Ginsenoside Rk1, a saponin component produced by heat-processed ginseng, possesses anti-inflammatory and antitumor activities. The aim of our study was to explore the effects of Rk1 on Lipopolysaccharide (LPS)-induced depression-like behavior in mice and to observe its effects on oxidative stress, the inflammatory response and brain-derived neurotrophic factor (BDNF) - tropomyosin-related kinase B (TrkB) signaling. After mice were pretreated with Rk1 (5, 10, and 20 mg/kg), the immobility time in both the forced swimming test (FST) and the tail suspension test (TST) was reduced, suggesting that Rk1 effectively improved depression-like symptoms. Rk1 (10 and 20 mg/kg) and Fluoxetine (Flu, 20 mg/kg) increased the activity of the antioxidant enzyme SOD in the brain and protected against lipid peroxidation. Different concentrations of Rk1 (10 and 20 mg/kg) and Flu significantly decreased the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1 in serum, while Rk1 (5, 10, and 20 mg/kg) and Flu reduced the concentrations of IL-6 in a dose-dependent manner. Western blot analysis showed that the administration of Rk1 (20 mg/kg) and Flu significantly downregulated the level of Sirt1 and that Rk1 (5, 10, and 20 mg/kg) and Flu inhibited the p-NF-κb/NF-κb and p-IκB-α/IκB-α ratios, which indicated that the neuroprotective effect of Rk1 may be related to the suppression of inflammation. In addition 5, 10 and 20 mg/kg Rk1 significantly attenuated the LPS-induced decreases in BDNF and TrkB. These results indicated that Rk1 acts as an antidepressant through its antioxidant activity, the inhibition of neuroinflammation, and the positive regulation of the BDNF-TrkB pathway. This study may help develop active ginsenoside-based compounds for neurodegenerative diseases.

人参皂苷Rk1是由人参热处理后产生的皂苷成分，具有抗炎和抗肿瘤的作用。我们的研究目的是探讨Rk1对脂多糖（LPS）诱导的小鼠抑郁样行为的影响，并观察其对氧化应激，炎症反应和脑源性神经营养因子（BDNF）-原肌球蛋白相关的影响激酶B（TrkB）信号传导。用Rk1（5、10和20 mg / kg）预处理小鼠后，在强迫游泳测试（FST）和尾部悬吊测试（TST）中的固定时间都减少了，这表明Rk1有效地改善了抑郁症样症状。Rk1（10和20 mg / kg）和Fluoxetine（Flu，20 mg / kg）增加了脑中抗氧化酶SOD的活性，并防止脂质过氧化。Rk1（10和20 mg / kg）和Flu的不同浓度显着降低血清中肿瘤坏死因子（TNF）-α和白介素（IL）-1的水平，而Rk1（5、10和20 mg / kg）流感以剂量依赖性方式降低了IL-6的浓度。Western blot分析表明，Rk1（20 mg / kg）和Flu的施用显着下调Sirt1的水平，Rk1（5、10和20 mg / kg）和Flu抑制p-NF-κb/NF-κb和p-IκB-α/IκB-α的比率，表明Rk1的神经保护作用可能与炎症抑制有关。此外，5、10和20 mg / kg Rk1显着减弱了LPS诱导的BDNF和TrkB下降。这些结果表明，Rk1通过其抗氧化活性，抑制神经发炎，和BDNF-TrkB通路的正调控。这项研究可能有助于开发用于神经退行性疾病的活性人参皂苷类化合物。