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Synergistic Interaction in the Analgesic-Like Effects of Maqui Berry and Citrus Is Antagonized by Sweeteners.

ABSTRACT: Although physiologically pain has a protective function, in many diseases, it is one of the most prominent symptoms. Today, new trends are focused on finding more natural alternatives to conventional treatments to alleviate it. Thereby, the purpose of this investigation was to obtain preclinical data of the antinociceptive properties of a lyophilized obtained from a newly designed maqui-citrus beverage alone and added with different sweeteners. To achieve this objective, maqui berry and citrus pharmacological activity were studied separately, as well as the interaction of both ingredients. In addition, due to the controversy generated regarding the intake of sugars, related to different metabolic diseases, the influence of different sweeteners (stevia, sucralose, or sucrose) was studied to determine their possible influence on the bioactive compounds of this product. For the attainment of our goals, a pharmacological evaluation, using the 1% formalin test, a nociceptive pain model in mice, was performed by using a sub-efficacious dosage of Maqui (25 mg/kg, i.p.) alone and combined with citrus, and then compared with the effects obtained in the presence of the different sweeteners. As a result, the antinociceptive response of the maqui was synergized in the presence of citrus in the neurogenic and inflammatory phases of the formalin test. However, this response was partially or totally reduced in the presence of the sweeteners. Our study gives preclinical evidence that a combination of maqui and citrus might exert beneficial actions to relieve pain, whereas the presence of sweeteners could reduce or avoid it.

SUBMITTER: Agullo V

PROVIDER: S-EPMC8308574 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Alternative Sweeteners Modify the Urinary Excretion of Flavanones Metabolites Ingested through a New Maqui-Berry Beverage.

Project description:Dietary sugar has been largely related to the onset of metabolic diseases such as type 2 diabetes and obesity, among others. The growing awareness on the close relationship between the dietary habits and this health disturbance has encouraged the development of new beverages using alternative sweeteners that could contribute to combat the above referred pathophysiological disorders. To gain further insight into this issue, the present work, upon an acute dietary intervention, evaluated the urinary excretion of flavanones ingested through polyphenols-rich beverages composed of maqui berry and citrus, with the aim of establishing the highest urinary excretion rate and metabolite profiles. The functional beverages evaluated were supplemented with a range of sweeteners including sucrose (natural and high caloric), stevia (natural and non-caloric), and sucralose (artificial and non-caloric) as an approach that would allow reducing the intake of sugars and provide bioactive phenolics (flavanones). The juices developed were ingested by volunteers (n = 20) and the resulting flavanones and their phase II metabolites in urine were analyzed by Ultra-High Performance Liquid Chromatography ElectroSpray Ionization Mass Spectrometry (UHPLC-ESI-MS/MS). A total of 16 metabolites were detected: eriodyctiol, naringenin, and homoeriodyctiol derivatives, where peak concentrations were attained 3.5 h after beverage intake. Sucralose and stevia were the sweeteners that provided the highest urinary excretion for most compounds. Sucrose did not provide a remarkable higher elimination through urine of any compounds in comparison with sucralose or stevia. These results propose two alternative sweeteners to sucrose (sucralose and stevia), an overused, high caloric sweetener that promotes some metabolic diseases.

| S-EPMC7022940 | biostudies-literature

Bioavailability Study of Maqui Berry Extract in Healthy Subjects.

Project description:Several health promoting effects have been reported for maqui berry, rich in anthocyanins. Direct effects of anthocyanins as well as bioactive metabolites might be involved. Within the study, bioavailability of a proprietary standardized maqui berry extract Delphinol® was investigated based on two selected anthocyanins (delphinidin-3-O-glucoside (DS) + cyanidin-3-O-sambubioside (CS)) and two breakdown products (protocatechuic acid (PCA) + gallic acid (GA)) after a single-dose supplementation in humans. Pharmacokinetic parameters were calculated from individual concentration time curves. In all 12 subjects a significant increase was noted in plasma values of DG and CS after intake of maqui berry extract. Maximum concentration of DG was observed after 1.0 ± 0.3 h and CS after 2.0 ± 1.1 h. Within 8 h, concentrations nearly returned to baseline levels. The results confirm a fast uptake and metabolism of the two selected key substances. Additionally, the phenolic acids GA and PCA were observed as breakdown products of anthocyanins. In summary, the study clearly confirms the bioavailability of maqui berry extract and its specific anthocyanin compounds and related breakdown products in healthy subjects.

| S-EPMC6267473 | biostudies-literature

Beverages Based on Second Quality Citrus Fruits and Maqui Berry, a Source of Bioactive (Poly)phenols: Sorting Out Urine Metabolites upon a Longitudinal Study.

Project description:The intake of sugar-sweetened beverages has been associated with an augmented prevalence of metabolic diseases, namely, obesity, type II diabetes, and metabolic syndrome. On the other hand, nowadays, it is broadly accepted that foods and beverages rich in (poly)phenols could contribute to reducing the incidence of these pathologies. In this sense, the objective of the work was to revalue second quality citrus fruits for the development of new beverages, rich in anthocyanins and flavanones (maqui berry and second qualities citrus-based), and evaluate the influence of alternative sweeteners (sucralose, sucrose, or stevia), regarding the bioaccessibility and bioavailability of these bioactive compounds in the frame of a chronic (longitudinal) intervention. To fulfill this objective, a longitudinal study of the urinary excretion of anthocyanins and flavanones, after 2-months of ingestion of the developed maqui-citrus beverage, by 138 volunteers (n = 46 per beverage) and the analysis of the resulting phenolic metabolites by ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-ESI-QqQ-MS/MS) was carried out. As major results, the bioavailable metabolites of caffeic acid (CA), catechol (CAT), 3,4-di-hydroxyphenylacetic acid (DHPAA), eriodictyol (E), homoeriodictyol (HE), hippuric acid (HA), naringenin (N), trans-ferulic acid (TFA), 2,4,6-tri-hydroxybenzaldehyde (THBA), trans-isoferulic acid (TIFA), and vanillic acid (VA) were detected. Accordingly, significantly different bioavailability was dependent on the sweetener used, allowing proposing stevia and, to a lower extent, sucralose, as valuable alternatives to sucrose.

| S-EPMC7910882 | biostudies-literature

Maqui berry extract prevents cigarette smoke induced oxidative stress in human osteoblasts <i>in vitro</i>.

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| S-EPMC7898044 | biostudies-literature

Physicochemical characteristics of citrus jelly with non cariogenic and functional sweeteners.

Project description:In this study the effect of sweeteners with low glycemic index and non-cariogenic characteristics (isomaltulose, oligofructose and tagatose) in jelly prepared with citrus juice has been evaluated considering a citrus jelly formulated with sucrose as reference. The soluble solids, moisture content, pH, water activity, antioxidant capacity, optical and mechanical properties of jelly made using different sweeteners was determined during storage. Besides, mesophilic aerobics and moulds and yeasts was also counted to determine their stability over time. Sensory evaluation of the citrus jelly has also been done. The results showed the antioxidant activity decreased during storage in all formulations. Tagatose increased lightness whereas coordinates a*, b* and chrome of all the jellies prepared using new sweeteners were lower than jellies with sucrose. However, citrus jelly with only oligofructose or tagatose or with the mixture of isomaltulose and tagatose were most closely resembled to the control jelly with respect to mechanical properties. Jelly prepared with the combination of isomaltulose and tagatose in equal proportions obtained the best score in the sensorial analysis.

| S-EPMC5147687 | biostudies-literature

Synergistic Antioxidant and Anti-Inflammatory Effects between Modified Citrus Pectin and Honokiol.

Project description:Inflammation is a normal physiological process; however, dysregulation of this process may contribute to inflammatory-based chronic disorders and diseases in animals and humans. Therefore, the antioxidant and anti-inflammatory properties of natural products, often recognized in traditional medicine systems, represent therapeutic modalities to reduce or prevent uncontrolled inflammatory processes which in turn potentially ameliorate or prevent sequelae of inflammatory-based symptoms of chronic diseases. We have investigated the antioxidant and anti-inflammatory effects of honokiol (HNK) and modified citrus pectin (MCP) in vitro and examined whether the MCP?:?HNK combination has synergistic effects on antioxidant and anti-inflammatory properties. Although both HNK and MCP induced a dose-dependent increase in antioxidant activity, the latter has a consistently higher antioxidant effect. The MCP?:?HNK (9?:?1) combination induced a synergistic effect on antioxidant activity suggesting that the combination is significantly more efficacious than individual compounds. In mouse monocytes, the lipopolysaccharide- (LPS-) induced tumor necrosis-? (TNF-?) synthesis was significantly inhibited by HNK and the MCP?:?HNK combination in a dose-dependent manner and synergistic effects were clearly demonstrated with the combination on TNF-? inhibition. This combination effect was also evident on inhibition of nuclear factor-kappa B activity, cyclooxygenase-II activity, and lipid peroxidation in mouse monocytes. Further research into the combination is warranted.

| S-EPMC5576403 | biostudies-literature

A Delphinidin-Enriched Maqui Berry Extract Improves Bone Metabolism and Protects against Bone Loss in Osteopenic Mouse Models.

Project description:In our previous investigation, delphinidin, one of the most abundant anthocyanins found in vegetables and berry fruits, had been shown to inhibit osteoclasts and prevent bone loss in mouse models of osteoporosis. In the present study, we investigated whether a delphinidin glycoside-enriched maqui berry extract (MBE, Delphinol®) exhibits beneficial effects on bone metabolism both in vitro and in vivo. MBE stimulated the osteoblastic differentiation of MC3T3-E1 cells, as indicated by enhanced mineralized nodule formation, and increased alkaline phosphatase activity, through the upregulation of bone morphogenetic protein 2 (Bmp2), runt-related transcription factor 2 (Runx2), Osterix (Osx), osteocalcin (Ocn), and matrix extracellular phosphoglycoprotein (Mepe) mRNA expression. Immunostaining and immunoprecipitation assays demonstrated that MBE suppressed NF-?B transnucleation through acting as a superoxide anion/peroxynitrite scavenger in MC3T3-E1 cells. Simultaneously, MBE inhibited both osteoclastogenesis in primary bone marrow macrophages and pit formation by maturated osteoclasts on dentine slices. Microcomputed tomography (micro-CT) and bone histomorphometry analyses of femurs demonstrated that the daily ingestion of MBE significantly increased BV/TV (ratio of bone volume to tissue volume), Tb.Th (trabecular thickness), Tb.N (trabecular number), N.Nd/N.Tm (node to terminus ratio), OV/TV (ratio of osteoid volume to tissue volume), BFR/TV (bone formation rate per tissue volume), and significantly decreased Tb.Sp (trabecular separation), ES/BS (ratio of eroded surface to bone surface) and N.Oc/BS (number of osteoclast per unit of bone surface, compared to vehicle controls in osteopenic mouse models. These findings suggest that MBE can be a promising natural agent for the prevention of bone loss in osteopenic conditions by not only inhibiting bone resorption, but also stimulating bone formation.

| S-EPMC6769591 | biostudies-literature

Stevia vs. Sucrose: Influence on the Phytochemical Content of a Citrus-Maqui Beverage-A Shelf Life Study.

Project description:The consumption of sugar-sweetened beverages has been related with the risk of cardiovascular diseases and other pathophysiological situations, such as obesity or diabetes mellitus. Given the increasing awareness on this fact, food industries are developing new products to reduce the amount of added sugar in development of food products development. Accordingly, in the present work, new functional beverages, constituting a dietary source of bioactive phenolics and supplemented with stevia or sucrose, were designed in order to study the influence of the sweetener during processing and shelf-life. This study is of critical for the informed selection of the sweetener based on its effect on the final phytochemical profile of beverages, especially taking into consideration that there are no previous studies on Stevia rebaudiana. Physicochemical features and phytochemical composition, as well as stability of the different beverages concerning these parameters, were evaluated for 90 days during storage under different conditions (refrigeration (4 °C) and room temperature (25 °C) under light or darkness conditions). Physicochemical parameters (pH, titratable acidity, total soluble solids, and color) did not display statistically significant differences between beverages. Storage temperature was the greatest determinant affecting the stability of all the analyzed bioactive compounds (vitamin C, anthocyanins, and flavanones). The main difference between sweeteners was observed in flavanones, which exhibited a higher loss during storage under day light conditions when stevia was added instead of sucrose. In addition, the juices' colors were rather stable, keeping a reddish coloration and natural appearance throughout the shelf life. Hence, stevia could be considered as an alternative sweetener by the beverage industry.

| S-EPMC7073640 | biostudies-literature

Lyophilized Maqui (Aristotelia chilensis) Berry Administration Suppresses High-Fat Diet-Induced Liver Lipogenesis through the Induction of the Nuclear Corepressor SMILE.

Project description:The liver is one of the first organs affected by accumulated ectopic lipids. Increased de novo lipogenesis and excessive triglyceride accumulation in the liver are hallmarks of nonalcoholic fatty liver disease (NAFLD) and are strongly associated with obesity, insulin resistance, and type 2 diabetes. Maqui dietary supplemented diet-induced obese mice showed better insulin response and decreased weight gain. We previously described that these positive effects of maqui are partially due to an induction of a brown-like phenotype in subcutaneous white adipose tissue that correlated with a differential expression of Chrebp target genes. In this work, we aimed to deepen the molecular mechanisms underlying the impact of maqui on the onset and development of the obese phenotype and insulin resistance focusing on liver metabolism. Our results showed that maqui supplementation decreased hepatic steatosis caused by a high-fat diet. Changes in the metabolic profile include a downregulation of the lipogenic liver X receptor (LXR) target genes and of fatty acid oxidation gene expression together with an increase in the expression of small heterodimer partner interacting leucine zipper protein (Smile), a corepressor of the nuclear receptor family. Our data suggest that maqui supplementation regulates lipid handling in liver to counteract the metabolic impact of a high-fat diet.

| S-EPMC8143281 | biostudies-literature

Berry and Citrus Phenolic Compounds Inhibit Dipeptidyl Peptidase IV: Implications in Diabetes Management.

Project description: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? ? 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? ? M), apigenin (0.14?±?0.02? ? M), and flavone (0.17?±?0.01? ? M), with IC50 values lower than diprotin A (4.21?±?2.01? ? 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.

| S-EPMC3773436 | biostudies-literature

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