基于网络药理学的17-甲氧基-7-羟基苯-糠醛通过AMPK/SIRT1通路改善心肌缺血/再灌注损伤后线粒体生物发生和氧化应激。

IF 3.4 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2025-09-12 DOI:10.1016/j.taap.2025.117560

Yuanheng Huang , Yan Zhou , Qiuhua Qin , Sirui Mo , Zudong Xu , Zhiwei Tang , Yaosheng Wu , Feizhang Qin

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引用次数: 0

摘要

背景：线粒体生物发生和氧化应激在心肌缺血/再灌注（I/R）损伤中起关键作用。17-甲氧基-7-羟基苯-呋喃醛酮（MHBFC）在心肌I/R损伤中具有显著的线粒体保护作用。然而，潜在的机制仍然未知。本研究旨在通过网络药理学、分子对接、分子动力学模拟和实验验证等方法探讨MHBFC对心肌I/R损伤的影响。方法和结果：采用冠脉阻断1 h，再灌注3 h的方法建立大鼠I/R模型。研究发现，MHBFC显著改善心功能，减少梗死面积和心肌酶，增加线粒体DNA拷贝数和ATP的产生。MHBFC暴露也显著提高了抗氧化酶活性，抑制了ROS的产生。网络药理学分析发现，MHBFC与心肌I/R损伤相关的核心靶点在腺苷5′-单磷酸活化蛋白激酶(AMPK)/沉默交配型信息调控2同源物-1 （SIRT1）信号通路中显著富集。分子对接分析显示MHBFC与AMPK和SIRT1有很强的结合。分子动力学模拟验证了对接物的稳定性。Western blot分析证实MHBFC激活了AMPK/SIRT1通路，在缺氧/再氧化-中进一步验证了其保护作用。治疗H9c2心肌细胞。结论：MHBFC通过激活AMPK/SIRT1通路，改善线粒体生物发生和氧化应激，从而减轻心肌I/R损伤。

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17-Methoxyl-7-hydroxy-benzene-furanchalcone improves mitochondrial biogenesis and oxidative stress following myocardial ischemia/reperfusion injury through the AMPK/SIRT1 pathway based on network pharmacology

Background

Mitochondrial biogenesis and oxidative stress are pivotal in myocardial ischemia/reperfusion (I/R) injury. 17-Methoxyl-7-hydroxy-benzene-furanchalcone (MHBFC) has been shown to significantly protect mitochondria during myocardial I/R injury. However, the potential mechanisms involved remain unknown. This study aimed to investigate the impact of MHBFC on myocardial I/R injury through network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation.

Methods and results

A rat I/R model was developed by inducing 1 h of coronary occlusion followed by 3 h of reperfusion. It was found that MHBFC significantly ameliorated cardiac function, reduced infarct size and cardiac enzymes, and increased the copy number of mitochondrial DNA and ATP production. MHBFC exposure also significantly elevated antioxidant enzyme activity and suppressed ROS production. Network pharmacology analysis identified that core targets of MHBFC associated with myocardial I/R injury were significantly enriched in the adenosine 5′-monophosphate activated protein kinase (AMPK)/silent mating type information regulation 2 homolog-1 (SIRT1) signaling pathway. Molecular docking analyses showed the strong binding of MHBFC with AMPK and SIRT1. Molecular dynamics simulation verified the stability of the docked complex. Western blot analysis confirmed that MHBFC activated the AMPK/SIRT1 pathway, and its protective effects were further validated in hypoxia/reoxygenation-.

treated H9c2 cardiomyocytes.

Conclusion

The study concludes that MHBFC mitigates myocardial I/R injury by improving mitochondrial biogenesis and oxidative stress through activation of the AMPK/SIRT1 pathway.

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.