Department of Pharmacology, College of Pharmacy, Chengdu University of TCM, Chengdu City, Sichuan Province 611137, China.
Neural Plast. 2020 Sep 21;2020:8841332. doi: 10.1155/2020/8841332. eCollection 2020.
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-, IDO, 5-HT, brain-derived neurotrophic factor, and -nerve growth factor were detected by enzyme-linked immunosorbent assay. mRNA levels of IL-6, TNF-, 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-, 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-, 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.
脂多糖（LPS）是一种促炎介质，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学。逍遥丸是一种经典的中药方剂，自宋代以来就一直用于治疗抑郁症等精神障碍。我们通过 LPS 建立了海马神经元细胞炎症模型，研究了逍遥丸的干预作用和机制。通过酶联免疫吸附试验检测了 IL-6、TNF-、IDO、5-HT、脑源性神经营养因子和-神经生长因子的表达水平。通过逆转录-聚合酶链反应检测了 IL-6、TNF-、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 反应元件结合蛋白的 mRNA 水平。为了进一步验证，通过 Western blot 和免疫荧光测定了蛋白质表达。脂多糖诱导的神经炎症状态导致 IL-6、TNF-和 IDO 的释放以及 BDNF、NGF、TrkB、TrkA、CREB、p-CREB、p-CREB/CREB 和 SYP 的减少，并抑制海马神经元中的海马神经发生。逍遥丸显著降低细胞上清液中 IL-6、TNF-和 IDO 的水平，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，脂多糖诱导海马神经元炎症和神经损伤，与抑郁症的病理机制密切相关。逍遥丸（XYW）发挥重要的神经保护作用，与其抑制神经元炎症和促进神经损伤恢复有关。这些结果为 XYW 在临床应用中治疗抑郁症提供了药理学基础。
