Matrine ameliorates cognitive deficits via inhibition of microglia mediated neuroinflammation in an Alzheimer's disease mouse model.

Amyloid β (Aβ) induced microglial activation and attendant neuroinflammation play pivotal roles in Alzheimer's disease (AD) pathogenesis. Matrine is a natural anti-inflammation compound from the Chinese herbal medicine Ait. (Kushen). This study aimed to investigate the effects of matrine on memory deficit and neuroinflammation in an oligomeric Aβ (oAβ)-induced AD mice model. Whether microglial activation and NADPH oxidase were involved in these effects were further studied. Different doses of matrine (10, 20, or 40 mg/kg) were intragastrically administered once a day after intracerebroventricular oAβ injection (2.5 μg/μl, 4 μl). 15 days after the oAβ injection, behavioral experiments including novel object recognition (NOR) test and Morris water maze (MWM) test were performed. 21 days after the oAβ injection, concentration of ROS, TNF-α, IL-1β and IL-6 as well as expression of NADPH oxidase subunits gp91phox and p47phox in mice hippocampal tissues were assessed, and microglial activation were evaluated by Iba-1 immunohistochemical staining. Results of NOR test and MWM test revealed that oAβ injection could remarkably impair learning and memory function in AD mice, and matrine administration could significantly ameliorate the impairment. ROS, TNF-α, IL-1β and IL-6 levels increased after oAβ injection, while matrine could significantly reduce the concentrations of these inflammatory factors. OAβ induced protein expression of NADPH oxidase subunits gp91phox and p47phox were also significantly reduced by matrine. Iba-1 immunohistochemistry results showed less activated microglia in matrine-treated mice brain. These results indicate that matrine could ameliorate learning and memory impairment and neuroinflammation induced by oAβ injection. These effects were found to be mediated through inhibition of microglial activation and NADPH oxidase expression in hippocampal tissue. The results suggest that matrine may be a valuable natural compound with therapeutic potential against AD.