Protective effects and mechanisms of Saikosaponin A against myocardial ischemia based on network pharmacology, molecular docking, and experimental validation.

Saikosaponin A (SSA) is the primary component of Bupleuri radix, which has a variety of pharmacological properties. However, the potential mechanism of SSA's anti-myocardial ischemia (MI) effect has not yet been clarified. We investigated the exact effects and potential mechanisms of SSA on isoproterenol (ISO)-induced MI. A range of network pharmacology approaches have been applied to explore central targets and their underlying mechanisms. Molecular docking was used to identify the binding ability of the potential active components to the hub targets. A rat model of MI was established by subcutaneous injection of ISO (85 mg/kg/day). The pathological myocardial morphology, myocardial enzymes, reactive oxygen species (ROS) production, myocardial mitochondrial structure, apoptosis level, and expression of key proteins in the apoptotic pathway were analyzed. Our animal studies revealed that SSA attenuated ISO-induced pathological cardiac injury and significantly reduced creatine kinase (CK), lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB) levels, ROS production, and damage to mitochondrial structures in the heart. In addition, SSA downregulated P53, Caspase-3, and BAX protein activities, upregulated BCL 2 protein activity, and attenuated cardiomyocyte apoptosis. Saikosaponin A alleviates ISO-induced MI by regulating the expression of proteins involved in the P53/BAX/Caspase-3 signaling pathway. Our data showed show that SSA can improve ISO-induced MI. In addition, the role of SSA may be related to its antioxidant stress, anti-apoptosis, and regulation of P53/BAX/Caspase-3 signaling pathway.