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. Magnolol is the primary biphenolic compound in Magnolia officinalis. It possesses various pharmacological properties, such as cardioprotective and neuroprotective properties, and inhibit tumor growth. However, its therapeutic effects on GPLs 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 simulation, and experimental verification. GPL-related targets were obtained from the GeneCards database, whereas magnolol targets were obtained from the STITCH database. The two group 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 epithelial-mesenchymal transition (EMT)-related proteins were evaluated via molecular docking. The protein-compound complexes with the optimal binding affinity were analysed via molecular dynamics simulation. The efficacy and mechanisms of Magnolol in the treatment of GPLs were further assessed using in-vitro models. Magnolol exerts its pharmacological effects by acting on multiple targets. ERBB2 might be a potential target of magnolol in GPL treatment.