{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:06:08Z","timestamp":1789391168123,"version":"build-2803163510"},"reference-count":74,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Special Project for Jiangxi Province Key Research and Development Program Project","award":["20261BCF320046"],"award-info":[{"award-number":["20261BCF320046"]}]},{"name":"Jiangxi Province Science and Technology Plan Project","award":["20213BCJ22027"],"award-info":[{"award-number":["20213BCJ22027"]}]},{"name":"Jiangxi University of Chinese Medicine Doctoral Research Startup Fund","award":["2023BSZR025"],"award-info":[{"award-number":["2023BSZR025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Ligusticum sinense Oliv. cv. Chaxiong (Chaxiong) has traditionally been used as a medicinal tea for headache relief in southern China, but its bioactive basis and mechanisms remain unclear. This study integrated ultra-performance liquid chromatography\u2013quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS\/MS), untargeted metabolomics, network pharmacology, molecular docking, reverse-transcription quantitative PCR (RT-qPCR), and Western blotting in a nitroglycerin-induced migraine-like rat model. Chaxiong extract alleviated migraine-like behavior, reduced calcitonin gene-related peptide (CGRP), nitric oxide (NO), and tumor necrosis factor-\u03b1 (TNF-\u03b1), increased 5-hydroxytryptamine (5-HT), and ameliorated brain histopathological alterations. A total of 48 constituents and 13 differential serum metabolites were annotated or putatively annotated, respectively. Glycerophospholipid metabolism was the principal metabolic pathway affected by treatment, whereas network pharmacology prioritized phosphatidylinositol 3-kinase\/protein kinase B (PI3K\/AKT) signaling. Pathway integration identified PIK3CA, PIK3CB, AKT1, AKT2, and INS as candidate bridging targets. Exploratory docking suggested potential interactions between five representative constituents and PIK3CA\/AKT1. RT-qPCR showed reduced Pik3ca and Akt1 mRNA expression, while Western blotting showed decreased p-PI3K p85\u03b1 (Tyr607)\/PI3K p85\u03b1 and p-AKT (Ser473)\/AKT1 ratios following treatment. These findings suggest that Chaxiong-associated alleviation of migraine-like responses was accompanied by altered glycerophospholipid metabolism and reduced PI3K\/AKT pathway activation.<\/jats:p>","DOI":"10.3390\/ijms27188169","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:09:51Z","timestamp":1789387791000},"page":"8169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ligusticum sinense Oliv. cv. Chaxiong Extract Alleviates Nitroglycerin-Induced Migraine-like Responses in Rats: Associations with Glycerophospholipid Metabolism and PI3K\/AKT Signaling"],"prefix":"10.3390","volume":"27","author":[{"given":"Yu","family":"Zhu","sequence":"first","affiliation":[{"name":"The Research Center for Traditional Chinese Medicine Resources and Ethnic Minority, Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjing","family":"Dong","sequence":"additional","affiliation":[{"name":"The Research Center for Traditional Chinese Medicine Resources and Ethnic Minority, Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyi","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Research Center for Traditional Chinese Medicine Resources and Ethnic Minority, Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Qin","sequence":"additional","affiliation":[{"name":"The Research Center for Traditional Chinese Medicine Resources and Ethnic Minority, Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"He","sequence":"additional","affiliation":[{"name":"The Research Center for Traditional Chinese Medicine Resources and Ethnic Minority, Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Wu","sequence":"additional","affiliation":[{"name":"The Research Center for Traditional Chinese Medicine Resources and Ethnic Minority, Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4922-3577","authenticated-orcid":false,"given":"Shouwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Research Center for Traditional Chinese Medicine Resources and Ethnic Minority, Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wei","sequence":"additional","affiliation":[{"name":"The Research Center for Traditional Chinese Medicine Resources and Ethnic Minority, Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s10194-023-01654-6","article-title":"Status of diagnosis and preventative treatment for primary headache disorders: Real-world data of unmet needs in China","volume":"24","author":"Liu","year":"2023","journal-title":"J. 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