Network pharmacology-based analysis in determining the mechanisms of Huoxin pill in protecting against myocardial infarction.

Network pharmacology-based analysis in determining the mechanisms of Huoxin pill in protecting against myocardial infarction.
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基于网络药理学分析活心丸抗心肌梗死的作用机制

DOI:
10.1080/13880209.2021.1964542
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发表时间:
2021-12
影响因子:
3.8
通讯作者:
Ren DN
Ren DN
中科院分区:
医学3区
文献类型:
--
作者:
He J;Wo D;Ma E;Wang Q;Chen J;Peng J;Zhu W;Ren DN

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摘要活心丸是治疗心血管疾病的常用中药方剂。然而,其保护心肌梗死(MI)的机制仍不清楚。目的通过网络药理学分析,探讨黄连汤的生物活性成分、治疗作用及其机制。材料与方法用高效液相色谱法鉴定主要生物活性物质,并与MI靶基因重叠。10周龄C57BL/6小鼠随机分为假手术对照组、MI + 磷酸盐缓冲盐水组和MI + HXP(3 mg/m L和9 mg/m L)治疗组,从MI前1周开始,每隔2天灌胃给药1次,随后建立MI模型,持续1周。结果在85个具有心肌梗死相关基因重叠的候选生物活性化合物中,AKT1、VEGFA、肿瘤坏死因子和RelA被确定为核心靶蛋白。HXP对心肌梗死的保护作用主要是通过调节炎症通路,尤其是肿瘤坏死因子信号通路。心肌梗死小鼠模型和心肌成肌细胞模型表明,HXP通过改善炎症反应的调节,改善了MI诱导的损伤。讨论与结论司他甾醇、脱氧胆酸、山奈酚和槲皮素是黄连素中重要的活性成分,具有抗炎作用,可用于治疗心肌梗塞。由于口服HXP药物的直接性和有效性,我们的发现为HXP在治疗心绞痛或心肌缺血患者中的临床应用提供了理论依据。未来关于外科手术或恢复血流的药物与HXP作为支持性药物的组合的研究将是值得的。
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.
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