Network Pharmacology-Based Prediction and Pharmacological Validation of Effects of Astragali Radix on Acetaminophen-Induced Liver Injury.
Network Pharmacology-Based Prediction and Pharmacological Validation of Effects of Astragali Radix on Acetaminophen-Induced Liver Injury.
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DOI：
10.3389/fmed.2022.697644
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发表时间：
2022
影响因子：
3.9
通讯作者：
中科院分区：
文献类型：
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作者：
黄芪是治疗急慢性肝损伤的常用中药方剂。然而，很少有人知道AR对乙酰氨基酚（APAP）诱导的肝损伤（ALI）的影响。本研究采用基于网络药理学的方法，探讨AR对ALI的作用机制。所有化合物均从相应的数据库中获得，并根据其口服生物利用度和药物相似性指数筛选活性化合物。AR的潜在基因来源于中药系统药理学数据库和分析平台（TCMSP）、中药分子机制生物信息学分析工具（BATMAN-TCM）和PubChem，而ALI的潜在相关基因来源于在线数据库（GeneCards和Online Mendelian Inheritance in Man）和基因表达综合图谱（Gene Expression Omnibus profiles）。参考检索工具检索相互作用基因/蛋白质数据库，分析疾病的富集过程、途径和靶基因。利用Cytoscape软件构建网络，对AR中化合物与ALI差异基因之间的靶蛋白进行鉴定。随后，在APAP诱导的小鼠肝损伤和与APAP孵育的HL 7702细胞中，实验验证了通过网络药理学分析预测的AR对ALI的潜在潜在作用机制。化合物-靶标网络包括181个靶标，而与ALI相关的潜在基因为4，621个。共筛选出49个AR-ALI交叉蛋白，对应于49个基因，构建成蛋白质相互作用网络复合物，并将其指定为AR对ALI的潜在靶点。在这些基因中，得分最高的三个基因MYC、MAPK 8和CXCL 8与ALI中的细胞凋亡高度相关。体内外实验证实，AR主要通过抑制MYC（c-Myc）、MAPK 8（JNK 1）和CXCL 8（IL-8）的表达，调节肝细胞凋亡，从而对ALI发挥显著的治疗作用。总之，我们的研究表明，网络药理学预测与实验验证相结合，可能会提供一个有用的工具来表征AR对ALI的分子机制。
Astragali Radix (AR) has been widely used in traditional Chinese medicine prescriptions for acute and chronic liver injury. However, little is known about the effects of AR on acetaminophen (APAP)-induced liver injury (ALI). In the current study, a network pharmacology–based approach was applied to characterize the action mechanism of AR on ALI. All compounds of AR were obtained from the corresponding databases, and active compounds were selected according to its oral bioavailability and drug-likeness index. The potential genes of AR were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) and PubChem, whereas the potential genes related to ALI were obtained from Online databases (GeneCards and Online Mendelian Inheritance in Man) and Gene Expression Omnibus profiles. The enriched processes, pathways, and target genes of the diseases were analyzed by referring to the Search Tool for the Retrieval of Interacting Genes/Proteins database. A network constructed through Cytoscape software was used to identify the target proteins that connected the compounds in AR with the differential genes of ALI. Subsequently, the potential underlying action mechanisms of AR on ALI predicted by the network pharmacology analyses were experimentally validated in APAP-induced liver injury in mice and HL7702 cells incubated with APAP. The compound-target network included 181 targets, whereas the potential genes related to ALI were 4,621. A total of 49 AR–ALI crossover proteins, corresponding to 49 genes, were filtered into a protein–protein interaction network complex and designated as the potential targets of AR on ALI. Among the genes, the three highest-scoring genes, MYC, MAPK8, and CXCL8 were highly associated with apoptosis in ALI. Then in vitro and in vivo experiments confirmed that AR exhibited its prominent therapeutic effects on ALI mainly via regulating hepatocyte apoptosis related to inhibiting the expressions of MYC (c-Myc), MAPK8 (JNK1), and CXCL8 (IL-8). In conclusion, our study suggested that the combination of network pharmacology prediction with experimental validation might offer a useful tool to characterize the molecular mechanism of AR on ALI.
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BATMAN-TCM：中药分子机制生物信息学分析工具
影响因子：
4.6
作者：
Liu Z;Guo F;Wang Y;Li C;Zhang X;Li H;Diao L;Gu J;Wang W;Li D;He F
通讯作者：
He F
影响因子：
14.9
作者：
Kim S;Chen J;Cheng T;Gindulyte A;He J;He S;Li Q;Shoemaker BA;Thiessen PA;Yu B;Zaslavsky L;Zhang J;Bolton EE
通讯作者：
Bolton EE
DOI：
10.1016/bs.apha.2018.12.004
发表时间：
2019-01-01
期刊：
Advances in pharmacology (San Diego, Calif.)
影响因子：
--
作者：
Fisher, Erik S;Curry, Steven C
通讯作者：
Curry, Steven C
影响因子：
5.6
作者：
Xu X;Zhang W;Huang C;Li Y;Yu H;Wang Y;Duan J;Ling Y
通讯作者：
Ling Y
影响因子：
9.7
作者：
Hsu, YL;Kuo, PL;Lin, CC
通讯作者：
Lin, CC