{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T21:00:10Z","timestamp":1787086810098,"version":"build-2736575974"},"reference-count":220,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T00:00:00Z","timestamp":1659139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"APC central fund of the university of Milan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The drugs used for treating bone diseases (BDs), at present, elicit hazardous side effects that include certain types of cancers and strokes, hence the ongoing quest for the discovery of alternatives with little or no side effects. Natural products (NPs), mainly of plant origin, have shown compelling promise in the treatments of BDs, with little or no side effects. However, the paucity in knowledge of the mechanisms behind their activities on bone remodeling has remained a hindrance to NPs\u2019 adoption. This review discusses the pathological development of some BDs, the NP-targeted components, and the actions exerted on bone remodeling signaling pathways (e.g., Receptor Activator of Nuclear Factor \u03ba B-ligand (RANKL)\/monocyte\/macrophage colony-stimulating factor (M-CSF)\/osteoprotegerin (OPG), mitogen-activated protein kinase (MAPK)s\/c-Jun N-terminal kinase (JNK)\/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB), Kelch-like ECH-associated protein 1 (Keap-1)\/nuclear factor erythroid 2\u2013related factor 2 (Nrf2)\/Heme Oxygenase-1 (HO-1), Bone Morphogenetic Protein 2 (BMP2)-Wnt\/\u03b2-catenin, PhosphatidylInositol 3-Kinase (PI3K)\/protein kinase B (Akt)\/Glycogen Synthase Kinase 3 Beta (GSK3\u03b2), and other signaling pathways). Although majority of the studies on the osteoprotective properties of NPs against BDs were conducted ex vivo and mostly on animals, the use of NPs for treating human BDs and the prospects for future development remain promising.<\/jats:p>","DOI":"10.3390\/ijms23158468","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T02:06:42Z","timestamp":1659319602000},"page":"8468","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["A Review on the Molecular Mechanisms of Action of Natural Products in Preventing Bone Diseases"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9424-7535","authenticated-orcid":false,"given":"Innocent U.","family":"Okagu","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka 410001, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7077-3282","authenticated-orcid":false,"given":"Timothy P. C.","family":"Ezeorba","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka 410001, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6690-4657","authenticated-orcid":false,"given":"Rita N.","family":"Aguchem","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka 410001, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6353-1429","authenticated-orcid":false,"given":"Ikenna C.","family":"Ohanenye","sequence":"additional","affiliation":[{"name":"School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel C.","family":"Aham","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka 410001, Nigeria"},{"name":"Natural Science Unit, School of General Studies, University of Nigeria, Nsukka 410001, Nigeria"},{"name":"School of Environment and Safety Engineering, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7476-3292","authenticated-orcid":false,"given":"Sunday N.","family":"Okafor","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka 410001, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5698-1325","authenticated-orcid":false,"given":"Carlotta","family":"Bollati","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, via Mangiagalli 25, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7428-4486","authenticated-orcid":false,"given":"Carmen","family":"Lammi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Milan, via Mangiagalli 25, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1021\/acs.jmedchem.0c01292","article-title":"Bisphosphonates, Old Friends of Bones and New Trends in Clinics","volume":"64","author":"Barbosa","year":"2021","journal-title":"J. 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