Flavonoids bridging the gut and the brain: Intestinal metabolic fate, and direct or indirect effects of natural supporters against neuroinflammation and neurodegeneration

Magni, Giulia; Riboldi, Benedetta; Petroni, Katia; Ceruti, Stefania

doi:10.1016/j.bcp.2022.115257

Cited by 15 publications

(16 citation statements)

References 234 publications

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“…Quercetin has been shown to have excellent modulation potential on bacteria in many types of diseases, including neurodegenerative disease, metabolic disease, and IBD [ 89 , 90 , 91 , 92 ]. As an important constituent of CHM-derived polyphenols, quercetin prevents the onset of IBD by inhibiting oxidative stress and inflammation, in which gut bacteria are indispensable players.…”

Section: Polyphenols Retard Oxidative Stress and Inflammation Via Mod...mentioning

confidence: 99%

Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?

Peng

Ding

et al. 2023

Antioxidants

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Inflammatory bowel disease (IBD) is a long-term, progressive, and recurrent intestinal inflammatory disorder. The pathogenic mechanisms of IBD are multifaceted and associated with oxidative stress, unbalanced gut microbiota, and aberrant immune response. Indeed, oxidative stress can affect the progression and development of IBD by regulating the homeostasis of the gut microbiota and immune response. Therefore, redox-targeted therapy is a promising treatment option for IBD. Recent evidence has verified that Chinese herbal medicine (CHM)-derived polyphenols, natural antioxidants, are able to maintain redox equilibrium in the intestinal tract to prevent abnormal gut microbiota and radical inflammatory responses. Here, we provide a comprehensive perspective for implementing natural antioxidants as potential IBD candidate medications. In addition, we demonstrate novel technologies and stratagems for promoting the antioxidative properties of CHM-derived polyphenols, including novel delivery systems, chemical modifications, and combination strategies.

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Section: Polyphenols Retard Oxidative Stress and Inflammation Via Mod...mentioning

confidence: 99%

Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?

Peng

Ding

et al. 2023

Antioxidants

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“…Flavonoids have therapeutic properties through their antioxidant and anti-inflammatory properties demonstrated in vitro. Some of the flavonoids can penetrate the blood–brain barrier from the systemic circulation to enter the brain directly, however, in general the bioavailability of intact flavonoids is limited due to poor absorption [ 29 , 344 , 345 , 346 , 347 , 348 , 349 ]. However, fortuitous generation of flavonoid metabolites by gut microbes that retain antioxidant and anti-inflammatory activity also needs to be considered in the overall therapeutic utility of these compounds [ 18 , 341 , 350 , 351 , 352 , 353 , 354 ].…”

Section: Catechin Metabolitesmentioning

confidence: 99%

“…Gut microbes thus have important roles to play in the transformation and utilization of natural dietary flavonoids through the diverse enzyme systems that process these components in the gut [ 351 , 353 , 354 ]. Flavonoids generally cannot be metabolized effectively by human digestive enzyme systems but they can be transformed by enzymes produced by gut microorganisms into bioactive metabolites that can be transported by the gut-brain axis, or they can enter the systemic circulation from the gut and be transported to the brain where they more effectively penetrate the blood–brain barrier and thus have improved bioavailability and therapeutic utility [ 29 , 351 , 353 , 354 ]. Flavonoid metabolites that retain or exceed the antioxidant and anti-inflammatory capacity of the intact flavonoid indicate these have potent therapeutic potential.…”

Section: Catechin Metabolitesmentioning

confidence: 99%

“…Psychedelics can produce sustained therapeutic benefit following a single administration, and also have broad therapeutic value and efficacy in the treatment of disorders, such as depression, post-traumatic stress, anxiety disorders, and addictive substance and alcohol abuse disorders [ 11 ]. A number of flavonoids have been identified with an ability to regulate neural functional properties of potential therapeutic value in the treatment of neurological disorders [ 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. One class of flavonoid metabolite (urolithins) shows particular promise in the treatment of neurodegenerative disorders and in the provision of general health and wellbeing [ 20 , 36 , 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

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The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline

Melrose

2023

Antioxidants

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Flavonoids are a biodiverse family of dietary compounds that have antioxidant, anti-inflammatory, antiviral, and antibacterial cell protective profiles. They have received considerable attention as potential therapeutic agents in biomedicine and have been widely used in traditional complimentary medicine for generations. Such complimentary medical herbal formulations are extremely complex mixtures of many pharmacologically active compounds that provide a therapeutic outcome through a network pharmacological effects of considerable complexity. Methods are emerging to determine the active components used in complimentary medicine and their therapeutic targets and to decipher the complexities of how network pharmacology provides such therapeutic effects. The gut microbiome has important roles to play in the generation of bioactive flavonoid metabolites retaining or exceeding the antioxidative and anti-inflammatory properties of the intact flavonoid and, in some cases, new antitumor and antineurodegenerative bioactivities. Certain food items have been identified with high prebiotic profiles suggesting that neutraceutical supplementation may be beneficially employed to preserve a healthy population of bacterial symbiont species and minimize the establishment of harmful pathogenic organisms. Gut health is an important consideration effecting the overall health and wellbeing of linked organ systems. Bioconversion of dietary flavonoid components in the gut generates therapeutic metabolites that can also be transported by the vagus nerve and systemic circulation to brain cell populations to exert a beneficial effect. This is particularly important in a number of neurological disorders (autism, bipolar disorder, AD, PD) characterized by effects on moods, resulting in depression and anxiety, impaired motor function, and long-term cognitive decline. Native flavonoids have many beneficial properties in the alleviation of inflammation in tissues, however, concerns have been raised that therapeutic levels of flavonoids may not be achieved, thus allowing them to display optimal therapeutic effects. Dietary manipulation and vagal stimulation have both yielded beneficial responses in the treatment of autism spectrum disorders, depression, and anxiety, establishing the vagal nerve as a route of communication in the gut-brain axis with established roles in disease intervention. While a number of native flavonoids are beneficial in the treatment of neurological disorders and are known to penetrate the blood–brain barrier, microbiome-generated flavonoid metabolites (e.g., protocatechuic acid, urolithins, γ-valerolactones), which retain the antioxidant and anti-inflammatory potency of the native flavonoid in addition to bioactive properties that promote mitochondrial health and cerebrovascular microcapillary function, should also be considered as potential biotherapeutic agents. Studies are warranted to experimentally examine the efficacy of flavonoid metabolites directly, as they emerge as novel therapeutic options.

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“…In addition to the immune and inflammatory contributions of the gut microbiome and stress, the gut microbiota also produce neurotransmitters including as gamma-aminobutyric acid (GABA), norepinephrine, epinephrine, dopamine, acetylcholine, melatonin, and histamine, which likely exert their effects via the ENS and vagal afferents ( 33 – 37 ). An estimated90% of serotonin alone is produced in the gut, primarily from enterochromaffin cells ( 36 ).…”

Section: The Crossroads Of Chronic Stress Immune Activation and The M...mentioning

confidence: 99%

Dangers of the chronic stress response in the context of the microbiota-gut-immune-brain axis and mental health: a narrative review

Warren,

Nyavor,

Beguelin

et al. 2024

Front. Immunol.

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More than 20% of American adults live with a mental disorder, many of whom are treatment resistant or continue to experience symptoms. Other approaches are needed to improve mental health care, including prevention. The role of the microbiome has emerged as a central tenet in mental and physical health and their interconnectedness (well-being). Under normal conditions, a healthy microbiome promotes homeostasis within the host by maintaining intestinal and brain barrier integrity, thereby facilitating host well-being. Owing to the multidirectional crosstalk between the microbiome and neuro-endocrine-immune systems, dysbiosis within the microbiome is a main driver of immune-mediated systemic and neural inflammation that can promote disease progression and is detrimental to well-being broadly and mental health in particular. In predisposed individuals, immune dysregulation can shift to autoimmunity, especially in the presence of physical or psychological triggers. The chronic stress response involves the immune system, which is intimately involved with the gut microbiome, particularly in the process of immune education. This interconnection forms the microbiota-gut-immune-brain axis and promotes mental health or disorders. In this brief review, we aim to highlight the relationships between stress, mental health, and the gut microbiome, along with the ways in which dysbiosis and a dysregulated immune system can shift to an autoimmune response with concomitant neuropsychological consequences in the context of the microbiota-gut-immune-brain axis. Finally, we aim to review evidenced-based prevention strategies and potential therapeutic targets.

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Flavonoids bridging the gut and the brain: Intestinal metabolic fate, and direct or indirect effects of natural supporters against neuroinflammation and neurodegeneration

Cited by 15 publications

References 234 publications

Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?

Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?

The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline

Dangers of the chronic stress response in the context of the microbiota-gut-immune-brain axis and mental health: a narrative review

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