神经炎症是抑郁的常见病理特征，与抑郁的发展密切相关。许多临床抗炎药物通过减轻神经炎症反应来发挥抗抑郁作用。以前的研究发现，三七皂苷及其生物活性物质三七皂苷-14 (GP-14) 对缺氧引起的损伤具有神经保护作用，并减轻了与神经炎症相关的高原脑水肿。在这里，我们调查了GP-14对脂多糖（LPS）诱导的抑郁样行为模型的影响。注射LPS（0.5 mg/kg）于小鼠腹腔内，连续7天诱导抑郁样行为，这被认为是抑郁加重的模型。同时以100 mg/kg的剂量通过灌胃给予GP-14连续7天。在LPS诱导的抑郁模型中，GP-14不仅减轻了抑郁样行为，还改善了小鼠的焦虑样行为。此外，GP-14处理减轻了抑郁小鼠的学习和认知衰退。ELISA和免疫荧光染色结果表明，GP-14抑制了前炎症细胞因子的上调，包括肿瘤坏死因子-α（TNF-α），白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6），并抑制了LPS诱导的星形胶质细胞的活化，表明其具有强效的抗炎作用。GP-14预处理C8细胞和原代星形胶质细胞能抑制NF-κB信号通路的活化，并下调前炎症因子的水平。总之，我们的研究结果表明，GP-14具有显著的抗炎和抗抑郁特性；因此，GP-14可能是治疗抑郁的有前景的前导化合物。

Neuroinflammation is a common pathogenetic sign of depression and is closely linked to the development of depression. Many clinical anti-inflammatory drugs act as antidepressants by reducing the neuroinflammatory response. Previous research found that gypenosides and their bioactive compound gypenoside-14 (GP-14) had neuroprotective effects against hypoxia-induced injury and reduced neuroinflammation-related high-altitude cerebral edema. Here we investigated the effects of GP-14 on the lipopolysaccharide (LPS)-induced depression-like behavior model. LPS (0.5 mg/kg) was injected into mice intraperitoneally for 7 consecutive days to induce depression-like behavior, which is considered a model for the exacerbation of depression. GP-14 in the amount of 100 mg/kg was simultaneously administered by gavage for 7 days. In the LPS-induced depression model, GP-14 not only attenuated depression-like behavior but also improved the anxiety-like behavior of the mice. Additionally, GP-14 treatment mitigated learning and cognitive decline in depressed mice. ELISA and immunofluorescence staining results revealed that GP-14 inhibited the upregulation of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), and suppressed the activation of astrocytes induced with LPS, indicating its potent anti-inflammatory effect. GP-14 pretreatment in C8 cells and primary astrocytes can inhibit the activation of the NF-κB signaling pathway and downregulate the levels of pro-inflammatory factors. In summary, our findings showed that GP-14 had significant anti-inflammation and anti-depression properties; thus, GP-14 could be a promising lead compound for treating depression.