It is well known that neurodegenerative diseases’ development and progression are accelerated due to oxidative stress and inflammation, which result in impairment of mitochondrial function, cellular damage, and dysfunction of DNA repair systems. The increased consumption of antioxidants can postpone the development of these disorders and improve the quality of patients’ lives who have already been diagnosed with neurodegenerative diseases. Prolonging life span in developed countries contributes to an increase in the incidence ratio of chronic age-related neurodegenerative disorders, such as PD (Parkinson’s disease), AD (Alzheimer’s disease), or numerous forms of age-related dementias. Dietary supplementation with neuroprotective plant-derived polyphenols might be considered an important element of healthy aging. Some polyphenols improve cognition, mood, visual functions, language, and verbal memory functions. Polyphenols bioavailability differs greatly from one compound to another and is determined by solubility, degree of polymerization, conjugation, or glycosylation resulting from chemical structure. It is still unclear which polyphenols are beneficial because their potential depends on efficient transport across the BBB (blood-brain barrier), bioavailability, and stability in the CNS (central nervous system). Polyphenols improve brain functions by having a direct impact on cells and processes in the CNS. For a direct effect, polyphenolic compounds must be able to overcome the BBB and accumulate in brain tissue. In this review, the latest achievements in studies (animal models and clinical trials) on the effect of polyphenols on brain activity and function are described. The beneficial impact of plant polyphenols on the brain may be summarized by their role in increasing brain plasticity and related cognition improvement. As reversible MAO (monoamine oxidase) inhibitors, polyphenols are mood modulators and improve neuronal self-being through an increase in dopamine, serotonin, and noradrenaline amounts in the brain tissue. After analyzing the prohealth effects of various eating patterns, it was postulated that their beneficial effects result from synergistic interactions between individual dietary components. Polyphenols act on the brain endothelial cells and improve the BBB’s integrity and reduce inflammation, thus protecting the brain from additional injury during stroke or autoimmune diseases. Polyphenolic compounds are capable of lowering blood pressure and improving cerebral blood flow. Many studies have revealed that a nutritional model based on increased consumption of antioxidants has the potential to ameliorate the cognitive impairment associated with neurodegenerative disorders. Randomized clinical trials have also shown that the improvement of cognitive functions resulting from the consumption of foods rich in flavonoids is independent of age and health conditions. For therapeutic use, sufficient quantities of polyphenols must cross the BBB and reach the brain tissue in active form. An important issue in the direct action of polyphenols on the CNS is not only their penetration through the BBB, but also their brain metabolism and localization. The bioavailability of polyphenols is low. The most usual oral administration also conflicts with bioavailability. The main factors that limit this process and have an effect on therapeutic efficacy are: selective permeability across BBB, gastrointestinal transformations, poor absorption, rapid hepatic and colonic metabolism, and systemic elimination. Thus, phenolic compounds have inadequate bioavailability for human applications to have any beneficial effects. In recent years, new strategies have been attempted in order to exert cognitive benefits and neuroprotective effects. Converting polyphenols into nanostructures is one of the theories proposed to enhance their bioavailability. The following nanoscale delivery systems can be used to encapsulate polyphenols: nanocapsules, nanospheres, micelles, cyclodextrins, solid lipid nanoparticles, and liposomes. It results in great expectations for the wide-scale and effective use of polyphenols in the prevention of neurodegenerative diseases. Thus far, only natural polyphenols have been studied as neuroprotectors. Perhaps some modification of the chemical structure of a given polyphenol may increase its neuroprotective activity and transportation through the BBB. However, numerous questions should be answered before developing neuroprotective medications based on plant polyphenols.

Epidemiological data indicate that a diet rich in plant polyphenols has a positive effect on brain functions, improving memory and cognition in humans. Direct activity of ingested phenolics on brain neurons may be one of plausible mechanisms explaining these data. This also suggests that some phenolics can cross the blood-brain barrier and be present in the brain or cerebrospinal fluid. We measured 12 phenolics (a combination of the solid-phase extraction technique with high-performance liquid chromatography) in cerebrospinal fluid and matched plasma samples from 28 patients undergoing diagnostic lumbar puncture due to neurological disorders. Homovanillic acid, 3-hydroxyphenyl acetic acid and caffeic acid were detectable in cerebrospinal fluid reaching concentrations (median; interquartile range) 0.18; 0.14 µmol/L, 4.35; 7.36 µmol/L and 0.02; 0.01 µmol/L, respectively. Plasma concentrations of caffeic acid (0.03; 0.01 µmol/L) did not correlate with those in cerebrospinal fluid (ρ = −0.109, p = 0.58). Because food (fruits and vegetables) is the only source of caffeic acid in human body fluids, our results indicate that the same dietary phenolics can cross blood-brain barrier in humans, and that transportation of caffeic acid through this barrier is not the result of simple or facilitated diffusion.

Various polyphenols are absorbed into the bloodstream following the consumption of polyphenol-rich foods. These compounds may exhibit divergent redox properties, particularly in relation to their antioxidant or pro-oxidant activities. We evaluated the effects of six binary equimolar combinations of polyphenols with pre-established redox profiles on hydroxyl radical-dependent ultra-weak photon emission (UPE) in an Fe²⁺–EGTA–H₂O₂ Fenton system: gallic acid and vanillic acid, gallic acid and 3,4-dihydroxyphenylacetic acid, gallic acid and homovanillic acid, ellagic acid and 3,4-dihydroxyphenyl acetic acid, ellagic acid and homovanillic acid, and vanillic acid and homovanillic acid. The first pair of phenolics gave the expected summed redox response. The second one gave a higher redox response than expected from the sum (512 ± 461% vs. 212 ± 222% of enhancement of UPE, p < 0.05). The remaining four pairs revealed a lower redox response than expected from the sum (p < 0.05). The biggest difference was found for elagic acid and homovanillic acid (357 ± 50% vs. 1689 ± 293% enhancement). These findings suggest that the predictive value of individual redox profiles of phenolics is limited for the calculation of the experimental effect of their binary mixtures on the UPE of the Fe²⁺–EGTA–H₂O₂ system. We hypothesize that polyphenol polymerization may be responsible for this phenomenon.

Obstructive sleep apnea (OSA) is associated with increased risks of systemic comorbidities, leading to significant morbidity and mortality. This study investigates predictors of all-cause mortality, emphasizing the interplay of clinical symptoms, polysomnographic findings, and comorbidities. The aim of this study was to identify and compare respiratory predictors of all-cause mortality over 5, 10, and 15 years. A single-center study was conducted at a Sleep Medicine Department between 2005 and 2019, 4025 patients with suspected OSA who underwent polysomnography were admitted, 853 died during the study. We performed Cox regression analyses with dynamic hazard ratios to evaluated predictors of mortality. Prevalence of OSA was high—75.6% in the cohort: 929 patients with mild OSA (23.1%), 770 with moderate OSA (19.1%), and 1343 with severe OSA (33.4%). Survival rates were 89.7%, 81.9%, and 78.8% at 5, 10, and 15 years, respectively. Cardiovascular causes dominated mortality (33.3%), followed by cancer (26.5%). AHI_REM was associated with higher mortality risk in 0–5, 0–10, 0–15 years of observation in contrast to AHIN_REM and AHI_TST. The hazard ratio analysis showed that mortality risk changed over time depending on sleep stage and event type: risk increased for AHI_REM and AHI_TST, while it stayed the same or decreased for AHI_NREM and most central apneas.

We hypothesized that compounds containing ether linkages within their backbone structures, when exposed to hydroxyl radicals (•OH), can generate ultra-weak photon emission (UPE) as a result of the formation of triplet excited carbonyl species (³R=O*). To evaluate this hypothesis, we investigated the UPE of four compounds, each at a final concentration of 185.2 µmol/L: EGTA (ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid), a potent chelator of divalent cations, and three crown ethers—12-crown-4, 15-crown-5, and 18-crown-6—containing two, four, five, and six ether bonds, respectively. •OH was generated using a modified Fenton reagent—92.6 µmol/L Fe²⁺ and 2.6 mmol/L H₂O₂. The highest UPE was recorded for the Fe²⁺–EGTA–H₂O₂ (2863 ± 158 RLU; relative light units), followed by 18-crown-6, 15-crown-5, and 12-crown-4 (1161 ± 78, 615± 86, and 579 ± 109 RLU, respectively; p < 0.05), corresponding to the number of ether groups present. Controls lacking either H₂O₂ or Fe²⁺ exhibited no significant light emission compared to the buffer medium. These findings support the hypothesis that ether bonds, when oxidatively attacked by •OH, undergo chemical transformations resulting in the formation of ³R=O* species, the decay of which is associated with UPE. In crown ethers exposed to Fe²⁺-H₂O₂, the intensity of UPE was correlated with the number of ether bonds in their structure.