Soybean isoflavone alleviates β-amyloid 1-42 induced inflammatory response to improve learning and memory ability by down regulation of Toll-like receptor 4 expression and nuclear factor-κB activity in rats

beta-amyloid 1-42 (A beta 1-42)-induced learning and memory impairment in rats is believed to be associated with inflammation. Cytokine production is a key pathologic event in the progression of inflammatory processes. In this rat study, soybean isoflavones (SIF) was used to investigate it's protective effects on inflammation caused by beta-amyloid 1-42 (A beta 1-42), which is associated with learning and memory impairment in Alzheimer disease. We characterized the learning and memory ability. cytokine profiles of circulating interleukin-10 (IL-1 beta), tumor necrosis factor-alpha (INF-alpha) in the serum and the expression of Toll like receptor4 (TLR4) and nuclear factor-kappa B p65 (NF-KB p65) mRNA and protein in the brain tissue following intracerebroventricular administration of A beta 1-42 by miniosmotic pump for 14 days. The results showed that functional deficits of learning and memory in SIF treatment groups were significantly improved compared to the control group without SIF treatment in water maze test. The serum IL-1 beta and TNF-alpha level were significantly increased, and the expressions of TLR4 and NF-kappa B p65 mRNA and protein in the brain were up-regulated, indicating inflammation response was initiated following administration of A beta 1-42. After intragastric pre-treatment with SIF, inflammatory cytokines was significantly reduced and also SIF reversed the A beta 1-42 induced up-regulation of TLR4 and NF-kappa B p65 mRNA and protein expression in the brain and expression of NF-kappa B p65 in nuclei. These results suggested that SIF reduced the cytokine cascade and inflammatory response induced by A beta 1-42 which could result in the improvement of spatial learning and memory ability impairment in the rats. (C) 2011 ISDN. Published by Elsevier Ltd. All rights reserved.