{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T18:15:15Z","timestamp":1784916915859,"version":"3.55.0"},"reference-count":66,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The Wnt\/\u03b2\u2010catenin signaling pathway is pivotal for osteoblast differentiation, bone formation, and skeletal homeostasis, with its dysregulation linked to osteoporosis and fracture non\u2010union. Phytochemicals offer promising alternatives to unstable Wnt ligands, which risk tumorigenesis due to non\u2010specific activation. In this study, we performed an extensive computational screening of selected phytochemicals\u2014including quercetin, kaempferol, apigenin, genistein, gallic acid, ursolic acid, 2\u03b1\u2010hydroxy ursolic acid, and berberine\u2014previously reported to modulate the Wnt\/\u03b2\u2010catenin pathway. These compounds, derived from diverse phytochemical classes including flavonoids, isoflavones, phenolic acids, triterpenoids, and alkaloids, have been shown in prior experimental studies to promote osteogenic responses by stabilizing \u03b2\u2010catenin, inhibiting GSK\u20103\u03b2, and upregulating osteogenic genes such as\n                    <jats:italic>Axin2<\/jats:italic>\n                    and\n                    <jats:italic>cyclin D1<\/jats:italic>\n                    . To complement these findings, we employed computational approaches, including gene\u2013drug interaction analysis (DGIdb), structural similarity screening (Data Warrior, &gt;\u200990% similarity to known drugs), and molecular docking (Maestro Schr\u00f6dinger Suite), to predict high\u2010affinity interactions with key regulatory proteins in the Wnt pathway. Our docking results revealed high binding affinities of phytochemicals to key targets that are involved in the modulation of the Wnt\/\u03b2\u2010catenin pathway, such as Casein Kinase (CK, docking scores: \u221210.652 to \u221211.39), Estrogen Receptor (ER, docking score: \u22127.337 to \u221211.314), Vitamin D Receptor (VDR, docking score: \u22127.40 to \u22129.97), and GSK\u20103\u03b2, with critical interactions involving residues like E305 and R346. Specifically, Caviunin glycoside from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Dalbergia sissoo<\/jats:italic>\n                    <\/jats:styled-content>\n                    demonstrated estrogenic modulation within the ER ligand\u2010binding domain (PDB ID: 1X7J; docking score: \u22125.29), supporting its role in osteoblast stimulation via ER\u2010Wnt crosstalk. Structure\u2013activity analyses identify flavanone glycosides and triterpenoids as promising scaffolds for medicinal chemistry optimization. Challenges, including poor bioavailability and off\u2010target effects, necessitate advanced delivery systems and computational modeling to enhance selectivity and therapeutic utility, positioning these phytochemicals as viable leads for bone\u2010related disorder treatments.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70304","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T11:42:16Z","timestamp":1775475736000},"page":"3504-3524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phytochemicals Targeting Wnt\/\u03b2\u2010Catenin in Osteoblasts: Mechanisms, Scaffolds, and Computational Insights for Bone Therapeutics"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9419-0364","authenticated-orcid":false,"given":"Aarti Abhishek","family":"Shah","sequence":"first","affiliation":[{"name":"Division of Pharmacology Anekant Education Society's 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