Network pharmacology and LC-MS approachs to explore the active compounds and mechanisms of Yuanjiang decoction for treating bradyarrhythmia

Abstract

Background: Yuanjiang decoction (YJD), a traditional Chinese medicinal prescription, has been found to have a significant heart rate-increasing effect and is effective in the treatment of symptomatic bradyarrhythmia in previous studies. However, its specific components and potential mechanisms remain unclear.

Methods: In this study, we detected and identified the main compounds of YJD using liquid chromatography-mass spectrometry (LC-MS). Through the approach of network pharmacology, we predicted the core targets of the active components, bradyarrhythmia targets, and obtained potential anti-bradyarrhythmia targets of YJD. We further performed protein to protein interaction (PPI), gene ontology (GO) enrichment analyses and kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analyses for core targets, and constructed network of key active ingredients-core targets of YJD. Finally, molecular docking and molecular dynamics simulation were performed for key active ingredients and core targets.

Results: The YJD contains a total of 35 main chemical components. The key active ingredients-core targets network contains 36 nodes and 90 edges, including 20 key active ingredients and 16 core targets. The core targets in the PPI network were TP53, TNF, HRAS, PPARG, IL1B, KCNH2, SCN5A, IDH1, LMNA, ACHE, F2, DRD2, CALM1, KCNQ1, TNNI3, IDH2 and TNNT2. KEGG pathway analysis showed that YJD treatment of bradyarrhythmia mainly involves neuroactive ligand-receptor interaction, adrenergic signaling in cardiomyocytes, cAMP signaling pathway, calcium signaling pathway, cholinergic synaptic and serotonergic synapse signaling pathway. The biological processes mainly include regulation of hormone levels, regulation of cardiac contraction, chemical synaptic transmission, circadian rhythm, positive regulation of heart rate, smooth muscle contraction, response to metal ion, oxidation-reduction process, neurotransmitter transport and import across plasma membrane. Molecular docking and molecular dynamics simulation results showed that hesperidin and tetrahydropalmatine had higher affinity with DRD2 and KCNQ1, respectively.

Conclusion: This study reveals the pharmacodynamic material basis of YJD and its potential multicomponent-multitarget-multipathway pharmacological effects, predicted its potential anti-bradyarrhythmia mechanism may be related to the regulation of myocardial autonomic nervous function and related ion channels. Our work demonstrates that YJD has great potential for treating bradyarrhythmias as a complementary medicine, and the results can provide a theoretical basis for the development and clinical application of YJD.

Keywords: Bradyarrhythmia; Bradycardia; Liquid chromatography-mass spectrometry (LC-MS); Molecular docking; Molecular dynamics simulation; Network pharmacology; Traditional Chinese medicine (TCM); Yuanjiang decoction.