The Cardiometabolic Impact of Rebaudioside A Exposure during the Reproductive Stage.

The consumption of non-sugar sweeteners (NSS) has increased during pregnancy. The European Food Safety Agency suggested that steviol glycosides, such as Rebaudioside A (RebA), the major sweetener component of stevia, are safe for humans up to a dose of 4 mg/kg body weight/day. However, the World Health Organization recommended in 2023 the restraint of using NSS, including stevia, at any life stage, highlighting the need to study NSS safety in early periods of development. We aimed to study the mitochondrial and cardiometabolic effects of long-term RebA consumption during the reproductive stage of the life cycle. Female rats were exposed to RebA (4 mg steviol equivalents/kg body weight/day) in the drinking water from 4 weeks before mating until weaning. Morphometry, food and water consumption, glucose and lipid homeostasis, heart structure, function, and mitochondrial function were assessed. RebA showed an atrophic effect in the heart, decreasing cardiomyocyte cross-sectional area and myocardial fibrosis without repercussions on cardiac function. Mitochondrial and myofilamentary functions were not altered. Glucose tolerance and insulin sensitivity were not affected, but fasting glycemia and total plasma cholesterol decreased. This work suggests that this RebA dose is safe for female consumption during the reproductive stage, from a cardiometabolic perspective. However, studies on the effects of RebA exposure on the offspring are mandatory.

A 3D printed hydrogel to promote human keratinocytes' spheroid-based growth.

Tissue engineering uses cells and biomaterials to develop bioartificial tissue substitutes for different purposes. For example, although several skin models have been developed for pharmaceutical and cosmetic research and skin wound healing, there are few studies on 3D cultures of keratinocytes in 3D printed scaffolds. So, this work aimed to develop a 3D-printed hydrogel scaffold to promote human keratinocyte growth. Mesh 3D scaffolds were printed using an extrusion-based method with a 20% gelatin/5% alginate hydrogel, where HaCaT cells were cultured for 7 days. Scaffolds kept their structure for over 1 week, and their stiffness only decreased after 7 days, showing good mechanical and structural characteristics and biodegradability (27% weight lost). Viable keratinocytes (MTT assay) are aggregated into spheroids, a 3D model capable of mimicking in vivo cell properties and phenotypes. Spheroids were formed on 47% of scaffolds pores and grew over time, showing promising cell proliferation. F-actin staining showed cells' irregular and interconnected shapes and organization over time. This method offers an easy and inexpensive solution for keratinocyte spheroid formation, which may be helpful in tissue engineering as a cell delivery system, for pharmacological or basic research, or wound healing medical applications.

Effects of chronic moderate alcohol consumption on right ventricle and pulmonary remodelling.

NEW FINDINGS: What is the central question of this study? Does the consumption of a moderate amount of alcohol differentially impact the heart ventricles and pulmonary vasculature. What is the main finding and its importance? Moderate alcohol consumption for a short period of time impaired pulmonary vascular cellular renewal through an apoptosis resistance pattern that ultimately affected the right ventricular function and structure. These findings support the need for a deeper understanding of effects of moderate alcohol consumption on the overall cardiovascular and pulmonary systems. ABSTRACT: Over the past decades, observational studies have supported an association between moderate alcohol consumption and a lower risk of cardiovascular disease and mortality. However, recent and more robust meta-analyses have raised concerns around the robustness of the evidence for the cardioprotective effects of alcohol. Also, studies of the functional, structural and molecular changes promoted by alcohol have focused primarily on the left ventricle, ignoring the fact that the right ventricle could adapt differently. The aim of this study was to evaluate the bi-ventricular impact of daily moderate alcohol intake, during a 4-week period, in a rodent model. Male Wistar rats were allowed to drink water (Control) or a 5.2% ethanol mixture (ETOH) for 4 weeks. At the end of the protocol bi-ventricular haemodynamic recordings were performed and samples collected for further histological and molecular analysis. ETOH ingestion did not impact cardiac function. However, it caused right ventricle hypertrophy, paralleled by an activation of molecular pathways responsible for cell growth (ERK1/2, AKT), proteolysis (MURF-1) and oxidative stress (NOX4, SOD2). Furthermore, ETOH animals also presented remodelling of the pulmonary vasculature with an increase in pulmonary arteries' medial thickness, which was characterized by increased expression of apoptosis-related proteins expression (BCL-XL, BAX and caspases). Moderate alcohol consumption for a short period of time impaired the lungs and the right ventricle early, before any change could be detected on the left ventricle. Right ventricular changes might be secondary to alcohol-induced pulmonary vasculature remodelling.

Vegetarian diets as a possible therapeutic approach to patients with metabolic syndrome: A brief review.

Approximately 25% of the adult worldwide population is estimated to have metabolic syndrome. Vegetarian diets have demonstrated effectiveness in improving each risk factor for developing metabolic syndrome, as compared with conventional dietary patterns and are useful in the prevention of metabolic syndrome. The present study reviews published literature concluding that following a vegetarian diet with the adequate nutritional support appears to be a mean to improve patients' metabolic condition and to decrease the risk of developing metabolic syndrome.

Handgrip Strength and Its Association With Hydration Status and Urinary Sodium-to-Potassium Ratio in Older Adults.

Objective: Older adults present higher risk of functional disability detected by handgrip strength and an increased risk of poor health conditions, such as dehydration and low values of the sodium-to-potassium (Na/K) ratio. This study aimed to quantify the association of hydration status and Na/K ratio with handgrip strength, based on the urinary excretion of older adults.Methods: A cross-sectional study was conducted in 735 older adults ≥ 65 years old. Handgrip strength was measured with a Jamar Dynamometer and low values were defined according to body mass index and to sex-specific cutoff points. The hydration status was evaluated based on free water reserve. Sodium and potassium intake were evaluated after converting 24-hour urinary sodium and potassium excretion, respectively. A logistic regression model was used to estimate the probability of presenting low handgrip strength, according to risk of hypohydration and to quartiles of Na/K, stratified by sex and adjusted for potential confounders.Results: The adjusted odds ratio (OR) for presenting low handgrip strength was higher in women at risk of hypohydration, but this association was not found in men. Both women and men with the highest values of Na/K ratio presented higher adjusted OR for low handgrip strength (OR in women was 2.03; 95% confidence interval [CI]: 1.12-3.68, and in men was 2.19; 95% CI: 1.11-4.29).Conclusions: The risk of hypohydration was directly associated with low handgrip strength in older women. In older adults, higher values of urinary Na/K ratio were also directly associated with low handgrip strength.

Perigestational high folic acid: impact on offspring's peripheral metabolic response.

Offspring of dams exposed to excess folic acid during the perigestational period have been shown by us to be predisposed to metabolic dysfunction revealed by hyperglycemia, glucose intolerance, increased insulin and decreased adiponectin in late adulthood. This work aims to characterize adipocyte phenotype and expression profile of genes in the regulation of lipid and glucose metabolism in visceral adipose tissue and in skeletal muscle. From mating until weaning, a recommended dose of folic acid for pregnancy (C, 2 mg of folic acid per kg of diet) or a high folic acid dose (HFA, 40 mg of folic acid per kg of diet) was administered to Sprague-Dawley females. At 10 months of age progeny were divided into groups fed the standard chow (C/STD and HFA/STD) and groups fed the standard chow plus drinking water with 10% fructose (C/FRU and HFA/FRU), as an additional metabolic challenge. Adipocyte morphology and quantification of key genes involved in lipid and glucose metabolism were studied in visceral adipose tissue and skeletal muscle of 13 months old offspring. HFA exposure led to an enlargement of visceral adipose cells most likely mediated by an upregulation of lipoprotein lipase, and it tended to downregulate Glut4 in visceral adipose tissue and skeletal muscle. Fructose exposure in a background of perigestational excess folic acid, but not in controls, induced an upregulation of lipogenesis pathway genes and it decreased jejunal expression of the proton-coupled folate transporter (Pcft1). In addition, fructose exposure led to a downregulation of jejunal Sglt1 in control animals. Our data suggest that high folic acid exposure during the perigestational period caused morphologic and genic alterations related to insulin resistant states indicating that this intervention may act as an effective programmer of long-term metabolic dysfunction.

Anti-Remodeling Effects of Xanthohumol-Fortified Beer in Pulmonary Arterial Hypertension Mediated by ERK and AKT Inhibition.

Polyphenols present in some alcoholic beverages have been linked to beneficial effects in preventing cardiovascular diseases. Polyphenols found in beer with anti-proliferative and anti-cancer properties are appealing in the context of the quasi-malignant phenotype of pulmonary arterial hypertension (PAH). Our purpose was to evaluate if the chronic ingestion of a xanthohumol-fortified beer (FB) would be able to modulate the pathophysiology of experimental PAH. Male Wistar rats with monocrotaline (MCT)-induced PAH (60 mg/kg) were allowed to drink either xanthohumol-fortified beer (MCT + FB) or 5.2% ethanol (MCT + SHAM) for a period 4 weeks. At the end of the protocol, cardiopulmonary exercise testing and hemodynamic recordings were performed, followed by sample collection for further analysis. FB intake resulted in a significant attenuation of the pulmonary vascular remodeling in MCT + FB animals. This improvement was paralleled with the downregulation in expression of proteins responsible for proliferation (ERK1/2), cell viability (AKT), and apoptosis (BCL-XL). Moreover, MCT + FB animals presented improved right ventricle (RV) function and remodeling accompanied by VEGFR-2 pathway downregulation. The present study demonstrates that a regular consumption of xanthohumol through FB modulates major remodeling pathways activated in experimental PAH.

Association of Anthropometric and Nutrition Status Indicators with Hand Grip Strength and Gait Speed in Older Adults.

BACKGROUND: How nutrition status indicators relate to function in older adults is an issue that needs to be explored. This study aimed to quantify the associations of anthropometric parameters and nutrition status indicators with hand grip strength (HGS) and gait speed (GS) in older adults. METHODS: A cross-sectional observational study was conducted in a population-based sample of 1500 older adults ≥65 years old. Logistic regression models were used to explore the associations between anthropometric, nutrition, and functional measures. RESULTS: Lower values of height, mid-arm muscle circumference, and calf circumference, as well as higher values of waist circumference, were associated with both low GS and HGS. The adjusted odds ratio (OR) for low GS was around 2-fold higher in participants presenting risk for undernutrition or undernutrition. The adjusted OR (95% confidence interval) for low HGS was 1.54 (1.01-2.36) in women and 1.57 (0.91-2.72) in men at risk for undernutrition/undernutrition. CONCLUSIONS: In older adults, lower values of height and calf circumference, as well as higher waist circumference, were associated with both low GS and HGS. Lower values of mid-arm muscle circumference were also associated with low values of both functional parameters only in men. The risk for undernutrition/undernutrition was more strongly associated with low GS than with low HGS in both women and men.

Autologous fat grafting: Harvesting techniques.

Autologous fat grafting is widely used for soft-tissue augmentation and replacement in reconstructive and aesthetic surgery providing a biocompatible, natural and inexpensive method. Multiple approaches have been developed in the past years, varying in the location of adipose tissue donor-sites, use of wetting solutions, harvesting, processing and placing techniques. Despite many advances in this subject, the lack of standardization in the protocols and the unpredictability of the resorption of the grafted tissue pose a significant limitation for graft retention and subsequent filling. In this review, we discuss several approaches and methods described over the last years concerning the harvesting of autologous fat grafts. We focus on contents such as the best donor-site, differences between existing harvesting techniques (namely tissue resection, hand aspiration or liposuction techniques), recommended harvesting cannula diameters, pressure application and volume of wetting solution injected prior aspiration. Results and comparisons between methods tend to vary according to the outcome measured, thus posing a limitation to pinpoint the most efficient methods to apply in fat grafting. Additionally, the lack of a standard assay to determine viability or volume augmentation of fat grafting remains another limitation to obtain universally accepted grafting procedures and protocols.

Nutritional status and gait speed in a nationwide population-based sample of older adults.

The association between nutritional status and gait speed remains unclear. This study described gait speed in older adults and quantified the association between overweight, obesity, undernutrition risk and gait speed. Gait speed as potential indicator of nutritional outcomes was also explored. A cross-sectional analysis was conducted in a population-based sample of 1,500 older adults ≥65 years old. Compared to "normal body mass index" women, odds ratio for a slow gait speed was approximately 2-fold higher in"overweight", 4-fold higher in "obese" and 6-fold higher in women at "undernutrition risk". "Undernutrition risk" category resulted from joining "undernutrition risk/undernutrition". For men, these associations were in the same direction, but the odds ratio estimates halved. In women, identified gait speed cut-offs were 0.87 m/s for "obesity" and 0.79 m/s for "undernutrition risk". In men, 0.94 m/s is the cut-off in which most older adults were correctly classified relative to "undernutrition risk". About half of Portuguese older adults presented a gait speed ≤0.8 m/s. Overweight, obesity and undernutrition risk were directly and increasingly associated with slow gait speed, but approximately twice as high in women compared to men. Gait speed revealed potential utility in marking nutritional problems, but further investigation is recommended.

Handgrip strength values of Portuguese older adults: a population based study.

BACKGROUND: Handgrip strength is used to identify sarcopenia and frailty phenotypes, being a potential predictor of mortality in older adults. However, uniformity is lacking in the reference values. This study aimed to describe handgrip strength values of older population aged ≥65 years in Portugal, considering the possible influence of anthropometric parameters. METHODS: A cross-sectional study was conducted in Portugal, among 1500 older adults aged ≥65 years old, according to "The Nutrition UP 65 Study Protocol". Demographic data were collected and cognitive performance, subjective general health, physical activity, anthropometric parameters and nutritional status were assessed and analysed. Handgrip strength data was obtained with a Jamar dynamometer. A Pubmed/Medline search was carried out to compare handgrip strength data between Portuguese older adults and other older populations. RESULTS: Handgrip strength was higher among men than among women (30.3 ± 9.2 Kgf vs 18 ± 5.4 Kgf, p < 0.001, respectively). In general, handgrip strength values of Portuguese older adults were lower than other older populations. In our sample, age, cognitive and nutritional status, self-reported sitting time and practice of physical activity were significantly correlated with handgrip strength in both sexes. Concerning anthropometric parameters, height was the most significantly correlated with handgrip strength (r = 0.34, p < 0.001, in women and r = 0.40, p < 0.001, in men). CONCLUSION: This study described, for the first time, handgrip strength values of Portuguese population aged ≥65 years, according to age and to sex-specific tertiles of height. The definition of handgrip strength reference values in this age group merits further reflection.

Xanthohumol and 8-prenylnaringenin ameliorate diabetic-related metabolic dysfunctions in mice.

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by metabolic disturbances in specific tissues. The present work aimed to analyze the effects of xanthohumol (XN) and 8-prenylnaringenin (8PN), two beer-derived polyphenols, in liver and skeletal muscle lipid and glycolytic metabolism in T2DM mice model. Thirty C57Bl/6 mice were randomly divided into five groups: standard diet (control), high-fat diet (DM), high-fat diet plus ethanol (DM-Ethanol), high-fat diet plus 10 mg/L XN (DM-XN) and high-fat diet plus 10 mg/L 8PN (DM-8PN) during 20 weeks. Fasting blood glucose and insulin tolerance tests were performed 1 week before sacrifice. At the end of the study, blood, liver and skeletal muscle were collected. Both XN and 8PN treatments prevented body weight gain; decreased glycemia, triglyceride, cholesterol and alkaline phosphatase levels; and improved insulin sensitivity. Polyphenols promoted hepatic and skeletal muscle AMP-activated protein kinase (AMPK) activation, diminishing the expression of target lipogenic enzymes (sterol regulatory element binding protein-1c and fatty acid synthase) and acetyl-CoA carboxylase activity. Moreover, both XN and 8PN treatments decreased VEGFR-1/VEGFB pathway, involved in fatty acid uptake, and increased AS160 expression, involved in GLUT4 membrane translocation. Presented data demonstrated that both XN and 8PN treatment resulted in AMPK signaling pathway activation, thus suppressing lipogenesis. Their consumption prevented body weight gain and improved plasma lipid profile, with significant improvement of insulin resistance and glucose tolerance. XN- or 8PN-enriched diet could ameliorate diabetic-associated metabolic disturbances by regulating glucose and lipid pathways.

Modulation of VEGF signaling in a mouse model of diabetes by xanthohumol and 8-prenylnaringenin: Unveiling the angiogenic paradox and metabolism interplay.

SCOPE: Imbalance in kidney and heart neovascularization is common in type2 diabetes (T2DM) patients. Nevertheless, the mechanisms governing this angiogenic paradox have not been elucidated. Xanthohumol (XN) and 8-prenylnaringenin (8PN) beer polyphenols modulate angiogenesis, being thus targets for T2DM-related complications. Our work examined whether polyphenols consumption affects angiogenic paradox and metabolism in a T2DM mouse model. METHODS AND RESULTS: An increase in kidney and a reduction in left ventricle (LV) microvessels of diabetic C57Bl/6 mice were observed. XN consumption reduced angiogenesis, VEGFR-2 expression/activity, VEGF-A and phosphofructokinase-2/fructose-2,6-bisphosphatase-3 enzyme expression, a metabolic marker present in endothelial tip cells in T2DM mice kidney. 8PN had opposite effects in T2DM mice LV. These XN and 8PN effects were dependent on VEGF levels as revealed by in vitro assays. These findings were accompanied by tissue and plasma reduced expression levels of VEGF-B and its receptors, VEGFR1 and neuropilin-1, by both polyphenols. CONCLUSION: Beer polyphenols modulate T2DM angiogenic paradox in a tissue-dependent manner. We also show for the first time that both polyphenols decreased VEGF-B pathway, which is implicated in endothelial-to-tissue lipid metabolism. Altogether, the effects of these polyphenols in the crosstalk between angiogenesis and metabolism render them potent agents for novel diabetic therapeutic interventions.

Xanthohumol modulates inflammation, oxidative stress, and angiogenesis in type 1 diabetic rat skin wound healing.

Type 1 diabetes mellitus is responsible for metabolic dysfunction, accompanied by chronic inflammation, oxidative stress, and endothelium dysfunction, and is often associated with impaired wound healing. Phenol-rich food improves vascular function, contributing to diabetes prevention. This study has evaluated the effect of phenol-rich beverage consumption in diabetic rats on wound healing, through angiogenesis, inflammation, and oxidative stress modulation. A wound-healing assay was performed in streptozotocin-induced diabetic Wistar rats drinking water, 5% ethanol, and stout beer with and without 10 mg/L xanthohumol (1), for a five-week period. Wounded skin microvessel density was reduced to normal values upon consumption of 1 in diabetic rats, being accompanied by decreased serum VEGF-A and inflammatory markers (IL-1ß, NO, N-acetylglucosaminidase). Systemic glutathione and kidney and liver H2O2, 3-nitrotyrosine, and protein carbonylation also decreased to healthy levels after treatment with 1, implying an improvement in oxidative stress status. These findings suggest that consumption of xanthohumol (1) by diabetic animals consistently decreases inflammation and oxidative stress, allowing neovascularization control and improving diabetic wound healing.

Isoxanthohumol modulates angiogenesis and inflammation via vascular endothelial growth factor receptor, tumor necrosis factor alpha and nuclear factor kappa B pathways.

Angiogenesis and inflammation are becoming distinguished players in the pathogenesis of many heterogeneous diseases, such as diabetes, cardiovascular disease, and cancer. Therefore, it is crucial to study new compounds that are able to modulate these events. Isoxanthohumol (IXN) is a polyphenol with antioxidant, anti-inflammatory, and antiangiogenic properties. The aim of this study was to evaluate the effects of IXN on blood vessel proliferation and maturation and describe underlying molecular mechanisms in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Angiogenic profile of IXN was analyzed by retinal angiogenesis at different time points. IXN modulation of angiogenic and inflammatory signaling pathways was evaluated by Western blotting on EC and VSMC cultures. IXN inhibited by 20% sprouting angiogenesis and decreased vascular coverage by mural cells up to 39%. IXN of 10 µM also decreased inflammatory signals, namely tumor necrosis factor alpha (TNF-α) (26 and 40%) and factor nuclear kappa B (24 and 42%) in human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs). Angiogenic regulators, including vascular endothelial growth factor receptor 2 (HUVEC, 55%), angiopoietins 1 (HUVEC, 39%; HASMC, 35%), angiopoietin 2 (HUVEC, 38%), and Tie2 (HUVEC, 56%) were also inhibited by 10 µM of IXN treatments. Akt activation was reduced by 47% in HUVEC-treated cells and Erk activation was also reduced by 52 and 69% upon IXN treatment of HUVEC and HASMC. IXN seems to regulate in vivo vascular proliferation and stabilization and the EC-VSMC-inflammatory crosstalk, leaving this molecule as an interesting nutritional player for angiogenesis and inflammation-related diseases.

Different effects of catechin on angiogenesis and inflammation depending on VEGF levels.

Although physiological and pathological angiogenesis develop through similar processes, during pathological angiogenesis, proangiogenic factors are exacerbated. Polyphenols have been considered therapeutic tools for conditions exhibiting enhanced angiogenesis. However, the possibility that these compounds may also prevent vascularization in physiological situations is a major drawback for their use. The purpose of the current study was to investigate the effects of 0.1-100 µM catechin on endothelial cells (EC) and vascular smooth muscle cells (VSMC) regarding angiogenic and inflammatory processes. Catechin modulation of angiogenesis and inflammation was also evaluated in vivo using different models of angiogenesis: one physiological (skin wound-healing assay) and another one resembling pathological angiogenesis, exhibiting higher vascular endothelial growth factor (VEGF)-A stimulation (Matrigel plug assay). The in vitro results showed that 100 µM catechin increased viability (to 165.58% and to 165.34%) and decreased apoptosis (53.45% and 92.65%) and proliferation (33.19% and 23.36%) of EC and VSMC, respectively. Catechin affected migration and invasion, tending to increase both in EC and decreasing them in VSMC; however, it did not change sprouting angiogenesis. Nevertheless, catechin diminished in vitro inflammatory modulators such as tumor necrosis factor α (58.66% for human umbilical vein endothelial cells and 85.46% for human aortic smooth muscle cells) and nuclear factor kappa-B (38.43% for VSMC). The in vivo results demonstrated that catechin did not change angiogenesis and inflammation in skin wound-healing model and substantially decreased these processes in Matrigel plug assay. Altogether, the current study showed that catechin has different effects in angiogenesis and inflammation depending on VEGF-A levels. The absence of adverse effects in mature vasculature favors catechin potential use against pathological situations where angiogenesis is stimulated.

Implanted neonatal human dermal fibroblasts influence the recruitment of endothelial cells in mice.

The vascularization of new tissue within a reasonable time is a crucial prerequisite for the success of different cell- and material-based strategies. Considering that angiogenesis is a multi-step process involving humoral and cellular regulatory components, only in vivo assays provide the adequate information about vessel formation and the recruitment of endothelial cells. The present study aimed to investigate if neonatal human dermal fibroblasts could influence in vivo neovascularization. Results obtained showed that fibroblasts were able to recruit endothelial cells to vascularize the implanted matrix, which was further colonized by murine functional blood vessels after one week. The vessels exhibited higher levels of hemoglobin, compared with the control matrix, implanted without fibroblasts, in which no vessel formation could be observed. No significant differences were detected in systemic inflammation. The presence of vessels originated from the host vasculature suggested that host vascular response was involved, which constitutes a fundamental aspect in the process of neovascularization. Fibroblasts implanted within matrigel increased the presence of endothelial cells with positive staining for CD31 and for CD34 and the production of collagen influencing the angiogenic process and promoting the formation of microvessels. New strategies in tissue engineering could be delineated with improved angiogenesis using neonatal fibroblasts.

Xanthohumol-supplemented beer modulates angiogenesis and inflammation in a skin wound healing model. Involvement of local adipocytes.

Angiogenesis and inflammation are two intermingled processes that play a role in wound healing. Nevertheless, whenever exacerbated, these processes result in nonhealing wounds. Xanthohumol (XN), a beer-derived polyphenol, inhibits these processes in many physiopathological situations. This study aimed at examining whether XN ingestion affects wound healing. Wistar rats drinking water, 5% ethanol, stout beer (SB) or stout beer supplemented with 10 mg/L XN (Suppl SB) for 4 weeks, were subjected to a 1.5 cm full skin-thickness longitudinal incision, and further maintained under the same beverage conditions for another week. No differences in beverage consumption or body weight were found throughout the study but food intake decreased in every group relative to controls. Consumption of Suppl SB resulted in decreased serum VEGF levels (18.42%), N-acetylglucosaminidase activity (27.77%), IL1ß concentration (9.07%), and NO released (77.06%), accompanied by a reduced redox state as observed by increased GSH/GSSG ratio (to 198.80%). Also, the number of blood vessels within the wound granulation tissue seems to reduce in animals drinking Suppl SB (23.08%). Interestingly, SB and primarily Suppl SB showed a tendency to increase adipocyte number (to 194.26% and 156.68%, respectively) and reduce adipocyte size (4.60% and 24.64%, respectively) within the granuloma. Liver function and metabolism did not change among the animal groups as analyzed by plasma biochemical parameters, indicating no beverage toxicity. This study shows that XN intake in its natural beer context reduced inflammation, oxidative stress, and angiogenesis, ameliorating the wound healing process, suggesting that this polyphenol may exert beneficial effect as a nutritional supplement.