A functional medicine and food homology composition discovery based on disease-related target and data mining against cardiac remodeling

Abstract

AbstractBackgroundMedicine and food homological (MFH) products exhibit enhanced safety and tolerability, minimizing notable side effects, making them pivotal for prolonged use in cardiovascular diseases. This study aims to identify functional compounds in MFH based on cardiac remodeling-related target, employing reliable, comprehensive, and high-throughput methods.MethodsBy bioinformatics andin vivoverifications, we initially investigated the key target in the progression of cardiac remodeling. Subsequently, we performed molecular docking among medical homology compound database (MHCD), and then performed drug-likeness evaluations to recognize functional component based on disease-related target. Pharmacological verifications and data mining including cardiac and medullary transcriptomics, neurotransmitter metabolomics, resting-state functional magnetic resonance imaging (rs-fMRI), and correlationship analysis were utilized to define the benefical effects of MFH functional components, as well as its in-depth mechanims.ResultsThe critical roles of oxidative stress and the key target of NRF2 in cardiac remodeling were discovered, and β-ecdysterone was screened as the most promising NRF2 enhancer in MHCD. Dose-dependent efficacy of β-ecdysterone in countering oxidative stress and ameliorating cardiac remodeling were then verfied byin vivoandex vivoexperiments. By data mining, the crosstalk mechanism between cardiac remodeling and neuromodulation was identified, and further unveiledSlc41a3as a potential key factor influenced by β-ecdysterone. Additionally, β-ecdysterone mitigated increases in norepinephrine (NE) and its metabolites DHPG in the sympathetic nerve center hypothalamic paraventricular (PVN), as indicated by rs-fMRI. Cardiac and medullary transcriptomes revealed central-peripheral regulation signaling pathways during cardiac remodeling with the involvement of core gene ofDhx37.ConclusionsOur study identified β-ecdysterone as a natural MFH functional compound countering cardiac remodeling by targeting NRF2 elevation. It elucidates crosstalk between cardiac remodeling and neuromodulation, facilitating precise drug screening and mechanistic insights, providing substantial evidence for β-ecdysterone application and molecular mechanisms in cardiovascular diseases.