PMID: 

Nutr Neurosci. 2019 Oct 4:1-10. Epub 2019 Oct 4. PMID: 31583972

Abstract Title: 

Anti-neuroinflammatory effects of a food-grade phenolic-enriched maple syrup extract in a mouse model of Alzheimer's disease.

Abstract: 

Alzheimer's disease (AD) is a growing global health crisis exacerbated by increasing life span and an aging demographic. Convergent lines of evidence, including genome-wide association studies, strongly implicate neuroinflammation in the pathogenesis of AD. Several dietary agents, including phenolic-rich foods, show promise for the prevention and/or management of AD, which in large part, has been attributed to their anti-inflammatory effects. We previously reported that a food-grade phenolic-enriched maple syrup extract (MSX) inhibited neuroinflammationbut whether these effects are translatableremain unknown. Herein, we assessed MSX's ability to attenuate early neuroinflammation in a transgenic mouse model of AD.The effects of MSX on AD-related neuroinflammation was evaluated by orally administering MSX (100 and 200 mg/kg/day for 30 days) to the 3xTg-AD mouse model of AD. The expression of inflammatory markers in mouse brains were analyzed with LC-MS/MS with SWATH acquisition.3xTg-AD mice dosed orally with MSX have decreased expression of several inflammatory proteins, including, most notably, the AD risk-associated protein 'triggering receptor expressed on myeloid cells-2' (TREM2), and stimulator of interferon genes TMEM173, and suppressor of cytokine signaling-6 (SOCS6). However, this decrease in inflammation did not coincide with a decrease in pathogenic amyloid generation or lipid peroxidation.These data demonstrate that oral administration of this maple syrup derived natural product reduces key neuroinflammatory indices of AD in the 3xTg-AD model of AD. Therefore, further studies to investigate MSX's potential as a dietary intervention strategy for AD prevention and/or management are warranted.

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PMID: 

Neurobiol Dis. 2019 Dec 11:104704. Epub 2019 Dec 11. PMID: 31837420

Abstract Title: 

Implications of gut microbiota dysbiosis and metabolic changes in prion disease.

Abstract: 

Evidence of the gut microbiota influencing neurodegenerative diseases has been reported for several neural diseases. However, there is little insight regarding the relationship between the gut microbiota and prion disease. Here, using fecal samples of 12 prion-infected mice and 25 healthy controls, we analyzed the structure of the gut microbiota and metabolic changes by 16S rRNA sequencing and LC-MS-based metabolomics respectively as multi-omic analyses. Additionally, SCFAs and common amino acids were detected by GC-MS and UPLC respectively. Enteric changes induced by prion disease affected both structure and abundances of the gut microbiota. The gut microbiota of infected mice displayed greater numbers of Proteobacteria and less Saccharibacteria at the phylum level and more Lactobacillaceae and Helicobacteraceae and less Prevotellaceae and Ruminococcaceae at the family level. A total of 145 fecal metabolites were found to be significantly different in prion infection, and most (114) of these were lipid metabolites. Using KEGG pathway enrichment analysis, we found that 3 phosphatidylcholine (PC) compounds significantly decreased and 4 hydrophobic bile acids significantly increased. Decreases of 8 types of short-chain acids (SCFAs) and increases of Cys and Tyr and decreases of His, Trp, and Arg were observed in prion infection. Correlation analysis indicated that the gut microbiota changes observed in our study may have been the shared outcome of prion disease. These findings suggest that prion disease can cause significant shifts in the gut microbiota. Certain bacterial taxa can then respond to the resulting change to the enteric environment by causing dramatic shifts in metabolite levels. Our data highlight the health impact of the gut microbiota and related metabolites in prion disease.

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PMID: 

Brain Res. 2019 Nov 26:146567. Epub 2019 Nov 26. PMID: 31783002

Abstract Title: 

Choline attenuates inflammatory hyperalgesia activating nitric oxide/cGMP/ATP-sensitive potassium channels pathway.

Abstract: 

New findings on neural regulation of immunity are allowing the design of novel pharmacological strategies to control inflammation and nociception. Herein, we report that choline, a 7-nicotinic acetylcholine receptor (α7nAChRs) agonist, prevents carrageenan-induced hyperalgesia without affecting inflammatory parameters (neutrophil migration or cytokine/chemokines production) or inducing sedation or even motor impairment. Choline also attenuates prostaglandin-E(PGE)-induced hyperalgesia viaα7nAChR activation and this antinociceptive effect was abrogated by administration of LNMMA (a nitric oxide synthase inhibitor), ODQ (an inhibitor of soluble guanylate cyclase; cGMP), andglibenclamide(an inhibitor of ATP-sensitive potassium channels). Furthermore, choline attenuates long-lasting Complete Freund's Adjuvant and incision-induced hyperalgesia suggesting its therapeutic potential to treat pain in rheumatoid arthritis or post-operative recovery, respectively. Our results suggest that choline modulates inflammatory hyperalgesia by activating the nitric oxide/cGMP/ATP-sensitive potassium channels without interfering in inflammatory events, and could be used in persistent pain conditions.

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PMID: 

Orthop J Sports Med. 2019 Oct ;7(10):2325967119879124. Epub 2019 Oct 25. PMID: 31696136

Abstract Title: 

Effect of Germanium-Embedded Knee Sleeve on Osteoarthritis of the Knee.

Abstract: 

Background: Knee osteoarthritis (OA) affects an estimated 1 in 5 individuals older than 45 years of age in the United Kingdom. Previous studies have suggested that germanium-infused garments may provide improved clinical outcomes in OA. Germanium-embedded (GE) knee sleeves embrace this fabric technology.Purpose: To assess the outcomes of GE knee sleeves for patients with knee OA.Study Design: Cohort study; Level of evidence, 2.Methods: This study was undertaken at a hospital in the United Kingdom. Patients who had radiographic features of OA, experienced knee pain for at least 6 months, and opted for nonsurgical intervention were included. Patients were recruited over 3 months. The University of California, Los Angeles activity score, Lysholm score, visual analog scale (VAS) score, and Oxford Knee Score (OKS) were collected at monthly intervals for 6 months. Patients were followed to determine their compliance with wearing the knee sleeves at all times, as advised, and whether any adverse effects had occurred.Results: A total of 50 participants were recruited for the study; 4 participants were excluded due to pain and were converted to surgical management. Therefore, 46 patients were analyzed and placed into 2 groups according to severity of OA, as classified by the Kellgren-Lawrence system: group A had grade 1 or 2 OA, and group B had grade 3 or 4 OA. There were 25 patients in group A and 21 in group B. Improvements were seen in OKS, VAS, and Lysholm scores in both groups. Clinically significant improvements were seen in group A only for OKS (mean increase, 14), VAS (mean decrease, 4.1), and Lysholm (mean increase, 17.2) scores. These results were also statistically significant (OKS,= 5.8× 10; VAS,= 7.7× 10; Lysholm,= 4.2× 10). The data from this study demonstrated that GE knee sleeves gave better outcomes for patients with grades 1 and 2 OA compared with patients with more advanced disease, which is consistent with previous studies. A total of 3 patients reported skin irritation, which resolved with simple skin ointment application. No patients reported infection, deep vein thrombosis, or circulation problems.Conclusion: GE knee sleeves could play an important role in optimizing nonsurgical management of patients with knee OA, especially patients with grades 1 and 2 OA, as demonstrated by the clinically significant improvements.

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PMID: 

Nutrients. 2019 Dec 6 ;11(12). Epub 2019 Dec 6. PMID: 31817768

Abstract Title: 

Neuroprotective Effects of Choline and Other Methyl Donors.

Abstract: 

Recent evidence suggests that physical and mental health are influenced by an intricate interaction between genes and environment. Environmental factors have been shown to modulate neuronal gene expression and function by epigenetic mechanisms. Exposure to these factors including nutrients during sensitive periods of life could program brain development and have long-lasting effects on mental health. Studies have shown that early nutritional intervention that includes methyl-donors improves cognitive functions throughout life. Choline is a micronutrient and a methyl donor that is required for normal brain growth and development. It plays a pivotal role in maintaining structural and functional integrity of cellular membranes. It also regulates cholinergic signaling in the brain via the synthesis of acetylcholine. Via its metabolites, it participates in pathways that regulate methylation of genes related to memory and cognitive functions at different stages of development. Choline-related functions have been dysregulated in some neurodegenerative diseases suggesting choline role in influencing mental health across the lifespan.

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PMID: 

Int J Mol Sci. 2019 Oct 11 ;20(20). Epub 2019 Oct 11. PMID: 31614552

Abstract Title: 

Identification of a Novel Oligosaccharide in Maple Syrup as a Potential Alternative Saccharide for Diabetes Mellitus Patients.

Abstract: 

The incidence of diabetes mellitus (DM) is increasing rapidly and is associated with changes in dietary habits. Although restrictions in the use of sweeteners may prevent the development of DM, this might reduce the quality of life of patients with DM. Therefore, there has been a great deal of research into alternative sweeteners. In the search for such sweeteners, we analyzed the carbohydrate content of maple syrup and identified a novel oligosaccharide composed of fructose and glucose, linked at the C-4 of glucose and the C-6 of fructose. This oligosaccharide inhibited the release of fructose from sucrose by invertase (IC: 1.17 mmol/L) and the decomposition of maltose byα-(1-4) glucosidase (IC: 1.72 mmol/L). In addition, when orally administered together with sucrose to rats with DM, the subsequent plasma glucose concentrations were significantly lower than if the rats had been administered sucrose alone, without having any effect on the insulin concentration. These findings suggest that this novel oligosaccharide might represent a useful alternative sweetener for inclusion in the diet of patients with DM and may also have therapeutic benefits.

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PMID: 

Nutr Metab (Lond). 2019 ;16:84. Epub 2019 Dec 4. PMID: 31827572

Abstract Title: 

A maple syrup extract alters lipid metabolism in obese type 2 diabetic model mice.

Abstract: 

Background: Some polyphenols are known to improve the symptoms of diabetes. In the present study, we investigated the effects of a polyphenol-rich extract of maple syrup (MSx) on a diabetic mouse model.Methods: KK-mice were fed a normal or 0.05% MSx-supplemented diet for 42 days. Body weight, food intake, serum biochemical parameters, and fecal total bile acid were measured. Gene expression of liver and epididymal white adipose tissue (WAT) and cecal microbiota were analyzed. Data were analyzed with an unpaired two-tailed Student'stest or Welch'stest according to the results of thetest.Results: Serum low-density lipoprotein cholesterol levels were significantly reduced in mice that consumed MSx. Hepatic genes related to fatty acid degradation and cholesterol catabolism were upregulated in mice that consumed MSx. In contrast, the expression of genes related to lipid metabolism in WAT was unaffected by the intake of MSx. There were no significant differences between the two groups in terms of total bile acid level in the feces and the relative abundance of bacteria in the cecum.Conclusion: Our results primarily indicate that MSx can help alleviate one of the symptoms of dyslipidemia.

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PMID: 

Mol Nutr Food Res. 2019 Dec 14:e1901017. Epub 2019 Dec 14. PMID: 31837654

Abstract Title: 

Neuroprotective Effects of apple-derived Drinks in a Mice Model of Inflammation.

Abstract: 

SCOPE: Fruit-derived drinks consumption is considered beneficial due to the antioxidant and neuroprotective effects of polyphenols separately, but studies including their total constituents are scarce. In this work, we determined the antioxidant and anti-inflammatory neuroprotective effects of apple-derived beverages in a mouse model of LPS-induced inflammation.METHODS AND RESULTS: Preliminary antioxidant and neuroinflammatory experiments were carried out with fifteen drink polyphenolic extracts in SH-SY5Y and BV2 cells, using HOas pro-oxidant and LPS as pro-inflammatory stimulus, respectively. Extracts improved antioxidant systems functioning and presented neuroprotective mitochondrial-related effects. In microglia, extracts reduced reactive oxygen species and modulated cytokine release. To better mimic human consumption, four concentrated dealcoholized apple-derived drinks (three ciders and apple juice) were supplied to mice for seven days in substitution of drinking water. Mice treated with beverages presented reduced brain oxidative stress and inflammatory markers (lipid peroxidation, NO, iNOS, TNF-α) after LPS injection. Interestingly, genetic expression of antioxidant enzymes and glutathione levels were also greatly augmented after drink intake.CONCLUSION: Our results confirm the antioxidant and anti-inflammatory-mediated neuroprotective properties of apple-derived drinks, suggesting that their consumption could be a good approach for prevention of neurodegenerative disorders. To our knowledge, this is the first description of cider neuroprotective effects. This article is protected by copyright. All rights reserved.

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PMID: 

J Agric Food Chem. 2019 Dec 12. Epub 2019 Dec 12. PMID: 31829012

Abstract Title: 

Beneficial Effects of Dietary Polyphenols on High-Fat Diet-Induced Obesity Linking with Modulation of Gut Microbiota.

Abstract: 

Obesity is caused by an imbalance of energy intake and expenditure. It is characterized by a higher accumulation of body fat with a chronic low-grade inflammation. Many reports have shown that gut microbiota in host plays a pivotal role in mediating the interaction between consumption of high-fat diet (HFD) and onset of obesity. Accumulative evidence has suggested that the change in the composition of gut microbiota may affect host's energy homeostasis, systemic inflammation, lipid metabolism, and insulin sensitivity. As one of the major components in human diet, polyphenols have demonstrated to be capable of modulating the composition of gut microbiota and reducing the HFD-induced obesity. The present review summarizes the findings of recent studies on dietary polyphenols regarding their metabolism and interaction with bacteria in the intestine as well as the underlying mechanisms by which they modulate the gut microbiota and alleviate the HFD-induced obesity.

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PMID: 

Nutrients. 2019 Dec 7 ;11(12). Epub 2019 Dec 7. PMID: 31817909

Abstract Title: 

High Oleic Acid Peanut Oil and Extra Virgin Olive Oil Supplementation Attenuate Metabolic Syndrome in Rats by Modulating the Gut Microbiota.

Abstract: 

Unhealthy dietary patterns are important risk factors for metabolic syndrome (MS), which is associated with gut microbiota disorder. High oleic acid peanut oil (HOPO) and extra virgin olive oil (EVOO), considered as healthy dietary oil, are rich in oleic acid and bioactive phytochemicals, yet efficacy of MS prevention and mechanisms linking to gut microbiota remain obscure. Herein, we investigated HOPO and EVOO supplementation in attenuating diet-induced MS, and the potential mechanisms focusing on modulation of gut microbiota. Physiological, histological and biochemical parameters and gut microbiota profiles were compared among four groups fed respectively with the following diets for 12 weeks: normal chow diet with ordinary drinking water, high-fat diet with fructose drinking water, HOPO diet with fructose drinking water, and EVOO diet with fructose drinking water. HOPO or EVOO supplementation exhibit significant lower body weight gain, homeostasis model assessment-insulin resistance (HOMA-IR), and reduced liver steatosis. HOPO significantly reduced cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) level, while EVOO reduced these levels without significant difference. HOPO and EVOO prevented gut disorder and significantly increased-diversity and abundance of. Moreover, HOPO significantly decreased abundance ofand. These findings suggest that both HOPO and EVOO can attenuate diet-induced MS, associated with modulating gut microbiota.

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