基于LC-MS关联网络药理学的当归鸡血藤汤治疗再生障碍性贫血的质量标志物(Q-Marker)预测分析  

Prediction analysis of quality markers(Q-Marker)of Danggui Jixueteng Decoction in treating aplastic anemia based on LC-MS combined with network pharmacology

作　　者：许桑 唐志安 胡志强 马铁梁 吴霞[2] 郭明鑫 XU Sang;TANG Zhi'an;HU Zhiqiang;MA Tieliang;WU Xia;GUO Mingxin(The Affiliated Yixing Clinical School of Medical School of Yangzhou University,Yixing 214200,China;New Drug Research and Development Center of Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]扬州大学医学院宜兴临床学院,江苏宜兴214200 [2]广东药科大学新药研发中心,广东广州510006

出　　处：《药物评价研究》2024年第8期1706-1714,共9页Drug Evaluation Research

基　　金：国家自然科学基金资助项目(81774314);无锡市中医药管理局项目(ZYYB29)。

摘　　要：目的基于液相色谱-质谱联用(LC-MS)分析当归鸡血藤汤(DJD)的化学成分,通过网络药理学探讨DJD治疗再生障碍性贫血(AA)的作用机制,并预测其潜在的质量标志物(Q-Marker)。方法通过LC-MS分析DJD化学成分,利用Swiss Target Prediction预测化学成分对应靶点,再通过GeneCards、OMIM、PharmGKB和TTD等数据库查询AA靶点,利用Cytoscape 3.9.1绘制“成分-靶点”及蛋白质-蛋白质相互作用(PPI)网络。基于R语言与微生信得到基因本体(GO)注释及京都基因与基因组百科全书(KEGG)通路富集分析可视化图,最后使用分子对接对网络药理学预测结果进行初步验证。结果经LC-MS鉴定出DJD中38个化合物,通过Swiss Target Prediction预测得到536个成分靶点,药物与疾病共有靶点196个,运用Cytoscape 3.9.1筛选出主要活性成分为白芍苷R1、芍药内酯苷、striatisporolide A、紫铆花素、黄芩素、高车前素、柚皮素、染料木苷、东莨菪内酯和隐丹参酮;经PPI分析得出前10名核心蛋白分别为磷酸甘油醛脱氢酶(GAPDH)、蛋白激酶B(Akt1)、白细胞介素-6(IL6)、肿瘤坏死因子(TNF)、Caspase-3、表皮生长因子受体(EGFR)、信号传导子及转录激活子3(STAT3)、热休克蛋白90A(HSP90AA1)、非受体酪氨酸激酶(SRC)和B细胞淋巴瘤/白血病-2蛋白(BCL2);经GO富集分析得2718条目,KEGG富集分析得到包含磷脂酰肌醇-3/蛋白激酶B(PI3K/Akt)等161条通路;分子对接结果显示关键靶点与活性成分结合效能较低,具较好的亲和力。结论基于DJD化学成分识别,结合网络药理学与分子对接验证,预测隐丹参酮、白芍苷R1、染料木苷及芍药内酯苷可以作为DJD治疗AA的候选Q-Markers。Objective To analyze the chemical constituents of Danggui Jixueteng decoction(DJD)based on LC-MS,and explore the mechanism of DJD in treating aplastic anemia(AA)through network pharmacology,and identify its potential quality markers(QMarker).Methods The chemical components of DJD were analyzed by LC-MS,and the corresponding targets were predicted by Swiss Target Prediction.Then AA targets were obtained by GeneCards,OMIM,PharmGKB and TTD datebase,and the"componenttarget"and protein-protein interaction(PPI)maps were drawn by Cytoscape 3.9.1.The visualization of GO and KEGG enrichment analysis was obtained by R language and micro-information.Finally,the content of network pharmacology prediction was preliminarily verified by molecular docking.Results 38 compounds were identified by LC-MS,536 targets were predicted by Swiss Target Prediction,and there were 196 common targets.The main active compounds were identified by Cytoscape3.9.1 as paeoniflorin R1,albiflorin,striatisporolide A,butein,baicalein,hispidulin,naringenin,genistin,scopolitin and cryptotanshinone;By PPI analysis,the top ten core proteins were glyceraldehyde-phosphate dehydrogenase(GAPDH),protein kinase B(AKT1),interleukin-6(IL-6),tumor necrosis factor(TNF),Caspase-3,epidermal growth factor receptor(EGFR),signal transducer and activator of transcription 3(STAT3),heat shock protein 90A(HSP90AA1),non-receptor tyrosine kinase(SRC protein,SRC)and Bcell lymphoma/leukemia-2 protein(BCL-2);2718 items were obtained by GO enrichment analysis,and 161 pathways such as PI3K/Akt were obtained by KEGG enrichment analysis.Molecular docking results showed that the binding efficiency of key targets and active components is low and they have good affinity.Conclusion Based on the identification of DJD chemical constituents,combined with network pharmacology and molecular docking verification,it was predicted that cryptotanshinone,paeoniflorin R1,genistin and genistin can be used as Q-Marker for DJD to treat AA.

关 键 词：当归鸡血藤汤 再生障碍性贫血 液相色谱-质谱联用 网络药理学 质量标志物 隐丹参酮 白芍苷R1 染料木苷 芍药内酯苷 

分 类 号：R285.5[医药卫生—中药学]