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基于代谢组学和网络药理学的当归- 苦参药对治疗缺血性心脏病作用机制研究。

Integrated metabolomics and network pharmacology study on the mechanism of herbal pair of danggui-kushen for treating ischemia heart disease.

机构信息

College of medicine, Heilongjiang University of traditional Chinese Medicine, Harbin, China.

Institute of traditional Chinese medicine, Heilongjiang University of traditional Chinese Medicine, Harbin, China.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2024 May 15;1239:124121. doi: 10.1016/j.jchromb.2024.124121. Epub 2024 Apr 10.

Abstract

DangGui-KuShen (DK) is a well-known classic traditional Chinese medicine recipe that improves blood circulation, eliminates moisture, and detoxifies, and is frequently used in the treatment of cardiovascular problems. Some protective effects of DK on cardiovascular disease have previously been identified, but its precise mechanism remains unknown. The goal of this study is to combine metabolomics and network pharmacology to investigate DK's protective mechanism in Ischemic Heart Disease(IHD) rat models. A combination of metabolomics and network pharmacology based on UPLC-Q-TOF/MS technology was used in this study to verify the effect of DK on IHD through enzyme-linked immunosorbent assay, HE staining, and electrocardiogram, and it was determined that DK improves the synergistic mechanism of IHD. In total, 22 serum differential metabolites and 26 urine differential metabolites were discovered, with the majority of them involved in phenylalanine, tyrosine, and tryptophan biosynthesis, glycine, serine, and threonine metabolism, arginine and proline metabolism, aminoacyl-tRNA biosynthesis, purine metabolism, and other metabolic pathways. Furthermore, using network pharmacology, a composite target pathway network of DangGui and KuShen for treating IHD was created, which is primarily associated to the tumor necrosis factor (TNF) signaling pathway, P53 signaling, and HIF-1 signaling pathways. The combined research indicated that the NF-B signaling pathway and the HIF-1 signaling pathway are critical in DK treatment of IHD. This study clearly confirms and expands on current knowledge of the synergistic effects of DG and KS in IHD.

摘要

当归-苦参(DK)是一种著名的经典中药方剂,具有活血化瘀、祛湿解毒的功效,常用于治疗心血管问题。DK 对心血管疾病有一定的保护作用,但其确切机制尚不清楚。本研究旨在结合代谢组学和网络药理学,探讨 DK 在缺血性心脏病(IHD)大鼠模型中的保护机制。本研究采用基于 UPLC-Q-TOF/MS 技术的代谢组学和网络药理学相结合的方法,通过酶联免疫吸附试验、HE 染色和心电图验证 DK 对 IHD 的作用,确定 DK 改善 IHD 的协同作用机制。共发现 22 种血清差异代谢物和 26 种尿液差异代谢物,其中大部分涉及苯丙氨酸、酪氨酸和色氨酸生物合成、甘氨酸、丝氨酸和苏氨酸代谢、精氨酸和脯氨酸代谢、氨酰-tRNA 生物合成、嘌呤代谢等代谢途径。此外,利用网络药理学构建了当归和苦参治疗 IHD 的复合靶标通路网络,主要与肿瘤坏死因子(TNF)信号通路、P53 信号通路和 HIF-1 信号通路相关。综合研究表明,NF-B 信号通路和 HIF-1 信号通路在 DK 治疗 IHD 中起关键作用。本研究明确证实并扩展了 DG 和 KS 在 IHD 中的协同作用的现有知识。

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