Effect of Linguizhugan decoction on neuroinflammation and expression disorder of the amyloid ß­related transporters RAGE and LRP­1 in a rat model of Alzheimer's disease.

Linguizhugan decoction (LGZG), a notable prescription in Traditional Chinese Medicine, is a classical formula for the treatment of Alzheimer's disease (AD), inflammatory injury and fluid retention. The present study aimed to investigate the neuroprotective effect of LGZG on an amyloid ß (Aß)­induced AD rat model. Sprague­Dawley rats were administered with Aß1­42 to induce AD and inflammatory responses, and subsequently with LGZG (4.8, 2.4 or 1.2 g/kg), donepezil (2 mg/kg) or distilled water for 30 consecutive days. Learning and memory behaviors were evaluated via Morris water maze test. The neuronal impairment of AD rats was observed via hematoxylin­eosin staining. The levels of pro­inflammatory cytokines, and Aß in the brain tissue were detected with ELISA kits. Protein expression levels of mitogen­activated protein kinase and nuclear factor­κB signalling were measured by western blot analysis. The expression of lipoprotein receptor­related protein­1 (LRP­1) and receptor for advanced glycation endproducts (RAGE) in the brain were detected by western blot analysis, reverse transcription­quantitative polymerase chain reaction and immunohistochemistry analysis. LGZG was demonstrated to significantly improve learning and memory ability, and ameliorate neuroinflammation in AD rats. LGZG increased the levels of LRP­1 and decreased the levels of RAGE. Furthermore, the present results demonstrated that LGZG treatment significantly inhibited MAPK and NF­κB signalling, and reduced the production of pro­inflammatory cytokines and Aß accumulation in AD rats. LGZG exhibited a potential protective effect on Aß1­42­induced AD by regulating Aß transportation, and inhibiting RAGE/MAPK and NF­κB signalling. These results suggest that LGZG may be considered for the treatment of AD.