Brain-derived neurotrophic factor (BDNF) is the potential link between depression and cardiovascular disease and estrogen receptor α (ERα), an estrogen-mediated major regulator, plays an important role in protecting against depression and cardiovascular disease. However, the relationship between BDNF and ERα remains obscure. Herein, quercetin (QUE), a kind of plant flavonoids and existed in many vegetables and fruits, was found to simultaneously reverse ERα^−/−-induced depression-like and cardiac dysfunction by reducing immobility time in the tail suspension test (TST) and forced swimming test (FST), and decreasing systolic blood pressure and activating the apoptosis-related proteins, BDNF, tropomyosin-related kinase B (TrkB), protein kinase B (AKT), and extracellular regulatory protein kinase (ERK1/2) in the hippocampal and cardiac tissues of female mice. These findings suggested that ERα might be involved in the regulation of BDNF activity, thereby regulating depression-like and cardiovascular responses in female mice, and QUE exerted significant antidepressant and cardioprotective effects, at least in part, through BDNF-TrkB-AKT/ERK1/2 to effectively inhibit ERα^−/−-induced hippocampal and cardiac dysfunction.

脑源性神经营养因子（BDNF）是抑郁症与心血管疾病之间的潜在联系，雌激素受体主要调节剂雌激素受体α（ERα）在预防抑郁症和心血管疾病中起着重要作用。然而，BDNF和ERα之间的关系仍然不清楚。在此，发现槲皮素（QUE）是一种植物类黄酮，存在于许多蔬菜和水果中，可同时逆转ERα ^-/-减少尾部悬吊试验（TST）和强迫游泳试验（FST）的不动时间，降低收缩压并激活凋亡相关蛋白，BDNF，原肌球蛋白相关激酶B（TrkB），从而诱发抑郁症样和心脏功能障碍），雌性小鼠海马和心脏组织中的蛋白激酶B（AKT）和细胞外调节蛋白激酶（ERK1 / 2）。这些发现表明，ERα可能参与了BDNF活性的调节，从而调节了雌性小鼠的抑郁样和心血管反应，而QUE至少部分地通过BDNF-TrkB-AKT / ERK1 /发挥了显着的抗抑郁和心脏保护作用。 2有效抑制ERα ^-/-引起的海马和心脏功能障碍。