Integrated chemical composition, transcriptomics, and network pharmacology to reveal the mechanism of Jia-Wei-Si-Miao-Yong-An Decoction in ACS model rats

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-07-02 DOI:10.1016/j.phymed.2025.157027

Ning Zhao , Mengya Dang , Yangyang Sun , Yan Ma , Yanan Xia , Qizhong Jin , Xiaoyun Yang , Yuan Gao , Jingqing Hu , Dong Bai

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Abstract

Background

Acute Coronary Syndrome (ACS), as the most critical pathological type of coronary atherosclerotic heart disease, has a high morbidity and lethality, and the long-term treatment of modern medicine is still faced with the problems of restenosis, microcirculation obstruction and drug resistance. The addition of Traditional Chinese Medicine provides new ideas for ACS treatment. Our previous study found that Jia-Wei-Si-Miao-Yong-An decoction (HJ11) can improve the inflammatory response and cardiac function in ACS. However, its mechanism of action needs to be studied in depth.

Purpose

This study aimed to combine transcriptomics and network pharmacology based on the study of HJ11 components, elucidate the mechanism of HJ11 in ameliorating ACS by experimental validation.

Methods

UPLC-QE-Orbitrap-MS was utilized for the preliminary identification of HJ11 decoction and blood-entry components. And based on the results of the compositional studies, combining with the transcriptomic results of ACS rat model, network pharmacological analysis was performed to identify the potential targets of HJ11 action. The ACS rat model and LPS-induced endothelial cells were further used for experimental validation using RT-PCR, Western blot techniques, immunofluorescence and other techniques.

Results

UPLC-QE-Orbitrap-MS analysis preliminarily identified 212 chemical constituents of HJ11 decoction, of which 49 were consistent with the blood-entered constituents, including organic acids, flavonoids, and amino acids. Combining the compositional studies and transcriptomics results with network pharmacology analysis, HJ11 may ameliorate ACS through various mechanisms (including inflammatory response, oxidative stress, etc.). We verified the mechanisms using rats and endothelial cells and found that HJ11 modulates eNOS levels; reduces inflammation-induced oxidative stress; reduces ADMA levels, which are closely related to inflammation, oxidative stress, and endothelial function and modulates DDAH/ADMA/NO pathway.

Conclusion

HJ11 exhibits a comprehensive multi-target mechanism against ACS, acting through the DDAH/ADMA/NO pathway, reducing inflammation, and attenuating oxidative stress. These findings highlight HJ11 as a promising, holistic therapeutic strategy for ACS, illustrating the potential of Chinese herbal formulas in addressing complex cardiovascular diseases.

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综合化学成分、转录组学、网络药理学等手段揭示加味四苗永安汤对ACS模型大鼠的作用机制

背景急性冠状动脉综合征（acute冠脉综合征，ACS）是冠状动脉粥样硬化性心脏病最关键的病理类型，具有较高的发病率和致死率，现代医学长期治疗仍面临再狭窄、微循环阻塞和耐药等问题。中医的加入为ACS的治疗提供了新的思路。我们前期研究发现加味四鼠永安汤（HJ11）可改善ACS的炎症反应和心功能。但其作用机理还有待深入研究。目的在研究HJ11成分的基础上，将转录组学与网络药理学相结合，通过实验验证阐明HJ11改善ACS的机制。方法采用suplc - qe - orbitrap - ms对HJ11汤剂及其血入口成分进行初步鉴定。并在组成研究结果的基础上，结合ACS大鼠模型转录组学结果，进行网络药理学分析，确定HJ11的潜在作用靶点。采用RT-PCR、Western blot、免疫荧光等技术进一步建立ACS大鼠模型和lps诱导的内皮细胞进行实验验证。结果hplc - qe - orbitrap - ms分析初步鉴定出HJ11汤剂212种化学成分，其中49种与血源性成分一致，包括有机酸、类黄酮、氨基酸等。结合组成研究和转录组学结果以及网络药理学分析，HJ11可能通过多种机制（包括炎症反应、氧化应激等）改善ACS。我们用大鼠和内皮细胞验证了机制，发现HJ11调节eNOS水平；减少炎症引起的氧化应激；降低与炎症、氧化应激和内皮功能密切相关的ADMA水平，并调节DDAH/ADMA/NO通路。结论hj11具有综合的多靶点抗ACS机制，通过DDAH/ADMA/NO通路发挥作用，减轻炎症，减轻氧化应激。这些发现强调了HJ11作为ACS的一种有前景的整体治疗策略，说明了中草药方剂在治疗复杂心血管疾病方面的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.