PMID: 

Mol Nutr Food Res. 2020 Apr 11:e1900991. Epub 2020 Apr 11. PMID: 32277569

Abstract Title: 

The Preventive Effects of Pterostilbene on the Exercise Intolerance and Circadian Misalignment of Mice Subjected to Sleep Restriction.

Abstract: 

SCOPE: The study investigates the effects of pterostilbene (PTE) on exercise endurance and circadian rhythm in sleep-restricted (SR) mice.METHODS AND RESULTS: The SR model is established by keeping mice awake during the first 8 h of light period for 5 d and PTE (100 mg kgd) is given once a day. PTE improves endurance in SR mice by significantly prolonging the exhaustive swimming time and ameliorating exercise fatigue biochemical parameters, including creatine kinase and lactate dehydrogenase. It is observed that PTE effectively regained mitochondrial function by improving mitochondrial swelling and maintaining oxidative phosphorylation system-related genes expression, and inhibited the decrease of mitochondrial biogenesis-related genes expression. Furthermore, PTE restores rhythms of AMP-activated protein kinase (AMPK) phosphorylation activity, silent information regulator 1 (SIRT1) deacetylation activity, and SIRT1-mediated peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) deacetylation in SR mice. Finally, the results demonstrate that the AMPK/SIRT1/PGC-1α pathway may be correlated with the relationships between mitochondrial function and circadian rhythms, markedly regulating the expression of skeletal muscle clock genes, circadian locomotor output cycles kaput, and brain and muscle arnt-like 1.CONCLUSIONS: PTE ameliorates SR-induced exercise intolerance associated with circadian misalignment and mitochondrial dysfunction through AMPK/SIRT1/PGC-1α pathway.

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PMID: 

Biomolecules. 2020 May 4 ;10(5). Epub 2020 May 4. PMID: 32375296

Abstract Title: 

Pterostilbene Enhances Cytotoxicity and Chemosensitivity in Human Pancreatic Cancer Cells.

Abstract: 

Gemcitabine (GEM) drug resistance causes high mortality rates and poor outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. Receptor for advanced glycation end products (RAGE) involvement in the GEM resistance process has been demonstrated. Therefore, finding a safe and effective way to inhibit receptors for RAGE-initiated GEM resistance is urgent. Pterostilbene (PTE), a natural methoxylated analogue derived from resveratrol and found in grapes and blueberries, has diverse bioactivities, such as antioxidative, anti-inflammatory, and anticancer qualities. The overall research objective was to determine the potential of PTE to enhance tumor cytotoxicity and chemosensitivity in PDAC cells. Our results have demonstrated that PTE induced S-phase cell cycle arrest, apoptosis, and autophagic cell death and inhibited multidrug resistance protein 1 (MDR1) expression by downregulating RAGE/PI3K/Akt signaling in both MIA PaCa-2 and MIA PaCa-2cells (GEM-resistant cells). Remarkably, convincing evidence was established by RAGE small interfering RNA transfection. Taken together, our study demonstrated that PTE promoted chemosensitivity by inhibiting cell proliferation and MDR1 expression via the RAGE/PI3K/Akt axis in PDAC cells. The observations in these experiments indicate that PTE may play a crucial role in MDR1 modulation for PDAC treatment.

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PMID: 

Food Funct. 2020 May 7. Epub 2020 May 7. PMID: 32377661

Abstract Title: 

Pterostilbene prevents LPS-induced early pulmonary fibrosis by suppressing oxidative stress, inflammation and apoptosis in vivo.

Abstract: 

Early pulmonary fibrosis after acute lung injury leads to poor prognosis and high mortality. Pterostilbene (Pts), a bioactive component in blueberries, possesses anti-inflammatory, antioxidative and antifibrotic properties. However, the effects of Pts on lipopolysaccharide (LPS)-induced pulmonary fibrosis are still unknown. In our study, the Pts group showed lower lung injury and fibrosis scores, and lower levels of hydroxyproline and protein (collagen I and transforming growth factor-β) than the scores and levels in mice treated with LPS. MMP-1 was the degrading enzyme of collagen I and LPS caused the inhibition of MMP-1, disturbing the degradation of collagen. Additionally, Pts remarkably reversed the LPS-induced inhibition of interleukin-10 and the release of tumor necrosis factor-α, interleukin-6 and interleukin-1β. In terms of cellular pathways, Pts treatment ameliorated LPS-activated nuclear factor kappa B (NF-κB) and NOD-like receptor NLRP3 signaling. Besides, LPS-induced low levels of A20 could be activated by Pts. In addition, Pts treatment reversed the high levels of Caspase-3, poly ADP-ribose polymerase (PARP) and Bcl2-associated X protein (Bax) expression and the low levels of B cell lymphoma/lewkmia-2 (Bcl2) that had been induced by LPS. Moreover, oxidative stress is also involved in the pathogenesis of fibrosis. Our findings indicate that LPS injection triggered the production of myeloperoxidase (MPO) and malondialdehyde (MDA) and the depletion of superoxide dismutase (SOD) and glutathione (GSH), and that these effects were notably reversed by treatment with Pts. In addition, Pts induced the dissociation of Kelch-like epichlorohydrin-associatedprotein-1 (Keap-1) and NF-E2 related factor-2 (Nrf2) and the activation of downstream genes (heme oxygenase-1, NAD(P)H:quinine oxidoreductase, glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modifier). In conclusion, oxidative stress, apoptosis and inflammation are involved in early pulmonary fibrosis and Pts exerts a protective effect by activating Keap-1/Nrf2, inhibiting caspase-dependent A20/NF-κB and NLRP3 signaling pathways.

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PMID: 

Anticancer Agents Med Chem. 2020 Mar 10. Epub 2020 Mar 10. PMID: 32160854

Abstract Title: 

Realizing the Potential of Blueberry as Natural inhibitor of Metastasis and Powerful Apoptosis Inducer: Tapping the Treasure Trove for Effective Regulation of Cell Signaling Pathways.

Abstract: 

Blueberries belong to the genus Vaccinium of the family Ericaceae. Rapidly accumulating experimentally verified data is uncovering tremendous pharmacological properties of biologically active constituents of Blueberries against different diseases. Our rapidly evolving knowledge about multifaceted nature of cancer has opened new horizons to search for different strategies to target multiple effectors of oncogenic networks to effectively inhibit cancer onset and progression. Excitingly, Whole blueberry powder and various bioactive constituents (Pterostilbene, malvidin-3-galactoside) of Blueberries have been shown to efficiently inhibit metastasis in animal models. These results are encouraging and future studies must converge on identification of cell signaling pathways effectively modulated by Blueberries in different cancers. It seems exciting to note that researchers are focusing on metastasis inhibitory effects of Blueberry, however, to reap full benefits it is necessary to take a step back and critically re-interpret the mechanisms used by active components of Blueberry to inhibit or prevent metastasis. Overview of the existing scientific evidence revealed visible knowledge gaps and better understanding of the targets of Blueberry will be helpful in efficient and meaningful translation of laboratory findings to clinically effective therapeutics.

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PMID: 

Food Funct. 2020 Apr 1 ;11(4):3167-3179. Epub 2020 Mar 24. PMID: 32208477

Abstract Title: 

Fermented blueberry pomace ameliorates intestinal barrier function through the NF-κB-MLCK signaling pathway in high-fat diet mice.

Abstract: 

The barrier-improving functions of fermented blueberry pomace (FBP) and its potential mechanism were investigated in this study. Polyphenols and the approximate composition of FBP were evaluated according to the National Standard of the People's Republic of China and the UPLC-MS system. Male C57BL/6 mice were fed a control diet (CD) or a high-fat diet (HFD) with or without FBP supplementation. Oxidative stress, inflammation, histological morphology and the expression of functional proteins in the small intestine of mice were evaluated using the enzyme linked immunosorbent assay (ELISA), quantitative polymerase chain reaction (qPCR) and western blotting. The content of protein, fat, soluble dietary fiber, insoluble dietary fiber and carbohydrates (non-dietary fiber) was 114.5± 1.5 g kg, 5.0± 0.2 g kg, 48.0± 0.1 g kg, 360.3± 2.2 g kgand 423 g kg(by difference), respectively. Thirty-six polyphenols were identified in FBP. FBP improved the growth of mice and attenuated hepatic and intestinal oxidative stress. Intestinal inflammation was significantly reduced through the decrease of tumor necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) as well as an increase of interleukin-10 (IL-10). FBP supplementation significantly improved the intestinal morphology and barrier function, potentially by mediating the NF-κB-MLCK signaling pathway. The supplementation of FBP in HFD mice enhanced the intestinal barrier function. This suggested that polyphenol-rich by-products might provide a similar health effect in HFD individuals.

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PMID: 

Am J Physiol Endocrinol Metab. 2020 Mar 31. Epub 2020 Mar 31. PMID: 32228321

Abstract Title: 

Blueberry proanthocyanidins and anthocyanins improve metabolic health through a gut microbiota-dependent mechanism in diet-induced obese mice.

Abstract: 

Blueberry consumption can prevent obesity-linked metabolic diseases and it has been proposed that its polyphenol content may contribute to these effects. Polyphenols have been shown to favourably impact metabolic health, but the role of specific polyphenol classes, and whether the gut microbiota is linked to these effects remains unclear. We aimed to evaluate the impact of whole blueberry and blueberry polyphenols against the development of obesity and insulin resistance, and to determine the potential role of gut microbes in these effects by using fecal microbiota transplantation (FMT). Seventy C57BL/6 male mice were assigned to one of the following diets for 12 weeks: balanced diet (Chow), high-fat high-sucrose (HFHS) diet, or HFHS supplemented with whole blueberry powder (BB), anthocyanidin (ANT) or proanthocyanidin (PAC)-rich extracts. After 8 weeks, mice were housed in metabolic cages and an oral glucose tolerance test (oGTT) was performed. Sixty germ-free mice fed HFHS diet received FMT from one of the above groups bi-weekly for 8 weeks, followed by an oGTT. PAC-treated mice were leaner than HFHS controls although they had the same energy intake and were more physically active. This observation was reproduced in germ-free mice receiving FMT from PAC-treated mice. PAC and ANT-treated mice showed improved insulin responses during oGTT, and this finding was also reproduced in germ-free mice following FMT. These results show that blueberry PAC and ANT polyphenols can reduce diet-induced body weight and improve insulin sensitivity, and that at least part of these beneficial effects are explained by modulation of the gut microbiota.

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PMID: 

Phytomedicine. 2020 Apr ;69:153209. Epub 2020 Mar 18. PMID: 32240928

Abstract Title: 

Phytotherapy using blueberry leaf polyphenols to alleviate non-alcoholic fatty liver disease through improving mitochondrial function and oxidative defense.

Abstract: 

BACKGROUND: Since non-alcoholic fatty liver disease (NAFLD) pathogenesis is multi-factorial, pharmacotherapy with a specific target commonly exhibits limited efficacy. Phytotherapy, whose therapeutic efficacy is based on the combined action of several active compounds, offers new treatment opportunity for NAFLD. As a representative, many natural polyphenols could be utilized in phytotherapy for NAFLD.PURPOSE: In present work, we aimed to investigate the therapeutic effects and underlying mechanism of polyphenols in blueberry leaves (PBL) on NAFLD from a mitochondria-centric perspective since mitochondrial dysfunction could play a dominant role in NAFLD.METHODS: Identification and quantification of PBL were performed using liquid chromatography coupled with tandem mass spectrometry. The beneficial effects, especially improving mitochondrial function, and potential mechanism of PBL on NAFLD were studied by in vitro and in vivo study.RESULTS: Polyphenols were abundant in blueberry leaves making it advantaged in NAFLD phytotherapy. PBL effectively alleviated hepatic steatosis, oxidative stress and inflammation as indicated by both in vitro and in vivo study. Furthermore, PBL mediated improvement of mitochondrial dysfunction and antioxidant capability through activation of AMPK/PGC-1α/SIRT3 signaling axis.CONCLUSION: Considering that mitochondrial dysfunction takes precedence over hepatic steatosis and induces NAFLD development, we conclude that PBL improve mitochondrial dysfunction and oxidative defense, subsequently alleviate hepatic steatosis, oxidative stress and inflammation, and eventually alleviate NAFLD.

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PMID: 

J Food Sci. 2020 Apr 3. Epub 2020 Apr 3. PMID: 32243587

Abstract Title: 

The effect of Chinese wild blueberry fractions on the growth and membrane integrity of various foodborne pathogens.

Abstract: 

The objective of this study was to evaluate the antibacterial effect of Chinese wild blueberry extract and its fractions against Listeria monocytogenes, Staphylococcus aureus, Salmonella Enteritidis, and Vibrio parahaemolyticus. Chinese wild blueberry (Vaccinium uliginosum) crude extract (BBE) was obtained using methanol extraction, and sugars plus organic acids (F1), phenolics fraction (F2), and anthocyanins plus proanthocyanidins (F3) fractions were separated using C-18 Sep-Pak columns. The minimal inhibitory concentration and minimal bactericidal concentration of each fractional component were determined using a two-fold-serial dilution method. Nucleic acid leakage (OD) and protein release (Bradford protein assay) were determined by spectrophotometry, to evaluate the permeability of the cell membrane. F3 was found to exhibit the greatest antimicrobial activity against the four tested strains, followed by F2, F1, and BBE. V. parahaemolyticus was the most sensitive to the all fractions, followed by S. Enteritidis, L. monocytogenes, and S. aureus. Survival curve analysis showed that the number of bacteria decreased from six log colony-forming units (CFU) to less than 10 CFU after bacteria were treated with fractions for 12 hr, which demonstrated the bactericidal effect of blueberry fractions. Furthermore, when the pathogens were treated with fractions for 2 hr, the ODand ODvalues increased significantly (P

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PMID: 

Curr Dev Nutr. 2020 Apr ;4(4):nzaa030. Epub 2020 Mar 9. PMID: 32337475

Abstract Title: 

Effect of Blueberry Consumption on Cardiometabolic Health Parameters in Men with Type 2 Diabetes: An 8-Week, Double-Blind, Randomized, Placebo-Controlled Trial.

Abstract: 

Background: Blueberries are dietary sources of polyphenols, specifically anthocyanins. Anthocyanins have been identified as having a strong association with type 2 diabetes risk reduction; however, to date few human clinical trials have evaluated the potential beneficial health effects of blueberries in populations with type 2 diabetes.Objectives: We investigated the effects of blueberry consumption for 8 wk on cardiometabolic parameters in men with type 2 diabetes.Methods: In a double-blind, parallel-arm, randomized controlled trial, 52 men who are US veterans [mean baseline characteristics: age, 67 y (range: 51-75 y); weight, 102 kg (range: 80-130 kg); BMI (in kg/m), 34 (range: 26-45)] were randomly assigned to 1 of 2 intervention groups. The interventions were either 22 g freeze-dried blueberries or 22 g placebo. The study participants were asked to consume 11 g freeze-dried blueberries or placebo with each of their morning and evening meals along with their typical diet.Results: Mean ± SE hemoglobin A1c (7.1% ± 0.1% compared with 7.5% ± 0.2%; = 0.03), fructosamine (275.5 ± 4.1 compared with 292.4 ± 7.9 µmol/L; = 0.04), triglycerides (179.6 ± 10.1 compared with 199.6 ± 19.9 mg/dL; = 0.03), aspartate transaminase (23.2 ± 1.4 compared with 30.5 ± 2.7 units/L;= 0.02), and alanine transaminase (35.6 ± 1.5 compared with 48.3 ± 2.9 units/L; = 0.0003) were significantly lower for those consuming blueberries for 8 wk than for those consuming the placebo. Fasting plasma glucose concentrations; serum insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, and C-reactive protein concentrations; blood pressure; and body weight werenot significantly different after 8 wk consumption of blueberries compared with the placebo.Conclusions: Consumption of 22 g freeze-dried blueberries for 8 wk may beneficially affect cardiometabolic health parameters in men with type 2 diabetes.This trial was registered at clinicaltrials.gov as NCT02972996.

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PMID: 

Nutrients. 2020 May 1 ;12(5). Epub 2020 May 1. PMID: 32369959

Abstract Title: 

Blueberry Prevents the Bladder Dysfunction in Bladder Outlet Obstruction Rats by Attenuating Oxidative Stress and Suppressing Bladder Remodeling.

Abstract: 

Various berries demonstrate antioxidant activity, and this effect is expected to prevent chronic diseases. We examined whether a diet containing blueberry powder could prevent the development of bladder dysfunction secondary to bladder outlet obstruction (BOO). Eighteen 8-week-old male Sprague-Dawley rats were randomly divided into three groups: Sham (sham operated + normal diet), N-BOO (BOO operated + normal diet) and B-BOO (BOO operated + blueberry diet). Four weeks after BOO surgery, the N-BOO group developed bladder dysfunction with detrusor overactivity. The B-BOO group showed significantly improved micturition volume and micturition interval. The urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were measured as oxidative stress markers. In the N-BOO group, 8-OHdG increased 1.6-fold and MDA increased 1.3-fold at 4 weeks after surgery, whereas the increase in 8-OHdG was significantly reduced by 1.1-fold, despite a similar increase in MDA, in the B-BOO group. Bladder remodeling was confirmed due to bladder hypertrophy, fibrosis and increased connexin43 expression in the N-BOO group, but these histological changes were reduced in the B-BOO group. The intake of blueberries prevented the development of bladder dysfunction secondary to BOO. This effect seems to be related to antioxidation and the inhibition of bladder remodeling.

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