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B"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Growing evidence suggests that esculetin, a 5-lipoxygenase inhibitor, has pharmacotherapeutic potential due to its various pharmacological properties, such as potent anti-inflammatory, anti-nociceptive, and \u03b3-aminobutyric acid type A (GABA\n                    <jats:sub>A<\/jats:sub>\n                    ) receptor partial agonist activities. However, the effects of this promising agent on migraine remain unexplored. This study therefore examined the impact of esculetin on relevant mechanisms in migraine-like conditions in rats. The systemic effects of esculetin at three distinct doses (5, 10, and 20 mg\/kg) were tested in a nitroglycerin (NTG)-induced migraine model using in vivo experimental sets. The direct action of esculetin on the release of calcitonin gene-related peptide (CGRP) from critical structures of the trigeminovascular system (trigeminal ganglion, trigeminal nucleus, and meningeal afferents) was also tested in ex vivo experimental sets. Sumatriptan was used as a positive control in both sets of experiments. The in vivo results showed that esculetin reduced NTG-induced mechanical hyperalgesia and decreased trigeminal CGRP and cellular Fos proto-oncogene (c-Fos) levels. It also decreased degranulation and meningeal mast cell numbers. The ex vivo results revealed that esculetin reduced NTG-stimulated CGRP release from trigeminovascular explants, with the exception of meningeal explants. Sumatriptan reversed the NTG-induced changes in both experimental sets. Our findings suggest that esculetin exhibits anti-nociceptive activities in experimental migraine conditions, alleviating trigeminovascular CGRP concentrations and the degranulation of meningeal mast cells. Esculetin may thus represent a therapeutic option for relieving migraine headaches, although further research is needed to confirm this.\n                  <\/jats:p>","DOI":"10.1631\/jzus.b2500147","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:52:26Z","timestamp":1777611146000},"page":"615-627","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Esculetin attenuates migraine-like pain via CGRP suppression and meningeal mast cell modulation in rat models","\u79e6\u76ae\u4e59\u7d20\u53ef\u901a\u8fc7\u6291\u5236\u964d\u9499\u7d20\u57fa\u56e0\u76f8\u5173\u80bd (CGRP) \u548c\u8c03\u8282\u8111\u819c\u80a5\u5927\u7ec6\u80de\u51cf\u8f7b\u5927\u9f20\u504f\u5934\u75db\u6837\u75bc\u75db"],"prefix":"10.1631","volume":"27","author":[{"given":"Ayca Nur","family":"Gonul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim Ethem","family":"Torun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin Baranoglu","family":"Kilinc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9261-2634","authenticated-orcid":false,"given":"Erkan","family":"Kilinc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"635","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"issue":"6","key":"833_CR1","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1111\/ejn.16106","volume":"59","author":"Y Baranoglu Kilinc","year":"2024","unstructured":"Baranoglu Kilinc Y, Torun IE, Kilinc E, 2024. 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The animals were treated in harmony with the National Institutes of Health guide for the care and use of laboratory animals.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethics guidelines"}},{"value":"No generative AI tools were used in the preparation of this manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration on the use of generative AI tools"}}]}}