Effect of Linguizhugan decoction on neuroinflammation and expression disorder of the amyloid [beta]-related transporters RAGE and LRP-1 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 [beta] (A[beta])-induced AD rat model. Sprague-Dawley rats were administered with A[beta]1-42 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 hematoxylin-eosin staining. The levels of pro-inflammatory cytokines, and A[beta] in the brain tissue were detected with ELISA kits. Protein expression levels of mitogen-activated protein kinase and nuclear factor-[kappa]B signalling were measured by western blot analysis. The expression of lipoprotein receptor-related protein-1 (LRP-1) and receptor for advanced glycation endproducts (RAGE) in the brain were detected by western blot analysis, reverse transcription-quantitative 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 LRP-1 and decreased the levels of RAGE. Furthermore, the present results demonstrated that LGZG treatment significantly inhibited MAPK and NF-[kappa]B signalling, and reduced the production of pro-inflammatory cytokines and A[beta] accumulation in AD rats. LGZG exhibited a potential protective effect on A[beta]1-42-induced AD by regulating A[beta] transportation, and inhibiting RAGE/MAPK and NF-[kappa]B signalling. These results suggest that LGZG may be considered for the treatment of AD. Key words: Alzheimer's disease, Lingguizhugan decoction, receptor for advanced glycation endproducts, lipoprotein receptor-related protein-1, amyloid [beta] protein fragment 1-42, mitogen-activated protein kinase, nuclear factor-kB