P23 Saikosaponin a ameliorate learning and memory impairment via anti-inflammation effect in an AD mouse model

Abstract

The present study investigated the effects of saikosaponin a (SSA), a natural bioactive compound from Radix bupleuri, on memory deficit and neuroinflammation in the Aβ-treated C57BL/6 mouse model of AD. Different doses of SSA (4, 8, or 16 mg/kg) were intragastrically administered once a day after intracerebroventricular Aβ injection (2.5 μg/μl, 4 μl). 15 days after Aβ injection, behavioural experiments including the Morris water maze and novel object recognition (NOR) tests were performed. 21 days after the Aβ injection, the concentrations of ROS, IL-1β and TNF-α, as well as expression of NADPH oxidase subunits in hippocampal tissue were all assessed. Results from the Morris water maze test revealed that Aβ injection could remarkably increase the escape latency time while SSA could significantly decrease it. In the NOR test, SSA significantly increased the Preference Index (PI), which remarkably decreased in the Aβ injection group. ROS, IL-1β and TNF-α levels all increased after Aβ injection, while SSA significantly reduced the concentration of ROS, IL-1β and TNF-α at doses of 8 mg/kg and 16 mg/kg. Protein expression of NADPH oxidase subunits gp91phox and p47phox were significantly reduced by SSA at doses of 8 and 16 mg/kg. The results indicated that SSA could ameliorate learning and memory impairment induced by Aβ treatment and these effects were mediated through inhibition of pro-inflammatory mediators in hippocampal tissue. Furthermore, NADPH oxidase may be involved in this effect. SSA may be a potent therapeutic drug for the treatment of neurodegenerative diseases associated with neuroinflammation and cognitive impairment such as AD.