基于网络药理学研究广藿香油抗抑郁的效应物质及作用机制

Effective Substances and Mechanism of Patchouli Oil in Depression Based on Network Pharmacology

目的:基于网络药理学方法探讨广藿香油抗抑郁的作用机制。方法:通过检索广藿香油中分离的化合物,利用TCMSP和SwissTargetPrediction数据库获取广藿香油有效成分靶点,通过GeneCards、OMIM和TTD数据库筛选抑郁症相关靶点,取交集靶点进行蛋白-蛋白相互作用网络(PPI)分析、GO功能富集、KEGG信号通路富集分析。通过皮质酮致PC12细胞损伤模型评价广藿香油对抑郁症的潜在作用。结果:从广藿香油中筛选出46个化学成分,在此基础上预测成分靶点265个,抑郁症靶点14230个,交集靶点200个。TP53、ESR1、PRKACA、MAPK3、JUN等是核心靶点,富集到神经活性配体-受体相互作用、内分泌抵抗、钙信号通路、化学致癌作用-受体激活、cAMP等信号通路。广藿香油能够降低皮质酮致PC12细胞损伤Ca^(2+)水平,从而发挥神经保护作用。结论:本研究采用网络药理学的手段分析了广藿香油治疗抑郁症的药效物质及作用机制,并通过皮质酮损伤的PC12细胞模型证实了其与调控Ca^(2+)水平密切相关。

Objective:The anti-depression mechanism of patchouli oil was studied based on network pharmacology.Methods:The compounds from patchouli oil were collected by literature.TCMSP and SwissTargetPrediction database were used to obtain the target of effective components of patchouli oil.GeneCards,OMIM and TTD databases were searched for depressive-related targets.The intersection targets were selected for protein-protein interaction network(PPI),GO function enrichment and KEGG signaling pathway enrichment.The potential effect of patchouli oil on depression was evaluated by corticosterone-induced PC12 cell injury model.Results:46 chemical constituents were screened from patchouli oil.On the basis,265 component targets,14230 depression targets and 200 intersection targets were predicted.TP53,ESR1,PRKACA,MAPK3 and JUN are the core targets,which are enriched in neuroactive ligand-receptor interaction,endocrine resistance,calcium signal pathway,chemical carcinogenesis-receptor activation,cAMP and other signal pathways.Patchouli oil can significantly reduce the Ca^(2+)level of corticosterone-induced damage to PC12 cells,so as to play a neuroprotective effect.Conclusion:In this study,the effective substances and mechanism of patchouli oil in the treatment of depression were analyzed by means of network pharmacology,and it was proved that patchouli oil was closely related to the regulation of Ca^(2+)level through the PC12 cell model damaged by corticosterone.