{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:30:16Z","timestamp":1787563816398,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Grant-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["19H01089"],"award-info":[{"award-number":["19H01089"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Grant-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["21K11606"],"award-info":[{"award-number":["21K11606"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Grant-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["JPMJFR205G"],"award-info":[{"award-number":["JPMJFR205G"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19H01089"],"award-info":[{"award-number":["19H01089"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K11606"],"award-info":[{"award-number":["21K11606"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JPMJFR205G"],"award-info":[{"award-number":["JPMJFR205G"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Polymethoxyflavonoids, such as nobiletin (abundant in Citrus depressa), have been reported to have antioxidant, anti-inflammatory, anticancer, and anti-dementia effects, and are also a circadian clock modulator through retinoic acid receptor-related orphan receptor (ROR) \u03b1\/\u03b3. However, the optimal timing of nobiletin intake has not yet been determined. Here, we explored the time-dependent treatment effects of nobiletin and a possible novel mechanistic idea for nobiletin-induced circadian clock regulation in mice. In vivo imaging showed that the PER2::LUC rhythm in the peripheral organs was altered in accordance with the timing of nobiletin administration (100 mg\/kg). Administration at ZT4 (middle of the light period) caused an advance in the peripheral clock, whereas administration at ZT16 (middle of the dark period) caused an increase in amplitude. In addition, the intraperitoneal injection of nobiletin significantly and potently stimulated corticosterone and adrenaline secretion and caused an increase in Per1 expression in the peripheral tissues. Nobiletin inhibited phosphodiesterase (PDE) 4A1A, 4B1, and 10A2. Nobiletin or rolipram (PDE4 inhibitor) injection, but not SR1078 (ROR\u03b1\/\u03b3 agonist), caused acute Per1 expression in the peripheral tissues. Thus, the present study demonstrated a novel function of nobiletin and the regulation of the peripheral circadian clock.<\/jats:p>","DOI":"10.3390\/nu16101491","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T06:14:42Z","timestamp":1715753682000},"page":"1491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Nobiletin Stimulates Adrenal Hormones and Modulates the Circadian Clock in Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Conn","family":"Ryan","sequence":"first","affiliation":[{"name":"Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo 162-0056, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3015-8883","authenticated-orcid":false,"given":"Yu","family":"Tahara","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo 162-0056, Japan"},{"name":"Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-0037, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4162-2474","authenticated-orcid":false,"given":"Atsushi","family":"Haraguchi","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo 162-0056, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-0037, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6177-1963","authenticated-orcid":false,"given":"Shigenobu","family":"Shibata","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo 162-0056, Japan"},{"name":"Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-0037, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1126\/science.1195027","article-title":"Circadian integration of metabolism and energetics","volume":"330","author":"Bass","year":"2010","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Franzago, M., Alessandrelli, E., Notarangelo, S., Stuppia, L., and Vitacolonna, E. 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