Anticoagulant effect of sodium astragaloside in hepatic fibrosis animal models: Therapeutic potential in chronic liver disease

Objective Astragali Radix (Huangqi in Chinese) is widely used in traditional Chinese medicine for fibrotic diseases and has thromboprophylactic properties. Sodium astragaloside (SA), a derivative of astragaloside IV, has shown antifibrotic activity in other organs. This study aimed to evaluate SA anticoagulant effect and therapeutic potential in chronic liver disease (CLD). Methods A carbon tetrachloride (CCl 4 )-induced liver injury model and a high-fat diet-induced metabolic dysfunction-associated steatohepatitis (MASH) model were established in mice to assess hepatic injury and fibrosis. Adenosine 5′-diphosphate (ADP)-stimulated platelet assays were performed to examine platelet adhesion, activation, and fibrin formation. A ponatinib-induced zebrafish thrombosis model was used to evaluate antithrombotic activity in vivo . RNA sequencing of liver endothelial cells was conducted to explore the underlying mechanisms. Results SA inhibited procoagulant platelet activity, reduced ADP-mediated platelet adhesion, activation, and fibrin formation, and suppressed thrombus formation in zebrafish in a dose-dependent manner. In MASH mice, RNA sequencing indicated that SA modulated complement and coagulation cascades in endothelial cells. SA also alleviated hepatic injury and fibrosis-related histopathological changes in mouse models. Conclusion SA exerts anticoagulant activity in vitro and in vivo and may be a promising candidate for CLD intervention. Its effects may be related to inhibition of platelet activation and regulation of complement and coagulation pathways in endothelial cells.