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）是抑郁症和心血管疾病之间的潜在联系，而雌激素受体α（ERα）是雌激素介导的主要调节因子，在预防抑郁症和心血管疾病方面发挥着重要作用。然而，BDNF 和 ERα 之间的关系仍然不清楚。槲皮素（QUE）是一种植物黄酮^类化合物，存在于许多蔬菜和水果中，在悬尾试验（TST）和强迫游泳试验 (FST)，降低收缩压并激活细胞凋亡相关蛋白、BDNF、原肌球蛋白相关激酶 B (TrkB)、蛋白激酶 B (AKT) 和细胞外调节蛋白激酶 (ERK1/2)。雌性小鼠的海马和心脏组织。这些发现表明 ERα 可能参与 BDNF 活性的调节，从而调节雌性小鼠的抑郁样反应和心血管反应，而 QUE 至少部分通过 BDNF-TrkB-AKT/ERK1/ 发挥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。