摘要
采用血清药物化学和网络药理学探讨七十味珍珠丸入血活性成分抑制复方中佐太组分肝肾毒性的相关机制,为七十味珍珠丸的临床安全应用提供依据。通过色谱串联质谱(HPLC-MS/MS)鉴定小鼠七十味珍珠丸含药血清中的小分子化合物。综合运用TCMSP、HERB、PubChem、GeneCards、SuperPred等多个数据库,检索七十味珍珠丸入血活性成分,预测其作用靶点,并与数据库检索到的汞毒性肝肾损伤相关靶点交集比对,筛选出七十味珍珠丸抑制佐太组分潜在汞毒性的作用靶点。采用Cytoscape软件构建七十味珍珠丸入血活性成分-靶点网络,使用STRING数据库构建交集靶点蛋白蛋白互作(PPI)网络,通过DAVID数据库对靶点基因进行GO功能与KEGG通路富集分析,构建活性成分-靶点-通路网络,并筛选出关键成分和靶点进行分子对接验证。结果显示,七十味珍珠丸含药血清中共鉴定出活性成分44种,其中13种可能是原型药物成分,作用于肝肾汞毒性的潜在靶点70个。通过PPI网络拓扑分析,得到12个关键靶点基因(HSP90AA1、MAPK3、STAT3、EGFR、MAPK1、APP、MMP9、NOS3、PRKCA、TLR4、PTGS2、PARP1)和6个子网络。通过对4个包含关键靶点基因的子网络进行GO功能与KEGG通路富集分析,构建活性成分-靶点-关键通路网络,并进行分子对接验证,发现牛磺脱氧胆酸、N-乙酰-L-亮氨酸、D-泛酸半钙等活性成分可能通过作用于MAPK1、STAT3、TLR4等主要靶点,调控代谢、免疫、炎症以及氧化应激相关的生物学功能及通路,从而抑制七十味珍珠丸中佐太成分潜在的汞毒性。因而推测,七十味珍珠丸的入血活性成分可能具有一定的减毒功效,抑制佐太潜在的汞毒性,发挥减毒增效的作用。
To explore the mechanism of the active ingredients of Qishiwei Zhenzhu Pills in inhibiting the hepatorenal toxicity of the zogta component based on serum pharmacochemistry and network pharmacology,thereby providing references for the clinical safety application of Qishiwei Zhenzhu Pills.The small molecular compounds in the serum containing Qishiwei Zhenzhu Pills of mice were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Then,by comprehensively using Traditional Chinese Medicines Systems Pharmacology(TCMSP),High-throughput Experiment-and Reference-guided Database(HERB),PubChem,GeneCards,SuperPred,and other databases,the active compounds in the serum containing Qishiwei Zhenzhu Pills were retrieved and their action targets were predicted.The predicted targets were compared with the targets of liver and kidney injury related to mercury toxicity retrieved from the database,and the action targets of Qishiwei Zhenzhu Pills to inhibit the potential mercury toxicity of zogta were screened out.Cytoscape was used to construct the active ingredient in Qishiwei Zhenzhu Pills-containing serum-action target network,and STRING database was used to construct the protein-protein interaction(PPI)network of intersection targets.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were carried out on the target genes by the DAVID database.The active ingredient-target-pathway network was constructed,and the key ingredients and targets were screened out for molecular docking verification.The results showed that 44 active compounds were identified from the serum containing Qishiwei Zhenzhu Pills,including 13 possible prototype drug ingredients,and 70 potential targets for mercury toxicity in liver and kidney were identified.Through PPI network topology analysis,12 key target genes(HSP90AA1,MAPK3,STAT3,EGFR,MAPK1,APP,MMP9,NOS3,PRKCA,TLR4,PTGS2,and PARP1)and 6 subnetworks were obtained.Through GO and KEGG analysis of 4 subnetworks containing key target genes
作者
严志祎
宗咏花
张程斐
吴丽丽
秦灵灵
刘铜华
YAN Zhi-yi;ZONG Yong-hua;ZHANG Cheng-fei;WU Li-li;QIN Ling-ling;LIU Tong-hua(Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China;Department of Tibetan Medicine,University of Tibetan Medicine,Lhasa 850000,China;Key Laboratory of Health-cultivation by Ministry of Education of the People′s Republic of China,Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2023年第9期2538-2551,共14页
China Journal of Chinese Materia Medica
基金
西藏自治区科技计划项目(XZ201901-GA-02)
藏医药区域协同创新中心项目(2018XTCX003,2019XTCX005)。
关键词
七十味珍珠丸
佐太
血清药物化学
网络药理学
分子对接
Qishiwei Zhenzhu Pills
zogta
serum pharmacochemistry
network pharmacology
molecular docking
