Beneficial Effects of Citrus-Derived Polymethoxylated Flavones for Central Nervous System Disorders

Abstract

The number of patients with central nervous system disorders is increasing. Despite diligent laboratory and clinical research over the past 30 years, most pharmacologic options for the prevention and long-term treatment of central nervous system disorders and neurodegenerative disorders have been unsuccessful. Therefore, the development of drugs and/or functional foods to prevent the onset of neurodegenerative disorders is highly expected. Several reports have shown that polymethoxylated flavones (PMFs) derived from citrus fruit, such as nobiletin, tangeretin, and 3,3′,4′,5,6,7,8-heptamethoxyflavone, are promising molecules for the prevention of neurodegenerative and neurological disorders. In various animal models, PMFs have been shown to have a neuroprotective effect and improve cognitive dysfunction with regard to neurological disorders by exerting favorable effects against their pathological features, including oxidative stress, neuroinflammation, neurodegeneration, and synaptic dysfunction as well as its related mechanisms. In this review, we describe the profitable and ameliorating effects of citrus-derived PMFs on cognitive impairment and neural dysfunction in various rat and murine models or in several models of central nervous system disorders and identify their mechanisms of action.

Activation of Extracellular Signal-Regulated Kinase 2 and cAMP Response Element-Binding Protein in Cultured Neurons by the Macrocyclic Ellagitannin Oenothein B

“…In conclusion, the addition of oenothein B to the culture medium of rat cortical neurons induced the prompt and significant activation of ERK2 and CREB. Active attempts are being made to apply polyphenols to the treatment of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease [36][37][38][39]. The present results and our previous findings [12] collectively suggest that oenothein B and possibly plant materials containing oenothein B are useful for the treatment of neurological disorders.…”

Perilla seed oil in combination with nobiletin-rich ponkan powder enhances cognitive function in healthy elderly Japanese individuals: a possible supplement for brain health in the elderly

“…Nobiletin was found to improve cognitive and motor dysfunction in various animal models of neurodegenerative disorders by exerting beneficial effects against pathological features, including neuroinflammation, oxidative stress, amyloid-β pathology, tau hyperphosphorylation, cholinergic neurodegeneration, dysfunctional synaptic plasticity, and related signalling cascades. 17–19 However, few intervention studies have been conducted in healthy elderly individuals to verify the effects of nobiletin supplementation on cognitive function.…”

Phytotherapeutic Approaches to the Prevention of Age-Related Changes and the Extension of Active Longevity

“…A similar effect was shown for cinnamon ( Cinnamomum Blume L.) extract [ 114 ]. A number of medicinal plants and their metabolites have a therapeutic effect in Alzheimer’s disease: nobiletin and narirutin, flavanoids from lemon fruits [ 115 , 116 ]; tangeretin has therapeutic potential in inflammatory and degenerative processes in the nervous tissue accompanied by microglial activation [ 117 ]; seeds and roots of Peganum harmala L. [ 118 ], Crocus sativus L. stigmas [ 119 ], Trigonella foenum-graecum L. seeds [ 120 , 121 ]. Experimental studies have shown that fenugreek seed extracts have a therapeutic effect on motor disorders in animal models of Parkinson’s disease.…”