Abstract

Context

Huoxin pill (HXP) is a commonly used TCM prescription for treatment of cardiovascular diseases. However, its mechanism in protecting against myocardial infarction (MI) remains unknown.

Objective

We performed a network pharmacology analysis to explore the bioactive ingredients, therapeutic effects, and mechanisms of HXP in protecting against MI.

Materials and methods

HPLC was used to identify major bioactive compounds, and overlap with MI target genes were visualised. 10-Week old C57BL/6 mice were randomly assigned as: Sham-operated control, MI + Phosphate buffered saline (PBS), and MI + HXP (3 mg/mL and 9 mg/mL) treatment groups, received oral gavage administration once every two-days starting from 1-week prior to MI, and subsequently MI models were established for one-week before sacrifice.

Results

AKT1, VEGFA, TNF and RELA were identified as core target proteins among eighty-five candidate bioactive compounds identified in HXP with overlapping MI-related genes. HXP protection against MI was mainly via regulation of inflammatory pathways, notably TNF signalling pathway. Mouse models of MI and cardiac myoblasts demonstrated that HXP improved MI-induced injury via improving regulation of inflammatory response.

Discussion and conclusion

Stellasterol, deoxycholic acid, kaempferol, and quercetin are important active compounds contained in HXP with anti-inflammatory properties in the therapeutic treatment of MI. Due to the straightforward nature and effectiveness of taking oral HXP medications, our findings provide a theoretical basis for the clinical application of HXP in treating patients with angina or myocardial ischaemia. Future research into the combination of surgical procedures or medications that restore blood flow together with HXP as supportive medication would be worthwhile.

中文翻译：

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基于网络药理学的活心丸防治心肌梗死作用机制分析

摘要

语境

活心丸（HXP）是治疗心血管疾病的常用中药方剂。然而，其预防心肌梗塞（MI）的机制仍然未知。

客观的

我们进行了网络药理学分析，以探索 HXP 在预防 MI 中的生物活性成分、治疗效果和机制。

材料和方法

HPLC 用于识别主要的生物活性化合物，并显示与 MI 靶基因的重叠。10周龄C57BL/6小鼠随机分为：假手术对照组、MI+磷酸盐缓冲液（PBS）、MI+HXP（3mg/mL和9mg/mL）治疗组，口服灌胃给药一次从MI前1周开始每两天一次，随后在处死前一周建立MI模型。

结果

AKT1、VEGFA、TNF 和 RELA 在 HXP 中鉴定的具有重叠 MI 相关基因的 85 种候选生物活性化合物中被鉴定为核心靶蛋白。HXP 对 MI 的保护主要是通过调节炎症通路，特别是 TNF 信号通路。MI 和心肌成肌细胞的小鼠模型表明，HXP 通过改善炎症反应的调节来改善 MI 引起的损伤。

讨论与结论

星甾醇、脱氧胆酸、山奈酚和槲皮素是 HXP 中含有的重要活性化合物，在 MI 的治疗中具有抗炎特性。由于口服 HXP 药物的直接性质和有效性，我们的研究结果为 HXP 治疗心绞痛或心肌缺血患者的临床应用提供了理论基础。未来对恢复血流的外科手术或药物与 HXP 作为支持性药物的组合进行研究是值得的。