PDF(Pubmed)
Abstract：
Astrocyte dysfunction and inflammation play a pivotal role in depression. In this study, we evaluated the antidepressant properties of Heracleum moellendorffii root extract (HME), which is traditionally used for inflammation-related diseases, in a mouse model with astrocyte depletion that resembles the prefrontal cortex pathology of depressive patients. Mice were divided into four groups, with 10 mice per group. To induce astrocyte ablation in the mice\'s prefrontal cortex (PFC), we used astrocytic toxin L-alpha-aminoadipic acid (L-AAA) and administered HME orally at 200 and 500 mg/kg for 22 days. We utilized the tail suspension test (TST) to assess depression-like behaviors and the open field test (OFT) to evaluate anxiety-like activities. Additionally, astrocytic and inflammatory markers in the PFC were evaluated using immunohistochemistry and ELISA. The results showed that infusion of L-AAA significantly decreased the expression of astrocytic glial fibrillary acidic protein (GFAP), which was accompanied by increased depression and anxiety-like behaviors. However, HME significantly reversed these effects by dose-dependently enhancing GFAP expression and modulating inflammatory markers, such as TNF-α, IL-6, and particularly lipocalin-2, a master proinflammatory mediator. These results imply that HME contributes to the alleviation of depression and anxiety-like behaviors by promoting astrocyte recovery and reducing neuroinflammation, especially through lipocalin-2 inhibition.
摘要：
星形胶质细胞功能障碍和炎症在抑郁症中起关键作用。在这项研究中,我们评估了Heracleummoellendorffii根提取物（HME）的抗抑郁特性，传统上用于炎症相关疾病，在星形胶质细胞耗竭的小鼠模型中，该模型类似于抑郁症患者的前额叶皮质病理学。将小鼠分成四组,每组10只小鼠。诱导小鼠前额叶皮质(PFC)星形胶质细胞消融,我们使用星形胶质细胞毒素L-α-氨基己二酸(L-AAA),并以200和500mg/kg口服HME22天.我们使用尾部悬吊测试（TST）来评估抑郁样行为，并使用空场测试（OFT）来评估焦虑样活动。此外,使用免疫组织化学和ELISA评估PFC中的星形细胞和炎症标志物。结果表明,输注L-AAA能显著降低星形胶质细胞纤维酸性蛋白(GFAP)的表达,伴随着抑郁和焦虑样行为的增加。然而,HME通过剂量依赖性地增强GFAP表达和调节炎症标志物显著逆转这些效应,如TNF-α，IL-6，特别是脂质运载蛋白-2，一种主要的促炎介质。这些结果表明，HME通过促进星形胶质细胞恢复和减少神经炎症，有助于减轻抑郁和焦虑样行为。特别是通过脂质运载蛋白-2抑制。
