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

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.

Keywords:

• Myocardial ischaemia
• cardiovascular disease
• bioactive compounds
• pharmacological analysis
• inflammatory response

Author contributions

J.H. performed most of the experiments, data analyses, and figure illustrations. D.W. and E.M. assisted in performing the experiments. Q.W., J.C., and J.P. contributed to new reagents/analytic tools. J.H., and D.W. wrote the manuscript. W.Z. and D-n.R. assisted in instructing students and critical discussion. D-n.R. conceived and supervised the entire project. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability

The data used and analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was supported by National Natural Science Foundation of China [82074190, 81903989], and Scientific Research Foundation for the High-level Talents, Fujian University of Traditional Chinese Medicine [X2019001-talent, X2021001-talent].