Dietary Polyphenols as Prospective Natural-Compound Depression Treatment from the Perspective of Intestinal Microbiota Regulation

Wang, Xuanpeng; Yu, Jing; Zhang, Xin

doi:10.3390/molecules27217637

Cited by 9 publications

(5 citation statements)

References 129 publications

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“…Ellagic acid has antioxidant, anti-inflammatory, and neuroprotective properties ( Ríos et al, 2022 ). Several recent reviews have discussed the antidepressant effects of compounds, such as amentoflavone, apigenin, chlorogenic acid, curcumin, and ferulic acid ( Pathak et al, 2013 ; Wang et al, 2022 ; Winiarska-Mieczan et al, 2023 ). In another study, Nigella sativa oil produced a positive motor coordinative effect on phenol-mediated essential tremors in a mouse model ( Folarin et al, 2020 ).…”

Section: Phenols and Neuropsychiatric Disordersmentioning

confidence: 99%

Phenols and GABAA receptors: from structure and molecular mechanisms action to neuropsychiatric sequelae

Menzikov,

Zaichenko,

Moskovtsev

et al. 2024

Front. Pharmacol.

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γ-Aminobutyric acid type A receptors (GABAARs) are members of the pentameric ligand-gated ion channel (pLGIC) family, which are widespread throughout the invertebrate and vertebrate central nervous system. GABAARs are engaged in short-term changes of the neuronal concentrations of chloride (Cl−) and bicarbonate (HCO3−) ions by their passive permeability through the ion channel pore. GABAARs are regulated by various structurally diverse phenolic substances ranging from simple phenols to complex polyphenols. The wide chemical and structural variability of phenols suggest similar and different binding sites on GABAARs, allowing them to manifest themselves as activators, inhibitors, or allosteric ligands of GABAAR function. Interest in phenols is associated with their great potential for GABAAR modulation, but also with their subsequent negative or positive role in neurological and psychiatric disorders. This review focuses on the GABAergic deficit hypotheses during neurological and psychiatric disorders induced by various phenols. We summarize the structure–activity relationship of general phenol groups concerning their differential roles in the manifestation of neuropsychiatric symptoms. We describe and analyze the role of GABAAR subunits in manifesting various neuropathologies and the molecular mechanisms underlying their modulation by phenols. Finally, we discuss how phenol drugs can modulate GABAAR activity via desensitization and resensitization. We also demonstrate a novel pharmacological approach to treat neuropsychiatric disorders via regulation of receptor phosphorylation/dephosphorylation.

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Section: Phenols and Neuropsychiatric Disordersmentioning

confidence: 99%

Phenols and GABAA receptors: from structure and molecular mechanisms action to neuropsychiatric sequelae

Menzikov,

Zaichenko,

Moskovtsev

et al. 2024

Front. Pharmacol.

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“…A part of ingested polyphenols is known to be degraded by intestinal bacteria in the colon. Several comprehensive reviews of these have been reported so far [20,150,151]. However, the amount and type of metabolic degradation of polyphenols by gut bacteria relative to the total polyphenols consumed, and the kinetics of this degradation, is not well understood.…”

Section: Bioavailability Of Polyphenolsmentioning

confidence: 99%

Sensory Nutrition and Bitterness and Astringency of Polyphenols

Osakabe,

Shimizu,

Fujii

et al. 2024

Biomolecules

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Recent studies have demonstrated that the interaction of dietary constituents with taste and olfactory receptors and nociceptors expressed in the oral cavity, nasal cavity and gastrointestinal tract regulate homeostasis through activation of the neuroendocrine system. Polyphenols, of which 8000 have been identified to date, represent the greatest diversity of secondary metabolites in plants, most of which are bitter and some of them astringent. Epidemiological studies have shown that polyphenol intake contributes to maintaining and improving cardiovascular, cognitive and sensory health. However, because polyphenols have very low bioavailability, the mechanisms of their beneficial effects are unknown. In this review, we focused on the taste of polyphenols from the perspective of sensory nutrition, summarized the results of previous studies on their relationship with bioregulation and discussed their future potential.

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“…Moreover, various inflammatory molecules originating from the gut microflora (lipopolysaccharides, endotoxins, etc.) may activate the peripheral immune system, reach the brain, activate microglia, and promote the development of depression through cytokine release [ 284 , 286 , 287 ]. The microbiota–inflammasome hypothesis of major depressive disorder states that the dysbiosis of the gut microbiota deteriorates the integrity of the blood–brain barrier through peripheral inflammation.…”

Section: Flavonols and Gut–brain Axismentioning

confidence: 99%

“…On the other hand, polyphenols, including flavonols, need to be metabolized and activated by microorganisms in the gut. Via microbial metabolism, dietary polyphenols are broken down into small aromatic metabolites, some of which may directly act as neurotransmitters [ 287 , 293 ]. In fact, interactions between the microbiota and polyphenols in the diet are important factors in determining the effects of polyphenols on brain functions and the biological hallmarks of depression.…”

Section: Flavonols and Gut–brain Axismentioning

confidence: 99%

“…In light of these findings, attempts have been made to evaluate the antidepressant potential of flavonols from the perspective of the regulation of gut microbiota [ 287 ]. Thus, in LPS-challenged laying hens and broiler chickens, quercetin ameliorated intestinal mucosal injury and inflammation, maintained intestinal functions, and modified microbial communities [ 298 , 299 ].…”

Section: Flavonols and Gut–brain Axismentioning

confidence: 99%

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Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder

Jembrek

Oršolić

Karlović

et al. 2023

IJMS

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Major depressive disorder is one of the most common mental illnesses that highly impairs quality of life. Pharmacological interventions are mainly focused on altered monoamine neurotransmission, which is considered the primary event underlying the disease’s etiology. However, many other neuropathological mechanisms that contribute to the disease’s progression and clinical symptoms have been identified. These include oxidative stress, neuroinflammation, hippocampal atrophy, reduced synaptic plasticity and neurogenesis, the depletion of neurotrophic factors, and the dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis. Current therapeutic options are often unsatisfactory and associated with adverse effects. This review highlights the most relevant findings concerning the role of flavonols, a ubiquitous class of flavonoids in the human diet, as potential antidepressant agents. In general, flavonols are considered to be both an effective and safe therapeutic option in the management of depression, which is largely based on their prominent antioxidative and anti-inflammatory effects. Moreover, preclinical studies have provided evidence that they are capable of restoring the neuroendocrine control of the HPA axis, promoting neurogenesis, and alleviating depressive-like behavior. Although these findings are promising, they are still far from being implemented in clinical practice. Hence, further studies are needed to more comprehensively evaluate the potential of flavonols with respect to the improvement of clinical signs of depression.

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Dietary Polyphenols as Prospective Natural-Compound Depression Treatment from the Perspective of Intestinal Microbiota Regulation

Cited by 9 publications

References 129 publications

Phenols and GABAA receptors: from structure and molecular mechanisms action to neuropsychiatric sequelae

Phenols and GABAA receptors: from structure and molecular mechanisms action to neuropsychiatric sequelae

Sensory Nutrition and Bitterness and Astringency of Polyphenols

Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder

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