Saikosaponin-d attenuated lipopolysaccharide-induced depressive-like behaviors via inhibiting microglia activation and neuroinflammation
Saikosaponin-d attenuated lipopolysaccharide-induced depressive-like behaviors via inhibiting microglia activation and neuroinflammation
复制标题
柴胡皂苷d通过抑制小胶质细胞活化和神经炎症减轻脂多糖诱导的抑郁样行为
DOI：
10.1016/j.intimp.2019.106181
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发表时间：
2020-03-01
影响因子：
5.6
通讯作者：
Ma, Shi-Ping
中科院分区：
文献类型：
--
作者：
Su, Jing;Pan, Yi-Wei;Ma, Shi-Ping
柴胡皂苷d（Saikosaponin-d，SSd）是从柴胡中提取的一种三萜皂苷类化合物，已被证明能有效缓解慢性轻度应激诱导的大鼠抑郁行为，但其分子机制尚不清楚。越来越多的证据表明，小胶质细胞活化和炎症反应参与了抑郁症的发病机制。因此，我们希望通过注射脂多糖（LPS）诱导小鼠炎症相关的抑郁样行为，以研究SSd的抗抑郁作用是否与抑制炎症有关。行为学实验结果表明，SSd可改善LPS诱导的抑郁样行为，表现为蔗糖偏好实验中蔗糖消耗量增加，悬尾实验和强迫游泳实验中不动时间减少。此外，免疫染色结果显示，SSd预处理抑制LPS诱导的小鼠海马和原代小胶质细胞中小胶质细胞的活化。酶联免疫吸附试验（ELISA）结果显示，SSd预处理抑制了LPS诱导的炎症因子如白细胞介素（IL）-1 β、IL-6、肿瘤坏死因子（TNF）-α的体内和体外过度表达。免疫组化和western blot分析结果表明，SSd预处理还抑制了LPS诱导的HMGB 1从核到细胞外的移位，并降低了TLR 4、p-I κ B-alpha、NF-κ Bp 65的蛋白水平。这些结果表明，SSd通过抑制LPS诱导的小胶质细胞活化和神经炎症，有效改善US诱导的炎症相关抑郁样行为，其机制可能与HMGB 1/TLR 4/NF-κ B信号通路的调节有关。
Saikosaponin-d (SSd), a triterpenoid saponins compound extracted from Radix Bupleuri, has been demonstrated to effectively alleviate chronic mild stress-induced depressive behaviors in rats, but the underlying molecular mechanisms are still uncertain. Increasing evidence indicated that microglia activation and inflammatory responses were involved in the pathogenesis of depression. Thus, we desired to induce inflammation-related depressive-like behaviors in mice by injecting lipopolysaccharide (LPS) to investigate whether the antidepressant effect of SSd is related to inhibiting inflammation. The results of behavioral tests showed that SSd administration ameliorated LPS-induced depressive-like behaviors, as shown by increased sucrose consumption in the sucrose preference test and decreased immobility time in the tail suspension test and forced swimming test. Furthermore, immunostaining results showed that SSd pretreatment inhibited LPS-induced microglia activation in the hippocampus of mice and primary microglia cells. Enzyme-linked immunosorbent assay (ELISA) results showed that SSd pretreatment suppressed LPS-induced overexpression of inflammatory factors such as interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha both in vivo and in vitro. Immunostaining and western blot analysis results demonstrated that SSd pretreatment also inhibited LPS-induced HMGB1 translocation from nuclear to extracellular and decreased the protein levels of TLR4, p-I kappa B-alpha, NF-kappa Bp65. These results suggested that SSd effectively improved US-induced inflammation-related depressive-like behaviors by inhibiting LPS-induced microglia activation and neuroinflammation, and the possible mechanism might associate with the regulation of the HMGB1/TLR4/NF-kappa B signaling pathway.