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

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.