Experimental Evidence and Network Pharmacology-Based Analysis Revealing the Effects and Mechanism of Branches of Sophora Japonica (L.) in Anti-Myocardial Ischemia

Background: Huai-Zhi (HZ), the fresh or dried branches of Sophora japonica (L.) are commonly used to treat several diseases such as heartache, red eyes, and metrorrhagia. The present study aimed to explore the potential mechanisms effects of HZ anti-myocardial ischemia by experiment and integrating network pharmacology. Methods: Isoproterenol was used in this study to establish the myocardial ischemia model in mice. Different extraction processes were used to obtain different HZ extracts with a screening of their anti-myocardial ischemia activities. Furthermore, the network pharmacology methods together with molecular docking were utilized to explore the active components, targets, and mechanism of anti-myocardial ischemia of HZ. Results: The ethyl acetate extract of HZ (HZ-EtOAc) significantly reduced the ST-segment elevation of mice in the preliminary test. The 95% ethanol fraction of the ethyl acetate extract of HZ (HZ-EtOAc-95) significantly reduced the ST-segment elevation, reduced the creatine kinase (CK) activity, reduced the levels of creatine kinase isoenzyme(CK-MB) and cardiac troponin I (cTnI) in serum, increased superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) levels in the myocardial tissues. Moreover, these results indicated that HZ-EtOAc extract in mice ameliorates myocardial tissue injury. Additionally, network pharmacology demonstrated that nine active components and 177 protein targets are related to the anti-myocardial ischemic effects of HZ. Its underlying mechanism might be involved in multiple signaling pathways, including mitogen-activated protein kinase, Toll-like receptor, and PI3K-Akt. Conclusion: This study used pharmacological experiments to determine the active site of HZ, and explored its potential mechanism in conjunction with network pharmacology.