Decoding the anti-thrombotic effects of leonurine: a multimodal approach combining TCM repositioning and mTOR signaling.

Background: As a natural small molecule compound, Leonurine have great potential for application in the treatment of cardiovascular diseases. However, there is still a gap in the treatment of thrombosis with Leonurine.

Methods: A multimodal heterogeneous network is constructed using ETCM and STRING databases, integrating herbs, ingredients, targets and diseases. A reposition model constructed by random walk and random forests is used to predict the relationship between Leonurine and diseases. In addition, network pharmacology, molecular docking and molecular dynamics are used as computer-aided methods to confirm the target of Leonurine. Finally, CCK-8 assay, Flow cytometry, Western Blotting, and mouse experiments are used to validate the therapeutic potential of Leonurine from the perspective of biological wet experiments.

Results: Firstly, based on the accurate prediction results evaluated by indicators, Leonurine is evaluated to have potential therapeutic effects on thrombotic diseases. Through computer-aided methods, mTOR is identified as a potential regulatory factor and may have a similar regulatory mechanism to the marketed drug Everolimus. Experimental results demonstrate that Leonurine reduces thrombotic cell apoptosis and promotes endothelial cell proliferation by inhibiting mTOR signaling. Additionally, in vivo studies show decrease mTOR expression in thrombotic tissues following Leonurine treatment.

Conclusions: These findings underscore mTOR's critical role in mediating Leonurine's anti-thrombotic effects, supported by both computational and experimental evidence. The study provides a foundation for the application of TCM-derived compounds in modern medicine, particularly in thrombosis treatment.