Major depressive disorder is a common but devastating mental disorder, and recent evidence shows that neuroinflammation may play a pivotal role in the etiology of depression. Astragaloside IV (AS-IV) is an active component purifed from Astragalus membranaceus (Fisch) Bge, which has shown anti-inflammatory, anti-oxidative and anti-apoptotic effects. In this study, we explored whether AS-IV produced antidepressant effects via its inhibition of neuroinflammation in mouse models of depression. Depressive-like behaviors including decreased sucrose consumption, reduced locomotor activity and increased immobility time were induced in mice using repeated restraint stress (RRS). We found that administration of AS-IV (16, 32 and 64 mg·kg^-1·d^-1, ig) significantly attenuated RRS-induced depressive-like behaviors. Furthermore, AS-IV administration significantly reduced the levels of TNF-α and IL-1β, increased PPARγ expression and GSK3β phosphorylation, decreased NF-κB phosphorylation, and reduced NOD-, LRR- and pyrin domain-containingprotein 3 (NLRP3) inflammasome and caspase-1 p20 generation in the hippocampus of the mice. LPS-induced depression-like behaviors were induced by LPS injection (1 mg·kg^-1·d^-1, ip), which were ameliorated by administration of AS-IV (20, 40 mg·kg^-1·d^-1, ig). The results of the LPS-induced mouse model were in accordance with those acquired from the RRS-induced mouse model: LPS injection significantly increased TNF-α and IL-1β expression in the mouse hippocampus, which was reversed by administration of AS-IV. Moreover, administration of AS-IV significantly increased PPARγ expression and GSK3β phosphorylation, and decreased NF-κB phosphorylation and NLRP3 inflammasome. These results suggest that AS-IV is a potential drug against depression, and its antidepressant effects are partially mediated by inhibition of neuroinflammation via the upregulation of PPARγ expression.

中文翻译：

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黄芪甲苷IV通过PPARγ/NF-κB/ NLRP3炎性体轴改善了小鼠神经炎症引起的抑郁样行为。

严重的抑郁症是一种常见但具有毁灭性的精神障碍，最近的证据表明，神经炎症可能在抑郁症的病因中起关键作用。黄芪甲苷IV（AS-IV）是从黄芪（Fisch）Bge中纯化的活性成分，具有抗炎，抗氧化和抗凋亡作用。在这项研究中，我们探讨了AS-IV是否通过抑制抑郁症小鼠模型中的神经炎症而产生抗抑郁作用。使用重复约束应激（RRS）在小鼠中诱发了抑郁样行为，包括减少蔗糖消耗，降低运动能力和增加不动时间。我们发现AS-IV（16、32和64 mg·kg ^-1 ·d ^-1（图ig）显着减弱了RRS诱发的抑郁样行为。此外，AS-IV给药显着降低了TNF-α和IL-1β的水平，增加了PPARγ表达和GSK3β的磷酸化，降低了NF-κB的磷酸化，并减少了NOD-，LRR-和含吡啶结构域的蛋白3（NLRP3）的炎性和小鼠海马中caspase-1 p20的产生。LPS注射（1 mg·kg ^-1 ·d ^-1，ip）可诱发LPS引起的抑郁样行为，而AS-IV（20，40 mg·kg ^-1 ·d ^-1）可以改善这种行为。，ig）。LPS诱导的小鼠模型的结果与从RRS诱导的小鼠模型获得的结果一致：LPS注射显着增加了小鼠海马中的TNF-α和IL-1β表达，这可通过给予AS-IV来逆转。而且，施用AS-IV显着增加PPARγ表达和GSK3β磷酸化，并降低NF-κB磷酸化和NLRP3炎性体。这些结果表明，AS-IV是一种潜在的抗抑郁药，其抗抑郁作用部分是通过上调PPARγ表达抑制神经炎症而介导的。