Bioactive components from Kaixin san alleviate bradyarrhythmia via modulation of the calcium signaling pathway: Integrated UPLC-Q-TOF/MS, network pharmacology, and experimental validation.

Kaixin San (KXS), a traditional Chinese medicine formula, has shown therapeutic potential in treating bradyarrhythmia (BA), yet its active constituents and pharmacological mechanisms remain insufficiently defined. In this study, an integrated approach combining UPLC-Q-TOF/MS, network pharmacology, molecular docking, and experimental validation was employed to investigate the bioactive compounds and potential mechanisms of KXS. A total of 23 representative compounds were identified, including saponins, flavonoids, phenylpropanoids, organic acids, and lignans. Network pharmacology analysis revealed calcium signaling as a key pathway implicated in the anti-arrhythmic effect of KXS, with CACNA1C and CAMKIIδ predicted as major targets. Molecular docking and dynamics simulation confirmed strong binding affinity between KXS compounds and these core proteins. In a propranolol-induced BA rat model, KXS significantly improved cardiac conduction, modulated heart rate, and attenuated myocardial injury. Further experimental results confirmed that KXS downregulated the expression of CACNA1C and CAMKIIδ in myocardial tissue, suggesting its role in regulating intracellular calcium homeostasis. In conclusion, KXS alleviates bradyarrhythmia in rats, potentially by modulating calcium signaling pathways. This study highlights the multi-component and multi-target nature of KXS and provides a scientific basis for its application in BA treatment.