Molecular Mechanisms of Magnolol in Gastric Precancerous Lesions: A Computational and Experimental Study

The formation of gastric precancerous lesions (GPLs) has been identified as a critical step in tumorigenesis, and patients with GPLs have an increased risk of gastric cancer (GC). Magnolol is the primary biphenolic compound in Magnolia officinalis. It possesses various pharmacological properties, such as cardio- and neuroprotective properties, and inhibits tumor growth. However, its therapeutic effects on GPL treatment and the related mechanisms have not yet been studied. To address this, the mechanisms by which magnolol affects GPLs were elucidated via protein-chemical interaction prediction analysis, molecular docking, molecular dynamics (MD) simulation, and experimental verification. GPL-related targets were obtained from the GeneCards database, whereas magnolol targets were obtained from the STITCH database. The two groups of targets were compared by constructing a Venn diagram, and potential key GPL-related targets of magnolol were identified. Next, the interactions between the active compounds of magnolol and various epithelial-mesenchymal transition (EMT)-related proteins were evaluated via molecular docking. The protein-compound complexes with the optimal binding affinity were analyzed via MD simulation. The efficacy of magnolol in the treatment of GPLs and the related mechanisms was further assessed using in vitro models. In this study, five core GPL-related targets of magnolol were identified. Molecular docking revealed that magnolol and ERBB2 had the strongest binding affinity, suggesting that ERBB2 is a potentially important target for the treatment of GPLs. Similarly, MD simulations revealed a strong affinity between magnolol and ERBB2. Overall, this study showed that magnolol can inhibit the malignant behavior of precancerous lesions in GC cells. Magnolol exerts its pharmacological effects by acting on multiple targets. ERBB2 might be a potential target of magnolol in GPL treatment.