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Impatiens shenglanii exerts antithrombotic effects by inhibiting the PI3K/Akt/GSK3B signaling pathway and
Sini Wang1, Huimin Zhou1, Kangbo Peng2
1Hubei Key Laboratory of Chinese Medicine Resources and Medicinal Chemistry, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
Abstract:
This study aims to elucidate the chemical characteristics of Impatiens shenglanii Q.L. Gan & X.W. Li (IS) through integrated omics analysis and experimental validation methods, and to investigate its antithrombotic effects and potential mechanisms. The compounds of IS were examined through UPLC-QTOF-MS/MS. In vitro, anti-inflammatory and antithrombotic effects were evaluated using RAW264.7 cell inflammation models, platelet aggregation assays, and coagulation four items. In vivo, a mouse model of carrageenan-induced thrombosis was employed to evaluate the impact of IS on thrombus formation, coagulation processes, and inflammatory responses. Integrated network pharmacology and plasma metabolomics analyses were performed to identify potential mechanisms, which were validated by western blot (WB) and immunohistochemistry (IHC). The 82 compounds of IS were analyzed, and mixed standards were used to identify 32 compounds. Among them, network pharmacology results found that diosmetin, kaempferol, tricin, and scopoletin are the main active components of IS. In vitro experiments indicated that IS possesses antiplatelet aggregation and anticoagulant properties, capable of downregulating the levels of inflammatory mediators in cells. In vivo experiments have revealed that IS ameliorated pathological tissue changes, inhibited thrombus formation, reduced inflammatory cytokine expression, and improved coagulation parameters. Network pharmacology, metabolomics, WB, and IHC results suggest that IS exerts its antithrombotic effects by inhibiting the PI3K/Akt/GSK3B pathway and arachidonic acid (AA) metabolism. IS exerts antithrombotic effects by inhibiting the PI3K/Akt/GSK3B signaling pathway and reprogramming AA metabolism.
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