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

Abstract

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.

Curcumin ameliorates LPS/D-GalN induced acute liver injury by regulating TLR4/NF-кB/NLRP3 signaling pathway in vivo and in vitro

“…In the obstructive nephropathy model, curcumin (50 mg/kg) by gavage inhibited the renal in ammatory response via suppressing TLR4/NF-κB signaling pathway [38] . Oral administration of curcumin (100 mg/kg) effectively reduced the expression of HMGB1 and the protein levels of TLR4 and NF-κB in the hippocampus of transgenic mice, thereby improving the memory de cit of transgenic mice [39] . Intraperitoneal injection of 100 mg/kg curcumin in rats down-regulated the expression of TLR4 and NF-κB, and inhibited the production of in ammatory cells, thereby improving hindlimb motor defects and spinal cord edema caused by spinal cord injury in rats [40] .…”

Curcumin Attenuates Lipopolysaccharide-Induced Neuroinflammation and Memory Deficiency by Inhibiting Microglia Activation in Mice Hippocampus

“…In this study, there was an increase in GFAP (a marker of astrocytes) expression in the dentate gyrus region of the hippocampus following LPS-induced neuroinflammation, though no significant increase in GFAP immunoreactivity was observed; curcumin was found to significant decrease GFAP immunoexpression. Chronic curcumin exposure has been documented to increase synaptophysin and actin expression and reduce GFAP expression in the hippocampus [36,37], while simultaneously reducing the reactive oxygen species (ROS) -related molecule, metallothionein 3 expression in the prefrontal cortex (PFC) and hippocampus [36]. This curcumin administration has been proposed to be a promising agent to attenuate memory deterioration in mice by inhibiting the HMGB1-RAGE/TLR4-NF-κB inflammatory signaling pathway [37].…”

Therapeutic Potential of Targeting the HMGB1/RAGE Axis in Inflammatory Diseases

“…Similarly, Han et al [ 43 ] also reported the potential of curcumin ( Figure 3 ) to treat the cognitive impairment in a transgenic mice model claiming the possibility of inhibiting the HMGB1/RAGE inflammatory pathway [ 43 ]. For the evaluation of curcumin, they used APP/PS1 transgenic mice for the diseased group, and wild type (WT) mice as the control.…”

“…The expression of all these proteins was significantly increased in the hippocampus of the diseased mice (APP/PS1 mice) compared to WT. It is noteworthy that curcumin did not affect the plaque load in the hippocampus of the transgenic mice suggesting the possible mechanism of curcumin to show neuroprotection specifically through the HMGB1/RAGE inflammatory pathway [ 43 ].…”