The Arachidonic Acid Metabolism Mechanism Based on UPLC-MS/MS Metabolomics in Recurrent Spontaneous Abortion Rats

Li, Meihe; Yang, Huiling; Kang, Min-Hee; An, Peng; Wu, Xiumei; Dang, Huimin; Xu, Xin

doi:10.3389/fendo.2021.652807

Cited by 12 publications

(9 citation statements)

References 53 publications

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“…Glycerophospholipids induce cyclotoxinase-2 (COX-2), which catalyzes the conversion of arachidonic acid, which plays an important role in female reproduction. Metabolites of arachidonic acid are involved in various reproductive activities such as luteolysis, endometrial gene expression, and development [ 47 ]. Arachidonic acid metabolism plays a crucial role in the inflammatory process [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

UPLC-Q-TOF/MS Based Plasma Metabolomics for Identification of Paeonol’s Metabolic Target in Endometriosis

et al. 2023

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Endometriosis is a common gynecological illness in women of reproductive age that significantly decreases life quality and fertility. Paeonol has been shown to play an important part in endometriosis treatments. Understanding the mechanism is critical for treating endometriosis. In this study, autologous transplantation combined with a 28 day ice water bath was used to create a rat model of endometriosis with cold clotting and blood stagnation. The levels of estradiol and progesterone in plasma were detected by ELISA, and the pathological changes of ectopic endometrial tissue were examined by H&E staining, which proved the efficacy of paeonol. For metabolomic analysis of plasma samples, UPLC-Q/TOF-MS was combined with multivariate statistical analysis to identify the influence of paeonol on small molecule metabolites relevant to endometriosis. Finally, the key targets were screened using a combination of network pharmacology and molecular docking approaches. The results showed that the pathological indexes of rats were improved and returned to normal levels after treatment with paeonol, which was the basis for confirming the efficacy of paeonol. Metabolomics results identified 13 potential biomarkers, and paeonol callbacks 7 of them, involving six metabolic pathways. Finally, four key genes were found for paeonol therapy of endometriosis, and the results of molecular docking revealed a significant interaction between paeonol and the four key genes. This study was successful in establishing a rat model of endometriosis with cold coagulation and blood stagnation. GCH1, RPL8, PKLR, and MAOA were the key targets of paeonol in the treatment of endometriosis. It is also demonstrated that metabolomic techniques give the potential and environment for comprehensively understanding drug onset processes.

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Section: Discussionmentioning

confidence: 99%

UPLC-Q-TOF/MS Based Plasma Metabolomics for Identification of Paeonol’s Metabolic Target in Endometriosis

et al. 2023

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“…The levels of arachidonic acid, PGF2α, PGE2 and thromboxane A2 in the amniotic fluid of abortion patients were significantly increased. The release of free arachidonic acid during abortion led to an increase in synthesis of PGF2α, PGE2-prostacyclin and thromboxane A2 in the fetal membranes and decidua, which might be related to abortion process of the patients ( Li et al, 2021 ). Previous studies had shown that PGE2 inhibited the production of Th1 cytokines, but not Th2 cytokines ( Betz and Fox, 1991 ).…”

Section: Discussionmentioning

confidence: 99%

Danggui-Yimucao Herb Pair Can Protect Mice From the Immune Imbalance Caused by Medical Abortion and Stabilize the Level of Serum Metabolites

Yue

Bai

et al. 2021

Front. Pharmacol.

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Unintended pregnancy is a situation that every woman may encounter, and medical abortion is the first choice for women, but abortion often brings many sequelae. Angelica sinensis Radix (Danggui) and Leonuri Herba (Yimucao) are widely used in the treatment of gynecological diseases, which can regulate menstrual disorders, amenorrhea, dysmenorrhea, and promote blood circulation and remove blood stasis, but the mechanism for the treatment of abortion is not clear. We determined the ability of Danggui and Yimucao herb pair (DY) to regulate the Th1/Th2 paradigm by detecting the level of progesterone in the serum and the expression of T-bet and GATA-3 in the spleen and uterus. Then, we detected the level of metabolites in the serum and enriched multiple metabolic pathways. The arachidonic acid pathway can directly regulate the differentiation of Th1/Th2 cells. This may be one of the potential mechanisms of DY in the treatment of abortion.

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“…Mouse serum was collected, and metabolites were extracted using methanol based on a previously described protocol 44 . Lipid‐related products were separated using UPLC (Sciex ExionLC™ AD) and further analyzed using MS (Sciex QTRAP 6500+) to determine specific m/z values of oxidized lipid products.…”

Section: Methodsmentioning

confidence: 99%

VNS‐mediated α7nAChR signaling promotes SPM synthesis via regulation of netrin‐1 expression during LPS‐induced ALI

Huang,

Dong,

et al. 2023

The FASEB Journal

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The α7 nicotinic acetylcholine receptor (α7nAChR) plays a crucial role in the cholinergic anti‐inflammatory pathway (CAP) during sepsis‐associated acute lung injury (ALI). Increasing evidence suggests that specialized pro‐resolving mediators (SPMs) are important in resolving α7nAChR‐mediated ALI resolution. Our study aims to elucidate the pivotal role of α7nAChR in the CAP during LPS‐associated acute lung injury (ALI). By employing vagus nerve stimulation (VNS), we identified α7nAChR as the key CAP subunit in ALI mice, effectively reducing lung permeability and the release of inflammatory cytokines. We further investigated the alterations in SPMs regulated by α7nAChR, revealing a predominant synthesis of lipoxin A4 (LXA4). The significance of α7nAChR‐netrin‐1 pathway in governing SPM synthesis was confirmed through the use of netrin‐1 knockout mice and siRNA‐transfected macrophages. Additionally, our evaluation identified a synchronous alteration of LXA4 synthesis in the α7nAChR‐netrin‐1 pathway accompanied by 5‐lipoxygenase (5‐LOX), thereby confirming an ameliorative effect of LXA4 on lung injury and macrophage inflammatory response. Concurrently, inhibiting the function of LXA4 annulled the lung‐protective effect of VNS. As a result, our findings reveal a novel anti‐inflammatory pathway wherein VNS modulates netrin‐1 expression via α7nAChR, ultimately leading to LXA4 synthesis and subsequent lung protection.

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The Arachidonic Acid Metabolism Mechanism Based on UPLC-MS/MS Metabolomics in Recurrent Spontaneous Abortion Rats

Cited by 12 publications

References 53 publications

UPLC-Q-TOF/MS Based Plasma Metabolomics for Identification of Paeonol’s Metabolic Target in Endometriosis

UPLC-Q-TOF/MS Based Plasma Metabolomics for Identification of Paeonol’s Metabolic Target in Endometriosis

Danggui-Yimucao Herb Pair Can Protect Mice From the Immune Imbalance Caused by Medical Abortion and Stabilize the Level of Serum Metabolites

VNS‐mediated α7nAChR signaling promotes SPM synthesis via regulation of netrin‐1 expression during LPS‐induced ALI

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