Effects of Curcumin on Oxidative Stress in Animal Models and Patients with Alzheimer Disease

Abstract

Curcumin is a powerful antioxidant. The antioxidant activity of curcumin is due to its chemical structure. In curcumin molecule the keto-enol-enolate equilibrium of the heptadienone moiety of curcumin dictates its antioxidant properties. The central CH2 group adjacent to the highly activated carbon atom in the heptadienone link is the antioxidant site, in which the delocalization of unpaired electron on the adjacent oxygen atoms contributes to antioxidant effects of curcumin. In addition, phenolic OH is the most preferable group for the loss of proton from the one-electron oxidized species. As the resultant phenoxyl radical is stabilized by delocalization of electrons, the ability for curcumin to scavenge the oxidizing free radicals is greatly increased. Studies on the effect of curcumin have indicated that curcumin can cross the blood-brain barrier and mediates its effects not only by retarding amyloid-β-protein (Aβ)-mediated aggregation, and oxidative stress and neuroinflammation, but also inhibits activities of β-secretase and acetylcholinesterase. In in vivo studies, oral administration of curcumin has resulted in the inhibition of Aβ deposition, Aβ oligomerization, and tau phosphorylation in the brains of AD animal models, and improvements in behavioral impairment in animal models. Curcumin also stimulates neuroplasticity by acting on Nrf2 and promoting the expression of superoxide dismutase, catalase, sulfaredoxin, thioredoxin, peroxiredoxin systems, glutathione peroxidase, glutathione reductase, γ-glutamine cysteine ligase and γ-glutamine cysteine synthase, quinone recycling (NAD(P)H quinone oxidoreducase, and heme oxygenase 1. These findings suggest that curcumin may be one of the most promising compounds for the development of AD therapies. Curcumin may provide neuroprotection by reducing protein misfolding and aggregation through the upregulation of heat shock proteins.