P24 Matrine ameliorates cognitive deficits and neuroinflammation via inhibition of microglial activation in an Alzheimer’s disease mouse model

Matrine is a natural anti-inflammatory compound from the Chinese herbal medicine Sophora flavescens Ait. (Kushen). This study aimed to investigate the effects of matrine on memory deficit and neuroinflammation in the Aβ-induced AD mouse model. Whether microglial activation and NADPH oxidase were involved in these effects were also examined. Different doses of matrine (10, 20, or 40 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 Aβ injection, the concentrations of ROS, IL-1β and TNF-α as well as the expression of NADPH oxidase subunits in hippocampal tissue were also assessed. Iba-1 and Neu-N immunohistochemistry were also performed. Results from the Morris water maze test and the NOR test revealed that Aβ injection could remarkably impair learning and memory function in AD mice, and matrine administration could significantly ameliorate the impairment. ROS, IL-1β and TNF-α levels were all increased after Aβ injection, while matrine significantly reduced their concentrations. Aβ induced protein expression of NADPH oxidase subunits gp91phox and p47phox were also significantly reduced by matrine. Iba-1 and Neu-N immunohistochemistry indicated less activated microglia and neuronal death in matrine-treated mouse brain. These results demonstrate that matrine ameliorated the learning and memory impairment and neuroinflammation induced by Aβ injection and that these beneficial effects were mediated through inhibition of microglial activation and NADPH oxidase expression. The results suggest that matrine may be a valuable natural product with therapeutic potential against AD.