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

Ayaz, Muhammad; Sadiq, Abdul; Junaid, Muhammad; Ullah, Farhat; Ovais, Muhammad; Ullah, Ikram; Ahmed, Jawad; Shahid, Muhammad

doi:10.3389/fnagi.2019.00155

Cited by 277 publications

(200 citation statements)

References 173 publications

(184 reference statements)

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“…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].…”

Section: Role Of Flavonoids As Cholinesterase Inhibitorsmentioning

confidence: 99%

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

et al. 2020

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Alzheimer’s disease (AD) is one of the utmost chronic neurodegenerative disorders, which is characterized from a neuropathological point of view by the aggregates of amyloid beta (Aβ) peptides that are deposited as senile plaques and tau proteins which form neurofibrillary tangles (NFTs). Even though advancement has been observed in order to understand AD pathogenesis, currently available therapeutic methods can only deliver modest symptomatic relief. Interestingly, naturally occurring dietary flavonoids have gained substantial attention due to their antioxidative, anti-inflammatory, and anti-amyloidogenic properties as alternative candidates for AD therapy. Experimental proof provides support to the idea that some flavonoids might protect AD by interfering with the production and aggregation of Aβ peptides and/or decreasing the aggregation of tau. Flavonoids have the ability to promote clearance of Aβ peptides and inhibit tau phosphorylation by the mTOR/autophagy signaling pathway. Moreover, due to their cholinesterase inhibitory potential, flavonoids can represent promising symptomatic anti-Alzheimer agents. Several processes have been suggested for the aptitude of flavonoids to slow down the advancement or to avert the onset of Alzheimer’s pathogenesis. To enhance cognitive performance and to prevent the onset and progress of AD, the interaction of flavonoids with various signaling pathways is proposed to exert their therapeutic potential. Therefore, this review elaborates on the probable therapeutic approaches of flavonoids aimed at averting or slowing the progression of the AD pathogenesis.

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Section: Role Of Flavonoids As Cholinesterase Inhibitorsmentioning

confidence: 99%

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

et al. 2020

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“…[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.…”

Section: Introductionmentioning

confidence: 99%

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

Alghamdi¹

2020

JPR

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Background: Postoperative pain remains a major clinical problem as there are limited analgesic strategies that have been proven to be effective in preventing and relieving this type of pain. Natural products, including flavonoids, have distinct pharmacological properties and play an important role in the discovery of analgesic drugs. Materials and Methods: In this study, the flavonoid eriocitrin (eriodictyol 7-O-rutinoside), which is the main flavonoid in lemon fruit (Citrus limon), was mechanistically investigated for its prospective antinociceptive effect in a mouse model of postoperative pain. The antinociceptive property was evaluated by utilizing both tonic (acetic acid-induced writhing behavior) and phasic (hot-plate) nociception modalities. The hindpaw incisional surgery was performed and hyperalgesia was assessed using von Frey filaments. Results: The tested doses of eriocitrin significantly attenuated (P<0.01, P<0.001) the chemically-induced tonic visceral nociception (5, 10, 15, and 30 mg/kg) and acute phasic thermal nociception (10, 15, and 30 mg/kg). A significant dose-dependent reduction in the incisional nociceptive hyperalgesia was exhibited by eriocitrin, with a marked antinociception observed at doses of 15 mg/kg (P<0.05 during 30-60 minutes) and 30 mg/kg (P<0.05, P<0.01 during 30-120 minutes). Conclusion: The antinociceptive effect of eriocitrin (30 mg/kg) was strongly blocked by the antagonists of the opioid receptor, naltrexone, and GABA A receptor, bicuculline, thereby suggesting the involvement of opioidergic and GABAergic mechanisms in the nociception, reducing proclivity of eriocitrin during transmission of incisional nociception. These results concluded that eriocitrin has a potent antinociceptive effect in postoperative pain conditions, probably mediated through opioid and GABA A receptors.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

Effects of nutraceutical intervention on serum proteins in aged rats

et al. 2020

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Aging is associated with many pathophysiological changes that could lead to the onset of degenerative disease. Some of the physiological changes that occur with aging include increased inflammation and decreased stem cell proliferation, leading to decreased capacity for tissue regeneration and loss of function. In previous studies, we and others have found nutraceutical intervention to ameliorate some of the deleterious effects associated with aging. In particular, we have previously shown that NT-020, a supplement composed of a proprietary blend of blueberries, green tea, vitamin D3, and carnosine, is able to rescue age-related cognitive deficits, impaired neurogenesis, and inflammation in rats. We have also previously demonstrated that stem cells cultured with old serum showed decreased proliferation; however, when stem cells were cultured in serum from old rats given a diet supplemented with NT-020, proliferation did not differ from that of cells cultured with serum from young rats. While it is clear that NT-020 is exerting a therapeutic, anti-aging effect, the mechanisms of action were yet to be fully elucidated.To that end, in the present study, we conducted a bioinformatics experiment to examine the rat proteome of serum from young and old control rats and young and old rats given a diet supplemented with NT-020. Serum from old rats showed an increase in some inflammatory and pro-aging factors while serum from old rats given a diet supplemented with NT-020 showed an increase in some anti-aging factors, most notably proteins associated with the complement system and autophagy. A number of immune functions that increase with age were shown to be downregulated with NT-020 treatment.

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

Cited by 277 publications

References 173 publications

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

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

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

Effects of nutraceutical intervention on serum proteins in aged rats

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