天然产物研究与开发 ›› 2025, Vol. 37 ›› Issue (增刊1): 123-136.

• 数据研究 • 上一篇    下一篇

基于网络药理学、转录组学和分子对接探讨参术汤治疗帕金森病的作用机制

王开达1,张明庆1,王缓缓1,姬  琳1*,袁月松2,刘小琳2,刘宗州2,王兴臣1   

  1. 1山东中医药大学第二附属医院,济南 250001;2山东中医药大学,济南 250014
  • 出版日期:2025-09-25 发布日期:2025-09-22
  • 基金资助:
    山东省医药卫生科技发展计划(202003070825);山东省中医药科技项目(2020M021)

Mechanism of Shenzhu Decoction in the treatment of Parkinson′s disease based on network pharmacology,transcriptomics,and molecular docking 

WANG Kai-da1,ZHANG Ming-qing1,WANG Huan-huan1,JI Lin1*,YUAN Yue-song2,LIU Xiao-lin2,LIU Zong-zhou2,WANG Xing-chen1   

  1. 1The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250001,China; 2Shandong University of Traditional Chinese Medicine,Jinan 250014,China
  • Online:2025-09-25 Published:2025-09-22

摘要:

基于网络药理学、转录组学和分子对接相结合的方法探究参术汤对帕金森病模型小鼠的治疗靶点,挖掘方中的核心单体成分,并推测该方的潜在作用机制。通过网络药理学探索参术汤中有效药物成分及其作用靶点,并进行GO和KEGG通路富集分析,预测参术汤的潜在作用通路及作用机制;对小鼠纹状体区域取材,使用转录组测序获得mRNA表达趋势,筛选差异表达基因;取上述两者的交集靶点进行分子对接验证及PCR验证。网络药理学结果表明,参术汤潜在的作用靶点共265个,经过GO、KEGG富集分析得出,这些靶点主要集中于丝裂原激活蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、磷脂酰肌醇3-激酶-蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B,PI3K/AKT)信号通路等凋亡、炎症、氧化应激相关通路;转录组学结果提示,参术汤组和模型组间符合表达趋势mRNA共319个(差异倍数(fold change,FC)≥1.5或≤0.67,P<0.05),经过GO、KEGG富集分析,差异表达的mRNA亦主要集中在上述相关通路上;转录组学和网络药理学得出的交集靶点基因有毒蕈碱型乙酰胆碱受体M1(muscarinic acetylcholine receptor M1,CHRM1)、FOS、蛋白激酶C delta(protein kinase C delta,PRKCD),核心成分为槲皮素、汉黄芩素、甘草素、去氢丹参酮IIA、蓝堇碱等。分子对接结果表明,这些靶点蛋白与上述分子具有较好的分子结合能力。参术汤可能通过MAPK信号通路、PI3K-AKT等信号通路起到帕金森病治疗作用,CHRM1、FOS、PRKCD等蛋白可能是参术汤治疗帕金森病的核心靶点,方中槲皮素、汉黄芩素等成分可能是参术汤治疗帕金森病的核心单体成分。

关键词: 帕金森病, 参术汤, 网络药理学, 转录组学, 分子对接

Abstract:

This study employed an integrated approach combining network pharmacology,transcriptomics,and molecular docking to explore the therapeutic targets of Shenzhu Decoction in a Parkinson′s disease (PD) mouse model,identify its core monomeric components,and elucidate its potential mechanism of action.Network pharmacology was utilized to identify the active compounds within Shenzhu Decoction and their corresponding targets.GO and KEGG pathway enrichment analyses were then performed to predict potential pathways and mechanisms of action for Shenzhu Decoction.Striatal tissue samples were collected from mice,and transcriptome sequencing was conducted to obtain mRNA expression profiles and screen for differentially expressed mRNAs.Overlapping targets identified from both the network pharmacology and transcriptomics analyses underwent molecular docking validation and PCR verification.Network pharmacology predicted 265 potential targets for Shenzhu Decoction.GO and KEGG enrichment analyses revealed that these targets were primarily enriched in apoptosis,inflammation,and oxidative stress-related pathways,such as the mitogen-activated protein kinase(MAPK) signaling pathway and the phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway.Transcriptomic results identified 319 significantly differentially expressed mRNAs (fold change (FC) ≥ 1.5 or≤0.67,P < 0.05) between the Shenzhu Decoction treatment group and the model group.GO and KEGG enrichment analyses similarly indicated that these differentially expressed mRNAs were predominantly concentrated in the aforementioned pathways.Intersection analysis between transcriptomics and network pharmacology identified three overlapping target genes:muscarinic acetylcholine receptor M1(CHRM1),FOS,and protein kinase C delta (PRKCD).Core monomeric components identified within the formula included quercetin,wogonin,shinpterocarpin,dehydrotanshinone IIA,and fumarine.Molecular docking results demonstrated favorable binding affinities between these target proteins and the corresponding molecules.This study suggests that Shenzhu Decoction may exert its therapeutic effects in PD primarily through modulating signaling pathways such as MAPK and PI3K-AKT.Proteins including CHRM1,FOS and PRKCD are likely core therapeutic targets,while components such as quercetin and wogonin represent potential core active monomeric constituents within the formula.

Key words: Parkinson′s disease, Shenzhu Decoction, network pharmacology, transcriptomics, molecular docking

中图分类号:  R285