Lixing Xu, Zhouye Ji, Liting Guo, Ruyi Zhang, Rong Qu, Shiping Ma
Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
Department of Pharmacology of Traditional Chinese Medical Formulae, Nanjing University of Chinese Medicine, Hanzhong Road 282, Nanjing 210046, PR China.
Toxicol Lett. 2018 Mar 1;284:79-85. doi: 10.1016/j.toxlet.2017.11.009. Epub 2017 Nov 10.
Saikosaponin-d (SSd), one of the main constituents of the total saikosaponins extracted from Bupleurum falcatum L, possesses anti-inflammatory and anti-apoptosis effect. Recently, SSd was proved to improve depressive symptoms although exhibit hepatotoxicity in animals, but the central nervous system (CNS) toxicity of SSd remains unclear. The present study investigated the SSd-induced impairment in hippocampal cognitive function and explored the possible mechanisms involved. After intragastric administration of SSd (4mg/kg, 8mg/kg) for 7days, the learning and memory abilities of mice were evaluated by behavioral experiments. In the step-down passive avoidance test, we found that the mice treated with SSd showed a significant decrease of step-down latency and increase of the frequency of errors. In the Morris water maze task, both the escape latency and swimming distance of the mice treated with SSd were increased, correspondingly, both the time of mice staying in the target zone and the frequency of crossing platform were decreased. These neurobehavioral changes were accompanied by the reduction of the expression of 5-bromo-2'-deoxyuridine (BrdU), nestin, doublecortin (Dcx) and microtubule associated protein 2 (MAP2). Moreover, SSd significantly inhibited the expression of p-Akt, Foxg-1 and fibroblast growth factor 2 (FGF2) in the hippocampus of mice. These results indicated that SSd had a toxic effect on cognitive function in mice, which was associated with inhibiting the hippocampal neurogenesis via Akt/Foxg1 pathway.
柴胡皂苷 d（SSd）是从柴胡中提取的总柴胡皂苷的主要成分之一，具有抗炎和抗凋亡作用。最近，尽管 SSd 在动物实验中表现出肝毒性，但已被证明可改善抑郁症状，但其对中枢神经系统（CNS）的毒性仍不清楚。本研究调查了 SSd 对海马认知功能的损害，并探讨了可能涉及的机制。在给予小鼠灌胃 SSd（4mg/kg，8mg/kg）7 天后，通过行为实验评估小鼠的学习和记忆能力。在被动回避试验中，我们发现用 SSd 处理的小鼠的跳下潜伏期显著缩短，错误频率增加。在 Morris 水迷宫任务中，用 SSd 处理的小鼠的逃避潜伏期和游泳距离均增加，相应地，小鼠在目标区域停留的时间和穿过平台的频率均降低。这些神经行为变化伴随着 5-溴-2'-脱氧尿苷（BrdU）、巢蛋白、双皮质素（Dcx）和微管相关蛋白 2（MAP2）表达的减少。此外，SSd 显著抑制小鼠海马中 p-Akt、Foxg-1 和成纤维细胞生长因子 2（FGF2）的表达。这些结果表明，SSd 对小鼠的认知功能有毒性作用，这与通过 Akt/Foxg1 途径抑制海马神经发生有关。
