Chemopreventive and immunomodulatory effects of phenolic-rich extract of Commiphora leptophloeos against inflammatory bowel disease: Preclinical evidence.

ETHNOPHARMACOLOGY RELEVANCE: Commiphora leptophloeos (Mart.) J.B. Gillet (Burseraceae) is a medicinal plant native to Brazil, popularly known as "imburana". Homemade leaf decoction and maceration were used to treat general inflammatory problems in the Brazilian Northeast population. Our previous research confirmed the anti-inflammatory activity of the C. leptophloeos hydroalcoholic leaf extract. AIM OF THE STUDY: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut with no ideal treatment to maintain the remissive status. This work aimed to characterize the phytochemical composition and physicochemical properties of the C. leptophloeos hydroalcoholic leaf extract and its efficacy in chemopreventive and immunomodulatory responses in inflammatory bowel disease in non-clinical models. MATERIALS AND METHODS: Mass spectrometry and physicochemical tests determined the phytochemical profile and physicochemical characteristics of the Commiphora leptophloeos (CL) extract. The chemopreventive and immunomodulatory effects of CL extract (50 and 125 µg/mL) were evaluated in vitro in the RAW 264.7 lipopolysaccharide (LPS) induced cell assay and in vivo in the model of intestinal inflammation induced by 2,4-Dinitrobenzenesulfonic acid (DNBS) in mice when they were treated with CL extract by intragastric gavage (i.g.) at doses of 300, 400 and 500 mg/kg. RESULTS: Phytochemical annotation of CL extract showed a complex phenolic composition, characterized as phenolic acids and flavonoids, and satisfactory physicochemical characteristics. In addition, CL extract maintained the viability of RAW macrophages, reduced ROS and NO production, and negatively regulated COX-2, iNOS, TNF-α, IL-1ß, IL-6, and IL-17 (p < 0.05). In the intestinal inflammation model, CL extract was able to downregulate NF-κB p65/COX-2, mTOR, iNOS, IL-17, decrease levels of malondialdehyde and myeloperoxidase and cytokines TNF-α, IL-1ß and IL-6 (p < 0.05). CONCLUSION: Based on these findings, CL extract reduced inflammatory responses by down-regulating pro-inflammatory markers in macrophages induced by LPS and DNBS-induced colitis in mice through NF-κB p65/COX-2 signaling. CL leaf extract requires further investigation as a candidate for treating inflammatory bowel disease.

Phenolic-rich extract of Nopalea cochenillifera attenuates gastric lesions induced in experimental models through inhibiting oxidative stress, modulating inflammatory markers and a cytoprotective effect.

Nopalea cochenillifera (Cactaceae), popularly known as "palma" or "palma doce", is from Mexico, but it was widely introduced in Brazil through crops. It has been used as food and in traditional medicine and is a good source of phenolic compounds. In this study the phytochemical profile and gastroprotective activity of phenolic-rich extract of N. cochenillifera in acute gastric lesion models induced by ethanol and indomethacin were evaluated. High-performance liquid chromatography coupled with mass spectrometry (HPLC/ESI/MSn) allowed the characterization of 12 compounds such as sugars, phenolics and flavonoids. Among polyphenols, the main peak was assigned to isorhamnetin-3-O-(2'',3''-O-di-rhamnose)-glucoside. The TPC and TFC in the dry extract were 67.85 mg of gallic acid equivalent per g/extract and 46.16 mg quercetin equivalent per g/extract, respectively. In the in vitro MTT assay, the extract showed no cytotoxicity and suppressed ROS levels in LPS-treated RAW 264.7 cells. Preclinical models in rats showed that a dose of 100 mg kg-1 (p < 0.0001) in the ethanol model and doses of 100 mg kg-1 (p < 0.5) and 200 mg kg-1 (p < 0.01) in the indomethacin model reduced the gastric lesions. Also, the extract reduced the MPO, MDA, TNF-α and IL-1ß levels and increased the GSH and IL-10 levels. The pre-treatment with the extract led to the upregulation of SOD and the downregulation of COX-2 by immunohistochemical analysis. It also showed a cytoprotective effect in the histopathological analysis and stimulated the restoration of the mucus content as observed in the periodic acid-Schiff analysis without modifying the pH, volume or total acidity of the gastric juice. Taken together, N. cochenillifera extract can be applied as a novel gastroprotective ingredient for food or pharmaceutical products.

Brassinosteroids control the inflammation, oxidative stress and cell migration through the control of mitochondrial function on skin regeneration.

INTRODUCTION: Brassinosteroids (BRs) are the class of phytohormones with great importance in agriculture and potential diverse effects on human welfare, including skin disease treatment. In this sense, BRs are a promising tool for promoting skin regeneration. AIMS: Therefore, the objective of the present work was to analyze the effect of BRs in wound repair, mainly the inflammatory and proliferative phases, and their influence on migratory abilities in human dermal fibroblasts (HDFa), and consequently understand the mitochondrial metabolism. MAIN METHODS: We measured nine natural and synthetic BRs for the inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We further evaluated the migration activity in HDFa modeling promotion of wound closure after BRs exposure. In addition, we evaluated the 84 gene profiles linked to wound healing response using RT2 Profiler PCR Array and examined cellular bioenergetics using an extracellular flux analyzer. KEY FINDINGS: Results showed that LPS-induced cells had around 10 % lower reactive oxygen species and nitric oxide accumulation when treated with some BRs compounds. HDFa treated with homobrassinolide-based and homocastasterone-based compounds resulted in the greatest migratory activity and presents the best results for mitochondrial responses. SIGNIFICANCE: Together, these results provided strong evidence for BRs' ability to promote skin health, particularly through contributions to both reducing excessive oxidative stress and controlling the inflammation process resulting in the best HDFa cell migration through the control of mitochondrial function.

Anti-Inflammatory, Antioxidant, and Skin Regenerative Potential of Secondary Metabolites from Plants of the Brassicaceae Family: A Systematic Review of In Vitro and In Vivo Preclinical Evidence (Biological Activities Brassicaceae Skin Diseases).

The Brassicaceae family constitutes some of the most well-studied natural products in the world, due to their anti-inflammatory, anti-oxidative, and pro-regenerative properties as well as their ubiquitous distribution across the world. To evaluate the potential efficacy of the Brassicaceae family in the treatment of inflammatory skin disorders and wounds, based on preclinical evidence from in vivo and in vitro studies. This systematic review was performed according to the PRISMA guidelines, using a structured search on the PubMed-Medline, Scopus, and Web of Science platforms. The studies included were those that used murine models and in vitro studies to investigate the effect of Brassicaceae on skin disorders. Bias analysis and methodological quality assessments were examined through SYRCLE's RoB tool. Brassicaceae have shown positive impacts on inflammatory regulation of the skin, accelerating the wound healing process, and inhibiting the development of edema. The studies showed that the Brassicaceae family has antioxidant activity and effects on the modulation of cyclooxygenase 2 and the nuclear factor kappa ß (NFκß) pathway. The secondary metabolites present in Brassicas are polyphenols (68.75%; n = 11), terpenes/carotenoids (31.25%; n = 5), and glycosylates (25%; n = 4), which are responsible for their anti-inflammatory, healing, and antioxidant effects. In addition, the current evidence is reliable because the bias analysis showed a low risk of bias. Our review indicates that compounds derived from Brassicaceae present exceptional potential to treat inflammatory skin diseases and accelerate cutaneous wound healing. We hope that our critical analysis can help to expedite clinical research and to reduce methodological bias, thereby improving the quality of evidence in future research. The registration number on the Prospero platform is CRD42021262953.

The First Optimization Process from Cultivation to Flavonoid-Rich Extract from Moringa oleifera Lam. Leaves in Brazil.

Flavonoids are significant antioxidant and anti-inflammatory agents and have multiple potential health applications. Moringa oleifera is globally recognized for its nutritional and pharmacological properties, correlated to the high flavonoid content in its leaves. However, the bioactive compounds found in plants may vary according to the cultivation, origin, season, and extraction process used, making it difficult to extract reliable raw material. Hence, this study aimed to standardize the best cultivation and harvest season in Brazil and the best extraction process conditions to obtain a flavonoid-rich extract from M. oleifera as a final product. Firstly, ultrasound-assisted extraction (UAE) was optimized to reach the highest flavonoid content by three-level factorial planning and response surface methodology (RSM). The optimal cultivation condition was mineral soil fertilizer in the drought season, and the optimized extraction was with 80% ethanol and 13.4 min of extraction time. The flavonoid-rich extract was safe and significantly decreased reactive oxygen species (ROS) and nitric oxide (NO) in LPS-treated RAW 264.7 cells. Lastly, the major flavonoids characterized by HPLC-ESI-QTRAP-MS/MS were compounds derived from apigenin, quercetin, and kaempferol glycosides. The results confirmed that it was possible to standardize the flavonoid-rich extract leading to a standardized and reliable raw material extracted from M. oleifera leaves.

Gel formulated with Bryophyllum pinnatum leaf extract promotes skin wound healing in vivo by increasing VEGF expression: A novel potential active ingredient for pharmaceuticals.

Bryophyllum pinnatum (Crassulaceae) is used in traditional medicine for treating skin wounds. In our previous study, a topical gel containing B. pinnatum aqueous leaf extract showed a preclinical anti-inflammatory effect in in vivo acute edema models. In continuation, the present study aims to evaluate the phytochemical content and the stability of a formulation in gel containing B. pinnatum aqueous leaf extract and its healing properties and mechanism of action through an experimental model of induction of skin wounds in rats and in vitro assays. The animals were treated topically for 7 or 14 days with a formulation in gel containing extract at 5% or a placebo or Fibrinase® in cream. In addition, to establish some quality control parameters, the total phenolic content (TPC), total flavonoid content (TFC), and a study focusing on the phytochemical and biological stability of a gel for 30 days at two different conditions (room temperature and 40°C/75% RH) were performed. Gel formulation containing extract showed a TPC and TFC of 2.77 ± 0.06 mg of gallic acid/g and 1.58 ± 0.03 mg of quercetin/g, respectively. Regarding the stability study, the formulation in gel showed no significant change in the following parameters: pH, water activity, chromatographic profile, and the content of the major compound identified in the extract. The gel formulation containing extract stimulated skin wound healing while reducing the wound area, as well as decreasing the inflammatory infiltrate, reducing the levels of IL-1ß and TNF-α, and stimulating angiogenesis with increased expression of VEGF, an effect similar to Fibrinase. In conclusion, the gel formulation containing extract exhibited relevant skin wound healing properties and, therefore, has the potential to be applied as a novel active ingredient for developing wound healing pharmaceuticals.

Chemical Composition and Bioactive Properties of Commercial and Non-Commercial Purple and White Açaí Berries.

Chemical composition analysis of açaí extracts revealed higher levels of total polyphenol content in purple açaí samples for both commercial (4.3-44.7 gallic acid equivalents mg/g) and non-commercial samples (30.2-42.0 mg/g) compared to white (8.2-11.9 mg/g) and oil samples (0.8-4.6 mg/g). The major anthocyanin compounds found in purple açaí samples were cyanidin-3-glucoside and cyanidin-3-rutinoside with total concentrations in the range of 3.6-14.3 cyanidin-3-glucoside equivalents mg/g. The oligomeric proanthocyanidins were quantified in the range of 1.5-6.1 procyanidin B1 equivalents mg/g. Moreover, açaí presented significant levels of calcium, magnesium, manganese, iron, zinc and copper, essential minor and trace elements, in comparison with other berries. All of the açaí extracts at 50 µg/mL potently inhibited the release of reactive oxygen species in lipopolysaccharide-stimulated RAW 264.7 murine macrophage cells, but none inhibited the release of nitric oxide. Furthermore, all the açaí samples demonstrated potential as wound healing agents due to the high levels of migration activity in human fibroblast cells.

Phenolic content, anti-inflammatory properties, and dermal wound repair properties of industrially processed and non-processed acai from the Brazilian Amazon.

Acai fruit is recognized for its health promoting properties. However, there is still a need to address the effects of industrial processing on this fruit. In this study, phenolic content, anti-inflammatory properties and dermal wound repair properties of 20 acai samples, before and after industrial processing, from various Amazon regions were investigated. Acai pulp was rich in total phenolics (18.9-58.8 mg g-1) and proanthocyanins (9.8-43.1 mg g-1), but contained trace anthocyanins (up to 0.1 mg g-1). Industrially processed samples lost substantial amounts of proanthocyanidins (up to 83.2%), while the anthocyanins inherently present were greatly enriched after processing (20-fold higher). Non-processed acai pulp extracts protected against early inflammation response which was correlated with proanthocyanidins, by significantly inhibiting nitric oxide production and suppressing pro-inflammatory gene expression including interleukin-1ß, cyclooxygenase-2, nitric oxide synthase, and interleukin-6. The promotion of dermal wound repair of acai seed and pulp extracts was mainly contributed by anthocyanins and other bioactive compounds. The anti-inflammatory effect was diminished but wound healing effect was retained after pulp processing, suggesting the processing technology needs to be improved to maintain biological properties of acai fruit.

Lily steroidal glycoalkaloid promotes early inflammatory resolution in wounded human fibroblasts.

ETHNOPHARMACOLOGICAL RELEVANCE: The bulbs and flowers of plants from the Lilium genus have historically been used in Asian and Greco-Roman medicine to treat burns and promote skin healing. AIM OF THE STUDY: To evaluate a steroidal glycoalkaloid isolated from Easter lily bulbs for its potential wound healing promoting properties. MATERIALS AND METHODS: A lily-derived steroidal glycoalkaloid (LSGA), (22R, 25R)-spirosol-5-en-3ß-yl O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranosyl-(1→4)-ß-D-glucopyranoside, was isolated from Easter lily bulbs, and its structure was confirmed by LC-MS and NMR spectrometry. LSGA effects on wound scratch closure were evaluated in a primary human dermal fibroblast cell culture, and the changes in gene expression profiles were quantitated using an 84 wound-related gene qPCR microarray. RESULTS: LSGA promoted migration of dermal fibroblasts into the wounded area. The treatment was associated with a rapid upregulation of early inflammatory (CD40LG, CXCL11, IFNG, IL10, IL2 and IL4), cell growth (CSF3 and TNF) and remodeling (CTSG, F13A1, FGA, MMP and PLG) genes both in the wounded and unwounded cells treated with LSGA. A selective decrease in gene expression profiles associated with inflammatory (CXCL2 and CCL7) and remodeling (MMP7 and PLAT) phases was observed in wounded cells treated with LSGA, in contrast to the wounded cells (control). CONCLUSION: This study demonstrates that a glycoalkaloid present in lilies promoted fibroblast migration in vitro and affected inflammatory, remodeling and growth factor gene expression. The decreases in expression of key genes may impact the wound healing process, possibly contributing to an earlier end of the inflammatory response and shortening the early phases of model tissue reconstitution. The results of this preliminary investigation may provide a basis for the historical use of lily bulbs to promote dermal healing after injury.

What Is the Impact of Depletion of Immunoregulatory Genes on Wound Healing? A Systematic Review of Preclinical Evidence.

Cytokines and growth factors are known to play an important role in the skin wound closure process; however, in knockout organisms, the levels of these molecules can undergo changes that result in the delay or acceleration of this process. Therefore, we systematically reviewed evidence from preclinical studies about the main immunoregulatory molecules involved in skin repair through the analysis of the main mechanisms involved in the depletion of immunoregulatory genes, and we carried out a critical analysis of the methodological quality of these studies. We searched biomedical databases, and only original studies were analyzed according to the PRISMA guidelines. The included studies were limited to those which used knockout animals and excision or incision wound models without intervention. A total of 27 studies were selected; data for animal models, gene depletion, wound characteristics, and immunoregulatory molecules were evaluated and compared whenever possible. Methodological quality assessments were examined using the ARRIVE and SYRCLE's bias of risk tool. In our review, the extracellular molecules act more negatively in the wound healing process when silenced and the metabolic pathway most affected involved in these processes was TGF-ß/Smad, and emphasis was given to the importance of the participation of macrophages in TGF-ß signaling. Besides that, proinflammatory molecules were more evaluated than anti-inflammatory ones, and the main molecules evaluated were, respectively, TGF-ß1, followed by VEGF, IL-6, TNF-α, and IL-1ß. Overall, most gene depletions delayed wound healing, negatively influenced the concentrations of proinflammatory cytokines, and consequently promoted a decrease of inflammatory cell infiltration, angiogenesis, and collagen deposition, compromising the formation of granulation tissue. The studies presented heterogeneous data and exhibited methodological limitations; therefore, mechanistic and highly controlled studies are required to improve the quality of the evidence.

Alaskan Berry Extracts Promote Dermal Wound Repair Through Modulation of Bioenergetics and Integrin Signaling.

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.

Changes in the bioactive properties of strawberries caused by the storage in oxygen- and carbon dioxide-enriched atmospheres.

The changes in the antioxidant capacity, anti-inflammatory, and wound healing properties of strawberry fruits as a consequence of the storage in atmospheres enriched in oxygen and carbon dioxide were investigated. Berries were exposed to two different gas compositions: 70% O2 + 20% CO2 and 90% O2 + 10% CO2, and stored for up to 20 days at 5°C. The antioxidant capacity, assessed through DPPH and FRAP methods, decreased around 17% in samples exposed to 70% O2 + 20% CO2 at day 20. However, the antioxidant activity of fruits stored in 90% O2 + 10% CO2 was maintained until day 20 and experienced an increase of around 10% on day 10. Moreover, strawberry stored in 90% O2 + 10% CO2 at days 5-10 showed an improved suppression of the pro-inflammatory genes Cox-2 and iNOS up to 30% higher than samples at day 0 in an in vitro LPS-stimulated RAW 264.7 macrophage culture. In addition, berries exposed to 90% O2 + 10% CO2 at day 10 showed a human dermal fibroblast migration 30% higher than samples at day 0 in an in vitro skin-fibroblast-migration model. Therefore, evidence suggests that strawberry storage in 90% O2 + 10% CO2 can be a promissory alternative to offer fruits with enhanced bioactivity.

Anti-inflammatory and wound healing properties of polyphenolic extracts from strawberry and blackberry fruits.

The polyphenolic profiles by HPLC-TOF-MS of strawberry 'San Andreas' and blackberry 'Black Satin' crude extracts (CE) were analyzed. Anthocyanin-enriched fractions (AEFs) and proanthocyanidin-enriched fractions (PEFs) were prepared, and all samples were probed for in vitro anti-inflammatory and wound healing effects in a LPS-stimulated RAW 264.7 macrophage model and in a skin fibroblast migration and proliferation assay, respectively. Blackberry samples exhibited higher ROS reduction than strawberry's (up to 50% ROS suppression). Berries CEs exhibited 20% inhibition in Cox-2 gene expression, while AEFs and PEFs were inactive at the same concentration. Strawberry AEF and PEF were more active against IL-1ß and IL-6 gene expressions than the similar fractions from blackberry, where PEF was more active than AEF (75% suppression by strawberry PEF). Moreover, berry PEFs were the active polyphenol fraction against iNOS gene expression (50% and 65% gen suppression by strawberry and blackberry PEF, respectively), mirroring results of NO synthesis suppression. The cell migration potential of berry polyphenolics was associated with anthocyanins. AEFs showed fibroblast migration around 50% of that registered for the positive control. Results obtained in this work highlight the anti-inflammatory properties of berry polyphenolics, especially due to proanthocyanidins. Moreover, promising results were obtained about the effects of berry anthocyanins on wound healing.

Dietary arachidonate in milk replacer triggers dual benefits of PGE2 signaling in LPS-challenged piglet alveolar macrophages.

BACKGROUND: Respiratory infections challenge the swine industry, despite common medicinal practices. The dual signaling nature of PGE2 (supporting both inflammation and resolution) makes it a potent regulator of immune cell function. Therefore, the use of dietary long chain n-6 PUFA to enhance PGE2 effects merits investigation. METHODS: Day-old pigs (n = 60) were allotted to one of three dietary groups for 21 d (n = 20/diet), and received either a control diet (CON, arachidonate = 0.5% of total fatty acids), an arachidonate (ARA)-enriched diet (LC n-6, ARA = 2.2%), or an eicosapentaenoic (EPA)-enriched diet (LC n-3, EPA = 3.0%). Alveolar macrophages and lung parenchymal tissue were collected for fatty acid analysis. Isolated alveolar macrophages were stimulated with LPS in situ for 24 h, and mRNA was isolated to assess markers associated with inflammation and eicosanoid production. Culture media were collected to assess PGE2 secretion. Oxidative burst in macrophages was measured by: 1) oxygen consumption and extracellular acidification (via Seahorse), 2) cytoplasmic oxidation and 3) nitric oxide production following 4, 18, and 24 h of LPS stimulation. RESULTS: Concentration of ARA (% of fatty acids, w/w) in macrophages from pigs fed LC n-6 was 86% higher than CON and 18% lower in pigs fed LC n-3 (P < 0.01). Following LPS stimulation, abundance of COX-2 and TNF-α mRNA (P <  0.0001), and PGE2 secretion (P < 0. 01) were higher in LC n-6 PAM vs. CON. However, ALOX5 abundance was 1.6-fold lower than CON. Macrophages from CON and LC n-6 groups were 4-fold higher in ALOX12/15 abundance (P < 0.0001) compared to LC n-3. Oxygen consumption and extracellular acidification rates increased over 4 h following LPS stimulation (P < 0.05) regardless of treatment. Similarly, increases in cytoplasmic oxidation (P < 0.001) and nitric oxide production (P <  0.002) were observed after 18 h of LPS stimulation but were unaffected by diet. CONCLUSIONS: We infer that enriching diets with arachidonic acid may be an effective means to enhance a stronger innate immunologic response to respiratory challenges in neonatal pigs. However, further work is needed to examine long-term safety, clinical efficacy and economic viability.

Blueberry polyphenol-protein food ingredients: The impact of spray drying on the in vitro antioxidant activity, anti-inflammatory markers, glucose metabolism and fibroblast migration.

Wild blueberry pomace extract complexed with wheat or chickpea flour or soy protein isolate produced spray dried and freeze-dried polyphenol-protein particles. To evaluate the impact of spray drying on the biological activity of these food ingredients in vitro antioxidant and anti-inflammatory activities, regulation of glucose metabolism and ability to stimulate fibroblast migration were tested. Extracts from polyphenol-protein particles significantly decreased reactive oxygen species (ROS) production and down-regulated the gene expression of inflammation markers (COX-2 and IL-1ß). Milder suppression of nitric oxide production and inducible nitric oxide synthase (iNOS) gene expression was evident. The extracts significantly inhibited phosphoenolpyruvate carboxykinase (PEPCK) and accelerated fibroblast cell migration up to 3-fold after 24 h. Complexed polyphenols retained their structural integrity and bioactive potency for both lyophilized and spray dried treatments. The data suggests that spray drying is a convenient and cost-effective technique to produce blueberry-polyphenol food ingredients with preserved phytochemicals with biological activities.

Simultaneous LC-MS quantification of anthocyanins and non-anthocyanin phenolics from blueberries with widely divergent profiles and biological activities.

A sensitive and straightforward LC-IT-TOF-MS method was validated for the profiling and simultaneous quantification of anthocyanins, flavan-3-ols, flavonols, phenolic acids, and resveratrol in blueberry genotypes with fruit color ranging from deep purple (Vaccinium angustifolium) to various shades of pink (crosses of V. corymbosum, V. darrowii, and V. ashei). Standard calibration curves were linear for all analytes with correlation coefficients >0.99. The relative standard deviation for intra- and inter-day precision was lower than 10%. The method allowed an easy and selective identification and quantification of phenolics in blueberries with divergent profiles. The in vitro antioxidant assay results were strongly correlated with total phenolics and total anthocyanin content. Lowbush blueberry extracts (50 µg/mL) reduced ROS and NO production, and inhibited the transcription of the proinflammatory cytokines IL-6ß, COX2, iNOS, and IL-6 in the in vitro assays at much lower concentrations than pink fruited berries (250 µg/mL).

Metabolic recovery from heavy exertion following banana compared to sugar beverage or water only ingestion: A randomized, crossover trial.

OBJECTIVES AND METHODS: Using a randomized, crossover, counterbalanced approach, cyclists (N = 20, overnight fasted state) engaged in the four 75-km time trials (2-week washout) while ingesting two types of bananas with similar carbohydrate (CHO) but different phenolic content (Cavendish, CAV; mini-yellow, MIY, 63% higher polyphenols), a 6% sugar beverage (SUG), and water only (WAT). CHO intake was set at 0.2 g/kg every 15 minutes. Blood samples were collected pre-exercise and 0 h-, 0.75 h-,1.5 h-, 3 h-, 4.5 h-, 21 h-, 45 h-post-exercise. RESULTS: Each of the CHO trials (CAV, MIY, SUG) compared to water was associated with higher post-exercise plasma glucose and fructose, and lower leukocyte counts, plasma 9+13 HODES, and IL-6, IL-10, and IL-1ra. OPLS-DA analysis showed that metabolic perturbation (N = 1,605 metabolites) for WAT (86.8±4.0 arbitrary units) was significantly greater and sustained than for CAV (70.4±3.9, P = 0.006), MIY (68.3±4.0, P = 0.002), and SUG (68.1±4.2, P = 0.002). VIP ranking (<3.0, N = 25 metabolites) showed that both CAV and MIY were associated with significant fold changes in metabolites including those from amino acid and xenobiotics pathways. OPLS-DA analysis of immediate post-exercise metabolite shifts showed a significant separation of CAV and MIY from both WAT and SUG (R2Y = 0.848, Q2Y = 0.409). COX-2 mRNA expression was lower in both CAV and MIY, but not SUG, versus WAT at 21-h post-exercise in THP-1 monocytes cultured in plasma samples. Analysis of immediate post-exercise samples showed a decrease in LPS-stimulated THP-1 monocyte extracellular acidification rate (ECAR) in CAV and MIY, but not SUG, compared to WAT. CONCLUSIONS: CHO ingestion from bananas or a sugar beverage had a comparable influence in attenuating metabolic perturbation and inflammation following 75-km cycling. Ex-vivo analysis with THP-1 monocytes supported a decrease in COX-2 mRNA expression and reduced reliance on glycolysis for ATP production following ingestion of bananas but not sugar water when compared to water alone. TRIAL REGISTRATION: ClinicalTrials.gov, U.S. National Institutes of Health, identifier: NCT02994628.