phytochemicals from Atractylis cancellata L. with antioxidant and anticholinesterase activities","volume":"35","author":"Badaoui","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"152956","DOI":"10.1016\/j.phymed.2019.152956","article-title":"Cepharanthine: An update of its mode of action, pharmacological properties and medical applications","volume":"62","author":"Bailly","year":"2019","journal-title":"Phytomedicine"},{"key":"B8","doi-asserted-by":"publisher","first-page":"108933","DOI":"10.1016\/j.steroids.2021.108933","article-title":"The steroidal alkaloids alpha-tomatine and tomatidine: Panorama of their mode of action and pharmacological properties","volume":"176","author":"Bailly","year":"2021","journal-title":"Steroids"},{"key":"B9","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1056\/NEJMcp1513724","article-title":"Clinical practice. Postmenopausal osteoporosis","volume":"374","author":"Black","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"128384","DOI":"10.1016\/j.foodchem.2020.128384","article-title":"Pyrrolizidine alkaloids and beehive products: A review","volume":"342","author":"Brugnerotto","year":"2021","journal-title":"Food Chem."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.3389\/fphar.2018.01046","article-title":"Boldine ameliorates estrogen deficiency-induced bone loss via inhibiting bone resorption","volume":"9","author":"Chen","year":"2018","journal-title":"Front. Pharmacol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.7150\/thno.30206","article-title":"Pseurotin a inhibits osteoclastogenesis and prevents ovariectomized-induced bone loss by suppressing reactive oxygen species","volume":"9","author":"Chen","year":"2019","journal-title":"Theranostics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbrc.2021.01.012","article-title":"Stachydrine hydrochloride inhibits osteoclastogenesis by regulating the NF-kappa B and p38 signaling pathways to alleviate postmenopausal osteoporosis","volume":"542","author":"Chen","year":"","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B14","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1007\/s00774-021-01225-2","article-title":"Protective effects of berberine on senile osteoporosis in mice","volume":"39","author":"Chen","year":"","journal-title":"J. Bone Min. Metab."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1038\/cdd.2015.168","article-title":"Fate decision of mesenchymal stem cells: Adipocytes or osteoblasts?","volume":"23","author":"Chen","year":"2016","journal-title":"Cell Death Differ."},{"key":"B16","doi-asserted-by":"publisher","first-page":"12853","DOI":"10.1038\/srep12853","article-title":"Lycorine suppresses RANKL-induced osteoclastogenesis in vitro and prevents ovariectomy-induced osteoporosis and titanium particle-induced osteolysis in vivo","volume":"5","author":"Chen","year":"2015","journal-title":"Sci. Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"4855","DOI":"10.1096\/fj.201700316R","article-title":"Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis","volume":"31","author":"Chen","year":"2017","journal-title":"Faseb J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"104755","DOI":"10.1016\/j.phrs.2020.104755","article-title":"A review of pharmacological and pharmacokinetic properties of stachydrine","volume":"155","author":"Cheng","year":"2020","journal-title":"Pharmacol. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/s0378-8741(99)00141-5","article-title":"Anti-inflammatory effects of fangchinoline and tetrandrine","volume":"69","author":"Choi","year":"2000","journal-title":"J. Ethnopharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"679","DOI":"10.3389\/fimmu.2019.00679","article-title":"Osteoimmunology of bone loss in inflammatory rheumatic diseases","volume":"10","author":"Coury","year":"2019","journal-title":"Front. Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1007\/s00011-006-6034-x","article-title":"Senile osteoporosis: Is it an immune-mediated disease?","volume":"55","author":"De Martinis","year":"2006","journal-title":"Inflamm. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/biof.1241","article-title":"Piperine alleviates osteoclast formation through the p38\/c-Fos\/NFATc1 signaling axis","volume":"41","author":"Deepak","year":"2015","journal-title":"Biofactors"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1002\/ijc.31965","article-title":"Therapeutic value of steroidal alkaloids in cancer: Current trends and future perspectives","volume":"145","author":"Dey","year":"2019","journal-title":"Int. J. Cancer"},{"key":"B24","doi-asserted-by":"publisher","first-page":"511799","DOI":"10.3389\/fphys.2020.511799","article-title":"The effect of inflammation on bone","volume":"11","author":"Epsley","year":"2021","journal-title":"Front. Physiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"4022","DOI":"10.2174\/1381612826666200423092602","article-title":"The efficacy and safety of bisphosphonates for osteoporosis in women older than 65 years: A meta-analysis","volume":"26","author":"Fan","year":"2020","journal-title":"Curr. Pharm. Des."},{"key":"B26","doi-asserted-by":"publisher","first-page":"104994","DOI":"10.1016\/j.bioorg.2021.104994","article-title":"Structure-activity relationship and biological evaluation of berberine derivatives as PCSK9 down-regulating agents","volume":"113","author":"Fan","year":"2021","journal-title":"Bioorg. Chem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2070","DOI":"10.3390\/ijms19072070","article-title":"Influence of menopause on inflammatory cytokines during murine and human bone fracture healing","volume":"19","author":"Fischer","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1016\/j.fct.2012.03.049","article-title":"Piperidine alkaloids: Human and food animal teratogens","volume":"50","author":"Green","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1097\/fjc.0000000000000788","article-title":"Role of NFATc1 in the bone-vascular axis calcification paradox","volume":"75","author":"Gu","year":"2020","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1186\/s13287-019-1498-0","article-title":"The shift in the balance between osteoblastogenesis and adipogenesis of mesenchymal stem cells mediated by glucocorticoid receptor","volume":"10","author":"Han","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"B31","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1002\/ptr.6855","article-title":"Piperine: A review of its biological effects","volume":"35","author":"Haq","year":"2021","journal-title":"Phytother. Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.ejphar.2016.03.014","article-title":"Sinomenine down-regulates TLR4\/TRAF6 expression and attenuates lipopolysaccharide-induced osteoclastogenesis and osteolysis","volume":"779","author":"He","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"295","DOI":"10.17305\/bjbms.2017.2596","article-title":"Berberine alleviates oxidative stress in rats with osteoporosis through receptor activator of NF-kB\/receptor activator of NF-kB ligand\/osteoprotegerin (RANK\/RANKL\/OPG) pathway","volume":"17","author":"He","year":"2017","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/s00223-013-9741-7","article-title":"Osteoclast-derived coupling factors in bone remodeling","volume":"94","author":"Henriksen","year":"2014","journal-title":"Calcif. Tissue Int."},{"key":"B35","doi-asserted-by":"publisher","first-page":"115458","DOI":"10.1016\/j.bone.2020.115458","article-title":"Gene regulatory landscape in osteoblast differentiation","volume":"137","author":"Hojo","year":"2020","journal-title":"Bone"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2574","DOI":"10.1096\/fj.201800920R","article-title":"Tomatidine suppresses osteoclastogenesis and mitigates estrogen deficiency-induced bone mass loss by modulating TRAF6-mediated signaling","volume":"33","author":"Hu","year":"2019","journal-title":"Faseb J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.ejphar.2007.11.013","article-title":"Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-kappaB and Akt pathways","volume":"580","author":"Hu","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"107720","DOI":"10.1016\/j.intimp.2021.107720","article-title":"Aloperine improves osteoporosis in ovariectomized mice by inhibiting RANKL-induced NF-kappa B, ERK and JNK approaches","volume":"97","author":"Hu","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3403","DOI":"10.3390\/ijms19113403","article-title":"Antiproliferative effects of alkaloid evodiamine and its derivatives","volume":"19","author":"Hu","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"103809","DOI":"10.1016\/j.bioorg.2020.103809","article-title":"Anti-inflammatory octahydroindolizine alkaloid enantiomers from Dendrobium crepidatum","volume":"100","author":"Hu","year":"2020","journal-title":"Bioorg. Chem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"5525","DOI":"10.1111\/jcmm.16562","article-title":"Harmine targets inhibitor of DNA binding-2 and activator protein-1 to promote preosteoclast PDGF-BB production","volume":"25","author":"Huang","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2435","DOI":"10.7150\/thno.22144","article-title":"Harmine enhances type H vessel formation and prevents bone loss in ovariectomized mice","volume":"8","author":"Huang","year":"2018","journal-title":"Theranostics"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/jb\/mvv112","article-title":"The role of osteoclast differentiation and function in skeletal homeostasis","volume":"159","author":"Ikeda","year":"2016","journal-title":"J. Biochem."},{"key":"B44","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.biopha.2018.01.008","article-title":"Evaluation of antidiabetic potential of steroidal alkaloid of Sarcococca saligna","volume":"100","author":"Jan","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B45","doi-asserted-by":"publisher","first-page":"684007","DOI":"10.3389\/fcell.2021.684007","article-title":"Oxymatrine attenuates osteoclastogenesis via modulation of ROS-mediated SREBP2 signaling and counteracts ovariectomy-induced osteoporosis","volume":"9","author":"Jiang","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1002\/med.21346","article-title":"Therapeutic potential of steroidal alkaloids in cancer and other diseases","volume":"36","author":"Jiang","year":"2016","journal-title":"Med. Res. Rev."},{"key":"B47","doi-asserted-by":"publisher","first-page":"3941","DOI":"10.1111\/jcmm.13674","article-title":"Oxymatrine exerts protective effects on osteoarthritis via modulating chondrocyte homoeostasis and suppressing osteoclastogenesis","volume":"22","author":"Jiang","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1001\/jama.2017.21640","article-title":"Vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling adults evidence report and systematic review for the US preventive services task force","volume":"319","author":"Kahwati","year":"2018","journal-title":"Jama-j. Am. Med. Assoc."},{"key":"B49","doi-asserted-by":"publisher","first-page":"35","DOI":"10.2478\/bjmg-2020-0021","article-title":"Do we use methylation of NFATC1 and FOS genes as a biomarker for postmenopausal osteoporosis?","volume":"23","author":"Kalkan","year":"2020","journal-title":"Balk. J. Med. Genet."},{"key":"B50","doi-asserted-by":"publisher","first-page":"3646","DOI":"10.3390\/ijms21103646","article-title":"The role of Ca2+-NFATc1 signaling and its modulation on osteoclastogenesis","volume":"21","author":"Kang","year":"","journal-title":"Int. J. Mol. Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1002\/tox.22996","article-title":"Cannabidiol induces osteoblast differentiation via angiopoietin1 and p38 MAPK","volume":"35","author":"Kang","year":"","journal-title":"Environ. Toxicol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1177\/0004563218759371","article-title":"The bone remodelling cycle","volume":"55","author":"Kenkre","year":"2018","journal-title":"Ann. Clin. Biochem."},{"key":"B53","doi-asserted-by":"publisher","first-page":"986","DOI":"10.2174\/1389200219666180628165643","article-title":"Diverse therapeutic potential of nitidine, a comprehensive review","volume":"19","author":"Khan","year":"2018","journal-title":"Curr. Drug Metab."},{"key":"B54","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.3390\/cells9092073","article-title":"Osteoblast-osteoclast communication and bone homeostasis","volume":"9","author":"Kim","year":"2020","journal-title":"Cells"},{"key":"B55","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/s00418-018-1640-6","article-title":"Runx2, an inducer of osteoblast and chondrocyte differentiation","volume":"149","author":"Komori","year":"2018","journal-title":"Histochem. Cell Biol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1111\/bph.15024","article-title":"Overview of treatment approaches to osteoporosis","volume":"178","author":"Langdahl","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1359\/jbmr.080325","article-title":"Berberine promotes osteoblast differentiation by Runx2 activation with p38 MAPK","volume":"23","author":"Lee","year":"2008","journal-title":"J. Bone Min. Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.phymed.2018.09.228","article-title":"Comparison of anti-inflammatory effects of berberine, and its natural oxidative and reduced derivatives from Rhizoma Coptidis in vitro and in vivo","volume":"52","author":"Li","year":"2019","journal-title":"Phytomedicine"},{"key":"B59","doi-asserted-by":"publisher","first-page":"e74274","DOI":"10.1371\/journal.pone.0074274","article-title":"Sinomenine suppresses osteoclast formation and mycobacterium tuberculosis H37Ra-induced bone loss by modulating RANKL signaling pathways","volume":"8","author":"Li","year":"2013","journal-title":"Plos One"},{"key":"B60","doi-asserted-by":"publisher","first-page":"101098","DOI":"10.1016\/j.arr.2020.101098","article-title":"Targeting autophagy in osteoporosis: From pathophysiology to potential therapy","volume":"62","author":"Li","year":"","journal-title":"Ageing Res. Rev."},{"key":"B61","doi-asserted-by":"publisher","first-page":"101771","DOI":"10.1016\/j.redox.2020.101771","article-title":"Songorine promotes cardiac mitochondrial biogenesis via Nrf2 induction during sepsis","volume":"38","author":"Li","year":"","journal-title":"Redox Biol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"511","DOI":"10.16438\/j.0513-4870.2020-1616","article-title":"Rutaecarpine exerted anti-osteroporosis","volume":"56","author":"Li","year":"","journal-title":"Acta Pharm. Sin."},{"key":"B63","doi-asserted-by":"publisher","first-page":"111972","DOI":"10.1016\/j.ejmech.2019.111972","article-title":"Quinolizidine alkaloids derivatives from Sophora alopecuroides linn: Bioactivities, structure-activity relationships and preliminary molecular mechanisms","volume":"188","author":"Li","year":"","journal-title":"Eur. J. Med. Chem."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1002\/jcp.29948","article-title":"Inhibitory effects of biochanin A on titanium particle-induced osteoclast activation and inflammatory bone resorption via NF-kappa B and MAPK pathways","volume":"236","author":"Liao","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.3390\/nu11092111","article-title":"The paradoxical role of uric acid in osteoporosis","volume":"11","author":"Lin","year":"2019","journal-title":"Nutrients"},{"key":"B66","doi-asserted-by":"publisher","first-page":"153195","DOI":"10.1016\/j.phymed.2020.153195","article-title":"Arecoline suppresses RANKL-induced osteoclast differentiation in vitro and attenuates LPS-induced bone loss in vivo","volume":"69","author":"Liu","year":"","journal-title":"Phytomedicine"},{"key":"B67","doi-asserted-by":"publisher","first-page":"36662","DOI":"10.1038\/srep36662","article-title":"Nitidine chloride prevents OVX-induced bone loss via suppressing NFATc1-mediated osteoclast differentiation","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1926947","DOI":"10.1155\/2020\/1926947","article-title":"Tetrandrine inhibits titanium particle-induced inflammatory osteolysis through the nuclear factor-kappa B pathway","volume":"2020","author":"Liu","year":"","journal-title":"Mediat. Inflamm."},{"key":"B69","doi-asserted-by":"publisher","first-page":"3686749","DOI":"10.1155\/2020\/3686749","article-title":"The interplay between Immune system and microbiota in osteoporosis","volume":"2020","author":"Locantore","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"B70","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."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1491","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":"B72","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.jpba.2008.11.019","article-title":"Simultaneous determination of tetrahydropalmatine, protopine, and palmatine in rat plasma by LC-ESI-MS and its application to a pharmacokinetic study","volume":"49","author":"Ma","year":"2009","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B73","doi-asserted-by":"publisher","first-page":"307","DOI":"10.26402\/jpp.2020.3.01","article-title":"Pharmacological agents and natural compounds: Available treatments for osteoporosis","volume":"71","author":"Martiniakova","year":"2020","journal-title":"J. Physiol. Pharmacol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/s10529-013-1348-6","article-title":"Oxidative stress and production of bioactive monoterpene indole alkaloids: Biotechnological implications","volume":"36","author":"Matsuura","year":"2014","journal-title":"Biotechnol. Lett."},{"key":"B75","doi-asserted-by":"publisher","first-page":"6730","DOI":"10.1111\/jcmm.14551","article-title":"Stachydrine prevents LPS-induced bone loss by inhibiting osteoclastogenesis via NF-kappa B and Akt signalling","volume":"23","author":"Meng","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"B76","doi-asserted-by":"publisher","first-page":"2538","DOI":"10.3390\/molecules23102538","article-title":"Molecular targets modulated by fangchinoline in tumor cells and preclinical models","volume":"23","author":"Merarchi","year":"2018","journal-title":"Molecules"},{"key":"B77","doi-asserted-by":"publisher","first-page":"3620","DOI":"10.3390\/ijms21103620","article-title":"Inflammatory skin-derived cytokines accelerate osteoporosis in mice with persistent skin inflammation","volume":"21","author":"Mizutani","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B78","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1159\/000371845","article-title":"The RANKL-RANK story","volume":"61","author":"Nagy","year":"2015","journal-title":"Gerontology"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cbi.2005.09.002","article-title":"Boldine and its antioxidant or health-promoting properties","volume":"159","author":"O'brien","year":"2006","journal-title":"Chem. Biol. Interact."},{"key":"B80","doi-asserted-by":"publisher","first-page":"646803","DOI":"10.3389\/fcell.2021.646803","article-title":"Sestrin2 regulates osteoclastogenesis via the p62-TRAF6 interaction","volume":"9","author":"Oh","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s41232-019-0111-3","article-title":"RANKL biology: Bone metabolism, the immune system, and beyond","volume":"40","author":"Ono","year":"2020","journal-title":"Inflamm. Regen."},{"key":"B82","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":"Mol. Cells"},{"key":"B83","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":"J. Cell. Mol. Med."},{"key":"B84","doi-asserted-by":"publisher","first-page":"104723","DOI":"10.1016\/j.phrs.2020.104723","article-title":"Anti-diabetic potential of plant alkaloids: Revisiting current findings and future perspectives","volume":"155","author":"Rasouli","year":"2020","journal-title":"Pharmacol. Res."},{"key":"B85","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.3390\/nu12061702","article-title":"Nutrients in the prevention of osteoporosis in patients with inflammatory bowel diseases","volume":"12","author":"Ratajczak","year":"2020","journal-title":"Nutrients"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1039\/c4np00055b","article-title":"Pyrrolizidine alkaloids","volume":"31","author":"Robertson","year":"2014","journal-title":"Nat. Prod. Rep."},{"key":"B87","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.biopha.2018.07.147","article-title":"Lycorine: A prospective natural lead for anticancer drug discovery","volume":"107","author":"Roy","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B88","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.mcna.2017.08.010","article-title":"Obesity pharmacotherapy","volume":"102","author":"Saunders","year":"2018","journal-title":"Med. Clin. North Am."},{"key":"B89","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/s41584-019-0172-3","article-title":"Antiresorptive and anabolic agents in the prevention and reversal of bone fragility","volume":"15","author":"Seeman","year":"2019","journal-title":"Nat. Rev. Rheumatol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1002\/med.21703","article-title":"Biologically active isoquinoline alkaloids covering 2014-2018","volume":"40","author":"Shang","year":"2020","journal-title":"Med. Res. Rev."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.3389\/fimmu.2018.01849","article-title":"Tumor necrosis factor receptor-associated factor regulation of nuclear factor kappa B and mitogen-activated protein kinase pathways","volume":"9","author":"Shi","year":"2018","journal-title":"Front. Immunol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"108168","DOI":"10.1016\/j.pharmthera.2022.108168","article-title":"Advances in pathogenesis and therapeutic strategies for osteoporosis","volume":"237","author":"Song","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"B93","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1002\/jbmr.4197","article-title":"Clinical phenotype and relevance of LRP5 and LRP6 variants in patients with early-onset osteoporosis (EOOP)","volume":"36","author":"Stuerznickel","year":"2021","journal-title":"J. Bone Min. Res."},{"key":"B94","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1248\/bpb.b12-00445","article-title":"Tetrandrine prevents bone loss in sciatic-neurectomized mice and inhibits receptor activator of nuclear factor kappa B ligand-induced osteoclast differentiation","volume":"35","author":"Takahashi","year":"2012","journal-title":"Biol. Pharm. Bull."},{"key":"B95","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1007\/s00109-004-0612-6","article-title":"Mechanistic insight into osteoclast differentiation in osteoimmunology","volume":"83","author":"Takayanagi","year":"2005","journal-title":"J. Mol. Med."},{"key":"B96","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.toxlet.2015.10.007","article-title":"Berberine promotes bone marrow-derived mesenchymal stem cells osteogenic differentiation via canonical Wnt\/\u03b2-catenin signaling pathway","volume":"240","author":"Tao","year":"2016","journal-title":"Toxicol. Lett."},{"key":"B97","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1080\/14397595.2018.1500736","article-title":"Osteoprotegrin interacts with biomarkers and cytokines that have roles in osteoporosis, skin fibrosis, and vasculopathy in systemic sclerosis: A potential multifaceted relationship between OPG\/RANKL\/TRAIL and Wnt inhibitors","volume":"29","author":"Taylan","year":"2019","journal-title":"Mod. Rheumatol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.phrs.2018.12.019","article-title":"Rutaecarpine: A promising cardiovascular protective alkaloid from evodia rutaecarpa (Wu Zhu yu)","volume":"141","author":"Tian","year":"2019","journal-title":"Pharmacol. Res."},{"key":"B99","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1002\/jbmr.2990","article-title":"LOX fails to substitute for RANKL in osteoclastogenesis","volume":"32","author":"Tsukasaki","year":"2017","journal-title":"J. Bone Min. Res."},{"key":"B100","doi-asserted-by":"publisher","first-page":"2176","DOI":"10.1021\/acschemneuro.8b00711","article-title":"DARK classics in chemical neuroscience: Arecoline","volume":"10","author":"Volgin","year":"2019","journal-title":"Acs Chem. Neurosci."},{"key":"B101","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/imr.12302","article-title":"Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system","volume":"266","author":"Walsh","year":"2015","journal-title":"Immunol. Rev."},{"key":"B102","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.2174\/1389450120666190618125816","article-title":"Phytochemical information and biological activities of quinolizidine alkaloids in sophora: A comprehensive review","volume":"20","author":"Wang","year":"2019","journal-title":"Curr. Drug Targets"},{"key":"B103","doi-asserted-by":"publisher","first-page":"3497","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. devel. Ther."},{"key":"B104","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1186\/s12916-020-01778-5","article-title":"Mendelian randomization study of inflammatory bowel disease and bone mineral density","volume":"18","author":"Wu","year":"2020","journal-title":"BMC Med."},{"key":"B105","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1002\/jsfa.10763","article-title":"Isoflavone-enriched soybean leaves attenuate ovariectomy-induced osteoporosis in rats by anti-inflammatory activity","volume":"101","author":"Xie","year":"2021","journal-title":"J. Sci. Food Agric."},{"key":"B106","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.biopha.2018.08.131","article-title":"Possible therapeutic potential of berberine in the treatment of STZ plus HFD-induced diabetic osteoporosis","volume":"108","author":"Xie","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B107","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1055\/s-0030-1250040","article-title":"Preventive effects of berberine on glucocorticoid-induced osteoporosis in rats","volume":"76","author":"Xu","year":"2010","journal-title":"Planta Med."},{"key":"B108","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1002\/jbmr.4398","article-title":"Rictor is a novel regulator of TRAF6\/TRAF3 in osteoclasts","volume":"36","author":"Xu","year":"2021","journal-title":"J. Bone Min. Res."},{"key":"B109","doi-asserted-by":"publisher","first-page":"15395","DOI":"10.1074\/jbc.RA119.010139","article-title":"STAT3 controls osteoclast differentiation and bone homeostasis by regulating NFATc1 transcription","volume":"294","author":"Yang","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B110","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1007\/s00774-020-01175-1","article-title":"Discovery of the RANKL\/RANK\/OPG system","volume":"39","author":"Yasuda","year":"2021","journal-title":"J. Bone Min. Metab."},{"key":"B111","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.ejphar.2010.10.048","article-title":"Harmine, a beta-carboline alkaloid, inhibits osteoclast differentiation and bone resorption in vitro and in vivo","volume":"650","author":"Yonezawa","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"B112","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.biochi.2018.11.008","article-title":"Neotuberostemonine inhibits osteoclastogenesis via blockade of NF-kappa B pathway","volume":"157","author":"Yun","year":"2019","journal-title":"Biochimie"},{"key":"B113","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41401-019-0289-6","article-title":"Artesunate attenuates LPS-induced osteoclastogenesis by suppressing TLR4\/TRAF6 and PLC gamma 1-Ca2+-NFATc1 signaling pathway","volume":"41","author":"Zeng","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"B114","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.3389\/fphar.2019.01587","article-title":"Vindoline inhibits RANKL-induced osteoclastogenesis and prevents ovariectomy-induced bone loss in mice","volume":"10","author":"Zhan","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B115","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1691\/ph.2019.9636","article-title":"Sinomenine can promote the proliferation and differentiation of osteoblasts by regulating the Akt\/Runx2 signaling pathway in MC3T3-E1 cells","volume":"74","author":"Zhang","year":"","journal-title":"Pharmazie"},{"key":"B116","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1007\/s12272-020-01283-6","article-title":"Pharmacological effects of harmine and its derivatives: A review","volume":"43","author":"Zhang","year":"","journal-title":"Arch. Pharm. Res."},{"key":"B117","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1208\/s12249-020-01865-z","article-title":"Transdermal delivery of salmon calcitonin using a dissolving microneedle array: Characterization, stability, and in vivo pharmacodynamics","volume":"22","author":"Zhang","year":"2021","journal-title":"Aaps Pharmscitech"},{"key":"B118","doi-asserted-by":"publisher","first-page":"325","DOI":"10.3389\/fcell.2020.00325","article-title":"Pros and cons of denosumab treatment for osteoporosis and implication for RANKL aptamer therapy","volume":"8","author":"Zhang","year":"","journal-title":"Front. Cell Dev. Biol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.phrs.2019.02.015","article-title":"Sinomenine inhibits osteolysis in breast cancer by reducing IL-8\/CXCR1 and c-Fos\/NFATc1 signaling","volume":"142","author":"Zhang","year":"","journal-title":"Pharmacol. Res."},{"key":"B120","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1002\/jbmr.4215","article-title":"Myeloperoxidase controls bone turnover by suppressing osteoclast differentiation through modulating reactive oxygen species level","volume":"36","author":"Zhao","year":"2021","journal-title":"J. Bone Min. Res."},{"key":"B121","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1111\/jcmm.14790","article-title":"L-tetrahydropalmatine suppresses osteoclastogenesis in vivo and in vitro via blocking RANK-TRAF6 interactions and inhibiting NF-kappa B and MAPK pathways","volume":"24","author":"Zhi","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"B122","doi-asserted-by":"publisher","first-page":"1530","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":"B123","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/j.biopha.2017.03.084","article-title":"Influence of sinomenine upon mesenchymal stem cells in osteoclastogenesis","volume":"90","author":"Zhou","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"B124","doi-asserted-by":"publisher","first-page":"210","DOI":"10.3389\/fphar.2018.00210","article-title":"Cepharanthine prevents estrogen deficiency-induced bone loss by inhibiting bone resorption","volume":"9","author":"Zhou","year":"2018","journal-title":"Front. Pharmacol."},{"key":"B125","doi-asserted-by":"publisher","first-page":"538137","DOI":"10.3389\/fphar.2020.538137","article-title":"A review on recent advances in aloperine research: Pharmacological activities and underlying biological mechanisms","volume":"11","author":"Zhou","year":"","journal-title":"Front. Pharmacol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"309","DOI":"10.7150\/ijbs.37162","article-title":"Fangchinoline protects against bone loss in OVX mice via inhibiting osteoclast formation, bone resorption and RANKL-induced signaling","volume":"16","author":"Zhou","year":"","journal-title":"Int. J. Biol. Sci."},{"key":"B127","doi-asserted-by":"publisher","first-page":"324","DOI":"10.12659\/msm.912624","article-title":"Fangchinoline promotes autophagy and inhibits apoptosis in osteoporotic rats","volume":"25","author":"Zhu","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"B128","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1146\/annurev.arplant.59.032607.092730","article-title":"Alkaloid biosynthesis: Metabolism and trafficking","volume":"59","author":"Ziegler","year":"2008","journal-title":"Annu. Rev. Plant Biol."},{"key":"B129","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/aps.2016.125","article-title":"Advances in the study of berberine and its derivatives: A focus on anti-inflammatory and anti-tumor effects in the digestive system","volume":"38","author":"Zou","year":"2017","journal-title":"Acta Pharmacol. Sin."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.1014173\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T12:13:56Z","timestamp":1663935236000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.1014173\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,23]]},"references-count":129,"alternative-id":["10.3389\/fphar.2022.1014173"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.1014173","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,23]]},"article-number":"1014173"}}