Work

Xanthium strumarium L. Exhibits Potent Antiplatelet and Antithrombotic Effects by Modulating MAPK and PI3K/AKT Signaling Pathways and Inhibiting Ferric Chloride-Induced Thrombosis

Year: 2025

Type: article

Abstract: Background: Cardiovascular diseases, driven by platelet hyperactivation and thrombosis, remain the leading global cause of death. Excessive platelet activation contributes to ath-erosclerosis and thrombo-inflammatory disorders, underscoring the urgent need for safer and more effective antiplatelet agents. Objectives: Xanthium strumarium L. (X. strumarium) has been reported to exhibit a wide range of pharmacological effects, including an-ti-inflammatory and antioxidant activities. However, its antiplatelet and antithrombotic effects remain unexplored. Therefore, the present study aimed to evaluate these effects us-ing integrated in vitro, in vivo, and network pharmacological approaches. Methods: In vitro antiplatelet effects were evaluated via light transmission aggregometry, ATP and cal-cium mobilization assays, αIIbβ3 signaling, and western blot analysis. In vivo ferric chlo-ride-induced (FeCl3) murine thrombus model was established to evaluate thrombogenesis. The major compounds identified by GC-MS analysis were analyzed for pharmacokinetics, drug-likeness, and network pharmacology. Results: Our results demonstrated that X. strumarium at 25, 50, or 100 μg/mL significantly inhibited agonist-induced platelet aggre-gation. The granule secretion, integrin-αIIbβ3 signaling, and the MAPK and PI3K/Akt pathways were also dose-dependently inhibited. The in vivo blood flow rate and the mice survival rates were improved. BOILED-Egg analysis revealed that catechol, 2,1,3-benzothiadiazole, and hydroquinone exhibited high gastrointestinal absorption (score ≥ 0.55), suggesting favorable pharmacokinetic properties. Finally, network phar-macological analysis linked these compounds to platelet- and inflammation-related genes enriched in KEGG pathways, including those related to the Toll-like receptor, HIF-1, and actin cytoskeleton regulation. Conclusions: Collectively, X. strumarium exhibited potent antiplatelet and antithrombotic properties with the identification of catechol, 2,1,3-benzothiadiazole, and hydroquinone as key bioactive compounds.

Source: Biomedicines

DOI: 10.3390/biomedicines13122924