基于网络药理学和分子对接技术分析加味五子衍宗汤治疗帕金森病伴抑郁的作用机制

Analysis of Mechanism of Modified Wuzi Yanzong Decoction for Parkinson's Disease with Depression Based on Network Pharmacology and Molecular Docking Technology

摘要:

目的：运用网络药理学及分子对接技术分析浙江省名中医胡万华教授所创加味五子衍宗汤治疗帕金森病伴抑郁（dPD） 的潜在作用机制。方法：利用中药系统药理学数据库与分析平台（TCMSP） 筛选出加味五子衍宗汤的有效化学成分及其对应靶点，从GeneCards和DisGeNET数据库中收集帕金森病伴抑郁靶点。利用STRING数据库构建交集靶点的蛋白互作（PPI） 网络，预测核心靶点。采用Metascape数据库对交集靶点进行基因本体（GO） 功能注释及京都基因与基因组百科全书（KEGG） 通路富集分析。最后采用AutoDock Tools对主要活性成分与核心靶点进行分子对接验证。结果：获得加味五子衍宗汤76个活性成分，对应276个靶点，获得538 个dPD 疾病靶点，48 个交集靶点。筛选出槲皮素、山奈酚、异鼠李素等主要活性成分，白细胞介素-6（IL-6）、蛋白激酶B1（AKT1）、肿瘤坏死因子（TNF）、核受体亚家族3 C组成员1（NR3C1） 等核心靶点。KEGG富集分析主要涉及环磷酸腺苷（cAMP）、钙信号、神经活性配体-受体相互作用、5-羟色胺能突触及胆碱能突触等信号通路。分子对接显示NR3C1与槲皮素、山奈酚、异鼠李素均具有较好的对接活性。结论：加味五子衍宗汤可能通过槲皮素、山奈酚、异鼠李素等活性成分，作用于IL-6、AKT1、TNF、NR3C1等靶点，调控cAMP、钙信号、神经活性配体-受体相互作用、5-羟色胺能突触及胆碱能突触等通路参与dPD的治疗过程。

Abstract:

Abstract： Objective： To analyze the potential mechanism of action of modified Wuzi Yanzong Decoction， a formula developed by Professor HU Wanhua， a renowned Zhejiang Provincial Chinese medicine practitioner， in treating Parkinson's disease with depression （dPD） using network pharmacology and molecular docking technology. Methods：The active ingredients and corresponding targets of modified Wuzi Yanzong Decoction were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The dPD-related targets were retrieved from the GeneCards， and DisGeNET databases. A protein-protein interaction （PPI） network of overlapping targets was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins （STRING） database to predict core targets. Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes（ KEGG） pathway enrichment analysis of the overlapping targets were performed using the Metascape database. Finally，molecular docking between active ingredients and core targets was validated using AutoDock Tools. Results： A total of 76 active ingredients of modified Wuzi Yanzong Decoction were identified， corresponding to 276 targets. A total of 538 dPD disease targets were retrieved， yielding 48 overlapping targets. The analysis highlighted key active ingredients such as quercetin， kaempferol， and isorhamnetin， and core targets including interleukin-6 （IL-6）， protein kinase B1 （AKT1）， tumor necrosis factor （TNF）， and nuclear receptor subfamily 3 group C member 1（ NR3C1）. KEGG enrichment analysis primarily involved pathways such as the cyclic adenosine monophosphate（ cAMP） signaling pathway， calcium signaling pathway， neuroactive ligand-receptor interaction， serotonergic synapse， and cholinergic synapse. Molecular docking showed that NR3C1 exhibited strong binding affinities with quercetin， kaempferol， and isorhamnetin. Conclusion： Modified Wuzi Yanzong Decoction may participate in the therapeutic process of dPD by acting on targets such as IL-6， AKT1， TNF， and NR3C1 through active ingredients including quercetin， kaempferol， and isorhamnetin， thereby regulating pathways including the cAMP signaling pathway， calcium signaling pathway，neuroactive ligand-receptor interaction，serotonergic synapse，and cholinergic synapse.