Curcumin improves memory deficits by inhibiting HMGB1‐RAGE/TLR4‐NF‐κB signalling pathway in APPswe/PS1dE9 transgenic mice hippocampus

Amyloid‐β (Aβ) deposition in the brain has been implicated in the development of Alzheimer's disease (AD), and neuroinflammation generates AD progression. Therapeutic effects of anti‐inflammatory approaches in AD are still under investigation. Curcumin, a potent anti‐inflammatory and antioxidant, has demonstrated therapeutic potential in AD models. However, curcumin's anti‐inflammatory molecular mechanisms and its associated cognitive impairment mechanisms in AD remain unclear. The high‐mobility group box‐1 protein (HMGB1) participates in the regulation of neuroinflammation. Herein, we attempted to evaluate the anti‐inflammatory effects of chronic oral administration of curcumin and HMGB1 expression in APP/PS1 transgenic mice AD model. We found that transgenic mice treated with a curcumin diet had shorter escape latencies and showed a significant increase in percent alternation, when compared with transgenic mice, in the Morris water maze and Y‐maze tests. Additionally, curcumin treatment could effectively decrease HMGB1 protein expression, advanced glycosylation end product‐specific receptor (RAGE), Toll‐like receptors‐4 (TLR4) and nuclear factor kappa B (NF‐κB) in transgenic mice hippocampus. However, amyloid plaques detected with thioflavin‐S staining in transgenic mice hippocampus were not affected by curcumin treatment. In contrast, curcumin significantly decreased GFAP‐positive cells, as assessed by immunofluorescence staining. Taken together, these data indicate that oral administration of curcumin may be a promising agent to attenuate memory deterioration in AD mice, probably inhibiting the HMGB1‐RAGE/TLR4‐NF‐κB inflammatory signalling pathway.