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基于网络药理学分析、分子对接和实验验证探讨丹红注射液对缺血/再灌注损伤细胞凋亡的抑制作用

Danhong Injection Inhibits Apoptosis in Ischemia/Reperfusion Injury Based on Network Pharmacology Analysis, Molecular Docking, and Experimental Verification.

作者信息

Shi Shennan, Lu Yalan, Long Qiwen, Wu Yanqing, Guo Yan, Chen Nipi, Wan Haitong, Jin Bo

机构信息

School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.

Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310007, China.

出版信息

ACS Omega. 2025 Feb 25;10(9):9604-9612. doi: 10.1021/acsomega.4c10868. eCollection 2025 Mar 11.

DOI:10.1021/acsomega.4c10868
PMID:40092804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11904842/
Abstract

Danhong injection (DHI), a Chinese patent compound injection, is widely used in the treatment of cardiovascular diseases (CVD) in China. However, the underlying mechanisms have not been fully elucidated. This study investigated the therapeutic effect and the underlying mechanisms of DHI against ischemia-reperfusion (I/R) injury and endothelial dysfunction (ED). Network pharmacology analysis revealed that DHI had six core active compounds (Danshensu, salvianolic acid A, salvianolic acid B, rosmarinic acid, protocatechualdehyde, and caffeic acid) and 19 potential targets in treating I/R injury. Notably, the regulation of apoptosis was significantly enriched, as indicated by the results of the gene ontology (GO) enrichment analysis. Molecular docking studies confirmed that these targets had high affinity with the active compounds of DHI. Finally, experimental validation in vivo and in vitro demonstrated that DHI could mitigate I/R injury and ED, potentially by reducing oxidative damage through the inhibition of apoptosis via the PTEN/AKT pathway. These findings significantly advance our understanding of the molecular mechanisms in DHI treatment and contribute further to promoting the clinical application of CVD.

摘要

丹红注射液(DHI)是一种中药复方注射剂,在中国广泛用于治疗心血管疾病(CVD)。然而,其潜在机制尚未完全阐明。本研究探讨了丹红注射液对缺血再灌注(I/R)损伤和内皮功能障碍(ED)的治疗作用及其潜在机制。网络药理学分析显示,丹红注射液具有六种核心活性成分(丹参素、丹酚酸A、丹酚酸B、迷迭香酸、原儿茶醛和咖啡酸)以及19个治疗I/R损伤的潜在靶点。值得注意的是,基因本体(GO)富集分析结果表明,凋亡调控显著富集。分子对接研究证实,这些靶点与丹红注射液的活性成分具有高亲和力。最后,体内和体外实验验证表明,丹红注射液可能通过PTEN/AKT途径抑制凋亡,减少氧化损伤,从而减轻I/R损伤和ED。这些发现显著推进了我们对丹红注射液治疗分子机制的理解,并进一步有助于促进心血管疾病的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e59/11904842/5656e41ec134/ao4c10868_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e59/11904842/85a6016584ce/ao4c10868_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e59/11904842/5f8a4397ce41/ao4c10868_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e59/11904842/3504b5c4ae0c/ao4c10868_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e59/11904842/43ef70ca359c/ao4c10868_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e59/11904842/5656e41ec134/ao4c10868_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e59/11904842/85a6016584ce/ao4c10868_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e59/11904842/5f8a4397ce41/ao4c10868_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e59/11904842/3504b5c4ae0c/ao4c10868_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e59/11904842/43ef70ca359c/ao4c10868_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e59/11904842/5656e41ec134/ao4c10868_0005.jpg

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本文引用的文献

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Biomedicines. 2024 Sep 12;12(9):2077. doi: 10.3390/biomedicines12092077.
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The Impact of miR-34a on Endothelial Cell Viability and Apoptosis in Ischemic Stroke: Unraveling the -Homocysteine Pathway.miR-34a 对缺血性脑卒中内皮细胞活力和凋亡的影响:揭示同型半胱氨酸通路。
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IL-10 deficiency aggravates cell senescence and accelerates BLM-induced pulmonary fibrosis in aged mice via PTEN/AKT/ERK pathway.
IL-10 缺乏通过 PTEN/AKT/ERK 通路加重衰老小鼠 BLM 诱导的肺纤维化中的细胞衰老。
BMC Pulm Med. 2024 Sep 11;24(1):443. doi: 10.1186/s12890-024-03260-x.
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Danhong injection attenuates doxorubicin-induced cardiotoxicity in rats suppression of apoptosis: network pharmacology analysis and experimental validation.丹红注射液减轻阿霉素诱导的大鼠心脏毒性:凋亡抑制作用的网络药理学分析与实验验证
Front Pharmacol. 2022 Aug 22;13:929302. doi: 10.3389/fphar.2022.929302. eCollection 2022.
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Mitochondrial dynamics related neurovascular approaches in cerebral ischemic injury.线粒体动力学相关的神经血管方法在脑缺血损伤中的作用。
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Selenium Alleviates Cerebral Ischemia/Reperfusion Injury by Regulating Oxidative Stress, Mitochondrial Fusion and Ferroptosis.硒通过调节氧化应激、线粒体融合和铁死亡缓解脑缺血/再灌注损伤。
Neurochem Res. 2022 Oct;47(10):2992-3002. doi: 10.1007/s11064-022-03643-8. Epub 2022 Jun 20.
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Danhong injection combined with tPA protects the BBB through Notch-VEGF signaling pathway on long-term outcomes of thrombolytic therapy.丹红注射液联合 tPA 通过 Notch-VEGF 信号通路对溶栓治疗的长期预后起保护作用。
Biomed Pharmacother. 2022 Sep;153:113288. doi: 10.1016/j.biopha.2022.113288. Epub 2022 Jun 16.
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Excitotoxicity Revisited: Mitochondria on the Verge of a Nervous Breakdown.兴奋性毒性再探:走向崩溃边缘的线粒体。
Trends Neurosci. 2021 May;44(5):342-351. doi: 10.1016/j.tins.2021.01.001. Epub 2021 Feb 16.
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Front Pharmacol. 2020 Oct 30;11:591197. doi: 10.3389/fphar.2020.591197. eCollection 2020.