Crosstalk mechanism exploration of the medical food homology compound β-ecdysterone with sympathetic overactivation-induced cardiac hypertrophy

β-ecdysterone, a functional component derived from medicine and food homologous herb Achyranthes bidentata, has shown potential in cardiovascular protection according to our previous studies. This study aims to further investigate its neuromodulatory mechanism in cardiac hypertrophy. The anti-hypertrophic effects of β-ecdysterone were validated both in vivo and in vitro. Transcriptomic analysis of cardiac and medullary tissues revealed the involvement of neuroregulatory pathways, including modulation of sympathetic acitivity. β-ecdysterone significantly reduced norepinephrine (NE) levels and its metabolites, which correlated with hypertrophic markers. Weighted Gene Co-Expression Network Analysis (WGCNA) identified Dhx37 as a key gene associated with cardiac hypertrophy. In a co-culture model of sympathetic neurons (PC-12) and cardiomyocytes (H9C2), β-ecdysterone suppressed NE secretion and calcium influx in PC-12 cells under Angiotensin II (AngII) stimulation, an effect abolished by .Dhx37 knockdown in cardiomyocytes. These findings suggest that β-ecdysterone alleviates cardiac hypertrophy by modulating cardiac-sympathetic neuron interaction via the Dhx37 pathway, offering a novel neurocardiac regulatory target for MFH-based therapies.