Integrated Network Pharmacology and Molecular Docking Analysis to Elucidate the Multi-Target Mechanism of Betulin in Cognitive Enhancement; [네트워크 약리학 및 분자 도킹 결합 분석을 통한 베툴린의 인지 기능 개선 다중 표적 기전 규명]

초록

Betulin has been reported to exhibit neuroprotective and memory-enhancing effects, but its underlying molecular mechanisms remain incompletely understood. AI-assisted computational analyses were performed to explore potential molecular targets and pathways associated with betulin. Putative targets were predicted using SwissTargetPrediction, followed by protein–protein interaction network analysis with the STRING database and pathway enrichment analysis using DAVID. The analysis identified multiple candidate targets, including enzymes, nuclear receptors, and G protein–coupled receptors. Network analysis revealed a significantly enriched protein–protein interaction network (PPI enrichment p = 0.002). Pathway enrichment highlighted metabolic and hormone-related pathways, such as steroid hormone biosynthesis, bile secretion, insulin resistance, and pentose and glucuronate interconversions, which are closely associated with neuroinflammatory regulation and cognitive function. Molecular docking simulations further validated these findings, revealing that betulin possesses exceptional binding affinities toward key targets, including BCHE (-10.5 kcal/mol), HSD11B1 (-10.7 kcal/mol), and NR1H4/FXR (-12.6 kcal/mol). The ligand was found to stably occupy the catalytic or regulatory sites of these proteins through robust hydrogen bonding and hydrophobic interactions. This study demonstrates that the cognitive-enhancing effects of betulin are attributed to its multi-target mechanism, involving the restoration of cholinergic signaling, mitigation of glucocorticoid-induced stress, and regulation of the metabolic-brain axis. These results provide a strong structural and systemic rationale for the use of betulin as a potential therapeutic candidate for complex neurodegenerative disorders. © 2026, Korean Society of Pharmacognosy. All rights reserved.

키워드