Integrating Network Pharmacology, Molecular Modeling and In Vitro Biological Evaluation to Elucidate the Cardioprotective Potential of Stereospermum suaveolens

Doxorubicin is a widely used anthracycline chemotherapeutic agent, but its clinical application is severely restricted by dose‐dependent cardiotoxicity, necessitating the development of effective cardioprotective strategies. This study elucidated the cardioprotective potential of Stereospermum suaveolens against cardiotoxicity by integrating network pharmacology, molecular modeling, and in vitro biological assays. LC‐MS profiling identified key bioactive compounds, including Dinatin, Apigenin, and β‐sitosterol. Network pharmacology analysis revealed 46 common targets linking these bioactives to cardiotoxicity mitigation, with topological analysis identifying PIK3R1, STAT3, MAPK1, and HIF1A as central hub proteins regulating the HIF‐1, PI3K‐Akt, and FoxO signaling pathways. Molecular docking studies demonstrated that Dinatin exhibited the strongest binding affinity toward PIK3R1 (−10.40 kcal/mol), whereas Apigenin demonstrated the highest binding affinity toward MAPK1 (−6.99 kcal/mol) compared to standard drugs, while 100 ns molecular dynamics simulations confirmed the dynamic stability of these protein‐ligand complexes. Furthermore, the Stereospermum suaveolens extract displayed potent antioxidant activity in the DPPH assay with an IC50 of 57.1 µg/mL, surpassing the standard ascorbic acid (IC50 61.5 µg/mL), and exhibited significant biological activity in the brine shrimp lethality assay (LC50 62.5 µg/mL). These findings support the traditional use of Stereospermum suaveolens and identify Dinatin as a promising multi‐target compound with potential against cardiotoxicity.