Flavonoid Actions on Receptors for the Inhibitory Neurotransmitter GABA

Hinton, Tina; Hanrahan, Jane R.; Johnston, Graham A.R.

doi:10.5772/67971

Cited by 6 publications

(8 citation statements)

References 59 publications

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“…Both hesperidin and hesperitin are capable of blocking the effects of increased calcium, and thus can be possibly effective in conditions dealing with the brain hyper-excitability ( Dimpfel, 2006 ). The antiseizure effect of hesperidin can be correlated with enhanced GABAergic transmission in the brain ( Hinton et al, 2017 ). Flavonoids have already been identified as a group of bioactive metabolites beneficial in CNS conditions associated with GABAergic transmission, particularly epilepsy, anxiety, depression, cognition deficit, sleep disorders, and many more ( Johnston, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Hesperidin Interacts With CREB-BDNF Signaling Pathway to Suppress Pentylenetetrazole-Induced Convulsions in Zebrafish

et al. 2021

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Hesperidin (3,5,7-trihydroxyflavanone 7-rhamnoglucoside) is a β-7-rutinoside of hesperetin (4′-methoxy-3′,5,7-trihydroxyflavanone), abundantly found in citrus fruits and known to interact with various cellular pathways to show a variety of pharmacological effects. The present study was envisaged to understand the anticonvulsant effect of hesperidin in a zebrafish model of pentylenetetrazole (PTZ)-induced convulsions, with the support of in silico docking. Healthy zebrafish larvae were preincubated with hesperidin (1, 5, and 10 µM) for 1 h, before PTZ exposure. Hesperidin treatment significantly increased the seizure latency and minimized PTZ-induced hyperactive responses. A significant reduction in c-fos expression further supported the suppression of neuronal excitation following hesperidin incubation in the larvae exposed to PTZ. The treatment also modulated larval bdnf expression and reduced the expression of il-10. The results of in vivo studies were further supported by in silico docking analysis, which showed the affinity of hesperidin for the N-methyl-d-aspartate receptor, the gamma-aminobutyric acid receptor, Interleukin 10 and the TrkB receptor of brain-derived neurotrophic factor. The results concluded that hesperidin suppresses PTZ-mediated seizure in zebrafish larvae through interaction with the central CREB–BDNF pathway.

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Section: Discussionmentioning

confidence: 99%

Hesperidin Interacts With CREB-BDNF Signaling Pathway to Suppress Pentylenetetrazole-Induced Convulsions in Zebrafish

et al. 2021

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“…It was shown that hispidulin crosses the blood-brain barrier and this is related to its anticonvulsant action (Kavvadias et al, 2004). for GABA (Hinton et al, 2017). They can act as positive or negative allosteric modulators, enhancing or reducing the effect of GABA.…”

Section: Fl Avonoidsmentioning

confidence: 99%

Milestone review: GABA, from chemistry, conformations, ionotropic receptors, modulators, epilepsy, flavonoids, and stress to neuro‐nutraceuticals

Johnston,

Beart

2024

Journal of Neurochemistry

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Arising out of a PhD project more than 50 years ago to synthesise analogues of the neurotransmitter GABA, a series of new chemical entities were found to have selective actions on ionotropic GABA receptors. Several of these neurochemicals are now commercially available. A new subtype of these receptors was discovered that could be a target for the treatment of myopia, the facilitation of learning and memory, and the improvement of post‐stroke motor recovery. The development of these new chemical entities over many years demonstrates the importance of neurochemicals with which to investigate selective aspects of GABA receptors and illustrates the significance of collaboration between chemists and biologists in neurochemistry. Vital were the improvements in synthetic organic chemistry and the use of functional human receptors expressed in oocytes. Current interest in ionotropic GABA receptors includes the clinical development of subtype‐specific agents and the role of gain‐of‐function receptor variants in epilepsy. Dietary flavonoids were found to cross the blood–brain barrier to influence brain function. Natural and synthetic flavonoids had a range of effects on GABA receptors, ranging from positive, silent, and negative allosteric modulators, to even second‐order modulation of first‐order modulators. Flavonoids have been called “a new family of benzodiazepines.” Like benzodiazepines, flavonoids reduce stress. Stress produces changes in GABA receptors in the brain that may be because of changes in endogenous modulators, such as neurosteroids and corticosteroids. GABA also occurs naturally in the diet leading to studies of the effects of oral GABA on brain function. This finding has resulted in studies of GABA and related neurochemicals as neuro‐nutraceuticals. GABA systems in the gut microbiome are essential to such studies. The actions of oral GABA and of GABA‐enriched beverages and foodstuffs are now an area of considerable scientific and commercial interest. GABA is a deceptively simple chemical that can take up many shapes, which may underlie its complex functions. The need for new chemical entities with selective actions for further studies highlights the need for continuing collaboration between chemists and biologists.

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“…Die natürlich vorkommende Aminosäure GABA ist der primäre inhibitorische Neurotransmitter im Gehirn von Säugetieren, der von bis zu 40 % der Neuronen freigesetzt wird. Apigenin wird als negativer Modulator der GABA-Wirkung beschrieben und hat komplexe modulatorische Wirkungen auf GABAA-Rezeptoren [31]. Eine weiterer Mechanismus für die Wirkung von Apigenin ist eine verringerte Aktivierung von N-Methyl-D-Aspartat(NMDA)-Rezeptoren durch L-Glutaminsäure [31].…”

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“…Apigenin wird als negativer Modulator der GABA-Wirkung beschrieben und hat komplexe modulatorische Wirkungen auf GABAA-Rezeptoren [31]. Eine weiterer Mechanismus für die Wirkung von Apigenin ist eine verringerte Aktivierung von N-Methyl-D-Aspartat(NMDA)-Rezeptoren durch L-Glutaminsäure [31]. Denn Apigenin hat nicht nur eine antagonistische Wirkung auf GABA-, sondern auch auf NMDA-Kanäle, und die hemmende Wirkung auf die glutamaterge Übertragung könnte die in vivo berichteten beruhigenden Wirkungen erklären [32].…”

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Sexuelle Unlust – Wirkmechanismen des natürlichen Aphrodisiakums Damiana (Turnera diffusa)

Kuchernig

2021

J. Gynäkol. Endokrinol. CH

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ZusammenfassungSexuelle Unlust bei Frauen ist eine häufig auftretende und meist multifaktorielle Symptomatik in jedem Alter. Entsteht daraus ein individueller Leidensdruck, einhergehend mit einer schlechten Lebensqualität, dann leiden Frauen daran umfassender und möglicherweise schwerwiegender als Männer. Ihre sexuellen Probleme werden jedoch im klinischen Umfeld oft nicht erkannt und bleiben unbehandelt, denn nur 20–34 % der Betroffenen suchen aktiv Hilfe bei einem Arzt. Die Auslöser mangelnder Libido können vielfältig sein und neben stressigen Lebensphasen auch an bestehende Medikationen, den demografischen Hintergrund, Probleme in der Partnerschaft oder Umstellungen der Hormone z. B. in den Wechseljahren gekoppelt sein. Pharmakotherapeutisch stehen jedoch nur relativ wenige Optionen für die Behandlung zur Verfügung. Neben einer nur in der Off-Label-Anwendung möglichen Verabreichung von transdermalem Testosteron oder Dehydroepiandrosteron, der Überweisung an andere Fachgebiete oder einer interdisziplinären Zusammenarbeit kann ein möglicher Baustein der Behandlung in der Verwendung geeigneter Phytopharmaka liegen. Durch eine Gesamtwirkung der beobachteten Einzelwirkungen von Inhaltsstoffen der Pflanze Damiana (Turnera diffusa) aus der Familie der Safranmalven (Turneraceae) können daraus hergestellte Arzneimittel eine gute Behandlungsoption mit einem positiven Einfluss auf eine verminderte Libido darstellen.

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Flavonoid Actions on Receptors for the Inhibitory Neurotransmitter GABA

Cited by 6 publications

References 59 publications

Hesperidin Interacts With CREB-BDNF Signaling Pathway to Suppress Pentylenetetrazole-Induced Convulsions in Zebrafish

Hesperidin Interacts With CREB-BDNF Signaling Pathway to Suppress Pentylenetetrazole-Induced Convulsions in Zebrafish

Milestone review: GABA, from chemistry, conformations, ionotropic receptors, modulators, epilepsy, flavonoids, and stress to neuro‐nutraceuticals

Sexuelle Unlust – Wirkmechanismen des natürlichen Aphrodisiakums Damiana (Turnera diffusa)

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