The Potential Mechanisms of Althaea rosea (Linn.) Cavan. Flower in Alleviating Tetrodotoxin Poisoning: An Integrated Metabolomics, Network Pharmacology and Experimental Validation.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-05-05 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S505270

Renjin Zheng, Youjia Wu, Lingyi Huang, Fanxiang Zeng, Liying Huang

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引用次数: 0

Abstract

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.

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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。

目的：河豚毒素中毒表现迅速且严重，目前尚无临床有效的治疗方法。玫瑰杜鹃花（属）卡文。“国家中草药纲目”中记载的花，传统上被认为具有减轻河豚毒素（TTX）中毒的潜力，并被临床应用。本研究旨在探讨玫瑰杜鹃花乙酸乙酯提取物（EAEAR）对ttx诱导大鼠模型的药效学成分及其作用机制。方法：采用超高效液相色谱-四极杆轨道阱高分辨率质谱法（UPLC-Q-Orbitrap-HRMS）对EAEAR中的有效成分进行鉴定。利用代谢组学与网络药理学相结合的方法，探讨EAEAR对ttx中毒大鼠的缓解作用机制。通过Western blotting或酶联免疫吸附试验对该途径的关键靶点进行实验验证。采用超高效液相色谱-三重四极杆串联质谱（UPLC-QqQ-MS/MS）进一步验证关键通路中的差异代谢物。结果：EAEAR共鉴定出35种有效成分，网络药理学筛选出12种核心成分和15种核心靶点，代谢组学显示出15种不同的代谢物。确定了精氨酸和脯氨酸代谢途径和精氨酸生物合成途径是EAEAR缓解TTX中毒的关键途径。结论：EAEAR可通过调节精氨酸和脯氨酸代谢途径及精氨酸生物合成途径中的靶点和代谢物缓解TTX中毒症状。本研究为进一步探索其治疗TTX中毒的潜力和机制提供了理论基础。

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

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

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.