{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T15:58:50Z","timestamp":1783612730475,"version":"3.55.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173975 81973483"],"award-info":[{"award-number":["82173975 81973483"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold><jats:italic>Curcumae<\/jats:italic> Radix (CW) is traditionally used to treat primary dysmenorrea (PD). However, the mechanisms of action of CW in the treatment of PD have not yet been comprehensively resolved.<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold> To investigate the therapeutic effects of CW on PD and its possible mechanisms of action.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> An isolated uterine spastic contraction model induced by oxytocin was constructed in an <jats:italic>in vitro<\/jats:italic> pharmacodynamic assay. An animal model of PD induced by combined estradiol benzoate and adrenaline hydrochloride-assisted stimulation was established. After oral administration of CW, a histopathological examination was performed and biochemical factor levels were measured to evaluate the therapeutic effect of CW on PD. The chemical compositions of the drug-containing serum and its metabolites were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Network pharmacology and serum untargeted metabolomics were used to predict the mechanism of CW treatment for PD, and the predicted results were validated by RT-qPCR, WB, and targeted fatty acid (FA) metabolism.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold><jats:italic>In vitro,<\/jats:italic> CW can relax an isolated uterus by reducing uterine motility. <jats:italic>In vivo<\/jats:italic>, the results showed that CW attenuated histopathological damage in the uterus and regulated PGF<jats:sub>2\u03b1<\/jats:sub>, PGE<jats:sub>2<\/jats:sub>, \u03b2-EP, 5-HT, and Ca<jats:sup>2+<\/jats:sup> levels in PD rats. A total of 66 compounds and their metabolites were identified in the drug-containing serum, and the metabolic pathways of these components mainly included hydrogenation and oxidation. Mechanistic studies showed that CW downregulated the expression of key genes in the 5-HTR\/Ca<jats:sup>2+<\/jats:sup>\/MAPK pathway, such as 5-HTR2A, IP3R, PKC, cALM, and ERK. Similarly, CW downregulated the expression of key proteins in the 5-HTR\/Ca<jats:sup>2+<\/jats:sup>\/MAPK pathway, such as p-ERK\/ERK. Indirectly, it ameliorates the abnormal FA metabolism downstream of this signaling pathway in PD rats, especially the metabolism of arachidonic acid (AA).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The development of PD may be associated with the inhibition of the 5-HTR\/Ca<jats:sup>2+<\/jats:sup>\/MAPK signaling pathway and FA metabolic pathways, providing a basis for the subsequent exploitation of CW.<\/jats:p>","DOI":"10.3389\/fphar.2023.1087654","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T06:19:12Z","timestamp":1678342752000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The therapeutic mechanism of Curcumae Radix against primary dysmenorrea based on 5-HTR\/Ca2+\/MAPK and fatty acids metabolomics"],"prefix":"10.3389","volume":"14","author":[{"given":"Yuwen","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghao","family":"Fei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianlin","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yabo","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunqin","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tulin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12906-022-03515-2","article-title":"Effects of curcumin supplementation on vitamin D levels in women with premenstrual syndrome and dysmenorrhea: A randomized controlled study","volume":"22","author":"Arabnezhad","year":"2022","journal-title":"BMC Complement. 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