Potential Benefits of Nobiletin, A Citrus Flavonoid, against Alzheimer’s Disease and Parkinson’s Disease

Abstract

Alzheimer’s disease (AD), which is characterized by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles, accompanied by neurodegeneration, is the most common form of age-related neurodegenerative disease. Parkinson’s disease (PD) is the second most common neurodegenerative disease after AD, and is characterized by early prominent loss of dopaminergic neurons in the substantia nigra pars compacta. As currently available treatments are not able to significantly alter the progression of these diseases, successful therapeutic and preventive interventions are strongly needed. In the course of our survey of substances from natural resources having anti-dementia and neuroprotective activity, we found nobiletin, a polymethoxylated flavone from the peel of Citrus depressa. Nobiletin improved cognitive deficits and the pathological features of AD, such as Aβ pathology, hyperphosphorylation of tau, and oxidative stress, in animal models of AD. In addition, nobiletin improved motor and cognitive deficits in PD animal models. These observations suggest that nobiletin has the potential to become a novel drug for the treatment and prevention of neurodegenerative diseases such as AD and PD.

Nobiletin Delays Aging and Enhances Stress Resistance of Caenorhabditis elegans

“…Recently, NOB has become a hotspot as one of candidates for the prevention of Alzheimer's disease (AD), which is a chronic and devastating progressive age-associated neurodegenerative disease. Nakajima et al [25] have shown that NOB improved the pathological features of AD. Qi et al [26] reported on the protective effects of NOB on neuroinflammation and cognitive deficits of three-month old mice.…”

Expression and functional analysis of the nobiletin biosynthesis-related gene CitOMT in citrus fruit

“…In recent years, the roles of nobiletin in human health have been investigated extensively, and it was suggested that nobiletin was beneficial to human health through its various activities, such as anti-depressant 25 , anti-allergy 26 , anti-pigmentation of skin 27 , and inhibition of heart failure progression 28 . Currently, the neuroprotective effect of nobiletin has attracted increasing attentions, and nobiletin has been expected to be a potential neuroprotectant for the treatment of cerebral ischemia-reperfusion injury 29 , Alzheimer's disease, and Parkinson's disease 30 . Therefore, the development of functional foods or supplements, which are rich in nobiletin, may be of great importance for human health.…”

Design, Synthesis and Biological Evaluation of Nobiletin Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease

“…Nobiletin (Figure 1), one kind of multimethoxyl flavone extracted from Citrus reticulate, has attracted great attention due to its extensive pharmacological effects, such as antioxidant and anti‐inflammation [16] . A resent research showed nobiletin exhibited activities in neuroprotection against serum withdrawal and hydrogen peroxide‐ induced cytotoxicity through down‐regulating the expression of pro‐apoptotic protein Bax [17] . Another study revealed neuro‐inflammation response could be inhibited by nobiletin through reducing the release of inflammatory mediators [18]…”