Anti-Cytokine Activity of Curcumin and Its Binding to a Fragment of AβPP

Abstract

Since it has been shown that Alzheimer's disease is accompanied by higher peripheral concentrations of cytokines, we focused on the correction of chronic inflammation causing Aβ excess and aggregation what should have a positive impact. Proinflammatory cytokines action is realized by NF-κB intracellular signals. Curcumin can inhibit activation of the proinflammatory transcription factor NF-κB and is able to be mounted in the amyloid-β fibrils and encourage their disaggregation. To study the influence of anti-inflammatory effect of curcumin and its ability to model complexes with a fragment of AβPP. Investigation was carried out on rats with model of Alzheimer's disease using nasal therapy with curcumin Concentration of cytokines in cerebral cortex, hippocampus and blood serum, and indicators of conditioned active escape reflex were determined in this study. Methods of molecular dynamics and docking were used to examine the interactions of curcumin with fragment of AβPP. Аβ42_Human in the hippocampus of rats provoked chronic neuroinflammation specifically and primarily at the injection site. Curcumin performance revealed specific depressing effect on cytokines in the cerebral cortex and in the hippocampus it appeared similar to the above, but of lower level. Anti-inflammatory activity of curcumin led to the recovery of memory parameters. Analysis of restriction sites of AβPP has shown that position of curcumin in Site II is energetically more favorable for binding. Our suggestion that curcumin is an effective anti-cytokine factor was confirmed by experimental results obtained in vivo and explain the mechanism describing its effect on NF-κB Curcumin doesn't block the excision Aβ but binding with its hydrophobic region.