College of Pharmacy, Jinan University, Guangzhou 510632, China.
Department of the First Affiliated Hospital, Jinan University, Guangzhou 510632, China; College of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China.
J Steroid Biochem Mol Biol. 2021 Feb;206:105795. doi: 10.1016/j.jsbmb.2020.105795. Epub 2020 Nov 24.
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，雌激素受体α（ERα）是雌激素介导的主要调节剂，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 之间的关系仍不清楚。在此，我们发现槲皮素（QUE），一种植物类黄酮，存在于许多蔬菜和水果中，通过减少悬尾试验（TST）和强迫游泳试验（FST）中的不动时间，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）、蛋白激酶 B（AKT）和细胞外调节蛋白激酶 1/2（ERK1/2），同时逆转 ERα 诱导的抑郁样和心脏功能障碍，在雌性小鼠的海马体和心脏组织中。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和心血管反应，而 QUE 通过 BDNF-TrkB-AKT/ERK1/2 发挥显著的抗抑郁和心脏保护作用，至少部分通过有效抑制 ERα 诱导的海马体和心脏功能障碍。
