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 <em>Achyranthes bidentata</em>, 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 <em>in vivo</em> and <em>in vitro</em>. 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 <em>Dhx37</em> 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 .<em>Dhx37</em> 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.