Insights into Molecular Mechanism of Nicotine Addiction Based on Network Pharmacology and Molecular Docking Strategy.

For exploring the molecular mechanism of nicotine addiction, nicotine addiction-related targets and signaling pathways were analyzed using network pharmacology and molecular docking. The target proteins of nicotine and addiction were obtained from SEA and Gene Cards database, respectively. Then, the overlapped targets of nicotine and addiction were considered as the targets of nicotine addiction. The protein–protein interaction (PPI) networks were constructed based on STRING and Cytoscape software, and the hub targets of nicotine addiction were screened based on CytoHubba and MCODE plug-ins. In addition, GO function analysis and KEGG pathway enrichment analysis were carried out for nicotine addiction targets. Finally, molecular docking was used to verify the key targets of nicotine addiction. The results showed that 87 target proteins were at least involved in nicotine addiction, and the hub targets included DRD2, CHRM1, MAOA, MAOB, CHRNA7 and SLC6A4. GO function analysis referred to 591 GO entries and 31 signaling pathways were obtained through the analysis of KEGG. Molecular docking showed that nicotine could bind to the surface-active pockets of protein MAOA, MAOB, CHRNA7, DRD2 and SLC6A4 using less minimum binding free energy (< −5 Kcal/moL), which was mainly from hydrogen bond and hydrophobic interaction. Summarily, molecular mechanism of nicotine addiction is very complex and involves in various target proteins and pathways based on network pharmacology analysis, in which target proteins MAOA, MAOB, CHRNA7, DRD2, SLC6A4 can directly interact with nicotine and cooperatively regulate different pathways such as neural ligand receptor interaction and nicotine addiction pathways to induce addiction. S-nicotine and R-nicotine had few differences in addiction based on network pharmacology. MAOA, MAOB, CHRNA7, DRD2 and SLC6A4 are the key addiction targets of nicotine. Nicotine induces addiction through multiple targets and signal pathways in synergy. [ABSTRACT FROM AUTHOR]