{"title":"玫瑰杜鹃花（Althaea rosea）的潜在作用机制卡文。花缓解河豚毒素中毒：综合代谢组学、网络药理学和实验验证。","authors":"Renjin Zheng, Youjia Wu, Lingyi Huang, Fanxiang Zeng, Liying Huang","doi":"10.2147/DDDT.S505270","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Tetrodotoxin (TTX) poisoning manifests rapidly and severely, and there are currently no clinically effective treatments. <i>Althaea rosea</i> (Linn.) Cavan. flower, documented in the \"National Compendium of Chinese Herbal Medicines\", is traditionally recognized and clinically applied for its potential to mitigate tetrodotoxin (TTX) poisoning. This study aims to explores the pharmacodynamic components and mechanisms of the ethyl acetate extract of <i>Althaea rosea</i> flower (EAEAR) in a TTX-induced rat model.</p><p><strong>Methods: </strong>Ultra-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS) was used to identify active components in EAEAR. Metabolomics combined with network pharmacology was used to explore the mechanisms underlying the mitigating effects of EAEAR in TTX-intoxicated rats. Experimental validation was performed on key targets of the pathway through Western blotting or enzyme-linked immunosorbent assay. And differential metabolites in key pathways were further validated using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS).</p><p><strong>Results: </strong>A total of 35 active components were identified in EAEAR, 12 core components and 15 core targets were screened in network pharmacology, and metabolomics revealed 15 different metabolites. The arginine and proline metabolism pathway and the arginine biosynthesis pathway were identified as critical pathways for EAEAR's effect in alleviating TTX poisoning. Validation results indicated that EAEAR treatment led to significant alterations (<i>P</i> <0.05) in six key targets (MAOA, AOC1, ALDH7A1, NAGS, NOS2, and NOS3) and three differential metabolites (GABA, Pro, and NAG) in TTX-intoxicated rats.</p><p><strong>Conclusion: </strong>EAEAR alleviates TTX poisoning symptoms by modulating targets and metabolites in the arginine and proline metabolism pathways and the arginine biosynthesis pathway. This study provides a theoretical basis for further exploration of its therapeutic potential and mechanisms against TTX poisoning.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3657-3680"},"PeriodicalIF":4.7000,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063623/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Potential Mechanisms of <i>Althaea rosea</i> (Linn.) Cavan. Flower in Alleviating Tetrodotoxin Poisoning: An Integrated Metabolomics, Network Pharmacology and Experimental Validation.\",\"authors\":\"Renjin Zheng, Youjia Wu, Lingyi Huang, Fanxiang Zeng, Liying Huang\",\"doi\":\"10.2147/DDDT.S505270\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Tetrodotoxin (TTX) poisoning manifests rapidly and severely, and there are currently no clinically effective treatments. <i>Althaea rosea</i> (Linn.) Cavan. flower, documented in the \\\"National Compendium of Chinese Herbal Medicines\\\", is traditionally recognized and clinically applied for its potential to mitigate tetrodotoxin (TTX) poisoning. This study aims to explores the pharmacodynamic components and mechanisms of the ethyl acetate extract of <i>Althaea rosea</i> flower (EAEAR) in a TTX-induced rat model.</p><p><strong>Methods: </strong>Ultra-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS) was used to identify active components in EAEAR. Metabolomics combined with network pharmacology was used to explore the mechanisms underlying the mitigating effects of EAEAR in TTX-intoxicated rats. Experimental validation was performed on key targets of the pathway through Western blotting or enzyme-linked immunosorbent assay. And differential metabolites in key pathways were further validated using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS).</p><p><strong>Results: </strong>A total of 35 active components were identified in EAEAR, 12 core components and 15 core targets were screened in network pharmacology, and metabolomics revealed 15 different metabolites. The arginine and proline metabolism pathway and the arginine biosynthesis pathway were identified as critical pathways for EAEAR's effect in alleviating TTX poisoning. Validation results indicated that EAEAR treatment led to significant alterations (<i>P</i> <0.05) in six key targets (MAOA, AOC1, ALDH7A1, NAGS, NOS2, and NOS3) and three differential metabolites (GABA, Pro, and NAG) in TTX-intoxicated rats.</p><p><strong>Conclusion: </strong>EAEAR alleviates TTX poisoning symptoms by modulating targets and metabolites in the arginine and proline metabolism pathways and the arginine biosynthesis pathway. This study provides a theoretical basis for further exploration of its therapeutic potential and mechanisms against TTX poisoning.</p>\",\"PeriodicalId\":11290,\"journal\":{\"name\":\"Drug Design, Development and Therapy\",\"volume\":\"19 \",\"pages\":\"3657-3680\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-05-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063623/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Design, Development and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/DDDT.S505270\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Design, Development and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DDDT.S505270","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
The Potential Mechanisms of Althaea rosea (Linn.) Cavan. Flower in Alleviating Tetrodotoxin Poisoning: An Integrated Metabolomics, Network Pharmacology and Experimental Validation.
Purpose: Tetrodotoxin (TTX) poisoning manifests rapidly and severely, and there are currently no clinically effective treatments. Althaea rosea (Linn.) Cavan. flower, documented in the "National Compendium of Chinese Herbal Medicines", is traditionally recognized and clinically applied for its potential to mitigate tetrodotoxin (TTX) poisoning. This study aims to explores the pharmacodynamic components and mechanisms of the ethyl acetate extract of Althaea rosea flower (EAEAR) in a TTX-induced rat model.
Methods: Ultra-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS) was used to identify active components in EAEAR. Metabolomics combined with network pharmacology was used to explore the mechanisms underlying the mitigating effects of EAEAR in TTX-intoxicated rats. Experimental validation was performed on key targets of the pathway through Western blotting or enzyme-linked immunosorbent assay. And differential metabolites in key pathways were further validated using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS).
Results: A total of 35 active components were identified in EAEAR, 12 core components and 15 core targets were screened in network pharmacology, and metabolomics revealed 15 different metabolites. The arginine and proline metabolism pathway and the arginine biosynthesis pathway were identified as critical pathways for EAEAR's effect in alleviating TTX poisoning. Validation results indicated that EAEAR treatment led to significant alterations (P <0.05) in six key targets (MAOA, AOC1, ALDH7A1, NAGS, NOS2, and NOS3) and three differential metabolites (GABA, Pro, and NAG) in TTX-intoxicated rats.
Conclusion: EAEAR alleviates TTX poisoning symptoms by modulating targets and metabolites in the arginine and proline metabolism pathways and the arginine biosynthesis pathway. This study provides a theoretical basis for further exploration of its therapeutic potential and mechanisms against TTX poisoning.
期刊介绍：
Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications.
The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas.
Specific topics covered by the journal include:
Drug target identification and validation
Phenotypic screening and target deconvolution
Biochemical analyses of drug targets and their pathways
New methods or relevant applications in molecular/drug design and computer-aided drug discovery*
Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes)
Structural or molecular biological studies elucidating molecular recognition processes
Fragment-based drug discovery
Pharmaceutical/red biotechnology
Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products**
Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development
Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing)
Preclinical development studies
Translational animal models
Mechanisms of action and signalling pathways
Toxicology
Gene therapy, cell therapy and immunotherapy
Personalized medicine and pharmacogenomics
Clinical drug evaluation
Patient safety and sustained use of medicines.
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