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抗类风湿关节炎药效物质筛选 Schltr.:体外成分分析与多技术代谢组学结合。

Anti-Rheumatoid Arthritis Pharmacodynamic Substances Screening of Schltr.: Component Analyses In Vitro and In Vivo Combined with Multi-Technical Metabolomics.

机构信息

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China.

School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China.

出版信息

Int J Mol Sci. 2023 Sep 5;24(18):13695. doi: 10.3390/ijms241813695.

Abstract

The purpose of this study was to elucidate the metabolic action patterns of against rheumatoid arthritis (RA) using metabolomics, and to obtain its potential effective substances for treating RA. First, the therapeutic effects of against RA were confirmed; second, the chemical composition of was analyzed, and 17 prototypes were absorbed into blood; subsequently, plasma metabolomics studies using UPLC-Triple-TOF-MS/MS and GC-MS were performed to disclose the metabolomics alterations in groups, which revealed 38 altered metabolites after drug intervention. These metabolites were all associated with the arthritis pathophysiology process (-log() > 1.6). Among them, sorted by variable important in projection (VIP), the metabolites affected (VIP ≥ 1.72) belonged to lipid metabolites. Finally, Pearson's analysis between endogenous metabolites and exogenous compounds was conducted to obtain potential pharmacological substances for the treatment of RA, which showed a high correlation between five blood-absorbed components and -regulated metabolites. This information provides a basis for the selection of metabolic action modes for clinical application dosage, and potential pharmacological substances that exerted anti-RA effects of were discovered. The study provided an experimental basis for further research on pharmacoequivalence, molecular mechanism validation, and even the development of new dosage forms in the future.

摘要

本研究旨在运用代谢组学阐明 治疗类风湿关节炎(RA)的代谢作用模式,并获得其治疗 RA 的潜在有效物质。首先,确认 治疗 RA 的疗效;其次,分析 的化学成分,有 17 个原型被吸收到血液中;随后,采用 UPLC-Triple-TOF-MS/MS 和 GC-MS 进行血浆代谢组学研究,揭示药物干预后组间的代谢组学变化,发现 38 个代谢物发生变化。这些代谢物均与关节炎病理生理过程相关(-log() > 1.6)。其中,根据投影变量重要性(VIP)排序,受影响的代谢物(VIP ≥ 1.72)属于脂质代谢物。最后,进行内源性代谢物与外源性化合物之间的 Pearson 分析,以获得 治疗 RA 的潜在药理物质,发现五种血液吸收成分与 -调节代谢物之间具有高度相关性。该信息为选择 临床应用剂量的代谢作用模式以及发现发挥抗 RA 作用的潜在药理物质提供了依据。该研究为进一步研究药代动力学等效性、分子机制验证甚至未来开发新剂型提供了实验依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e068/10530683/0a4dbcc8a7cd/ijms-24-13695-g001a.jpg

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