Integrated Metabolomics and Network Pharmacology Study on the Mechanism of Rehmanniae radix Extract for Treating Thrombosis.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL Drug Design, Development and Therapy Pub Date : 2024-10-31 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S475838

Hongling Du, Shunjie Zhang, Kezhu Yuan, Zhirui Yang, Mingquan Wu

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Abstract

Background: Rehmanniae Radix (RR) has received attention for its antithrombotic effect. However, few studies have independently explored the bioactive components responsible for its antithrombotic bioactivity and the potential mechanism. We aimed to reveal the antithrombotic mechanisms of RR by using metabolomics integrated with network pharmacology.

Methods: A thrombosis model was established by intraperitoneal injection of type I carrageenan in rats, and antithrombotic function was evaluated at different doses of RR. Metabolomics was used to identify the differential metabolites in the serum. Network pharmacology was then applied to identify the potential targets for the antithrombotic activity of the RR. An integrated network of metabolomics and network pharmacology was constructed using Cytoscape. Finally, key targets were verified using molecular docking.

Results: RR at 5.4 g/kg significantly alleviated the thrombosis. Thirteen potentially significant metabolites were involved in the therapeutic effects of RR against thrombosis, most of which were regulated for recovery after RR treatment. An integrated analysis of metabolomics and network pharmacology showed that the antithrombosis effect of RR was closely associated with the regulation of PLA2G2A, PTGS1, ALOX5, and CYP2C9. Molecular docking showed high affinity between the key targets and components of RR. We speculated that the components of RR, such as catalpol, ferulic acid methyl ester, and methyl 4-hydroxycinnamate, might act on key proteins, including PLA2G2A, PTGS1, and ALOX5, to exert antithrombosis effects.

Conclusion: This study confirmed the antithrombotic effect of high-dose RR, revealed the antithrombotic mechanism and potential material basis, and laid the foundation for the antithrombotic clinical application of RR. Furthermore, it provides a successful case reference for screening natural herbal components and exploring their potential pharmacological mechanisms.

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地黄提取物治疗血栓机制的代谢组学和网络药理学综合研究

背景：地黄因其抗血栓作用而备受关注。然而，很少有研究对地黄的抗血栓生物活性成分及其潜在机制进行独立探索。我们旨在利用代谢组学与网络药理学相结合的方法揭示 RR 的抗血栓机制：方法：通过向大鼠腹腔注射 I 型卡拉胶建立血栓模型，评估不同剂量 RR 的抗血栓功能。代谢组学用于鉴定血清中的不同代谢物。然后应用网络药理学确定了 RR 抗血栓活性的潜在靶点。使用 Cytoscape 构建了代谢组学和网络药理学的综合网络。最后，通过分子对接验证了关键靶点：结果：5.4 g/kg 的 RR 能明显缓解血栓形成。13种潜在的重要代谢物参与了RR对血栓形成的治疗作用，其中大部分代谢物在RR治疗后的恢复过程中受到调控。代谢组学和网络药理学的综合分析表明，RR的抗血栓作用与PLA2G2A、PTGS1、ALOX5和CYP2C9的调节密切相关。分子对接显示，RR 的关键靶点与组分之间具有很高的亲和力。我们推测 RR 的成分，如梓醇、阿魏酸甲酯和 4- 羟基肉桂酸甲酯，可能作用于关键蛋白，包括 PLA2G2A、PTGS1 和 ALOX5，从而发挥抗血栓作用：本研究证实了大剂量 RR 的抗血栓作用，揭示了其抗血栓机制和潜在的物质基础，为 RR 的抗血栓临床应用奠定了基础。此外，该研究还为筛选天然草药成分、探索其潜在药理机制提供了成功的案例参考。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.