Potential Neuroprotective Results of Polyphenolic Compounds


The human intestine microbiota has a wide-reaching impression on well being. One of many methods this complicated group of micro-organisms advantages us is by enhancing the bioavailability of meals elements, similar to polyphenols, that are metabolized into easier, extra simply absorbed merchandise(1).

Polyphenols can act as prebiotics, modifying the composition of microbial colonies, which additionally has advantages for human well being.

Though phenolic metabolites can have an effect on the mind not directly—for instance, by growing ranges of neurotransmitters similar to dopamine—this text is targeted on these which are in a position to cross the blood–mind barrier and exert direct neurocognitive results. The perform of this essential physiological barrier is to forestall dangerous substances from reaching the mind, however it might additionally hold out xenobiotics, together with polyphenols.

Due to this fact, the flexibility to penetrate the blood–mind barrier largely situations the results of phenolic compounds on

the central nervous system.  Whereas the technology of phenolic metabolites by microbiota has been extensively studied, analysis on their blood–mind barrier permeability has solely just lately gained consideration.

The primary perform described for the blood–mind barrier was the safety of the mind from uncontrolled diffusion of drugs from the blood. It’s now understood to be a posh and dynamic interface that regulates the change of drugs between the blood and the central nervous system(2).  

Particularly, the capabilities of the blood–mind barrier are to:

  • – Defend the mind from potential bloodborne toxins
  • – Meet the metabolic calls for of the mind, and
  • – Regulate the homeostatic setting within the central nervous system for correct neuronal perform.

Mind microvascular endothelial cells management the motion of vitamins, vitality metabolites, and different very important molecules from the blood to the mind and removing of metabolic waste merchandise from the mind’s interstitial fluid into the blood. Nonessential molecules like phenolic compounds, that stop oxidative stress, may also cross the barrier and

exert useful results on the mind(2).

The determine under illustrates that phenolic bioavailability within the mind is affected by physicochemical traits, together with molecular weight, hydrophobicity, and lipophilicity, in addition to physiological components.

Determine: Abstract of blood–mind barrier permeability of microbial phenolic metabolites(3)

A current evaluate explored the potential of dietary polyphenols, as soon as ingested, making their manner from

the intestine to the mind and the doubtless exerting direct neuroprotective results.  

This analysis highlights potential polyphenolic compounds

(or their metabolites produced by way of bacterial metabolism within the intestines) that will impression mind perform and cognition(3).


Dietary flavonoids are principally metabolized into phenolic acids by the intestine microbiota. Isoflavonoids similar to genistin and daidzin, in addition to their aglycones genistein and daidzein, are nearly solely present in soybeans and soy-derived merchandise (eg, tofu, soymilk, miso soup), which generally include 0.01%–0.3% isoflavonoids(4).

Equol is considered a phytoestrogen resulting from its structural similarity to 17β-estradiol and is believed to exert its results by way of the estrogen sign transduction pathway(5). Equol demonstrates the potential to modulate glial cell migration and improve hippocampal synaptic plasticity.

A number of mechanisms of motion have been described by which equol improves mind well being. Research reveal that equol enhances glial cell migration, a vital course of for mind improvement, and possesses neuroprotective properties that counteract the cytotoxicity of β-amyloid plaques generated in a mobile mannequin of Alzheimer’s illness(6)

It has additionally been reported that equol enhances hippocampus and synaptic plasticity. Different proof signifies that equol reduces oxidative stress and protects towards cerebral ischemia and neuronal apoptosis (i.e., programmed cell demise).


Ellagitannins and ellagic acid are present in nuts and a few fruits, similar to pomegranates and berries, and are usually poorly absorbed. Within the intestinal tract, ellagitannins are metabolized by

the intestine microbiota to ellagic acid, and ellagic acid is hydrolyzed into urolithins, which, along with well being advantages, have potential software as dietary biomarkers(7).

Promising results on neurocognitive well being have been reported for urolithin A and B. Based on quite a few in vivo and preclinical research, urolithin A is concerned in a number of molecular mechanisms that stop cognitive deterioration. It reduces the formation of ß-amyloid plaques, decreases apoptosis, and enhances neurogenesis.


The mammalian lignans enterodiol and enterolactone are generated within the colon by

micro organism performing on lignan plant precursors, similar to secoisolariciresinol diglycoside, that are plentiful in fiber-rich meals similar to cereals, with decrease quantities present in greens and fruits.

Flaxseed is likely one of the greatest sources of dietary lignans. In a medical research, blood enterolactone focus was doubled by including floor flaxseed and flaxseed oil to 1 or 2 every day meals. The provision of lignans in flaxseed is enhanced by crushing or grinding the entire seeds, doubtless resulting from improved accessibility for the microbiota to work together with the lignans.

Sesame seeds and rye grain even have a excessive focus of lignans and are due to this fact an alternative choice to flaxseed as wealthy sources of enterodiol and enterolactone precursors. Common consumption of rye bread will increase serum concentrations and urinary excretion of enterolactone rather more than consuming refined-wheat cereal.

Whereas dietary lignans have been related to neurological advantages, the function of the metabolite enterolactone has been much less studied. This enterolignan has proven neuroprotective properties, because it suppresses nitric oxide manufacturing and proinflammatory cytokines.  It might probably additionally inhibit enzymes concerned within the improvement of Alzheimer’s illness(8).

Phenolic Acids

Espresso, fruits, entire grains, and nuts are essentially the most plentiful dietary sources of phenolic acids. The cognitive results of caffeic acid have been extensively investigated. Notable for its function in reducing tau hyperphosphorylation and β-amyloid accumulation, it additionally helps neurogenesis within the hippocampus.  Though the advantages of espresso on cognitive well being have been reported, they can’t be attributed solely to caffeic acid because of the presence of different identified neuroprotective substances similar to caffeine.


Cocoa and tea are the principle dietary sources of flavan-3-ols, an essential group of flavonoids which are extensively metabolized within the colon to phenyl-γ-valerolactones. Inexperienced tea is one other good supply of flavan-3-ols.  The useful results of phenyl-γ-valerolactone metabolites in relation to ß-amyloid plaques is that they scale back neuroinflammation and stop the formation of ß-amyloid oligomers(9).


Cumulative proof highlights that the intestine microbiota performs a key function within the relationship between polyphenols and cognition by way of the intestine–mind axis, because it transforms dietary polyphenols into biologically energetic metabolites in a position to cross the blood-brain barrier and exert advantages for cognitive well being.

Determine: Abstract of the molecular mechanisms of phenolic compounds within the mind. Abbreviations: AChE, acetylcholinesterase; BChE, butylcholinesterase; CA, carbonic anhydrase; MAO, monoamine oxidase(3).

Promising outcomes have been obtained for these microbial phenolic metabolites, lots of which may regulate mechanisms concerned in neurodegenerative illness pathogenesis—for instance, by decreasing oxidative stress, apoptosis, or neuroinflammation.

The intestine microbiome performs a important function in your well being and and immune system by way of the gut-brain axis, nevertheless it takes greater than consuming a weight loss program wealthy in polyphenols to really feel the complete advantages.

It entails

a complete life-style dedication that may pay big dividends in improved well being irrespective of how previous you might be.

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By serving to to steadiness intestinal microflora, PRO+ FLORA can play an essential function in regulating intestinal perform and digestion to fortify your immune system towards invaders.

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    1.    Cardona F, Andrés-Lacueva C, Tulipani S, et al: Advantages of polyphenols on intestine microbiota and implications in human well being. J Nutr Biochem 24:1415-22, 2013
    2.    Velásquez-Jiménez D, Corella-Salazar DA, Zuñiga-Martínez BS, et al: Phenolic compounds that cross the blood-brain barrier exert optimistic well being results as central nervous system antioxidants. Meals Funct 12:10356-10369, 2021
    3.    Domínguez-López I, López-Yerena A, Vallverdú-Queralt A, et al: From the intestine to the mind: the lengthy journey of phenolic compounds with neurocognitive results. Diet Critiques, 2024
    4.    Franke AA, Hebshi SM, Pagano I, et al: Urine precisely displays circulating isoflavonoids and ascertains compliance throughout soy intervention. Most cancers Epidemiol Biomarkers Prev 19:1775-83, 2010
    5.    Sekikawa A, Ihara M, Lopez O, et al: Impact of S-equol and Soy Isoflavones on Coronary heart and Mind. Curr Cardiol Rev 15:114-135, 2019
    6.    Tsai MC, Lin SH, Hidayah Ok, et al: Equol Pretreatment Safety of SH-SY5Y Cells towards Aβ (25-35)-Induced Cytotoxicity and Cell-Cycle Reentry by way of Sustaining Estrogen Receptor Alpha Expression. Vitamins 11, 2019
    7.    Cerdá B, Tomás-Barberán FA, Espín JC: Metabolism of antioxidant and chemopreventive ellagitannins from strawberries, raspberries, walnuts, and oak-aged wine in people: identification of biomarkers and particular person variability. J Agric Meals Chem 53:227-35, 2005
    8.    Köse LP GI: Inhibition results of some lignans on carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase enzymes. Rec Nat Prod. 11:558–561, 2017
    9.    Ruotolo R, Minato I, La Vitola P, et al: Flavonoid-Derived Human Phenyl-γ-Valerolactone Metabolites Selectively Detoxify Amyloid-β Oligomers and Stop Reminiscence Impairment in a Mouse Mannequin of Alzheimer’s Illness. Mol Nutr Meals Res 64:e1900890, 2020


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