{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:36:57Z","timestamp":1792467417705,"version":"4.5.0"},"reference-count":93,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T00:00:00Z","timestamp":1650672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Flavonoids are natural phytochemicals that have therapeutic effects and act in the prevention of several pathologies. These phytochemicals can be found in seeds, grains, tea, coffee, wine, chocolate, cocoa, vegetables and, mainly, in citrus fruits. Neohesperidin, hesperidin and hesperetin are citrus flavonoids from the flavanones subclass that have anti-inflammatory and antioxidant potential. Neohesperidin, in the form of neohesperidin dihydrochalcone (NHDC), also has dietary properties as a sweetener. In general, these flavanones have been investigated as a strategy to control bone diseases, such as osteoporosis and osteoarthritis. In this literature review, we compiled studies that investigated the effects of neohesperidin, hesperidin and its aglycone, hesperetin, on bone health. In vitro studies showed that these flavanones exerted an antiosteoclastic and anti- inflammatory effects, inhibiting the expression of osteoclastic markers and reducing the levels of reactive oxygen species, proinflammatory cytokines and matrix metalloproteinase levels. Similarly, such studies favored the osteogenic potential of preosteoblastic cells and induced the overexpression of osteogenic markers. In vivo, these flavanones favored the regeneration of bone defects and minimized inflammation in arthritis- and periodontitis-induced models. Additionally, they exerted a significant anticatabolic effect in ovariectomy models, reducing trabecular bone loss and increasing bone mineral density. Although research should advance to the clinical field, these flavanones may have therapeutic potential for controlling the progression of metabolic, autoimmune or inflammatory bone diseases.<\/jats:p>","DOI":"10.3390\/biom12050626","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T21:39:45Z","timestamp":1650749985000},"page":"626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Therapeutic Effects of Citrus Flavonoids Neohesperidin, Hesperidin and Its Aglycone, Hesperetin on Bone Health"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0783-3246","authenticated-orcid":false,"given":"Adriana de C\u00e1ssia","family":"Ortiz","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Bauru School of Dentistry (FOB\/USP), University of S\u00e3o Paulo, Bauru 17012-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone Ortiz Moura","family":"Fideles","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Bauru School of Dentistry (FOB\/USP), University of S\u00e3o Paulo, Bauru 17012-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Henrique Bertoni","family":"Reis","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Bauru School of Dentistry (FOB\/USP), University of S\u00e3o Paulo, Bauru 17012-901, Brazil"},{"name":"UNIMAR Beneficent Hospital (HBU), Faculty of Medicine, University of Marilia (UNIMAR), Mar\u00edlia 17525-160, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rcia Zilioli","family":"Bellini","sequence":"additional","affiliation":[{"name":"Pro-Rectory of Research and Graduate Studies, University Center of Adamantina (UniFAI), Adamantina 17800-000, 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School, University of Marilia (UNIMAR), Mar\u00edlia 17525-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna Trazzi","family":"Pagani","sequence":"additional","affiliation":[{"name":"Dentistry School, University of Marilia (UNIMAR), Mar\u00edlia 17525-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Burgos","family":"Ponce","sequence":"additional","affiliation":[{"name":"Medicine Department, University Center of Adamantina (UniFAI), Adamantina 17800-000, Brazil"},{"name":"Medicine Department, Faculties of Dracena (FUNDEC Unifadra), Dracena 17900-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiane Priscila","family":"Gardizani","sequence":"additional","affiliation":[{"name":"Medicine Department, University Center of Adamantina (UniFAI), Adamantina 17800-000, Brazil"},{"name":"Faculty of Medicine S\u00e3o Leopoldo Mandic (SLMANDIC), Araras 13606-134, 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Leone","family":"Buchaim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Bauru School of Dentistry (FOB\/USP), University of S\u00e3o Paulo, Bauru 17012-901, Brazil"},{"name":"Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of S\u00e3o Paulo (FMVZ\/USP), S\u00e3o Paulo 05508-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1196\/annals.1365.035","article-title":"Bone Remodeling","volume":"1092","author":"Hadjidakis","year":"2006","journal-title":"Ann. 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