巴戟天盐制工艺优化及其治疗阿尔茨海默病的网络药理学研究

Optimization of Salt-Processing Technology of Morindae Officinalis Radix and Its Network Pharmacological Research on Alzheimer's Disease

摘要:

目的：探讨巴戟天盐制工艺对寡糖成分的影响，并基于网络药理学和分子对接方法分析盐巴戟天改善阿尔茨海默病（AD） 的潜在机制。方法：采用均匀设计法优化巴戟天盐制工艺，通过HPLC-ELSD技术分析盐制前后巴戟天中寡糖类成分的变化。通过TCMSP、SwissTargetPrediction、SuperPred平台收集巴戟天活性成分作用靶点，从OMIM、TTD、Harmonizome、GeneCards、DisGeNET数据库及GEO芯片获取AD相关靶点；利用STRING数据库和Cytoscape分析关键靶点，DAVID数据库进行GO功能注释和KEGG通路富集分析；利用CB-dock2进行分子对接初步验证。结果：优化后的盐制工艺制得的盐巴戟天耐斯糖含量最高，盐制后的巴戟天中果糖含量增加，蔗糖、蔗果三糖、耐斯糖及蔗果五糖等寡糖成分含量下降。网络药理学分析共获得交集靶点35个，主要作用于PI3K-Akt、IL-17、MAPK等信号通路。分子对接结果表明，熊果酸、β-谷甾醇、大黄素甲醚等活性成分与PTGS2、MET、GSK3B等靶点结合能力高。结论：本研究明确了巴戟天盐制的最佳工艺参数，揭示了盐制对寡糖成分的影响。盐制工艺通过增加熊果酸、β-谷甾醇、大黄素甲醚等三萜、甾醇及蒽醌类成分的含量，同时改变寡糖组成，多成分协同作用于AD病理相关靶点，通过调控PI3K-Akt信号通路、抑制神经炎症、调节胆碱能系统及抗细胞凋亡等多途径协同作用，改善AD的病理状态。

Abstract:

Abstract： Objective： To explore the effect of salt-processing technology on oligosaccharides of Morindae Officinalis Radix，and to analyze the potential mechanism of salt-processed Morindae Officinalis Radix in ameliorating Alzheimer's disease （AD） based on network pharmacology and molecular docking. Methods：Uniform design method was adopted to optimize the salt-processing parameters of Morindae Officinalis Radix. HPLC-ELSD was used to detect the changes of oligosaccharides before and after processing. Active ingredient targets of Morindae Officinalis Radix were retrieved from TCMSP， SwissTargetPrediction， and SuperPred databases. AD-related targets were collected from OMIM，TTD，Harmonizome，GeneCards，DisGeNET，and GEO datasets. STRING database and Cytoscape software were applied to screen core targets. DAVID database was used for GO functional annotation and KEGG pathway enrichment analyses. CB-dock2 was employed for preliminary molecular docking verification. Results：The optimized salt-processing technology yielded salt-processed Morindae Officinalis Radix with the highest nystose content. After salt processing， fructose content increased，while the levels of oligosaccharides including sucrose，kestose，nystose ，and fructopentaose decreased. A total of 35 intersecting targets were obtained， which mainly involved PI3K-Akt， IL-17， and MAPK signaling pathways. Molecular docking results demonstrated that ursolic acid，β-sitosterol，and physcion possessed strong binding activity with PTGS2， MET， and GSK3B. Conclusion： This study determines the optimal salt-processing parameters and clarifies its influence on oligosaccharides of salt-processing technology of Morindae Officinalis Radix. Salt processing elevates the contents of triterpenoids，sterols，and anthraquinones including ursolic acid，β-sitosterol，and physcion，and alters oligosaccharides profiles. Multiple ingredients synergistically act on ADrelated targets， regulating PI3K-Akt pathway， restraining neuroinflammation， modulating cholinergic system and resisting cell apoptosis，so as to improve pathological conditions of AD.