The analgesic mechanism of Xi Shao Formula research on neuropathic pain based on metabolomics

Xinyi Li , Sheng Lin , Yi Lin , Youxiang Su , Chao Wang , Liangqing Huang , Jing Zhao , Guihua Tian
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Abstract

Objective

To explore the mechanism of Xi Shao Formula (XSF) in treating neuropathic pain (NP) through metabolomics and network pharmacology.

Methods

A chronic compression injury (CCI) of the sciatic nerve model was established to simulate NP; following CCI induction, animals were gavaged with normal saline, XSF, or the positive control drug pregabalin for 21 days. Serum metabolomics methods and enrichment analysis were employed to identify significant serum metabolites and metabolic pathways influenced by XSF. Through network pharmacology and liquid chromatograph with mass spectrometer analyses, the active compounds and targets of XSF for treating NP were analyzed. Additionally, the serum metabolomics and network pharmacology analysis results were integrated, drawing network diagrams illustrating the relationships between “target, metabolic pathway, and metabolite” using Cytoscape 3.9.1. The findings were further validated through molecular docking.

Results

Based on metabolomics, 11 differential endogenous metabolites were identified as potential biomarkers related to XSF for treating NP; functional enrichment analysis revealed eight metabolic pathways in XSF for treating NP. Based on integrated metabolomics and network pharmacology, the “monoamine oxidase A (MAOA)/MAOB/tyrosinase (TYR)–tyrosine metabolism pathway–gentisic acid” emerged as a significant network pathway in XSF for treating NP. The molecular docking results revealed high affinity and stable interaction between the active components of XSF and their respective target, namely MAOA, MAOB, and TYR (binding energy < −5 kcal/mol).

Conclusion

Our findings supported and enhanced our current understanding of the therapeutic effects of XSF on NP, providing a scientific basis for the clinical application and mechanism research of XSF.

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喜少方对神经性疼痛镇痛机制的代谢组学研究
目的通过代谢组学和网络药理学探讨Xi少方治疗神经性疼痛(NP)的作用机制。方法建立坐骨神经慢性压迫性损伤(CCI)模型,模拟NP;CCI诱导后,用生理盐水、XSF或阳性对照药物普瑞巴林灌胃动物21天。采用血清代谢组学方法和富集分析来确定XSF影响的重要血清代谢产物和代谢途径。通过网络药理学和液相色谱-质谱分析,对XSF治疗NP的活性成分和靶点进行了分析。此外,还整合了血清代谢组学和网络药理学分析结果,使用Cytoscape 3.9.1绘制了说明“靶标、代谢途径和代谢物”之间关系的网络图。这些发现通过分子对接得到了进一步验证。结果基于代谢组学,11种不同的内源性代谢产物被鉴定为XSF治疗NP的潜在生物标志物;功能富集分析揭示了XSF治疗NP的8条代谢途径。基于综合代谢组学和网络药理学,“单胺氧化酶A(MAOA)/MAOB/酪氨酸酶(TYR)-酪氨酸代谢途径-龙胆酸”成为XSF治疗NP的重要网络途径。分子对接结果显示,XSF的活性成分与其各自的靶标MAOA、MAOB和TYR(结合能<;−5 kcal/mol)之间具有高亲和力和稳定的相互作用,为XSF的临床应用和机理研究提供了科学依据。
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
Journal of Traditional Chinese Medical Sciences
Journal of Traditional Chinese Medical Sciences Medicine-Complementary and Alternative Medicine
CiteScore
1.90
自引率
0.00%
发文量
53
审稿时长
36 weeks
期刊介绍: Production and Hosting by Elsevier B.V. on behalf of Beijing University of Chinese Medicine Peer review under the responsibility of Beijing University of Chinese Medicine. Journal of Traditional Chinese Medical Sciences is an international, peer-reviewed publication featuring advanced scientific research in Traditional Chinese medicine (TCM). The journal is sponsored by Beijing University of Chinese Medicine and Tsinghua University Press, and supervised by the Ministry of Education of China. The goal of the journal is to serve as an authoritative platform to present state-of-the-art research results. The journal is published quarterly. We welcome submissions of original papers on experimental and clinical studies on TCM, herbs and acupuncture that apply modern scientific research methods. The journal also publishes case reports, reviews, and articles on TCM theory and policy.
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