生仙汤抑制急性高原心肌损伤的作用及机制探讨

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-05-26 DOI:10.1016/j.phymed.2025.156896

Zhihan Chen , Lingyuan Zhong , Mengsong Liu , Peiwen Ding , Nan Jia , Qian Chen , Junling Liu , Yitong Wang , Jianyuan Tang

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引用次数: 0

摘要

心脏是急性低气压缺氧暴露下最脆弱的器官，急性高原心肌损伤（acute high altitude myocardial injury， AHMI）通常发生在从低地地区迅速上升到高海拔地区的人群中。AHMI的有效干预策略已经引起了人们的极大关注，生仙汤（SXD）成为潜在的治疗剂；然而，其潜在机制尚不清楚。目的探讨SXD改善AHMI的有效成分、潜在靶点及调控机制。本研究创新性地采用网络药理学、转录组学、蛋白质组学、分子对接、分子生物学等综合策略，分析SXD改善AHMI的靶点和机制通路。采用超高效液相色谱/ qexactive HFX质谱（UHPLC-QE-MS）和网络药理学方法鉴定有效成分并分析其功能。在此基础上，结合转录组学和蛋白质组学技术，在基因和蛋白质水平上进一步研究和验证其机制。此外，我们还构建了草药-成分-靶标-通路（HCTP）网络进行探索和分析。分子对接用于深入检查筛选的组分与靶标之间的结合活性。最后，应用分子生物学技术重新确认了其作用靶点和机制。结果ssxd能有效降低心脏异常电活动，抑制各种心肌酶、肌钙蛋白和炎症因子向血液中的释放。网络药理学、转录组学、蛋白质组学显示，炎症反应对SXD在AHMI中的作用很重要。结合网络药理学、转录组学、蛋白质组学等分析，构建了包含5种中药、13种有效成分、146个靶点和20条信号通路的HCTP网络，阐明了SXD对AHMI的作用机制，进一步分析表明SXD通过调节IL-17、MAPK/ERK、Ras信号通路缓解AHMI。结论SXD对AHMI的积极作用是通过调节炎症相关通路（IL-17、MAPK/ERK、Ras信号通路），抑制炎症因子释放，调节炎症反应来实现的。

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The exploration of the effect and mechanism of Shengxian decoction inhibiting acute high-altitude myocardial injury

Background

The heart is the most vulnerable organ to acute hypobaric hypoxia exposure, acute high-altitude myocardial injury (AHMI) typically occurs in individuals who rapidly ascend from lowland areas to high-altitude regions. Effective intervention strategies for AHMI have garnered significant attention, with Shengxian decoction (SXD) emerging as a potential therapeutic agent; however, the underlying mechanism remains unclear.

Purpose

The objective of this study was to explore the effective components, potential targets and regulatory mechanisms of SXD in improving AHMI.

Study design

This study innovatively employed the combined strategy including network pharmacology, transcriptomics, proteomics, molecular docking, and molecular biology to analyze the targets and mechanism pathways of SXD for improving AHMI. Ultra-high-performance liquid chromatography/Q Exactive HFX mass spectrometry (UHPLC-QE-MS) and network pharmacology were adopted to identify active ingredients and analyze their functions. On this basis, transcriptomics and proteomics technologies were integrated to further investigate and validate the mechanisms at both gene and protein levels. Additionally, a herbs-components-targets-pathways (HCTP) network was generated for exploration and analysis. Molecular docking was utilized for an in-depth examination of the binding activity between screened components and targets. Finally, molecular biology techniques were applied to re-confirm the targets and mechanisms involved.

Results

SXD effectively reduced heart’s abnormal electrical activity, inhibited the release of various myocardial enzymes, troponins and inflammatory factors into the blood. Network pharmacology, transcriptomics, proteomics revealed that inflammatory response was important for the effects of SXD in AHMI. The combined analysis of network pharmacology, transcriptomics, proteomics constructed the HCTP network encompassing 5 herbs, 13 active ingredients, 146 targets and 20 signaling pathways to elucidate the mechanism by which SXD exerts its effects on AHMI, further analysis suggested that SXD regulated IL-17, MAPK/ERK, and Ras signaling pathways to alleviate AHMI.

Conclusion

The positive effect of SXD on AHMI was achieved through the regulation of inflammation-related pathways (IL-17, MAPK/ERK, and Ras signaling pathways), the inhibition of inflammatory factors releases and the modulation of the inflammatory response.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.