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网络药理学与实验验证探索玉屏风宁心片抗偏头痛的作用机制。

Network pharmacology and experimental verification to explore the anti-migraine mechanism of Yufeng Ningxin Tablet.

机构信息

School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, China.

Beijing Institution of Tongrentang, Beijing, 100071, China.

出版信息

J Ethnopharmacol. 2023 Jun 28;310:116384. doi: 10.1016/j.jep.2023.116384. Epub 2023 Mar 15.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Yufeng Ningxin Tablet (YNT) is a traditional Chinese medicine formula, that has been used clinically to treat migraine for many years. It is composed of one herb Pueraria lobata var. lobata (Willd.) Ohwi (Relevant Chinese name: Gegen). Previously, it has been recorded by traditional Chinese doctor that Gegen could be used as medicine to treat migraine. However, the underlying mechanism of action remains to be investigated.

AIM OF THE STUDY

It was to explore the effect and mechanism of YNT on migraine based on network pharmacology and experimental verification.

MATERIALS AND METHODS

First, with the network pharmacology, the effective chemical components and target genes of YNT were filtrated, the YNT-compound-migraine-targets network was constructed. The protein-protein interaction network (PPI) and literature reports were combined to identify potential targets of YNT in the treatment of migraine. Then, the representative compounds of YNT were characterized by LC-MS/MS and the major effect components were identified. Finally, the prediction results of network pharmacology were verified by animal and cell experiments.

RESULTS

7 bioactive components of YNT could act on 97 migraine potential targets. The 5 bioactive components could be characterized comprehensively of YNT. The key therapeutic targets and pathways were collected including 5-HT, CGRP, inflammation and nociceptive factors, and NF-κB signaling pathway. Animal experiments showed that YNT could increase the expression level of 5-HT and reduce the expression of CGRP, NF-κB, c-fos and IL-1β. YNT could inhibit LPS-induced neuroinflammation by NF-κB in BV2 cells in vitro. Western blotting analysis results showed YNT inhibited the NF-κB and phospho-NF-κB levels.

CONCLUSIONS

It is the first time to verify the consistency between the metabolic components of YNT by LC-MS/MS and the active components predicted by network pharmacology. Meanwhile, the potential mechanism of YNT in the treatment of migraine was studied by combining network pharmacology and in vitro and in vivo experiments.

摘要

民族药理学相关性

愈风宁心片(YNT)是一种中药方剂,临床上多年来一直用于治疗偏头痛。它由一种草药葛根组成(相关的中文名称:葛根)。以前,传统中医记录葛根可作为治疗偏头痛的药物。然而,其作用机制仍有待研究。

研究目的

基于网络药理学和实验验证,探讨 YNT 对偏头痛的作用机制。

材料与方法

首先,采用网络药理学方法,筛选 YNT 的有效化学成分和靶基因,构建 YNT-化合物-偏头痛-靶标网络。结合蛋白质-蛋白质相互作用网络(PPI)和文献报道,确定 YNT 治疗偏头痛的潜在靶标。然后,通过 LC-MS/MS 对 YNT 的代表性化合物进行表征,鉴定主要药效成分。最后,通过动物和细胞实验验证网络药理学的预测结果。

结果

YNT 的 7 种生物活性成分可作用于 97 个偏头痛潜在靶标。全面表征了 YNT 的 5 种生物活性成分。收集到的关键治疗靶标和途径包括 5-HT、CGRP、炎症和伤害性因子以及 NF-κB 信号通路。动物实验表明,YNT 可增加 5-HT 的表达水平,降低 CGRP、NF-κB、c-fos 和 IL-1β的表达。YNT 可通过体外 NF-κB 抑制 LPS 诱导的 BV2 细胞神经炎症。Western blotting 分析结果表明,YNT 抑制 NF-κB 和磷酸化 NF-κB 水平。

结论

这是首次通过 LC-MS/MS 验证 YNT 的代谢成分与网络药理学预测的活性成分之间的一致性。同时,通过网络药理学结合体内外实验研究了 YNT 治疗偏头痛的潜在机制。

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