Metabolomics analysis of anaphylactoid reactions induced by Xueshuantong injection in normal and immunocompromised mice

BackgroundXueshuantong injection (Lyophilized) (XSTI) is widely used to treat cardiovascular and cerebrovascular diseases. However, anaphylactoid reactions (ARs) are frequently reported as one of its side effects, and the mechanisms of ARs and their relationship with the different immune status are...

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Main Authors: Xiaoqian Guo, Chi Zhang, Yingyu Li, Wen Wen, Yinghui He, Feng Tang, Chunming Chen, Chao Hu, Linqi OuYang, Wenlong Liu, Zhenhua Zhu, Hongyu Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2024.1526875/full
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author Xiaoqian Guo
Xiaoqian Guo
Chi Zhang
Chi Zhang
Yingyu Li
Yingyu Li
Yingyu Li
Wen Wen
Wen Wen
Wen Wen
Yinghui He
Feng Tang
Chunming Chen
Chao Hu
Linqi OuYang
Wenlong Liu
Wenlong Liu
Zhenhua Zhu
Hongyu Liu
author_facet Xiaoqian Guo
Xiaoqian Guo
Chi Zhang
Chi Zhang
Yingyu Li
Yingyu Li
Yingyu Li
Wen Wen
Wen Wen
Wen Wen
Yinghui He
Feng Tang
Chunming Chen
Chao Hu
Linqi OuYang
Wenlong Liu
Wenlong Liu
Zhenhua Zhu
Hongyu Liu
author_sort Xiaoqian Guo
collection DOAJ
description BackgroundXueshuantong injection (Lyophilized) (XSTI) is widely used to treat cardiovascular and cerebrovascular diseases. However, anaphylactoid reactions (ARs) are frequently reported as one of its side effects, and the mechanisms of ARs and their relationship with the different immune status are still not well understood.PurposeThis article aims to examine the sensitizing effect of XSTI, explore the impact of normal and immunocompromised states on ARs, and analyze AR-related metabolic pathways by metabolomics.MethodsAn immunocompromised mouse model was established through intraperitoneal injection of cyclophosphamide (CTX). Normal and immunocompromised mice were then treated with normal saline (NS), histamine (HIS), and XSTI, respectively. Behavioral responses, auricle blue staining, and Evans blue (EB) exudation were used as indices to evaluate the sensitization of XSTI on both normal and immunocompromised mice. Subsequently, ARs models with different immune statuses were established, and validated by measuring four serum indicators using enzyme-linked immunosorbent assay (ELISA). Finally, LC-MS metabolomics analysis was performed on mouse serum to evaluate the metabolic pathways.ResultsThe intensity of ARs induced by XSTI in mice was found to increase with the administered dose, with normal mice exhibiting higher AR intensities compared to immunocompromised mice. Metabolomic analysis revealed significant metabolic changes in XSTI-treated mice. The metabolic pathways predicted from these different metabolites include biotin metabolism, histidine metabolism, glycerolipid metabolism, bile secretion, arachidonic acid metabolism, sphingolipid metabolism, niacin and nicotinamide metabolism, tryptophan metabolism, steroid biosynthesis, and arginine and proline metabolism.ConclusionResearch indicated that the sensitization of XSTI is dose-dependent, and mice with weakened immune functions exhibit lower sensitivity. Through metabolomics research, the differential metabolites in mice were analyzed, and the metabolic pathways inducing ARs were predicted. This study offers guidance on safe medication from the perspective of organism susceptibility and lays a foundation for research on the potential mechanisms of ARs.
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spelling doaj-art-14b8b46df2714a0793842df9b37f0a5c2025-01-06T06:59:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15268751526875Metabolomics analysis of anaphylactoid reactions induced by Xueshuantong injection in normal and immunocompromised miceXiaoqian Guo0Xiaoqian Guo1Chi Zhang2Chi Zhang3Yingyu Li4Yingyu Li5Yingyu Li6Wen Wen7Wen Wen8Wen Wen9Yinghui He10Feng Tang11Chunming Chen12Chao Hu13Linqi OuYang14Wenlong Liu15Wenlong Liu16Zhenhua Zhu17Hongyu Liu18The First Hospital of Hunan University of Chinese Medicine, Changsha, ChinaHunan Key Laboratory of Druggability and Preparation Modification of Traditional Chinese Medicine, Changsha, ChinaThe First Hospital of Hunan University of Chinese Medicine, Changsha, ChinaHunan Key Laboratory of Druggability and Preparation Modification of Traditional Chinese Medicine, Changsha, ChinaThe First Hospital of Hunan University of Chinese Medicine, Changsha, ChinaHunan Key Laboratory of Druggability and Preparation Modification of Traditional Chinese Medicine, Changsha, ChinaHunan Industry and Commerce Career Academy, Hengyang, ChinaThe First Hospital of Hunan University of Chinese Medicine, Changsha, ChinaHunan Key Laboratory of Druggability and Preparation Modification of Traditional Chinese Medicine, Changsha, ChinaChangsha Hospital of Traditional Chinese Medicine, Changsha, ChinaThe First Hospital of Hunan University of Chinese Medicine, Changsha, ChinaThe First Hospital of Hunan University of Chinese Medicine, Changsha, ChinaThe First Hospital of Hunan University of Chinese Medicine, Changsha, ChinaThe First Hospital of Hunan University of Chinese Medicine, Changsha, ChinaThe First Hospital of Hunan University of Chinese Medicine, Changsha, ChinaHunan Key Laboratory of Druggability and Preparation Modification of Traditional Chinese Medicine, Changsha, ChinaCollege of Pharmacy, Hunan University of Chinese Medicine, Changsha, ChinaThe First Hospital of Hunan University of Chinese Medicine, Changsha, ChinaThe First Hospital of Hunan University of Chinese Medicine, Changsha, ChinaBackgroundXueshuantong injection (Lyophilized) (XSTI) is widely used to treat cardiovascular and cerebrovascular diseases. However, anaphylactoid reactions (ARs) are frequently reported as one of its side effects, and the mechanisms of ARs and their relationship with the different immune status are still not well understood.PurposeThis article aims to examine the sensitizing effect of XSTI, explore the impact of normal and immunocompromised states on ARs, and analyze AR-related metabolic pathways by metabolomics.MethodsAn immunocompromised mouse model was established through intraperitoneal injection of cyclophosphamide (CTX). Normal and immunocompromised mice were then treated with normal saline (NS), histamine (HIS), and XSTI, respectively. Behavioral responses, auricle blue staining, and Evans blue (EB) exudation were used as indices to evaluate the sensitization of XSTI on both normal and immunocompromised mice. Subsequently, ARs models with different immune statuses were established, and validated by measuring four serum indicators using enzyme-linked immunosorbent assay (ELISA). Finally, LC-MS metabolomics analysis was performed on mouse serum to evaluate the metabolic pathways.ResultsThe intensity of ARs induced by XSTI in mice was found to increase with the administered dose, with normal mice exhibiting higher AR intensities compared to immunocompromised mice. Metabolomic analysis revealed significant metabolic changes in XSTI-treated mice. The metabolic pathways predicted from these different metabolites include biotin metabolism, histidine metabolism, glycerolipid metabolism, bile secretion, arachidonic acid metabolism, sphingolipid metabolism, niacin and nicotinamide metabolism, tryptophan metabolism, steroid biosynthesis, and arginine and proline metabolism.ConclusionResearch indicated that the sensitization of XSTI is dose-dependent, and mice with weakened immune functions exhibit lower sensitivity. Through metabolomics research, the differential metabolites in mice were analyzed, and the metabolic pathways inducing ARs were predicted. This study offers guidance on safe medication from the perspective of organism susceptibility and lays a foundation for research on the potential mechanisms of ARs.https://www.frontiersin.org/articles/10.3389/fphar.2024.1526875/fullanaphylactoid reactiondifferent immunization statusXueshuantong injectionmetabolic pathwaymetabolomics
spellingShingle Xiaoqian Guo
Xiaoqian Guo
Chi Zhang
Chi Zhang
Yingyu Li
Yingyu Li
Yingyu Li
Wen Wen
Wen Wen
Wen Wen
Yinghui He
Feng Tang
Chunming Chen
Chao Hu
Linqi OuYang
Wenlong Liu
Wenlong Liu
Zhenhua Zhu
Hongyu Liu
Metabolomics analysis of anaphylactoid reactions induced by Xueshuantong injection in normal and immunocompromised mice
Frontiers in Pharmacology
anaphylactoid reaction
different immunization status
Xueshuantong injection
metabolic pathway
metabolomics
title Metabolomics analysis of anaphylactoid reactions induced by Xueshuantong injection in normal and immunocompromised mice
title_full Metabolomics analysis of anaphylactoid reactions induced by Xueshuantong injection in normal and immunocompromised mice
title_fullStr Metabolomics analysis of anaphylactoid reactions induced by Xueshuantong injection in normal and immunocompromised mice
title_full_unstemmed Metabolomics analysis of anaphylactoid reactions induced by Xueshuantong injection in normal and immunocompromised mice
title_short Metabolomics analysis of anaphylactoid reactions induced by Xueshuantong injection in normal and immunocompromised mice
title_sort metabolomics analysis of anaphylactoid reactions induced by xueshuantong injection in normal and immunocompromised mice
topic anaphylactoid reaction
different immunization status
Xueshuantong injection
metabolic pathway
metabolomics
url https://www.frontiersin.org/articles/10.3389/fphar.2024.1526875/full
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