We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The therapeutic mechanism of Curcumae Radix against primary dysmenorrea based on 5-HTR/Ca<sup>2+</sup>/MAPK and fatty acids metabolomics.
- Authors
Yuwen Qin; Wei Zhang; Zhenhua Bian; Chenghao Fei; Lianlin Su; Rong Xue; Qian Zhang; YuLi; Peng Chen; Yabo Shi; Mingxuan Li; Chunqin Mao; Xiaoli Zhao; De Ji; Tulin Lu
- Abstract
Background: Curcumae 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. Objective: To investigate the therapeutic effects of CW on PD and its possible mechanisms of action. Methods: An isolated uterine spastic contraction model induced by oxytocin was constructed in an in vitro pharmacodynamic assay. An animal model of PD induced by combined estradiol benzoate and adrenaline hydrochlorideassisted 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. Results: In vitro, CW can relax an isolated uterus by reducing uterine motility. In vivo, the results showed thatCWattenuated histopathological damage in the uterus and regulated PGF2α, PGE2, β-EP, 5-HT, and Ca2+ 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/Ca2+/MAPK pathway, such as 5-HTR2A, IP3R, PKC, cALM, and ERK. Similarly, CW downregulated the expression of key proteins in the 5-HTR/Ca2+/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). Conclusion: The development of PD may be associated with the inhibition of the 5-HTR/Ca2+/MAPK signaling pathway and FA metabolic pathways, providing a basis for the subsequent exploitation of CW.
- Subjects
METABOLOMICS; ARACHIDONIC acid; FATTY acids; TANDEM mass spectrometry; TIME-of-flight mass spectrometry; ORAL drug administration; UTERINE contraction
- Publication
Frontiers in Pharmacology, 2023, Vol 14, p01
- ISSN
1663-9812
- Publication type
Article
- DOI
10.3389/fphar.2023.1087654