Lipopolysaccharides (LPS) are proinflammation mediators that can induce the inflammatory model of the hippocampal neuron, and neuroinflammation participates in the pathophysiology of depression. Xiaoyao Pill is a classical Chinese medicine formula that has been used for the treatment of mental disorders such as depression in China since the Song dynasty. We established a hippocampal neuronal cell inflammation model by LPS and investigate the intervention effect and mechanism of Xiaoyao Pills. The expression levels of IL-6, TNF-α, IDO, 5-HT, brain-derived neurotrophic factor, and β-nerve growth factor were detected by enzyme-linked immunosorbent assay. mRNA levels of IL-6, TNF-α, 5-HT1A, IDO-1, brain-derived neurotrophic factor, nerve growth factor, tropomyosin receptor kinase B, tropomyosin receptor kinase A, and cAMP response element-binding protein were detected by reverse transcription-polymerase chain reaction. To further validate, protein expression was determined by western blot and immunofluorescence. Lipopolysaccharide-induced neuroinflammatory state resulted in the release of IL-6, TNF-α, and IDO and a decrease of BDNF, NGF, TrkB, TrkA, CREB, p-CREB, p-CREB/CREB, and SYP and inhibited hippocampal neurogenesis in the hippocampal neuron. Xiaoyao Pills significantly decreased the levels of IL-6, TNF-α, and IDO in cell supernatant and increased the expression of BDNF, NGF, TrkB, TrkA, CREB, p-CREB, p-CREB/CREB, and SYP as well as the average optical density of BrdU/NeuN double-labelled positive cells. Our study shows that lipopolysaccharides induce inflammation and nerve damage in hippocampal neurons, which are closely related to the pathological mechanism of depression. Xiaoyao Pills (XYW) play an important neuroprotective effect, which is related to its inhibition of neuronal inflammation and promoting the recovery of nerve injury. These results provide a pharmacologic basis for the treatment of depression of XYW in clinical application.

中文翻译：

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逍遥丸在体外减轻脂多糖诱导的海马神经元炎症和神经损伤

脂多糖（LPS）是一种促炎症介质，可以诱导海马神经元的炎症模型，神经炎症参与抑郁症的病理生理过程。逍遥丸是我国自宋代以来用于治疗抑郁症等精神障碍的经典中药方剂。我们通过LPS建立海马神经元细胞炎症模型，探讨逍遥丸的干预作用及机制。酶联免疫吸附法检测IL-6、TNF- α、IDO、5-HT、脑源性神经营养因子、β-神经生长因子的表达水平。IL-6、TNF- α 的mRNA 水平通过逆转录聚合酶链反应检测5-HT1A、IDO-1、脑源性神经营养因子、神经生长因子、原肌球蛋白受体激酶B、原肌球蛋白受体激酶A和cAMP反应元件结合蛋白。为了进一步验证，通过蛋白质印迹和免疫荧光测定蛋白质表达。脂多糖诱导的神经炎症状态导致 IL-6、TNF- α和 IDO的释放以及 BDNF、NGF、TrkB、TrkA、CREB、p-CREB、p-CREB/CREB ​​和 SYP 的减少并抑制海马神经发生在海马神经元中。逍遥丸显着降低IL-6、TNF- α水平和 IDO 在细胞上清液中增加 BDNF、NGF、TrkB、TrkA、CREB、p-CREB、p-CREB/CREB ​​和 SYP 的表达以及 BrdU/NeuN 双标记阳性细胞的平均光密度。我们的研究表明，脂多糖引起海马神经元炎症和神经损伤，这与抑郁症的病理机制密切相关。逍遥丸具有重要的神经保护作用，这与其抑制神经元炎症、促进神经损伤的恢复有关。这些结果为临床应用治疗XYW抑郁症提供了药理基础。