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The cytotoxic effect of nymphaeols on human DPSCs was observed using a 3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u20102,5\u2010diphenyltetrazolium bromide (MTT) assay. The effect of nymphaeols on odontoblast differentiation was analysed with Alizarin Red S staining and odontoblast marker expression was assessed using real\u2010time polymerase chain reaction and Western blot analysis. The molecular mechanism was investigated with Western blot analysis. In order to examine the effect of INB on dentine formation in the developing tooth germ, INB\u2010soaked beads were placed under the tooth bud explants in the collagen gel; thereafter, the tooth bud explant\u2010bead complexes were implanted into the sub\u2010renal capsules for 3\u00a0weeks. Tooth root formation was analysed using micro\u2010computed tomography and histological analysis. Data are presented as mean\u00a0\u00b1\u00a0standard error (SEM) values of three independent experiments, and results are compared using a two\u2010tailed Student's <jats:italic>t<\/jats:italic>\u2010test. The data were considered to have statistical significance when the <jats:italic>P<\/jats:italic>\u2010value was less than 0.05.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three of the compounds, NB, INB, and GN, did not exert a cytotoxic effect on human DPSCs. However, INB was most effective in promoting the deposition of calcium minerals <jats:italic>in vitro<\/jats:italic> (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and induced the expression of odontogenic marker genes (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Moreover, this compound strongly induced the phosphorylation of mitogen\u2010activated protein (MAP) kinases and protein kinase B (AKT) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). The inhibition of p38 MAP, c\u2010Jun N\u2010terminal kinase (JNK), and AKT substantially suppressed the INB\u2010induced odontoblast differentiation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). In addition, isonymphaeol B significantly induced the formation of dentine and elongation of the tooth root <jats:italic>in vivo<\/jats:italic> (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Prenylflavonoids, including INB, exerted stimulatory effects on odontoblast differentiation and tooth root and dentine formation via the MAP kinase and AKT signalling pathways. These results suggest that nymphaeols could stimulate the repair processes for dentine defects or injuries.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.13503","type":"journal-article","created":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T12:59:08Z","timestamp":1614517148000},"page":"1142-1154","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Prenylflavonoids isolated from <i>Macaranga tanarius<\/i> stimulate odontoblast differentiation of human dental pulp stem cells and tooth root formation via the mitogen\u2010activated protein kinase and protein kinase B pathways"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9226-8482","authenticated-orcid":false,"given":"S. H.","family":"Nam","sequence":"first","affiliation":[{"name":"Department of Oral Pathology and Regenerative Medicine School of Dentistry Kyungpook National University Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Yamano","sequence":"additional","affiliation":[{"name":"Faculty of Education University of the Ryukyu Nakagami\u2010gun Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. A.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology and Regenerative Medicine School of Dentistry Kyungpook National University Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3277-9330","authenticated-orcid":false,"given":"J.","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology and Regenerative Medicine School of Dentistry Kyungpook National University Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. H.","family":"Baek","sequence":"additional","affiliation":[{"name":"Orthognathic\/Oral &amp; Maxillofacial Surgery Cha &amp; Baek Dental Clinic Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. E.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine School of Medicine Kyungpook National University Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2799-0510","authenticated-orcid":false,"given":"T.G.","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery School of Dentistry Kyungpook National University Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Saito","sequence":"additional","affiliation":[{"name":"Faculty of Education University of the Ryukyu Nakagami\u2010gun Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Teruya","sequence":"additional","affiliation":[{"name":"Faculty of Education University of the Ryukyu Nakagami\u2010gun Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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