Blueberries are a rich source of antioxidants and other beneficial compounds that can protect against disease. Identifying genes involved in synthesis of bioactive compounds could enable the breeding of berry varieties with enhanced health benefits.

Polyphenol supplementation was tested as a countermeasure to inflammation and oxidative stress induced by 3-d intensified training.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta and the presence in surviving neurons of Lewy body inclusions enriched with aggregated forms of the presynaptic protein α-synuclein (aSyn). Although current therapies provide temporary symptomatic relief, they do not slow the underlying neurodegeneration in the midbrain. In this study, we analyzed contemporary herbal medicinal practices used by members of the Lumbee tribe to treat PD-related symptoms, in an effort to identify safe and effective herbal medicines to treat PD.

Blueberry is well recognized as a rich source of health promoting phytochemicals such as flavonoids and phenolic acids. Multiple studies in blueberry and other crops indicated that flavonoids and phenolic acids function as bioactive compounds in the human body promoting multiple health effects. Despite their importance, information is limited about the levels of variation in bioactive compounds within and between ploidy level and species, and their association with fruit quality traits. Such information is crucial to define a strategy to study the genetic mechanisms controlling these traits and to select for these traits in blueberry breeding programs. Here we evaluated 33 health related phytochemicals belonging to four major groups of flavonoids and phenolic acids across 128 blueberry accessions over two years together with fruit quality traits, including fruit weight, titratable acidity, total soluble acids and pH. Highly significant variation between accessions, years, and accession by year interaction were identified for most of the traits. Cluster analysis grouped phytochemicals by their functional structure (e.g., anthocyanins, flavanols, flavonols, and phenolic acids). Multivariate analysis of the traits resulted in separation of diploid, tetraploid and hexaploid accessions. Broad sense heritability of the traits estimated in 100 tetraploid accessions, ranged from 20 to 90%, with most traits revealing moderate to high broad sense heritability (H2 > 40%), suggesting that strong genetic factors control these traits. Fruit size can be estimated as a proxy of fruit weight or volume and vice versa, and it was negatively correlated with content of most of phytochemicals evaluated here. However, size-independent variation for anthocyanin content and profile (e.g., acylated vs. non-acylated anthocyanin) exists in the tetraploid accessions and can be explored to identify other factors such as genes related to the biosynthetic pathway that control this trait. This result also suggests that metabolite concentrations and fruit size, to a certain degree can be improved simultaneously in breeding programs. Overall, the results of this study provide a framework to uncover the genetic basis of bioactive compounds and fruit quality traits and will be useful to advance blueberry-breeding programs focusing on integrating these traits.

Plant polyphenols have a natural binding affinity for proteins, and their interaction can be exploited to form diverse aggregate particles. Protein-polyphenol particles utilized as food ingredients allow consumers to incorporate more health-benefiting plant bioactives into their diets. The functional properties of the protein-polyphenol particles can be influenced by many factors, including complexation conditions and starting material properties. Here, cranberry polyphenols extracted from pomace were complexed with nine pea protein isolate starting materials with different physical (particle size and protein content) and chemical (hydrolyzed and oxidized) properties to investigate the impact of protein characteristics on particle functionality. Chemical differences between proteins affected polyphenol binding; oxidized protein isolate (specifically, VegOtein N) bound 12%-27% more polyphenols than other isolates. Polyphenol binding to proteins decreased digestion rates in vitro, averaging 25% slower gastric (pepsin) digestion and a 35% slower intestinal (pancreatin) digestion. Physical differences in protein starting materials affected digestibility; isolate with the largest particle size (specifically, Nutralys F85G) produced particles with the lowest digestion rate. Solubility was impacted by both the process of forming particles and by polyphenol binding; control particles were 56% less soluble, and protein-polyphenol particles up to 75% less soluble, than unmodified proteins. The solubility of unmodified protein isolate starting materials varied widely according to the manufacturing process, but, after complexation, protein-polyphenol particles produced from all protein sources exhibited a similar depressed level of solubility. The desired functional properties of the protein-polyphenol particle food ingredients will be considerably influenced by the properties of the protein isolate starting material.

Ozone (O3) exposure has been reported to contribute to various cutaneous inflammatory conditions, such as eczema, psoriasis, rush etc. via a redox-inflammatory pathway. O3 is too reactive to penetrate cutaneous tissue; it interacts with lipids present in the outermost layer of skin, resulting in formation of oxidized molecules and hydrogen peroxide (H2O2). Interestingly, several inflammatory skin pathologies demonstrate altered levels of antimicrobial peptides (AMPs). These small, cationic peptides are found in various cells, including keratinocytes, eccrine gland cells, and seboctyes. Classically, AMPs function as antimicrobial agents. Recent studies indicate that AMPs also play roles in inflammation, angiogenesis, and wound healing. Since altered levels of AMPs have been detected in pollution-associated skin pathologies, we hypothesized that exposure to O3 could affect the levels of AMPs in the skin. We examined levels of AMPs using qRT-PCR, Western blotting, and immunofluorescence in vitro (human keratinocytes), ex vivo (human skin explants), and in vivo (human volunteer subjects exposed to O3) and observed increased levels of all the measured AMPs upon O3 exposure. In addition, in vitro studies have confirmed the redox regulation of AMPs in keratinocytes. This novel finding suggests that targeting AMPs could be a possible defensive strategy to combat pollution-associated skin conditions.

Epidemiological studies have shown associations between polyphenol-rich fruit intake and bone health, and preclinical studies have shown that blueberries improve bone health. To determine the genotype and dose of blueberries that are effective in ameliorating age-related bone loss, a multi-institutional team of investigators performed in vitro, preclinical, and clinical studies on blueberry varieties that differed in flavonoid profiles. Principal component analysis was used to select blueberry genotypes that varied in anthocyanin profiles. Total phenolic content did not predict the bioavailability of polyphenolic compounds in rats. A range in bioavailability was observed in individual polyphenolic compounds across genotypes. Both alpha and beta diversity analyses indicated that gut microbiome profiles varied with blueberry dose in rats. Additionally, the identification of specific taxa, such as Prevotellaceae_UCG-001 and Coriobacteriales, increasing after blueberry consumption adds to the mounting evidence of their role in polyphenol metabolism. All of the sources of variation can inform blueberry breeding practices to influence precision nutrition.

Using a randomized, double-blinded, placebo-controlled, parallel group design, this investigation determined if the combination of two weeks of flavonoid supplementation (329 mg/day, quercetin, anthocyanins, flavan-3-ols mixture) and a 45-minute walking bout (62.2 ± 0.9% VO2max (maximal oxygen consumption rate)) enhanced the translocation of gut-derived phenolics into circulation in a group of walkers (n = 77). The walkers (flavonoid, placebo groups) were randomized to either sit or walk briskly on treadmills for 45 min (thus, four groups: placebo⁻sit, placebo⁻walk, flavonoid⁻sit, flavonoid⁻walk). A comparator group of runners (n = 19) ingested a double flavonoid dose for two weeks (658 mg/day) and ran for 2.5 h (69.2 ± 1.2% VO2max). Four blood samples were collected (pre- and post-supplementation, immediately post- and 24 h post-exercise/rest). Of the 76 metabolites detected in this targeted analysis, 15 increased after the 2.5 h run, and when grouped were also elevated post-exercise (versus placebo⁻sit) for the placebo⁻ and flavonoid⁻walking groups (p < 0.05). A secondary analysis showed that pre-study plasma concentrations of gut-derived phenolics in the runners were 40% higher compared to walkers (p = 0.031). These data indicate that acute exercise bouts (brisk walking, intensive running) are linked to an increased translocation of gut-derived phenolics into circulation, an effect that is amplified when combined with a two-week period of increased flavonoid intake or chronic training as a runner.

In the present study, we applied a novel high-throughput in vitro gastrointestinal digestion model to phenotype bioaccessibility of phenolics in a diverse germplasm collection representing cultivated highbush blueberries. Results revealed significant (P < 0.05) differences between accessions, years, and accession by year interaction for relative and absolute bioaccessibility of flavonoids and phenolic acids. Broad sense heritability estimates revealed low to moderate inheritances of relative and absolute bioaccessibility, suggesting that besides environmental variables, genetics factors could control bioaccessibility of phenolics. Acylated anthocyanins had significantly higher relative bioaccessibility than non-acylated anthocyanins. Correlation analysis indicated that relative bioaccessibility did not show significant association with fruit quality or raw concentration of metabolites. The study also identified accessions that have high relative and absolute bioaccessibility values. Overall, combining the bioaccessibility of phenolics with genetic and genomic approaches will enable the identification of genotypes and genetic factors influencing these traits in blueberry.

Skeletal muscle mass and strength are lost with aging. Phytoecdysteroids, in particular 20-hydroxyecdysone (20E), increase protein synthesis in C2C12 skeletal muscle cells and muscle strength in young rats. The objective of this study was to determine whether an extract from Ajuga turkestanica (ATE), enriched in phytoecdysteroids, and 20E affect skeletal muscle mass and fiber size, fiber type, activation of the PI3K-Akt signaling pathway, and the mRNA levels of MAFbx, MuRF-1, and myostatin in sedentary aging mice. Aging male C57BL/6 mice (20 months old) received ATE, 20E, or vehicle (CT) once per day for 28 days or a single acute dose. Treatment did not alter body, muscle, or organ mass; fiber cross-sectional area; or fiber type in the triceps brachii or plantaris muscles. Likewise, protein synthesis signaling markers (i.e., phosphorylation of AktSer473 and p70S6kThr389) measured after either 28 days or acutely were unchanged. Neither ATE nor 20E treatment for 28 days affected the mRNA levels of MAFbx, MuRF-1, and myostatin. In conclusion, these data indicate that phytoecdysteroid treatment does not alter muscle mass or fiber type, nor does it activate protein synthesis signaling in the skeletal muscle of sedentary aging mice.

Several pollutants have been shown to affect skin physiology, among which ozone (O3) is one of the most toxic. Prolonged exposure to O3 leads to increased oxidative damage and cutaneous inflammation. The correlation between O3 exposure and inflammatory cutaneous conditions (atopic dermatitis, psoriasis, acne and eczema) has been already suggested, although the mechanism involved is still unclear. In the last few decades, a new multiprotein complex, the inflammasome, has been discovered and linked to tissue inflammation, including inflammatory skin conditions. The inflammasome activates inflammatory responses and contributes to the maturation of cytokines such as interleukin 1β (IL-1β) and interleukin 18. This complex is also responsive to reactive oxygen species (ROS), which plays a role in triggering the activation of the complex. On this basis it is possible hypothesize that the activation of the inflammasome could be the link between the inflammatory skin conditions associated to O3 exposure. In the present work, the ability of O3 to induce inflammasome activation was determined in different skin models, ranging from 2D (human keratinocytes) to 3D models in vitro and ex vivo. Results clearly showed that O3 exposure increased both transcript and protein levels of the main inflammasome complex, such as ASC and caspase-1. Furthermore, by using both immunofluorescence and an ASC oligomerization assay the formation of the complex was determined together with increased secreted levels of both IL-18 and IL-1β. Of note is that H2O2 and to a less extent 4HNE (both considered the main mediators of O3 interaction with cellular membranes) were also able to activate skin inflammasome while the use of catalase prevents the activation. This study demonstrated that O3 can activate cutaneous inflammasome in a redox dependent manner suggesting a possible role of this new pathway in pollution induced inflammatory skin conditions.

Fruit quality traits play a significant role in consumer preferences and consumption in blueberry (Vaccinium corymbosum L). The objectives of this study were to construct a high-density linkage map and to identify the underlying genetic basis of fruit quality traits in blueberry. A total of 287 F1 individuals derived from a cross between two southern highbush blueberry cultivars, 'Reveille' and 'Arlen', were phenotyped over three years (2016-2018) for fruit quality-related traits, including titratable acidity, pH, total soluble solids, and fruit weight. A high-density linkage map was constructed using 17k single nucleotide polymorphisms markers. The linkage map spanned a total of 1397 cM with an average inter-loci distance of 0.08 cM. The quantitative trait loci interval mapping based on the hidden Markov model identified 18 loci for fruit quality traits, including seven loci for fruit weight, three loci for titratable acidity, five loci for pH, and three loci for total soluble solids. Ten of these loci were detected in more than one year. These loci explained phenotypic variance ranging from 7 to 28% for titratable acidity and total soluble solid, and 8-13% for pH. However, the loci identified for fruit weight did not explain more than 10% of the phenotypic variance. We also reported the association between fruit quality traits and metabolites detected by Proton nuclear magnetic resonance analysis directly responsible for these fruit quality traits. Organic acids, citric acid, and quinic acid were significantly (P < 0.05) and positively correlated with titratable acidity. Sugar molecules showed a strong and positive correlation with total soluble solids. Overall, the study dissected the genetic basis of fruit quality traits and established an association between these fruit quality traits and metabolites.

Various wild berry species endemic to Alaska and the circumpolar North that exhibit unique medicinal properties have long been appreciated by indigenous Arctic communities. Traditional use of Alaskan berry preparations in the treatment of skin wounds is recorded but has not been scientifically evaluated. Alaskan wild berries feature diverse phytochemical compositions that contain a variety of bioactive polyphenols exhibiting anti-inflammatory, antioxidant, and antimicrobial properties, making them ideal for wound healing interventions and natural anti-aging cosmeceutical formulations. Given increasing interest in identifying biologically active plant constituents for wound care and cosmeceutical applications, the objective of this study was to screen several wild berry species endemic to Alaska and the circumpolar Artic for wound healing and in the crude, polyphenol-enriched, and further fractionated extracts of: Empetrum nigrum (crowberry), Vaccinium uliginosum (bog blueberry), and V. vitis-idaea (low-bush cranberry or lingonberry). A cell migration assay with human dermal fibroblasts (HDFa) was performed to model promotion of wound closure, revealing that bog blueberry extract most actively promoted migration, whereas divergent effects observed with other berry extracts were related to compositional disparities. Lipopolysaccharide (LPS)-stimulated inflammatory response variables measured in RAW 264.7 macrophages [reactive oxygen species (ROS), NO production, prostaglandin-endoperoxide synthase 2 (COX-2), and inducible nitric oxide synthase (iNOS) expression] were suppressed by most extracts/fractions, but especially bog blueberry and proanthocyanidin (PAC) fractions. Wild berry germplasm contained abundant complex flavonoid structures such as PAC and anthocyanins (ANCs), associated with enhanced repair and inflammatory resolution in these models. Next, underlying mechanisms by which PACs and bioactive metabolites (B2 dimer and epicatechin) could influence wound repair and tissue regeneration were examined. PAC metabolites promoted scratch-wound closure and appeared to exert the highest impacts on early stages of wound healing through stimulating mitochondrial bioenergetics (basal respiration, ATP production, and maximum respiratory capacity) and upregulating expression of important extracellular matrix (ECM) proteins (integrin-ß1 and collagen type I α2 chain). Targeting cellular bioenergetics and integrin-mediated cell-ECM signaling with bioactives from Alaskan wild berries shows considerable therapeutic promise to treat chronic skin wounds and inflammatory skin disorders, as well as more generally to support regenerative healing responses and restore function in a variety of tissue and organ settings after injury or aging.

Parkinson's disease (PD) is a neurodegenerative disorder involving motor symptoms caused by a loss of dopaminergic neurons in the substantia nigra region of the brain. Epidemiological evidence suggests that anthocyanin (ANC) intake is associated with a low risk of PD. Previously, we reported that extracts enriched with ANC and proanthocyanidins (PAC) suppressed dopaminergic neuron death elicited by the PD-related toxin rotenone in a primary midbrain culture model. Here, we characterized botanical extracts enriched with a mixed profile of polyphenols, as well as a set of purified polyphenolic standards, in terms of their ability to mitigate dopaminergic cell death in midbrain cultures exposed to another PD-related toxicant, paraquat (PQ), and we examined underlying neuroprotective mechanisms. Extracts prepared from blueberries, black currants, grape seeds, grape skin, mulberries, and plums, as well as several ANC, were found to rescue dopaminergic neuron loss in PQ-treated cultures. Comparison of a subset of ANC-rich extracts for the ability to mitigate neurotoxicity elicited by PQ versus rotenone revealed that a hibiscus or plum extract was only neuroprotective in cultures exposed to rotenone or PQ, respectively. Several extracts or compounds with the ability to protect against PQ neurotoxicity increased the activity of the antioxidant transcription factor Nrf2 in cultured astrocytes, and PQ-induced dopaminergic cell death was attenuated in Nrf2-expressing midbrain cultures. In other studies, we found that extracts prepared from hibiscus, grape skin, or purple basil (but not plums) rescued defects in O 2 consumption in neuronal cells treated with rotenone. Collectively, these findings suggest that extracts enriched with certain combinations of ANC, PAC, stilbenes, and other polyphenols could potentially slow neurodegeneration in the brains of individuals exposed to PQ or rotenone by activating cellular antioxidant mechanisms and/or alleviating mitochondrial dysfunction.

Beneficial health effects of fruits and vegetables in the diet have been attributed to their high flavonoid content. Dipeptidyl peptidase IV (DPP-IV) is a serine aminopeptidase that is a novel target for type 2 diabetes therapy due to its incretin hormone regulatory effects. In this study, well-characterized anthocyanins (ANC) isolated from berry wine blends and twenty-seven other phenolic compounds commonly present in citrus, berry, grape, and soybean, were individually investigated for their inhibitory effects on DPP-IV by using a luminescence assay and computational modeling. ANC from blueberry-blackberry wine blends strongly inhibited DPP-IV activity (IC50, 0.07 ± 0.02 to >300  μ M). Of the twenty-seven phenolics tested, the most potent DPP-IV inhibitors were resveratrol (IC50, 0.6 ± 0.4 nM), luteolin (0.12 ± 0.01  μ M), apigenin (0.14 ± 0.02  μ M), and flavone (0.17 ± 0.01  μ M), with IC50 values lower than diprotin A (4.21 ± 2.01  μ M), a reference standard inhibitory compound. Analyses of computational modeling showed that resveratrol and flavone were competitive inhibitors which could dock directly into all three active sites of DPP-IV, while luteolin and apigenin docked in a noncompetitive manner. Hydrogen bonding was the main binding mode of all tested phenolic compounds with DPP-IV. These results indicate that flavonoids, particularly luteolin, apigenin, and flavone, and the stilbenoid resveratrol can act as naturally occurring DPP-IV inhibitors.

The objective of this study was to determine if consuming an extractable or nonextractable fraction of table grapes reduced the metabolic consequences of consuming a high-fat, American-type diet. Male C57BL/6J mice were fed a low fat (LF) diet, a high fat (HF) diet, or an HF diet containing whole table grape powder (5% w/w), an extractable, polyphenol-rich (HF-EP) fraction, a nonextractable, polyphenol-poor (HF-NEP) fraction or equal combinations of both fractions (HF-EP+NEP) from grape powder for 16weeks. Mice fed the HF-EP and HF-EP+NEP diets had lower percentages of body fat and amounts of white adipose tissue (WAT) and improved glucose tolerance compared to the HF-fed controls. Mice fed the HF-EP+NEP diet had lower liver weights and triglyceride (TG) levels compared to the HF-fed controls. Mice fed the HF-EP+NEP diets had higher hepatic mRNA levels of hormone sensitive lipase and adipose TG lipase, and decreased expression of c-reactive protein compared to the HF-fed controls. In epididymal (visceral) WAT, the expression levels of several inflammatory genes were lower in mice fed the HF-EP and HF-EP+NEP diets compared to the HF-fed controls. Mice fed the HF diets had increased myeloperoxidase activity and impaired localization of the tight junction protein zonula occludens-1 in ileal mucosa compared to the HF-EP and HF-NEP diets. Several of these treatment effects were associated with alterations in gut bacterial community structure. Collectively, these data demonstrate that the polyphenol-rich, EP fraction from table grapes attenuated many of the adverse health consequences associated with consuming an HF diet.

The present study investigated the effect of spray-dried algae-rosemary particles against pollution-induced damage using ex-vivo human biopsies exposed to diesel engine exhaust (DEE). For this, the complexation of hydroalcoholic rosemary extract with Chlorella (RCH) and Spirulina (RSP) protein powders was conducted. The process efficiency and concentration of rosmarinic acid (RA), carnosic acid (CA), and carnosol (CR) phenolic compounds of both products were compared. The RSP spray-dried production was more efficient, and RSP particles presented higher CR and CA and similar RA concentrations. Therefore, spray-dried RSP particles were prioritized for the preparation of a gel formulation that was investigated for its ability to mitigate pollution-induced skin oxinflammatory responses. Taken altogether, our ex-vivo data clearly demonstrated the ability of RSP gel to prevent an oxinflammatory phenomenon in cutaneous tissue by decreasing the levels of 4-hydroxynonenal protein adducts (4HNE-PA) and active matrix metalloproteinase-9 (MMP-9) as well as by limiting the loss of filaggrin induced by DEE exposure. Our results suggest that the topical application of spirulina-rosemary gel is a good approach to prevent pollution-induced skin aging/damage.

Overconsumption of energy dense foods and sedentary lifestyle are considered as major causes of obesity-associated insulin resistance and abnormal glucose metabolism. Results from both cohort studies and randomized trials suggested that anthocyanins from berries may lower metabolic risks, however these reports are equivocal. The present study was designed to examine effects of six berries with structurally diverse anthocyanin profiles (normalized to 400 µg/g total anthocyanin content) on development of metabolic risk factors in the C57BL/6 mouse model of polygenic obesity. Diets supplemented with blackberry (mono-glycosylated cyanidins), black raspberry (acylated mono-glycosylated cyanidins), blackcurrant (mono- and di-glycosylated cyanidins and delphinidins), maqui berry (di-glycosylated delphinidins), Concord grape (acylated mono-glycosylated delphinidins and petunidins), and blueberry (mono-glycosylated delphinidins, malvidins, and petunidins) showed a prominent discrepancy between biological activities of delphinidin/malvidin-versus cyanidin-type anthocyanins that could be explained by differences in their structure and metabolism in the gut. Consumption of berries also resulted in a strong shift in the gastrointestinal bacterial communities towards obligate anaerobes that correlated with decrease in the gastrointestinal luminal oxygen and oxidative stress. Further work is needed to understand mechanisms that lead to nearly anoxic conditions in the gut lumens, including the relative contributions of host, diet and/or microbial oxidative activity, and their implication to human health.

Oxylipins are bioactive lipid oxidation products, have vital regulatory roles in numerous physiological processes including inflammation, and can be impacted by diet. This study determined if 2-weeks of blueberry and/or acute banana ingestion influenced generation of n-6 and n-3 PUFA-derived oxylipins during recovery from exercise-induced physiological stress. Cyclists (n = 59, 39 ± 2 years of age) were randomized to freeze-dried blueberry or placebo groups, and ingested 26 grams/d (1 cup/d blueberries equivalent) for 2 weeks. Cyclists reported to the lab in an overnight fasted state and engaged in a 75-km cycling time trial (185.5 ± 5.2 min). Cyclists from each group (blueberry, placebo) were further randomized to ingestion of a water-only control or water with a carbohydrate source (Cavendish bananas, 0.2 g/kg carbohydrate every 15 min) during exercise. Blood samples were collected pre- and post-2-weeks blueberry supplementation, and 0, 1.5, 3, 5, 24, and 48 h-post-exercise. Plasma oxylipins and blueberry and banana metabolites were measured with UPLC-tandem MS/MS. Significant time by treatment effects (eight time points, four groups) were found for 24 blueberry- and seven banana-derived phenolic metabolites in plasma (FDR adjusted p < 0.05). Significant post-exercise increases were observed for 64 of 67 identified plasma oxylipins. When oxylipins were grouped relative to fatty acid substrate [arachidonic acid (ARA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), α-linolenic acid (ALA), linoleic acid (LA)], and enzyme systems [cytochrome P450 (CYP), lipoxygenase (LOX)], banana and blueberry ingestion were independently associated with significant post-exercise reductions in pro-inflammatory ARA-CYP hydroxy- and dihydroxy-eicosatetraenoic acids (HETEs, DiHETrEs) (treatment effects, FDR adjusted p < 0.05). These trial differences were especially apparent within the first 3 h of recovery. In summary, heavy exertion evoked a transient but robust increase in plasma levels of oxylipins in cyclists, with a strong attenuation effect linked to both chronic blueberry and acute banana intake on pro-inflammatory ARA-CYP oxylipins.

The World Health Organization estimates that 7 million people die every year due to pollution exposure. Among the different pollutants to which living organism are exposed, ozone (O3) represents one of the most toxic, because its location which is the skin is one of the direct tissues exposed to the outdoor environment. Chronic exposure to outdoor stressors can alter cutaneous redox state resulting in the activation of inflammatory pathways. Recently, a new player in the inflammation mechanism was discovered: the multiprotein complex NLRP1 inflammasome, which has been shown to be also expressed in the skin. The topical application of natural compounds has been studied for the last 40 years as a possible approach to prevent and eventually cure skin conditions. Recently, the possibility to use blueberry (BB) extract to prevent pollution-induced skin toxicity has been of great interest in the cosmeceutical industry. In the present study, we analyzed the cutaneous protective effect of BB extract in several skin models (2D, 3D, and human skin explants). Specifically, we observed that in the different skin models used, BB extracts were able to enhance keratinocyte wound closure and normalize proliferation and migration responses previously altered by O3. In addition, pretreatment with BB extracts was able to prevent ozone-induced ROS production and inflammasome activation measured as NRLP1-ASC scaffold formation and also prevent the transcripts of key inflammasome players such as CASP1 and IL-18, suggesting that this approach as a possible new technology to prevent cutaneous pollution damage. Our data support the hypothesis that BB extracts can effectively reduce skin inflammation and be a possible new technology against cutaneous pollution-induced damage.