Integrated Network Pharmacology and Metabolomics Analysis to Reveal the Potential Mechanism of Siwu Paste on Aplastic Anemia Induced by Chemotherapy Drugs

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2022-04-28 DOI:10.2147/DDDT.S327433

Dan He, Wan Dan, Qing Du, Bing-Bing Shen, Lin Chen, Liangliang Fang, Jian-Jun Kuang, Chunbian Tang, Ping Cai, Rong Yu, Shuihan Zhang, Jianhua Huang

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引用次数: 1

Abstract

Purpose This study aimed to reveal the multicomponent synergy mechanisms of SWP based on network pharmacology and metabolomics for exploring the relationships of active ingredients, biological targets, and crucial metabolic pathways. Materials Network pharmacology, including TRRUST, GO, and KEGG, enrichment was used to discover the active ingredients and potential regulation mechanisms of SWP. LC-MS and multivariate data analysis method were further applied to analyze serum metabolomics profiling for discovering the potential metabolic mechanisms of SWP on AA induced by Cyclophosphamide (CTX) and 1-Acetyl-2-phenylhydrazine (APH). Results A total of 27 important bioactive ingredients meeting the ADME (absorption, distribution, metabolism, and excretion) screening criteria from SWP were selected. Interaction networks were constructed and validated based on the 10 associated ingredients with the relevant targets. A total of 125 biomarkers were found by Metabolomics approach, which associated with the development of AA, mainly involved in amino acid metabolism and lipid metabolism. While SWP can reverse the above 12 metabolites changed by AA. Network analysis revealed the synergistic effects of SWP through the 43 crucial pathways, including Sphingolipid signaling pathway, Sphingolipid metabolism, Arginine and proline metabolism, VEGF signaling pathway, Estrogen signaling pathway. Conclusion The study suggested that SWP is a useful alternative for the treatment of AA induced by CTX + APH. Its potential mechanisms are to improve hematopoietic microenvironment and promote bone marrow hematopoiesis therapies.

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综合网络药理学和代谢组学分析揭示四物膏治疗化疗药物所致再生障碍性贫血的潜在机制

目的基于网络药理学和代谢组学，揭示SWP的多组分协同作用机制，探索其有效成分、生物学靶点和关键代谢途径之间的关系。通过TRRUST、GO、KEGG富集等网络药理学方法，发现SWP的有效成分及可能的调控机制。进一步应用LC-MS和多变量数据分析方法进行血清代谢组学分析，探索SWP对环磷酰胺(Cyclophosphamide, CTX)和1-乙酰-2-苯肼(1-Acetyl-2-phenylhydrazine, APH)诱导AA的代谢机制。结果从SWP中筛选出27种符合ADME(吸收、分布、代谢和排泄)筛选标准的重要生物活性成分。基于10种相关成分与相关靶标构建相互作用网络并进行验证。通过代谢组学方法共发现125个与AA发生相关的生物标志物，主要涉及氨基酸代谢和脂质代谢。而SWP能逆转AA对上述12种代谢物的影响。网络分析显示SWP通过鞘脂信号通路、鞘脂代谢、精氨酸和脯氨酸代谢、VEGF信号通路、雌激素信号通路等43条关键通路发挥协同作用。结论SWP是治疗CTX + APH诱导的AA的有效选择。其潜在机制是改善造血微环境，促进骨髓造血治疗。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.