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基于代谢组学和网络药理学探究麻杏石甘汤治疗哮喘的潜在机制

Investigating the Underlying Mechanisms of Ma-Xing-Shi-Gan-Tang on Asthma via Metabolomics and Network Pharmacology.

作者信息

Yu Yang, Wu Songquan, Sun Tiantian, Zhou Zhiyi, Xu Linyan, Peng Dinghan, Fu Xin

机构信息

College of Medicine, Lishui University, Lishui, 323000, People's Republic of China.

College of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, 150040, People's Republic of China.

出版信息

J Inflamm Res. 2025 Aug 18;18:11245-11262. doi: 10.2147/JIR.S515631. eCollection 2025.

DOI:10.2147/JIR.S515631
PMID:40860950
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12372829/
Abstract

OBJECTIVE

Ma-xing-shi-gan-tan (MXSGT) was first published in "Shang-han-lun". It functions as a heat-clearing agent, lung-clearing formula, and asthma reliever. This study aims to evaluate the therapeutic effect of MXSGT on asthma and elucidate its underlying mechanisms.

METHODS

Key components of MXSGT were identified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). A rat model of asthma induced by ovalbumin (OVA) was employed to assess MXSGT efficacy. The fundamental mechanisms of MXSGT in asthma treatment were investigated through metabolomic analysis, network pharmacology, and molecular docking.

RESULTS

MXSGT treatment demonstrated significant protective effects in OVA-induced asthmatic rats, evidenced by its suppression of inflammatory mediators including nuclear factor kappa B complex p65 (NF-κBp65), p38 mitogen-activated protein kinase (p38-MAPK), and transforming growth factor-β1 (TGF-β1). Metabolomic analysis revealed 9 MXSGT blood components and 12 differential metabolites associated with MXSGT treatment. Further analysis indicated that MXSGT's therapeutic benefit in asthma involves modulation of metabolic pathways such as the citric acid cycle (TCA cycle), alanine and aspartate metabolism, tyrosine metabolism, among others. Succinic acid was identified as the metabolite most prominently involved in these pathways. Additionally, network pharmacology identified TNF as a key target linking blood components and differential metabolites, mediating anti-asthma effects through MAPK and NF-κB signaling pathways.

CONCLUSION

Our findings demonstrate that MXSGT exerts anti-inflammatory effects in asthma treatment by inhibiting MAPK and NF-κB signaling pathways and regulating host metabolites and metabolic pathways. These insights provide novel perspectives on MXSGT's role in asthma management.

摘要

目的

麻杏石甘汤最早记载于《伤寒论》。它具有清热、宣肺、平喘的功效。本研究旨在评估麻杏石甘汤对哮喘的治疗效果并阐明其潜在机制。

方法

采用超高效液相色谱 - 串联质谱法(UPLC-MS)鉴定麻杏石甘汤的关键成分。使用卵清蛋白(OVA)诱导的大鼠哮喘模型评估麻杏石甘汤的疗效。通过代谢组学分析、网络药理学和分子对接研究麻杏石甘汤治疗哮喘的基本机制。

结果

麻杏石甘汤治疗对OVA诱导的哮喘大鼠具有显著的保护作用,表现为抑制包括核因子κB复合物p65(NF-κBp65)、p38丝裂原活化蛋白激酶(p38-MAPK)和转化生长因子-β1(TGF-β1)在内的炎症介质。代谢组学分析揭示了9种麻杏石甘汤血液成分和12种与麻杏石甘汤治疗相关的差异代谢物。进一步分析表明,麻杏石甘汤对哮喘的治疗作用涉及对柠檬酸循环(TCA循环)、丙氨酸和天冬氨酸代谢、酪氨酸代谢等代谢途径的调节。琥珀酸被确定为这些途径中最主要涉及的代谢物。此外,网络药理学确定肿瘤坏死因子(TNF)是连接血液成分和差异代谢物的关键靶点,通过MAPK和NF-κB信号通路介导抗哮喘作用。

结论

我们的研究结果表明,麻杏石甘汤通过抑制MAPK和NF-κB信号通路以及调节宿主代谢物和代谢途径,在哮喘治疗中发挥抗炎作用。这些见解为麻杏石甘汤在哮喘管理中的作用提供了新的视角。

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