Integrating network pharmacology and experimental validation to investigate the mechanism of Gualou Xiebai Banxia decoction against myocardial ischemia.

BACKGROUND: Gualou Xiebai Banxia Decoction (GXBD), a traditional Chinese medicine, is used to treat myocardial ischemia (MI). However, the molecular mechanisms underlying its effects remain unclear. This study integrated network pharmacology and experimental validation to investigate the efficacy and potential mechanisms of GXBD in MI treatment. METHODS: Network pharmacology was used to predict the mechanism of action of GXBD in MI. The predicted results were verified using ECG, echocardiography, HE staining, TTC staining, DHE, JC-1, immunofluorescence, and Western blot analysis in an isoproterenol (ISO)-induced MI rat model. RESULTS: Network pharmacology identified 33 active components in GXBD and 139 potential targets against MI, with the PI3K/AKT signaling pathway playing a key role. Compared to the model group, GXBD improved the activities of BNP, CK-MB, and LDH, ameliorated the general condition and cardiac function, and repaired heart damage in MI rats. GXBD decreased MDA and ROS levels, increased SOD and GSH-Px levels, and protected cardiac tissues from oxidative stress. Moreover, GXBD increased ATP content, mitochondrial membrane potential, and the levels of p-PI3K, p-AKT, nuclear NRF2, and MFN2, while decreasing the levels of cytoplasmic NRF2 and DRP1. CONCLUSION: This study suggested that GXBD alleviates myocardial ischemia by ameliorating mitochondrial dysfunction through the PI3K/AKT/NRF2 signaling pathway.