Study on the Anti-obesity Mechanism of Action of Moringa oleifera Lam. Leaves by Network-Based Pharmacology and Molecular Docking Techniques

Objects: In this study, the molecular targets and pathways of anti-obesity of the active ingredients of Moringa oleifera Lam. leaves were predicted and validated by network pharmacology and molecular docking techniques, and the anti-obesity effects of the active ingredients of Moringa oleifera Lam. leaves and their potential mechanisms were investigated. Methods: The active ingredient targets of Moringa oleifera Lam. leaves and obesity-related targets were obtained through PubChem, DisGeNET database and SwissADME, Swiss Target Prediction online prediction platform. The active ingredient targets and obesity-related targets were intersected by Venny 2.0.1 platform, and the key targets were screened out, then the PPI network analysis of the core targets was performed by STRING 11.0 database. The "component-target" interaction network was construct by Cytoscape 3.8.2 software, and the core active ingredients were screened out. GO functional enrichment and KEGG pathway analysis were performed on the core targets by the David database. Finally, molecular docking of pathway enrichment targets to core components was performed using Auto Dock 4.2 software. Results: Fifty active ingredients of Moringa oleifera Lam. leaves were screened, and a total of 126 core targets of Moringa oleifera Lam. leaves anti-obesity were identified, among which the main active ingredients were rhamnetin, cholest-5-en-3-ol, yangmeiin, lignan, etc. GO and KEGG analyses showed that the active ingredients of Moringa oleifera Lam. leaves exerted anti-obesity effects through multiple pathways such as HIF-1, insulin resistance, type 2 diabetes and insulin signalling pathway, and through biological processes such as positive regulation of RNA polymerase II promoter transcription, signalling, positive regulation of gene expression, negative regulation of protein phosphorylation and apoptotic expression. The molecular docking results showed that all 11 core components bound to the targets. Among them, PIK3R1 showed the lowest affinity with rhamnetin (−9.2 kcal/mol), followed by PIK3CA with cholest-5-en-3-ol (−9.1 kcal/mol), PIK3R1 with myricetin (−8.8 kcal/mol), and AKT1 with luteolin (−8.7 kcal/mol). Conclusion: The above results reveals that Moringa oleifera Lam. leaves could aganist obesity through multi-component, multi-target and multi-pathway mecanism. These results will provide a theoretical basis for the in-depth study of the anti-obesity of Moringa oleifera Lam. leaves and its molecular mechanism.