Amelioration of behavioral and neural deficits in animal models of neurodegenerative disease by nanoformulations of curcumin and quercetin.

Neurodegenerative diseases are increasing in prevalence due largely to aging populations worldwide and improved medical care for the elderly. Currently approved drugs can reduce some of the symptoms of neurodegenerative diseases but cannot cure them. Inflammation is involved in the development and progression of neurodegenerative diseases, and oxidative stress is implicated in neurodegeneration associated with cognitive decline and age-related cognitive impairment. Polyphenols such as curcumin, quercetin, and resveratrol possess potent anti-inflammatory and antioxidant properties. Nanoformulations of curcumin and quercetin can optimize their pharmacological effects in the treatment of neurodegenerative diseases. Nanocarriers play a crucial role in delivering drugs across the blood-brain barrier, thereby lowering the risk of peripheral side effects. Various nanoforms have been developed to induce bioavailability and solubility of curcumin and quercetin, including nanoparticles and nanoemulsions. The studies reviewed included 17 using curcumin nanoformulations and seven with quercetin nanoformulations and were tested in widely used animal models of Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. Many of the curcumin and quercetin nanoformulations brought about improvements in learning and memory in behavioral tests of Alzheimer's disease models and were effective in reducing oxidative stress in the brain. Both nanocurcumin and nanoquercetin decreased the levels of inflammatory markers in the brain. Nanocurcumin formulations improved motor behavior, gait, and memory in Parkinson's disease models and increased dopaminergic neurons in the striatum and substantia nigra. Furthermore, nanocurcumin improved locomotor activity, memory, and learning, and the number of dendrites of medium spiny neurons in Huntington's disease models. Nanocurcumin formulations decreased oxidative stress and inflammation in a model of demyelination. Several important limitations were identified in the studies reviewed and these need to be considered in future studies. Also, clinical trials could be performed using the currently available nanoforms of curcumin and quercetin.