基于整合药理学的金铃子散治疗消化性溃疡的质量标志物发现及分子机制研究

Discovery of quality marker and molecular mechanism of Jinlingzi san in treatment of peptic ulcer based on integrated pharmacology

目的通过整合药理学平台寻找金铃子散治疗消化性溃疡的质量标志物并探讨其作用机制。方法以整合药理学平台为基础建立金铃子散"药材-成分""疾病-靶标-成分"数据库,筛选关键靶标并进行通路富集分析,以Score≥0.8为相似度,采用AI技术对数据库进行分析和相互关联,进行金铃子散治疗消化性溃疡的"中药-成分-靶标-通路"多维网络分析,筛选出金铃子散抗溃疡的质量标志物,并对其分子机制进行预测。结果通过整合药理学平台中药成分数据库搜索,川楝子共收集7个成分,主要为三萜类成分,共预测到2个潜在的疾病靶标;延胡索共收集31个化学成分,主要为生物碱类成分,共预测到9个潜在疾病靶标。经筛选与通路富集分析,筛选出与治疗消化性溃疡相关的关键靶标7个RAC1、RAC2、NCF1、NCF2、NCF4、CYBA、ATP1A1,基因功能主要有血管内皮生长因子(VEGF)受体信号通路、谷氨酸受体活性及相关通道、磷脂酰肌醇、血小板活化及其生长因子、Ras鸟苷核苷酸交换因子活性等。对数据库进行分析互联,最后筛选出海罂粟碱为金铃子散抗溃疡的质量标志物,金铃子散可能是通过神经系统、免疫系统、细胞通信、RAS通路、RAP1通路及黏合连接通路等达到治疗溃疡效果。结论金铃子散应以延胡索和海罂粟碱做为进一步研究抗消化性溃疡的主要目标。

Objective To find the quality marker and explore the mechanism of peptic ulcer by integrating pharmacology platform. Methods Based on integrated pharmacology platform, the database of "medicinal herbs-ingredients" and "disease targetsingredients" of Jinlingzi san were established, screening key targets for channel enrichment analysis. Using Score≥0.8 as a similarity, then the AI technology was used to analyze and interrelate the database. The multi-dimensional network analysis of "traditional Chinese medicine-component-target-pathway" for Jinlingzi powder in treating peptic ulcer was carried out. Finally the quality markers of the anti ulcer were screened and the molecular mechanism was predicted. Results By searching the database of TCM components on the platform of integrated pharmacology, seven components were collected from toosendan, mainly triterpenoids, and two potential disease targets were predicted. Thirty-one chemical components were collected from Corydalis yanhusuo, mainly alkaloids, and nine potential disease targets were predicted. Seven key targets related to the treatment of peptic ulcer, including RAC1, RAC2, NCF1, NCF2, NCF4, CYBA and ATP1A1, were screened through screening and pathway enrichment analysis. The main gene functions were vascular endothelial growth factor (VEGF) receptor signaling pathway, glutamate receptor activity and related pathways, phosphatidylinositol, platelet activation and its growth factor, Ras guanosine nucleotide exchange factor activity, etc. The database was analyzed and interlinked. finally the Glaucine was selected as the anti ulcer marker component (Q- marker). Jinlingzi san may be used to treat ulcer through nervous system, immune system, cell communication, RAS pathway, RAP1 pathway and adhesion pathway. Conclusion Jinlingzi san should study the primary target in Corydlis Rhizoma and Glaucine for further study of the anti peptic ulcer.