Meisi Liu , Qing Wang , Zihan Lu , Liwei Wang , Shibo Zhao , Selinda Shi , Yonglie Zhao
{"title":"血浆代谢组学和网络药理学分析相结合，确定了雄栀地龙汤治疗偏头痛的作用","authors":"Meisi Liu , Qing Wang , Zihan Lu , Liwei Wang , Shibo Zhao , Selinda Shi , Yonglie Zhao","doi":"10.1016/j.jtcms.2023.09.005","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>To elucidate the mechanism of action of Xiongzhi Dilong decoction (XZDLD) in calcitonin gene-related peptide (CGRP)-induced migraine using network pharmacology and plasma metabolomic analyses.</p></div><div><h3>Methods</h3><p>Ultra-high-performance liquid chromatography-linear trap quadrupole orbitrap mass spectrometry (UPLC-LTQ-Orbitrap-MS) was used to identify the chemical components of XZDLD. A rat model of migraine was established by injecting a calcitonin gene-related peptide into the dura mater cannula. Migraine-like behavior was observed. Mechanical and thermal pain thresholds were measured to evaluate the efficacy of XZDLD in treating migraine. Crucial XZDLD targets in migraine were identified using network pharmacology and plasma metabolomics. Relevant proteins were validated using western blotting and immunohistochemistry.</p></div><div><h3>Results</h3><p>UPLC-LTQ-Orbitrap-MS was used to identify 38 compounds. Compared with the model rats, XZDLD significantly improved behavior at the first 30 min (all <em>P</em> < .05) and increased mechanical pain thresholds on day 19–22 (all <em>P</em> < .05) and thermal pain thresholds on day 20–22 (all <em>P</em> < .05). Moreover, network pharmacology identified 128 potential targets of XZDLD related to migraine. The metabolomic results suggested 17 differential endogenous metabolites, mainly involved in tryptophan and tyrosine metabolic pathways, in the control, model, and XZDLD groups. Six key targets were identified and used for molecular validation: MAOA, MAOB, CYP1A1, CYP1A2, CYP1B1, and ADH1C. Compared with the model group, XZDLD significantly decreased the expression of MAOA, MAOB, and CYP1B1 proteins (<em>P</em> = .024, <em>P</em> = .004, <em>P</em> = .039, respectively) and elevated the expression of CYP1A1, CYP1A2, and ADH1C (<em>P</em> = .033, <em>P</em> = .045, <em>P</em> = .027, respectively).</p></div><div><h3>Conclusion</h3><p>XZDLD can improve behavior and increase pain threshold. Moreover, XZDLD exerts anti-migraine effects primarily by modulating tryptophan and tyrosine metabolic pathways, providing a novel perspective on migraine research that is beneficial for its clinical application.</p></div>","PeriodicalId":36624,"journal":{"name":"Journal of Traditional Chinese Medical Sciences","volume":"10 4","pages":"Pages 427-439"},"PeriodicalIF":0.0000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Plasma metabolomics and network pharmacology analyses combined identify the action of Xiongzhi Dilong decoction in migraine treatment\",\"authors\":\"Meisi Liu , Qing Wang , Zihan Lu , Liwei Wang , Shibo Zhao , Selinda Shi , Yonglie Zhao\",\"doi\":\"10.1016/j.jtcms.2023.09.005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>To elucidate the mechanism of action of Xiongzhi Dilong decoction (XZDLD) in calcitonin gene-related peptide (CGRP)-induced migraine using network pharmacology and plasma metabolomic analyses.</p></div><div><h3>Methods</h3><p>Ultra-high-performance liquid chromatography-linear trap quadrupole orbitrap mass spectrometry (UPLC-LTQ-Orbitrap-MS) was used to identify the chemical components of XZDLD. A rat model of migraine was established by injecting a calcitonin gene-related peptide into the dura mater cannula. Migraine-like behavior was observed. Mechanical and thermal pain thresholds were measured to evaluate the efficacy of XZDLD in treating migraine. Crucial XZDLD targets in migraine were identified using network pharmacology and plasma metabolomics. Relevant proteins were validated using western blotting and immunohistochemistry.</p></div><div><h3>Results</h3><p>UPLC-LTQ-Orbitrap-MS was used to identify 38 compounds. Compared with the model rats, XZDLD significantly improved behavior at the first 30 min (all <em>P</em> < .05) and increased mechanical pain thresholds on day 19–22 (all <em>P</em> < .05) and thermal pain thresholds on day 20–22 (all <em>P</em> < .05). Moreover, network pharmacology identified 128 potential targets of XZDLD related to migraine. The metabolomic results suggested 17 differential endogenous metabolites, mainly involved in tryptophan and tyrosine metabolic pathways, in the control, model, and XZDLD groups. Six key targets were identified and used for molecular validation: MAOA, MAOB, CYP1A1, CYP1A2, CYP1B1, and ADH1C. Compared with the model group, XZDLD significantly decreased the expression of MAOA, MAOB, and CYP1B1 proteins (<em>P</em> = .024, <em>P</em> = .004, <em>P</em> = .039, respectively) and elevated the expression of CYP1A1, CYP1A2, and ADH1C (<em>P</em> = .033, <em>P</em> = .045, <em>P</em> = .027, respectively).</p></div><div><h3>Conclusion</h3><p>XZDLD can improve behavior and increase pain threshold. Moreover, XZDLD exerts anti-migraine effects primarily by modulating tryptophan and tyrosine metabolic pathways, providing a novel perspective on migraine research that is beneficial for its clinical application.</p></div>\",\"PeriodicalId\":36624,\"journal\":{\"name\":\"Journal of Traditional Chinese Medical Sciences\",\"volume\":\"10 4\",\"pages\":\"Pages 427-439\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Traditional Chinese Medical Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2095754823000546\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Traditional Chinese Medical Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2095754823000546","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
Plasma metabolomics and network pharmacology analyses combined identify the action of Xiongzhi Dilong decoction in migraine treatment
Objective
To elucidate the mechanism of action of Xiongzhi Dilong decoction (XZDLD) in calcitonin gene-related peptide (CGRP)-induced migraine using network pharmacology and plasma metabolomic analyses.
Methods
Ultra-high-performance liquid chromatography-linear trap quadrupole orbitrap mass spectrometry (UPLC-LTQ-Orbitrap-MS) was used to identify the chemical components of XZDLD. A rat model of migraine was established by injecting a calcitonin gene-related peptide into the dura mater cannula. Migraine-like behavior was observed. Mechanical and thermal pain thresholds were measured to evaluate the efficacy of XZDLD in treating migraine. Crucial XZDLD targets in migraine were identified using network pharmacology and plasma metabolomics. Relevant proteins were validated using western blotting and immunohistochemistry.
Results
UPLC-LTQ-Orbitrap-MS was used to identify 38 compounds. Compared with the model rats, XZDLD significantly improved behavior at the first 30 min (all P < .05) and increased mechanical pain thresholds on day 19–22 (all P < .05) and thermal pain thresholds on day 20–22 (all P < .05). Moreover, network pharmacology identified 128 potential targets of XZDLD related to migraine. The metabolomic results suggested 17 differential endogenous metabolites, mainly involved in tryptophan and tyrosine metabolic pathways, in the control, model, and XZDLD groups. Six key targets were identified and used for molecular validation: MAOA, MAOB, CYP1A1, CYP1A2, CYP1B1, and ADH1C. Compared with the model group, XZDLD significantly decreased the expression of MAOA, MAOB, and CYP1B1 proteins (P = .024, P = .004, P = .039, respectively) and elevated the expression of CYP1A1, CYP1A2, and ADH1C (P = .033, P = .045, P = .027, respectively).
Conclusion
XZDLD can improve behavior and increase pain threshold. Moreover, XZDLD exerts anti-migraine effects primarily by modulating tryptophan and tyrosine metabolic pathways, providing a novel perspective on migraine research that is beneficial for its clinical application.
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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