Possible neuroprotective mechanisms of action involved in the neurobehavioral property of naringin in mice

Ben‐Azu, Benneth; Nwoke, Ekene Enekabokom; Aderibigbe, Adegbuyi Oladele; Omogbiya, Itivere Adrian; Ajayi, Abayomi Mayowa; Olonode, Elizabeth Toyin; Umukoro, Solomon; Iwalewa, Ezekiel O.

doi:10.1016/j.biopha.2018.10.055

Cited by 64 publications

(37 citation statements)

References 66 publications

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“…Furthermore, since donepezil exposure decreased AChE levels in zebrafish brain (Figure 2), these findings parallel rodent and human data on donepezil-evoked changes in brain AChE activity (Ben-Azu et al, 2019;Kasa et al, 2000;Shin et al, 2018), and corroborate the proposed link between cholinergic signaling and stress responses (Janowsky and Risch, 1984). However, the dose-dependent aspect of such effects on zebrafish behavior, cortisol, and AChE activity merit further consideration, since behavior and cortisol showed a clear dose-dependent curve here, whereas the AChE activity did not (Figures 1 and 2).…”

Section: Discussionsupporting

confidence: 81%

“…Consistently producing promnestic effects in humans and rodents (Alachkar et al, 2017;Ben-Azu et al, 2019;Raghavendra et al, 2013;Riedel et al, 2009), donepezil nevertheless evokes unclear or mixed effects on anxiety phenotypes. For example, while in some rodent studies its acute or repeated administration does not affect anxiety-like behavior (Hernandez et al, 2006;Poole et al, 2014), in healthy animals it improves affective responses, but can also produce hypolocomotion (Cutuli et al, 2008;Poole et al, 2014;Soliani et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

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An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish

et al. 2020

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Background: A potent acetylcholinesterase inhibitor, donepezil is a cognitive enhancer clinically used to treat neurodegenerative diseases. However, its complete pharmacological profile beyond cognition remains unclear. The zebrafish ( Danio rerio) is rapidly becoming a powerful novel model organism in neuroscience and central nervous system drug screening. Aim: Here, we characterize the effects of 24-h donepezil administration on anxiety-like behavioral and endocrine responses in adult zebrafish. Methods: We evaluated zebrafish anxiety-like behaviors in the novel tank, the light-dark and the shoaling tests, paralleled by assessing brain acetylcholinesterase activity and whole-body cortisol levels. Results: Overall, donepezil dose-dependently decreased zebrafish locomotor activity in the novel tank test and reduced time in light in the light-dark test, likely representing hypolocomotion and anxiety-like behaviors. Donepezil predictably decreased brain acetylcholinesterase activity, also increasing whole-body cortisol levels, thus further linking acetylcholinesterase inhibition to anxiety-like behavioral and endocrine responses. Conclusion: Collectively, these findings suggest negative modulation of zebrafish affective behavior by donepezil, support the key role of cholinergic mechanisms in behavioral regulation in zebrafish, and reinforce the growing utility of zebrafish models for studying complex behavioral processess and their neuroendocrine and neurochemical regulation.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish

et al. 2020

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“…Studies have demonstrated that naringin inhibits lipid peroxidation and nitrosative processes by reducing levels of ROS and nitrogen species [44]. Finally, the extract of Cirsium japonicum at doses of 200 and 400 mg/kg has shown the ability to reduce immobility time on FST in a similar manner to that of 5 mg/kg of the antidepressant imipramine.…”

Section: Flavonoids With Antidepressant Effects: Preclinical Researchmentioning

confidence: 96%

Neuropharmacology of Secondary Metabolites from Plants with Anxiolytic and Antidepressant Properties

García-Ríos¹,

Mora-Pérez²,

Ramos-Molina³

et al. 2020

Behavioral Pharmacology - From Basic to Clinical Research

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Depression and anxiety currently rank as the second and fifth most common causes worldwide of years lived with disability-a reality that has intensified the search for new treatments. There are many studies of herbal extracts and secondary metabolites from plants used in traditional medicine due to their antidepressant and anxiolytic properties. Clinical and preclinical studies about some of the mechanisms of action of metabolites like alkaloids, terpenes, flavonoids, and sterols, among others, have documented effects similar to those produced by clinically effective drugs. These metabolites have shown anxiolytic and antidepressant effects in various experimental models of anxiety by interacting with γ-aminobutyric acid subtype A receptors (GABA A-receptors) and by stimulating the serotonergic, noradrenergic, and dopaminergic neurotransmitter systems. These pharmacological effects can be attributed to plant metabolites that share structural similarities with monoamines, which allow them to bind to receptors. The objective of this chapter is to summarize the various mechanisms of action that have been identified in secondary metabolites with anxiolytic and antidepressant properties. Terpenes, alkaloids, flavonoids, and sterols can interact at different levels of the neurotransmission systems involved in the neurobiology of anxiety and depression, suggesting their potential for treating these mental illnesses.

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“…Naringin, also known as citrus or isohesperidin, is a kind of dihydroflavonoid ( Figure 1(a) ), which is a natural pale yellow pigment that exists in the peel and fruit of Citrus grandis, Citrus paradisi, and Citrus (Rutaceae) aurantium [ 13 ]. Naringin exhibits multiple biological activities and pharmacological effects, including antitumor [ 14 ], antihypercholesterolemic [ 15 ], desensitization [ 16 ], antiallergy, antiphotoaging [ 17 ], cytoprotective [ 18 ], anti-inflammatory, heart-protective [ 7 , 13 , 19 , 20 ], and neuroprotective activities [ 21 – 23 ]. Naringin could also regulate glucose and lipid metabolism [ 24 ] and oxidative stress [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

A Dihydroflavonoid Naringin Extends the Lifespan of C. elegans and Delays the Progression of Aging-Related Diseases in PD/AD Models via DAF-16

Zhu

Yuan

Zhou

et al. 2020

Oxidative Medicine and Cellular Longevity

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Naringin is a dihydroflavonoid, which is rich in several plant species used for herbal medicine. It has a wide range of biological activities, including antineoplastic, anti-inflammatory, antiphotoaging, and antioxidative activities. So it would be interesting to know if naringin has an effect on aging and aging-related diseases. We examined the effect of naringin on the aging of Caenorhabditis elegans (C. elegans). Our results showed that naringin could extend the lifespan of C. elegans. Moreover, naringin could also increase the thermal and oxidative stress tolerance, reduce the accumulation of lipofuscin, and delay the progress of aging-related diseases in C. elegans models of AD and PD. Naringin could not significantly extend the lifespan of long-lived mutants from genes in insulin/IGF-1 signaling (IIS) and nutrient-sensing pathways, such as daf-2, akt-2, akt-1, eat-2, sir-2.1, and rsks-1. Naringin treatment prolonged the lifespan of long-lived glp-1 mutants, which have decreased reproductive stem cells. Naringin could not extend the lifespan of a null mutant of the fox-head transcription factor DAF-16. Moreover, naringin could increase the mRNA expression of genes regulated by daf-16 and itself. In conclusion, we show that a natural product naringin could extend the lifespan of C. elegans and delay the progression of aging-related diseases in C. elegans models via DAF-16.

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Possible neuroprotective mechanisms of action involved in the neurobehavioral property of naringin in mice

Cited by 64 publications

References 66 publications

An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish

An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish

Neuropharmacology of Secondary Metabolites from Plants with Anxiolytic and Antidepressant Properties

A Dihydroflavonoid Naringin Extends the Lifespan of C. elegans and Delays the Progression of Aging-Related Diseases in PD/AD Models via DAF-16

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