The research progress on the anxiolytic effect of plant‐derived flavonoids by regulating neurotransmitters

Wang, Chao; Yang, Shanbo; Deng, Junwen; Shi, Lingyu; Chang, Jing; Meng, Jingsen; Liu, Wenjing; Zeng, Jun; Xing, Kunyue; Wen, Jialian; Liang, Bing; Xing, Dongming

doi:10.1002/ddr.22038

Cited by 6 publications

(2 citation statements)

References 74 publications

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“…The effects of quercetin as an anxiolytic acting through interaction with GABA receptors has been studied in vivo and in silico (Islam et al., 2022). The anxiolytic effects of plant‐derived flavonoids may involve other neurotransmitters than GABA (Wang et al., 2023).…”

Section: Flavonoidsmentioning

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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Section: Flavonoidsmentioning

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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“…Liu et al, 2021; López-Rubalcava & Estrada-Camarena, 2016; Rodrigues et al, 2008). Experimental results show that flavonoids and their conjugates derivatives may cross the bloodbrain barrier and exert pharmacological action on the central nervous system (Jäger & Saaby, 2011; Youdim et al, 2003) by activating neuronal signaling pathways (Spencer, 2007) and neurotransmitter systems (i.e., serotonergic, GABAergic, noradrenergic, and dopaminergic, among others) involved in neuropsychiatric disorders as anxiety and depression (German-Ponciano et al, 2018; C. Wang et al, 2023; H. Wang et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Flavonoids as anxiolytics in animal tests: Bibliometry and meta-analysis of the effects of flavonoids on anxiety-like behavior in animal tests

Machado,

Araújo,

Lima-Maximino

et al. 2024

Preprint

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FigureFlavonoids are natural secondary compounds of plants with a basic composition derived from polyphenols that can produce a plethora of different neurochemical effects, some of which are relevant to anxiety disorders. As such, many flavonoids have been evaluated in behavioral screens in preclinical research on anxiolytics. Given the many different molecular subclasses of flavonoids, the many different molecular targets that have been proposed for these compounds, and the different research priorities that arise in preclinical research, we sought to map the potential of flavonoids as anxiolytics by bibliometric analysis and a meta-analysis of animal tests using these compounds. Bibliometric analysis suggest that the field is highly concentrated on few research groups that are mostly located in the Global South, suggesting the need to improve international collaborations. The themes which emerged in the bibliometric analysis are driven by the exploratory steps of pharmacological research, including finding anxioselective effects and looking for dose-response patterns; this suggests that the field, as a whole, could benefit from more mechanistic and confirmatory research. The meta-analysis showed strong evidence for an anxiolytic-like effect of flavonoids on animal tests, including assays made in rats, mice, and zebrafish (SMD = -1.4398, 95%CI[-1.7319, - 1.1477]). Subgroup analysis suggested that this effect is present in acute treatment (SMD = -1.14, 95%CI[-1.36, -0.93]), but not after chronic treatment (SMD = -1.96, 95%CI[-4.93; 1.01]). For all molecule subclasses included in the study, only isoflavones, glycoside derivatives, and flavanolignans did not show evidence of an anxiolytic-like effect, although the low number of studies including these subclasses is low. We finish with a set of recommendations for preclinical research on the anxiolytic potential of flavonoids.

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Dietary flavonoids: Role in preventing neurodegenerative diseases caused by brain aging by modulating the gut microbiota

Liu,

Dai,

Wang

et al. 2024

Food Bioscience

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The research progress on the anxiolytic effect of plant‐derived flavonoids by regulating neurotransmitters

Cited by 6 publications

References 74 publications

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

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

Flavonoids as anxiolytics in animal tests: Bibliometry and meta-analysis of the effects of flavonoids on anxiety-like behavior in animal tests

Dietary flavonoids: Role in preventing neurodegenerative diseases caused by brain aging by modulating the gut microbiota

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