Exploring the protective effect and potential mechanism of acutumidine on myocardial ischemia based on “compound-target-pathway” network

Abstract

Background Menispermi Rhizoma is a traditional Chinese medicine with significant anti-myocardial ischemia (MI) effects. Acutumidine is a major alkaloid component of Menispermi Rhizoma. However, the effect and mechanism of acutumidine on MI remain unknown. This research aims to explore the effect and potential mechanism of acutumidine in treating myocardial ischemia (MI). Methods The oxygen glucose deprivation (OGD) model of H9c2 cardiomyocytes was established to simulate MI in vitro. The protective effect of acutumidine against MI was evaluated by MTT assay, Hoechst/PI staining, lactate dehydrogenase (LDH), creatine kinase (CK) release, the levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) and cell apoptosis rate. Based on network pharmacology, the potential the anti-MI mechanism of acutumidine is explored by constructing a "compound-target-pathway" network. GO and KEGG enrichment analysis were performed via metascape database. Finally, the key targets of acutumidine were validated by molecular docking. Results The experiment results showed that acutumidine could protect H9c2 cardiomyocytes against OGD injury by increasing the levels of SOD and GSH, and decreasing the release of LDH, CK and MDA significantly. The apoptosis rate of OGD H9c2 cells were reduced. All research results suggested that acutumidine could inhibit oxidative stress and cell apoptosis. Network pharmacology showed that the protective effect of acutumidine on MI was related to PI3K/AKT, HIF-1, and Ras signaling pathways. Molecular docking studies further showed that MAPK1, IGF1, EGFR, and KDR are the core targets of acutumidine in the treatment of MI. Conclusions Acutumidine was shown to have notable effects to inhibit oxidative stress and cell apoptosis in H9c2 cells through PI3K/AKT, HIF-1 and Ras signaling pathway. This study not only provides new insights into the anti-MI effect and mechanism of acutumidine, but also offers a promising candidate drug for the treatment of MI.