Flavonoids as Prospective Neuroprotectants and Their Therapeutic Propensity in Aging Associated Neurological Disorders

Abstract

Modern research has revealed that dietary consumption of flavonoids and flavonoids-rich foods significantly improve cognitive capabilities, inhibit or delay the senescence process and related neurodegenerative disorders including Alzheimer’s disease (AD). The flavonoids rich foods such as green tea, cocoa, blue berry and other foods improve the various states of cognitive dysfunction, AD and dementia-like pathological alterations in different animal models. The mechanisms of flavonoids have been shown to be mediated through the inhibition of cholinesterases including acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), β-secretase (BACE1), free radicals and modulation of signaling pathways, that are implicated in cognitive and neuroprotective functions. Flavonoids interact with various signaling protein pathways like ERK and PI3-kinase/Akt and modulate their actions, thereby leading to beneficial neuroprotective effects. Moreover, they enhance vascular blood flow and instigate neurogenesis particularly in the hippocampus. Flavonoids also hamper the progression of pathological symptoms of neurodegenerative diseases by inhibiting neuronal apoptosis induced by neurotoxic substances including free radicals and β-amyloid proteins (Aβ). All these protective mechanisms contribute to the maintenance of number, quality of neurons and their synaptic connectivity in the brain. Thus flavonoids can thwart the progression of age-related disorders and can be a potential source for the design and development of new drugs effective in cognitive disorders.

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

“…Acetylcholine (ACh) is the neurotransmitter responsible for the signaling among synapses, which is degraded via enzymes such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) [234]. As there are copious studies reporting low levels of ACh in AD brains [47,235,236], cholinesterase inhibitors thus represent the best therapeutic remedy to increase ACh levels at synaptic junctions [237].…”

<p>Antinociceptive Effect of the Citrus Flavonoid Eriocitrinon Postoperative Pain Conditions</p>

“…[24][25][26] Citrus limon (family: Rutaceae) has been widely studied as an important source of natural flavonoids. The fruit, peel, essential oil, and isolated compounds from Citrus limon possess strong antioxidant and antinociceptive, 27 antiinflammatory, 28 antibacterial, 29,30 antifungal, 29 antiviral, 31 anticancer, 32 antidiabetic and hypolipidemic, 33 hepatoprotective, 34 antiproliferative, 35 nephroprotective, 36 and neuroprotective 37,38 properties. Eriocitrin (eriodictyol 7-O-rutinoside) is the major flavonoid found in lemon fruit.…”

Effects of nutraceutical intervention on serum proteins in aged rats

“…Aging is a complex and multifactorial physiological process associated with decreased stem cell proliferation in stem cell niches throughout the body, leading to reduced tissue rejuvenation and loss of organ function (Murshid et al 2013;Bickford et al 2015). The decline in stem cell regeneration is global, occurring both in the periphery (Ning et al 2019;Jung et al 2019;Chambers et al 2007) and in the central nervous system (CNS) (Villeda et al 2011;Lazarov et al 2010;Kozareva et al 2019;Ayaz et al 2019;Kase et al 2019;Stankiewicz et al 2019;Bickford et al 2015;Flowers et al 2015;Acosta et al 2010). While the exact biological mechanisms underlying dampened stem cell proliferation with age remain unclear, two areas of investigation are being explored: cellautonomous changes and cell non-autonomous changes.…”

“…Polyphenols have been shown to rescue age-related dysfunctions within the CNS including chronic inflammation, impaired synaptic plasticity, and decreased neurogenesis (Zhu et al 2008;Ayaz et al 2019;Flowers et al 2015;Dias et al 2012;Rahman et al 2006;Vauzour 2012). Furthermore, polyphenolic compounds have also been shown to have beneficial effects in mouse models of Alzheimer's disease (AD) (Rezai-Zadeh et al 2005;Rezai-Zadeh et al 2009;Rezai-Zadeh et al 2008;Singh et al 2008).…”