Chronic stress can impair hippocampal neurogenesis, increase neuronal apoptosis, and cause depressive-like behaviors. Our previous studies found that Radix Scutellariae (RS) can rescue the stress-induced neuronal injury, but the mechanism is not clear. Here, we continued to investigate the underlying antidepressant mechanisms of the RS extract. A 7-week chronic unpredictable mild stress (CUMS) procedure was used to establish a murine depression model. 0.75 g/kg or 1.5 g/kg RS was administered daily to the mice during the last 4 weeks. Depressive-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and tail suspension test (TST). The neuroprotective effect of RS was evaluated with the expression of hippocampal neuron-related markers and apoptosis-associated proteins by Nissl staining, immunohistochemistry, and western blot. Transforming growth factor-β3 (TGFβ3) pathway-related proteins were detected by western blot. Results showed that RS could ameliorate depressive-like behaviors, increase the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL-2), reduce the expression of the proapoptotic protein BCL-2-associated X (BAX), and increase the number of doublecortin- (DCX-), microtubule-associated protein 2- (MAP2-), and neuronal nucleus- (NeuN-) positive cells in the hippocampus. Moreover, RS could reverse the CUMS-induced decrease of TGFβ3 protein, promote the phosphorylation of SMAD2/3, and increase the expression of downstream NEDD9 protein. These results suggest that RS could exert antidepressant effects via protecting neurons. And the molecular mechanism might be related to the regulation of the TGFβ3-SMAD2/3-NEDD9 pathway.

中文翻译：

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黄芩通过 TGFβ3-Smad2/3-Nedd9 信号通路保护神经元改善压力诱导的抑郁样行为

慢性压力会损害海马神经发生，增加神经元凋亡，并导致抑郁样行为。我们以往的研究发现黄芩（RS）可以挽救应激性神经元损伤，但机制尚不清楚。在这里，我们继续研究 RS 提取物的潜在抗抑郁机制。7 周慢性不可预测轻度应激 (CUMS) 程序用于建立小鼠抑郁症模型。在过去 4 周内，每天向小鼠施用 0.75 g/kg 或 1.5 g/kg RS。抑郁样行为通过蔗糖偏好试验（SPT）、强迫游泳试验（FST）、旷场试验（OFT）和悬尾试验（TST）进行评估。通过Nissl染色，通过海马神经元相关标志物和凋亡相关蛋白的表达来评估RS的神经保护作用，免疫组织化学和蛋白质印迹。转化生长因子-通过蛋白质印迹检测β 3 (TGF β 3)途径相关蛋白。结果表明，RS可以改善抑郁样行为，增加抗凋亡蛋白B细胞淋巴瘤2（BCL-2）的表达，降低促凋亡蛋白BCL-2相关X（BAX）的表达，并增加数量海马中双皮质素- (DCX-)、微管相关蛋白 2- (MAP2-) 和神经元核- (NeuN-) 阳性细胞。此外，RS 可以逆转 CUMS 诱导的 TGF β 3 蛋白减少，促进 SMAD2/3 的磷酸化，并增加下游 NEDD9 蛋白的表达。这些结果表明 RS 可以通过保护神经元发挥抗抑郁作用。其分子机制可能与TGF的调控有关β 3-SMAD2/3-NEDD9 通路。