Pre-clinical evidence for the therapeutic effect of Pitaya (Hylocereus lemairei) on diabetic intestinal microenvironment.

Intestinal glucose absorption plays a central role in the regulation of glucose plasmatic; however, current clinical management does not target the gut for treating diabetes. This study evaluated the effects of peel and pulp aqueous extract from Hylocereus lemairei on human enterocytes under high glucose concentration. Anti-hyperglycemic and antiobesity activities in vitro were also evaluated. Extracts did not cause cytotoxicity at 1 to 500 µg/mL. Moreover, they were effective in attenuating oxidative stress (DCFH-DA assay) and inflammation (•ON production) caused by high glucose. Intestinal enzymes (α- glucosidase and pancreatic lipase) were inhibited by pulp and peel extracts (>60% and >95%, respectively). Extracts exhibited a redox capacity superior to ascorbic and chlorogenic acids, presenting high phenolic content, mainly anthocyanins. The main compounds for both extracts were chlorogenic acid and naringin, and peel stood both qualitatively and quantitatively. Data suggest red Pitaya has potential as a new medicine for diabetes.

Dual effect of the herbal matcha green tea (Camellia sinensis L. kuntze) supplement in EA.hy926 endothelial cells and Artemia salina.

ETHNOPHARMACOLOGICAL RELEVANCE: Matcha green tea (Camellia sinensis) based-supplements have been widely used since they present a greater content of phenolic compounds than traditional green tea, which is popularly used in the treatment of diabetes. However, there are few studies on the effectiveness and safety of matcha supplements. AIM OF THE STUDY: This work aimed to evaluate the efficacy and safety of this supplement in endothelial cells (EA.hy926) in the hyperglycemic model and in vivo Artemia salina. MATERIALS AND METHODS: To assess the effect of Matcha herbal supplement (MHS), EA. hy926 endothelial cells were treated with 20 µg/mL of MHS for 24 h, in a hyperglycemic medium with 35 mM glucose. After treatment, cells were trypsinized and centrifuged at 4 °C and 47×g for 5 min. The pellet was used to determine the reaction products to thiobarbituric acid and the levels of nitric oxide. Electron transport chain activity and ATP levels were also evaluated. Intracellular pH, apoptosis, and mitochondrial membrane depolarization were evaluated by flow cytometry. MHS chemical characterization was performed by HPLC-UV and total phenolic content analysis. The evaluation of the antioxidant capacity of MHS was performed by 2,2-diphenyl-1-picrylhydrazyl radical scavenger assay. To determine the in vivo acute toxicity of MHS, an A. salina assay was conducted, using 0,2 mL of different concentrations of MHS (10, 50, 100, 250, 500, 750 and 1000 µg/mL). The LD50 values were obtained by interpolation of 50% (y = 50) of the dead individuals in the trend curves. RESULTS: Our data showed that MHS was able to avoid oxidative and nitrosative stress induced by hyperglycemia, demonstrating important antioxidant activity. However, it was observed that MHS reduced up to 90% the activity of the four-electron transport complexes, reducing the ATP production of the endothelial cells. In the toxicity assay performed in Artemia salina, MHS showed mild toxicity (LD50 = 0,4 mg/mL). The major compounds found in MHS were epigallocatechin gallate, epicatechin, rutin, kaempferol, and quercetin. CONCLUSIONS: This data draws attention to the fact that supplements with high content of phenolic compounds, capable of avoiding oxidative and nitrosative stress can have a dual effect and, simultaneously to antioxidant activity, can induce toxicity in different cell types.

Mutual Effects of Free and Nanoencapsulated Phenolic Compounds on Human Microbiota.

Phenolic compounds (PC) have many health benefits such as antioxidant, anticarcinogenic, neuroprotective, and anti-inflammatory activities. All of these activities depend on their chemical structures and their interaction with biological targets in the body. PC occur naturally in polymerized form, linked to glycosides and require metabolic transformation from their ingestion to their absorption. The gut microbiota can transform PC into more easily absorbed metabolites. PC, in turn, have prebiotic and antimicrobial actions on the microbiota. Despite this, their low oral bioavailability still compromises biological performance. Therefore, the use of nanocarriers has been demonstrated to be a useful strategy to improve PC absorption and, consequently, their health effects. Nanotechnology is an excellent alternative able to overcome the limits of oral bioavailability of PC, since it offers protection from degradation during their passage through the gastrointestinal tract. Moreover, nanotechnology is also capable of promoting controlled PC release and modulating the interaction between PC and the microbiota. However, little is known about the impact of nanotechnology on PC effects on the gut microbiota. This review highlights the use of nanotechnology for PC delivery on gut microbiota, focusing on the ability of such formulations to enhance oral bioavailability by applying nanocarriers (polymeric nanoparticles, nanostructured lipid carriers, solid lipid nanoparticles). In addition, the effects of free and nanocarried PC or nanocarriers per se on gut microbiota are also described.

Polyphenolic Content and Antioxidant Activity of Mycelia and Basidiomes of Oyster Mushrooms Pleurotus spp. (Agaricomycetes) from Brazil.

This study aimed to examine the antioxidant activity, total phenolic content, and phenolic profile of nine strains of Pleurotus spp. isolated in southern Brazil. Basidiomes were obtained from a solid-state culture in medium containing Pinus sp. sawdust (SCM-PSW), coffee grounds (CG), or organic grape waste (OGW). Mycelia were obtained from submerged culture-potato dextrose broth (MSC-PDB). Basidiomes had the highest total phenolic content (between 31.30 ± 0.26 and 47.00 ± 0.12 mg gallic acid equivalents [GAE]/g) compared with mycelia (between 8.15 ± 0.26 and 15.96 ± 0.82 mg GAE/g). Antioxidant activity of the basidiomes showed an IC50 value between 5.36 ± 0.27 (88F.13) and 10.68 ± 0.22 mg/mL (189H.3). Mushrooms produced in the OGW and CG media had higher total phenolic content than those from MSC, indicating that they can serve as sources of bioactive compounds on culture media. These findings show the potential of natural wastes to be used as a strategy for increasing secondary metabolites in edible mushrooms, proposing an interesting approach for the nutraceutical and pharmaceutical industries.

Targeting Inflammatory-Mitochondrial Response in Major Depression: Current Evidence and Further Challenges.

The prevalence of psychiatric disorders has increased in recent years. Among existing mental disorders, major depressive disorder (MDD) has emerged as one of the leading causes of disability worldwide, affecting individuals throughout their lives. Currently, MDD affects 15% of adults in the Americas. Over the past 50 years, pharmacotherapy, psychotherapy, and brain stimulation have been used to treat MDD. The most common approach is still pharmacotherapy; however, studies show that about 40% of patients are refractory to existing treatments. Although the monoamine hypothesis has been widely accepted as a molecular mechanism to explain the etiology of depression, its relationship with other biochemical phenomena remains only partially understood. This is the case of the link between MDD and inflammation, mitochondrial dysfunction, and oxidative stress. Studies have found that depressive patients usually exhibit altered inflammatory markers, mitochondrial membrane depolarization, oxidized mitochondrial DNA, and thus high levels of both central and peripheral reactive oxygen species (ROS). The effect of antidepressants on these events remains unclear. Nevertheless, the effects of ROS on the brain are well known, including lipid peroxidation of neuronal membranes, accumulation of peroxidation products in neurons, protein and DNA damage, reduced antioxidant defenses, apoptosis induction, and neuroinflammation. Antioxidants such as ascorbic acid, tocopherols, and coenzyme Q have shown promise in some depressive patients, but without consensus on their efficacy. Hence, this paper provides a review of MDD and its association with inflammation, mitochondrial dysfunction, and oxidative stress and is aimed at thoroughly discussing the putative links between these events, which may contribute to the design and development of new therapeutic approaches for patients.

Grape seed proanthocyanidins improves mitochondrial function and reduces oxidative stress through an increase in sirtuin 3 expression in EA.hy926 cells in high glucose condition.

Proanthocyanidins are phenolic compounds abundant in the diet, commonly found in grapes and derivatives, foods known for their health-promoting benefits. There is previous evidence showing the antidiabetic activity of proanthocyanidins, however, their mechanisms of action have not been fully elucidated. This study evaluated the capacity of grape seed proanthocyanidins extract (GSPE) to modulate oxidative stress, nitric oxide levels, mitochondrial dysfunction, apoptosis, and sirtuin expression in endothelial cells EA.hy926 under high glucose condition. In addition, the possible toxic effects of GSPE was evaluated in a zebrafish embryos model. The results showed that GSPE was able to enhance cell viability and avoid the disturbance in redox metabolism induced by high glucose. Moreover, GSPE was able to avoid mitochondria dysfunction and the increased in p53 and poly-(ADP-ribose) polymerase expression induced by high glucose exposition. These effects were attributed to the increase in expression of sirtuin 3, a protein able to regulate mitochondrial function. GSPE in an effective concentration did not show toxic effects in zebrafish embryos model. Taken together, these data elucidate the key molecular target of GSPE for future pharmacological interventions in diabetic patients.

Grape seed proanthocyanidins prevent H2 O2 -induced mitochondrial dysfunction and apoptosis via SIRT 1 activation in embryonic kidney cells.

Grape proanthocyanidins are compounds widely ingested in the diet. This study evaluated their effects on mitochondrial function, apoptosis, and sirtuin 1 and 3 expressions in HEK-293 cells exposed to H2 O2 . High-resolution mass spectrometry and high-performance liquid chromatography characterized the proanthocyanidins extract and the presence of procyanidins B and C was detected. The extract prevented H2 O2 -induced oxidative damage to proteins and lipids and depletion in superoxide dismutase activity. Moreover, it was able to regulate the expression of NADH: Ubiquinone oxidoreductase core subunit S7 and prevent mitochondrial electron transport chain dysfunction, ATP depletion, and apoptosis induced by H2 O2 . Finally, the extract was able to regulate sirtuin 1 and 3 expressions, thus maintaining cell viability. These data show that the grape seed proanthocyanidins can target mitochondrial proteins, which may represent an important approach for the management of numerous chronic illnesses associated with mitochondrial dysfunction. PRACTICAL APPLICATIONS: Proanthocyanidins are phenolic compounds abundant in regular diet, commonly found in grapes and derivatives, pomegranates, apples, and red fruits, all foods known for their beneficial effects on health. The current study highlights the role of proanthocyanidins as mitochondrial modulators that may explain the biological activity attributed to these compounds. This study brings evidence that proanthocyanidins might be considered as a value-added agent for the development of new nutraceutical and or pharmaceutical approaches.

Dietary total antioxidant capacity as a preventive factor against depression in climacteric women.

Depression is characterized by physical or psychological distress and in many cases can lead to suicide. OBJECTIVE: to assess the prevalence of depression and its possible relationship with dietary total antioxidant capacity (DTAC) and nutritional parameters in climacteric women participating in an extension university program in a Southern Brazilian city. METHODS: data were obtained through questionnaires and anthropometric measurements. Diet was assessed using a 24-hour dietary recall. The Beck Depression Inventory (BDI) was used to assess the intensity of symptoms of depression. RESULTS: DTAC of the population ranged from 435.60 to 4502.62 mg VCE/day. Among the most consumed antioxidant food/beverages, coffee ranked highest. Polyphenols were found to be directly linked to the antioxidant capacity of fresh foods (r=0.905; p=0.0001). Prevalence of depression in the population was 44%, and depressed women had lower intake levels of polyphenols (p=0.022; Cohen's d=0.80), and vitamin B6 (p=0.038; Cohen's d=0.65), vitamin A (p=0.044; Cohen's d =0.63), and vitamin C (p=0.050; Cohen's d =0.61). There was a significant negative correlation between BDI scores and polyphenol intake (r=-0.700; p=0.002). CONCLUSION: these results may contribute to a better understanding of the recommended dietary antioxidant intake as an adjuvant for preventing depression in women.

Depressão é caracterizada por causar sofrimento físico ou psicológico e em muitos casos pode levar ao suicídio. OBJETIVO: avaliar a prevalência de depressão e sua possível relação com a capacidade antioxidante total da dieta (DTAC) e parâmetros nutricionais em mulheres climatéricas participantes de um programa universitário de extensão em uma cidade do sul do Brasil. MÉTODOS: os dados foram obtidos por meio de questionários e medidas antropométricas. A dieta foi avaliada através de um recordatório alimentar de 24 horas. O Inventário de Depressão de Beck (BDI) foi usado para avaliar a intensidade dos sintomas de depressão. RESULTADOS: a DTAC da população variou de 435,60 a 4502,62 mg VCE/dia. Entre os alimentos/bebidas antioxidantes mais ingeridos, o café destacou-se em primeiro. Os polifenóis mostraram estar diretamente ligados à capacidade antioxidante dos alimentos in natura (r=0,905; p=0,0001). A prevalência de depressão na população foi de 44%, e as mulheres depressivas apresentaram menores níveis de ingestão de polifenóis (p=0,022; Cohen's d=0,80) e vitaminas B6 (p=0,038; Cohen's d=0,65), A (p=0,044; Cohen's d=0,63) e C (p=0,050; Cohen's d=0,61). Houve uma correlação negativa significativa entre os escores do BDI e a ingestão de polifenóis (r=-0,700; p=0,002). CONCLUSÃO: estes resultados podem contribuir para uma melhor compreensão da ingestão dietética recomendada de antioxidantes como adjuvante na prevenção da depressão feminina.

Dietary total antioxidant capacity as a preventive factor against depression in climacteric women / Capacidade antioxidante total dietética como um fator de prevenção contra a depressão em mulheres climatéricas

ABSTRACT Depression is characterized by physical or psychological distress and in many cases can lead to suicide. Objective: to assess the prevalence of depression and its possible relationship with dietary total antioxidant capacity (DTAC) and nutritional parameters in climacteric women participating in an extension university program in a Southern Brazilian city. Methods: data were obtained through questionnaires and anthropometric measurements. Diet was assessed using a 24-hour dietary recall. The Beck Depression Inventory (BDI) was used to assess the intensity of symptoms of depression. Results: DTAC of the population ranged from 435.60 to 4502.62 mg VCE/day. Among the most consumed antioxidant food/beverages, coffee ranked highest. Polyphenols were found to be directly linked to the antioxidant capacity of fresh foods (r=0.905; p=0.0001). Prevalence of depression in the population was 44%, and depressed women had lower intake levels of polyphenols (p=0.022; Cohen's d=0.80), and vitamin B6 (p=0.038; Cohen's d=0.65), vitamin A (p=0.044; Cohen's d =0.63), and vitamin C (p=0.050; Cohen's d =0.61). There was a significant negative correlation between BDI scores and polyphenol intake (r=-0.700; p=0.002). Conclusion: these results may contribute to a better understanding of the recommended dietary antioxidant intake as an adjuvant for preventing depression in women.

RESUMO Depressão é caracterizada por causar sofrimento físico ou psicológico e em muitos casos pode levar ao suicídio. Objetivo: avaliar a prevalência de depressão e sua possível relação com a capacidade antioxidante total da dieta (DTAC) e parâmetros nutricionais em mulheres climatéricas participantes de um programa universitário de extensão em uma cidade do sul do Brasil. Métodos: os dados foram obtidos por meio de questionários e medidas antropométricas. A dieta foi avaliada através de um recordatório alimentar de 24 horas. O Inventário de Depressão de Beck (BDI) foi usado para avaliar a intensidade dos sintomas de depressão. Resultados: a DTAC da população variou de 435,60 a 4502,62 mg VCE/dia. Entre os alimentos/bebidas antioxidantes mais ingeridos, o café destacou-se em primeiro. Os polifenóis mostraram estar diretamente ligados à capacidade antioxidante dos alimentos in natura (r=0,905; p=0,0001). A prevalência de depressão na população foi de 44%, e as mulheres depressivas apresentaram menores níveis de ingestão de polifenóis (p=0,022; Cohen's d=0,80) e vitaminas B6 (p=0,038; Cohen's d=0,65), A (p=0,044; Cohen's d=0,63) e C (p=0,050; Cohen's d=0,61). Houve uma correlação negativa significativa entre os escores do BDI e a ingestão de polifenóis (r=-0,700; p=0,002). Conclusão: estes resultados podem contribuir para uma melhor compreensão da ingestão dietética recomendada de antioxidantes como adjuvante na prevenção da depressão feminina.

Araucaria angustifolia (Bertol.) Kuntze has neuroprotective action through mitochondrial modulation in dopaminergic SH-SY5Y cells.

Brain disorders (BD) including neuropsychiatric and neurodegenerative diseases, are often associated with impairments in mitochondrial function and oxidative damage that can lead to neuronal injury. The mitochondrial complex I enzyme is one of the main sites of ROS generation and is implicated in many BD pathophysiologies. Despite advances in therapeutics for BD management, conventional pharmacotherapy still cannot efficiently control neuronal redox imbalance and mitochondrial dysfunction. Araucaria angustifolia is one of the main pine species in South America and presents a notable therapeutic history in folk medicine. A. angustifolia extract (AAE), obtained from the natural waste named bracts, is rich in flavonoids; molecules able to regulate cell redox metabolism. We examined the effects of AAE on rotenone-induced mitochondrial complex I dysfunction in human dopaminergic SH-SY5Y cells. AAE restored complex I assembly and activity mainly through overexpression of NDUFS7 protein and NDUFV2 gene levels. These findings were accompanied by a reduction in the generation of neuronal reactive oxygen species and lipid peroxidation. Our data demonstrates, for the first time, that AAE exerts in vitro neuroprotective effects, thus making it an interesting source for future drug development in BD-associated mitochondrial dysfunctions.

White grape juice increases high-density lipoprotein cholesterol levels and reduces body mass index and abdominal and waist circumference in women.

OBJECTIVES: Grape juice is a drink that is rich in phenolic compounds, which are important natural antioxidants that reduce the incidence of diseases linked to oxidative stress including cardiovascular disease. Studies on the effects of purple grape juice supplementation have already been conducted; however, there are no data on the effects of the consumption of white grape juice (WGJ) to date. The aim of this study was to evaluate the effects of WGJ supplementation on body mass index, waist and abdominal circumference, blood pressure and glucose, insulin, oxidative damage, and lipid profile in women. METHODS: A total of 25 women, ages 50 to 67 y, were included in this study. The volunteers were instructed to consume 7 mL/Kg/d of WGJ (Vitis labrusca) without other changes in diet energy consumption or habitual lifestyle. The supplementation occurred over 30 d. Anthropometric data and blood samples were collected before and after the intervention. RESULTS: Supplementation with WGJ reduced the women's body mass index and waist and abdominal circumference (P < 0.001). There were no significant differences in blood pressure before and after the consumption of WGJ. In addition, no changes in blood glucose, insulin, and levels of oxidative damage were found. Women who supplemented with WGJ showed an increase of 16% in high-density lipoprotein cholesterol levels. CONCLUSIONS: These results demonstrate that the consumption of WGJ can improve metabolic parameters in women, which may help reduce the risk of cardiovascular diseases.

Antioxidant defences and haemocyte internalization in Limnoperna fortunei exposed to TiO2 nanoparticles.

TiO2 nanoparticles (TiO2-NP) have been incorporated into a large range of materials for different applications in the last decades and are very likely to appear in wastewater and effluents, eventually reaching the aquatic environment. Therefore, the assessment of the biological impact of TiO2-NP on aquatic ecosystem is of a major concern. The mussels represent a target group for TiO2-NP toxicity, as they are filter feeders and are capable of bioaccumulating toxic compounds. Furthermore, the exotic organism Limnoperna fortunei, golden mussel, is a freshwater bivalve that has been used in biomonitoring environmental conditions. In this work, the TiO2-NP's ability to interact with haemocytes of golden mussel was assessed by transmission electron microscopy. The enzymatic and non-enzymatic antioxidant defenses were evaluated by superoxide dismutase (Sod) and catalase (Cat) activities and protein sulfhydryl content, which were measured after the golden mussel was exposed to TiO2-NP (1, 5, 10 and 50µgmL(-1)). Results demonstrate that TiO2-NP was internalized by cells, causing alterations in haemocytes membrane. Antioxidant activity of Sod and Cat decreased after 2h TiO2-NP exposure. After 4h exposure, the enzymatic antioxidant activity was restored. Notably, the protein sulfhydryl content decreased after 2h to all the TiO2-NP concentrations and no alterations were observed after 4h of TiO2-NP exposure. These results demonstrate the potential of golden mussel as sentinel organism to TiO2-NP exposure.