Oligomeric proanthocyanidins ameliorates osteoclastogenesis through reducing OPG/RANKL ratio in chicken's embryos.

Skeletal disorders can seriously threaten the health and the performance of poultry, such as tibial dyschondroplasia (TD) and osteoporosis (OP). Oligomeric proanthocyanidins (OPC) are naturally occurring polyphenolic flavonoid compounds that can be used as potential substances to improve the bone health and the growth performance of poultry. Eighty 7-day-old green-eggshell yellow feather layer chickens were randomly divided into 4 groups: basal diet and basal diet supplementation with 25, 50, and 100 mg/kg OPC. The results have indicated that the growth performance and bone parameters of chickens were significantly improved supplementation with OPC in vivo, including the bone volume (BV), the bone mineral density (BMD) and the activities of antioxidative enzymes, but ratio of osteoprotegerin (OPG)/receptor activator of NF-κB (RANK) ligand (RANKL) was decreased. Furthermore, primary bone marrow mesenchymal stem cells (BMSCs) and bone marrow monocytes/macrophages (BMMs) were successfully isolated from femur and tibia of chickens, and co-cultured to differentiate into osteoclasts in vitro. The osteogenic differentiation derived from BMSCs was promoted treatment with high concentrations of OPC (10, 20, and 40 µmol/L) groups in vitro, but emerging the inhibition of osteoclastogenesis by increasing the ratio of OPG/RANKL. In contrary, the osteogenic differentiation was also promoted treatment with low concentrations of OPC (2.5, 5, and 10 µmol/L) groups, but osteoclastogenesis was enhanced by decreasing the ratio of OPG/RANKL in vitro. In addition, OPG inhibits the differentiation and activity of osteoclasts by increasing the autophagy in vitro. Dietary supplementation of OPC can improve the growth performance of bone and alter the balance of osteoblasts and osteoclasts, thereby improving the bone health of chickens.

Nrf2 regulates downstream genes by targeting miR-29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid-insensitive asthma.

CONTEXT: Grape seed proanthocyanidin extract (GSPE) is effective in treating severe asthma (SA). OBJECTIVE: To examine the relationship between Nrf2-miR-29b axis and SA, and to detect whether preventive use of GSPE relieves SA via it. MATERIALS AND METHODS: We recruited 10 healthy controls, 10 patients with non-severe asthma (nSA), and 9 patients with SA from February 2017 to December 2017. Peripheral blood mononuclear cells from these volunteers were extracted. A murine model of steroid-insensitive asthma was established in six-week-old female BALB/c mice that were sensitised and challenged with OVA, Al(OH)3 and LPS for 31 days. Mice in the treated groups were injected with DXM (5 mg/kg/d), with or without GSPE (100 mg/kg/d). Control group received PBS. We performed quantitative real-time PCR, western blot and luciferase reporter assay in animal and cell models. RESULTS: SA group demonstrated significantly lower concentrations of Nrf2 protein, Nrf2 mRNA, and miR-29b than nSA group and control group. Conversely, higher levels of platelet derived growth factor C (PDGFC), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and collagen type III alpha 1 (COL3A1) were measured in SA than in the other two groups. PDGFC, PIK3R1, and COL3A1 were the target genes of miR-29b. GSPE + DXM significantly elevated the expression of Nrf2 (+188%), Nrf2 mRNA (+506%), and miR-29b (+201%), and significantly reduced the expression of PDGFC (-72%), PIK3R1 (-40%), and COL3A1 (-65%) compared with OVA + LPS. CONCLUSIONS: Nrf2-miR-29b axis is involved in the pathogenesis of SA. GSPE, as an adjuvant drug, maybe a potential therapeutic agent for SA.

Consumption of cranberry as adjuvant therapy for urinary tract infections in susceptible populations: A systematic review and meta-analysis with trial sequential analysis.

The efficacy of cranberry (Vaccinium spp.) as adjuvant therapy in preventing urinary tract infections (UTIs) remains controversial. This study aims to update and determine cranberry effects as adjuvant therapy on the recurrence rate of UTIs in susceptible groups. According to PRISMA guidelines, we conducted a literature search in Web of Science, PubMed, Embase, Scopus, and the Cochrane Library from their inception dates to June 2021. We included articles with data on the incidence of UTIs in susceptible populations using cranberry-containing products. We then conducted a trial sequential analysis to control the risk of type I and type II errors. This meta-analysis included 23 trials with 3979 participants. We found that cranberry-based products intake can significantly reduce the incidence of UTIs in susceptible populations (risk ratio (RR) = 0.70; 95% confidence interval(CI): 0.59 ~ 0.83; P<0.01). We identified a relative risk reduction of 32%, 45% and 51% in women with recurrent UTIs (RR = 0.68; 95% CI: 0.56 ~ 0.81), children (RR = 0.55; 95% CI: 0.31 ~ 0.97) and patients using indwelling catheters (RR = 0.49; 95% CI: 0.33 ~ 0.73). Meanwhile, a relative risk reduction of 35% in people who use cranberry juice compared with those who use cranberry capsule or tablet was observed in the subgroup analysis (RR = 0.65; 95% CI: 0.54 ~ 0.77). The TSA result for the effects of cranberry intake and the decreased risk of UTIs in susceptible groups indicated that the effects were conclusive. In conclusion, our meta-analysis demonstrates that cranberry supplementation significantly reduced the risk of developing UTIs in susceptible populations. Cranberry can be considered as adjuvant therapy for preventing UTIs in susceptible populations. However, given the limitations of the included studies in this meta-analysis, the conclusion should be interpreted with caution.

Comparative analysis on immunity of volleyball players before and after taking grape procyanidins sports supplement / Análise comparativa da função de voleibol em suplemento extra-corpóreo para vegetarianos desportivos / Análisis comparativo de la función de inmunodeficiencia del voleibol utilizado por el suplemento deportivo vitro vegetariano

ABSTRACT Grape proanthocyanidin is a good health product, without side effects and excellent biological activity, but research in the field of sports tonic is still relatively slow. Currently, the technology of preparation and extraction of grape proanthocyanidins is relatively mature. This fact laid the groundwork for sports tonic proanthocyanidin research. This study first described the biological structure of proanthocyanidin in grapes, and built the immune system of volleyball players before and after taking proanthocyanidin sports supplements. He then analyzed the factors that influence immunity. The results show that the primary index subsystem is consistent with the total system in each phase, but there are still few differences over time, which can be divided into four phases: development, recession, recovery and stability; at the level of scientific training it is reasonable. Male and female athletes take exercise supplements containing proanthocyanidin at each level of training. Regarding humoral immunity and cellular immunity, there was no adverse reaction. This study may offer some reference value for other athletes before and after taking proanthocyanidin as a sports supplement.

RESUMO A proantocianidina da uva é um produto bom para a saúde, sem efeitos colaterais e excelente atividade biológica, mas a pesquisa no campo do tônico esportivo ainda é relativamente lenta. Atualmente, a tecnologia de preparação e extração das proantocianidinas de uva está relativamente madura. Este fato lançou as bases para a investigação da proantocianidina desportiva tónica. Este estudo descreveu, em primeiro lugar, a estrutura biológica da proantocianidina das uvas, e construiu o sistema imunitário dos jogadores de voleibol antes e depois de tomar suplementos desportivos de proantocianidina. Em seguida analisou os fatores que influenciam a imunidade. Os resultados mostram que o subsistema de índice primário é coerente com o sistema total em cada fase, mas ainda há poucas diferenças no tempo, que podem ser divididas em quatro fases: desenvolvimento, recessão, recuperação e estabilidade; no plano de formação científico e razoável. Os atletas do sexo masculino e feminino tomam suplementos de exercício contendo proantocianidina em cada estágio de treinamento. Com respeito à imunidade humoral e à imunidade celular não houve reação adversa. Este estudo pode oferecer algum valor de referência para outros atletas antes e depois de tomar proantocianidina como suplemento desportivo.

RESUMEN La proantocianidina de la uva es un producto bueno para la salud, sin efectos colaterales y excelente actividad biológica, pero la investigación en el campo del tónico deportivo aun es relativamente lenta. Actualmente, la tecnología de preparación y extracción de las proantocianidinas de uva está relativamente madura. Este hecho lanzó las bases para la investigación de la proantocianidina deportiva tónica. Este estudio describió, en primer lugar, la estructura biológica de la proantocianidina de las uvas, y construyó el sistema inmunitario de los jugadores de voleibol antes y después de tomar suplementos deportivos de proantocianidina. Enseguida analizó los factores que influencian la inmunidad. Los resultados muestran que el subsistema de índice primario es coherente con el sistema total en cada fase, pero aun hay pocas diferencias en el tiempo, que pueden ser divididas en cuatro fases: desarrollo, recesión, recuperación y estabilidad; en el plano de la formación científica es razonable. Los atletas del sexo masculino y femenino toman suplementos de ejercicio conteniendo proantocianidina en cada nivel de entrenamiento. Con respecto a la inmunidad humoral y a la inmunidad celular no hubo reacción adversa. Este estudio puede ofrecer algún valor de referencia para otros atletas antes y después de tomar proantocianidina como suplemento deportivo.

Glucagon Shows Higher Sensitivity than Insulin to Grapeseed Proanthocyanidin Extract (GSPE) Treatment in Cafeteria-Fed Rats.

The endocrine pancreas plays a key role in metabolism. Procyanidins (GSPE) targets ß-cells and glucagon-like peptide-1 (GLP-1)-producing cells; however, there is no information on the effects of GSPE on glucagon. We performed GSPE preventive treatments administered to Wistar rats before or at the same time as they were fed a cafeteria diet during 12 or 17 weeks. We then measured the pancreatic function and GLP-1 production. We found that glucagonemia remains modified by GSPE pre-treatment several weeks after the treatment has finished. The animals showed a higher GLP-1 response to glucose stimulation, together with a trend towards a higher GLP-1 receptor expression in the pancreas. When the GSPE treatment was administered every second week, the endocrine pancreas behaved differently. We show here that glucagon is a more sensitive parameter than insulin to GSPE treatments, with a secretion that is highly linked to GLP-1 ileal functionality and dependent on the type of treatment.

High dose versus low dose standardized cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection in healthy women: a double-blind randomized controlled trial.

PURPOSE: Our objective was to assess the efficacy of a high dose cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection. MATERIAL AND METHODS: We recruited 145 healthy, adult women with a history of recurrent urinary tract infection, defined as ≥ 2 in the past 6 months or ≥ 3 in the past 12 months in this randomized, controlled, double-blind clinical trial. Participants were randomized to receive a high dose of standardized, commercially available cranberry proanthocyanidins (2 × 18.5 mg daily, n = 72) or a control low dose (2 × 1 mg daily, n = 73) for a 24-week period. During follow-up, symptomatic women provided urine samples for detection of pyuria and/or bacteriuria and received an appropriate antibiotic prescription. The primary outcome for the trial was the mean number of new symptomatic urinary tract infections during a 24-week intervention period. Secondary outcomes included symptomatic urinary tract infection with pyuria or bacteriuria. RESULTS: In response to the intervention, a non-significant 24% decrease in the number of symptomatic urinary tract infections was observed between groups (Incidence rate ratio 0.76, 95%CI 0.51-1.11). Post-hoc analyses indicated that among 97 women who experienced less than 5 infections in the year preceding enrolment, the high dose was associated with a significant decrease in the number of symptomatic urinary tract infections reported compared to the low dose (age-adjusted incidence rate ratio 0.57, 95%CI 0.33-0.99). No major side effects were reported. CONCLUSION: High dose twice daily proanthocyanidin extract was not associated with a reduction in the number of symptomatic urinary tract infections when compared to a low dose proanthocyanidin extract. Our post-hoc results reveal that this high dose of proanthocyanidins may have a preventive impact on symptomatic urinary tract infection recurrence in women who experienced less than 5 infections per year. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT02572895.

A Ten-Day Grape Seed Procyanidin Treatment Prevents Certain Ageing Processes in Female Rats over the Long Term.

Adaptive homeostasis declines with age and this leads to, among other things, the appearance of chronic age-related pathologies such as cancer, neurodegeneration, osteoporosis, sarcopenia, cardiovascular disease and diabetes. Grape seed-derived procyanidins (GSPE) have been shown to be effective against several of these pathologies, mainly in young animal models. Here we test their effectiveness in aged animals: 21-month-old female rats were treated with 500 mg GSPE/kg of body weight for ten days. Afterwards they were kept on a chow diet for eleven weeks. Food intake, body weight, metabolic plasma parameters and tumor incidence were measured. The GSPE administered to aged rats had an effect on food intake during the treatment and after eleven weeks continued to have an effect on visceral adiposity. It prevented pancreas dysfunction induced by ageing and maintained a higher glucagon/insulin ratio together with a lower decrease in ketonemia. It was very effective in preventing age-related tumor development. All in all, this study supports the positive effect of GSPE on preventing some age-related pathologies.

Change of Serum Metabolome and Cecal Microflora in Broiler Chickens Supplemented With Grape Seed Extracts.

Grape seed is rich in vitamin E, flavonoids, and proanthocyanidins and has the potential to be used as an antibiotic substitute in broilers. We investigated the effects of grape seed proanthocyanidin extract (GSPE) on growth performance, immune responses, cecal microflora, and serum metabolism in early stage broilers. Data indicated that GSPE improved broiler growth performance by strengthening antioxidant capacity, enhancing immune responses, and increasing cecal short chain fatty acids. 16S rRNA sequencing indicated that GSPE changed the predominant cecal microflora and induced the metabolism of amino acids, lipids, and carbohydrates. An UPLC-Q-TOF/MS-based metabolomics analysis identified 23 serum metabolites (mainly related to lipid, amino acid, and alkaloid) were extremely changed by GSPE treatment. The correlations between the changes of cecal microflora and serum metabolites in birds fed with GSPE were analyzed. Hence, GSPE potentially provides active ingredients that may be used as antibiotic substitute and reduces environmental pollution by grape by-products.

Grape seed proanthocyanidins protect retinal ganglion cells by inhibiting oxidative stress and mitochondrial alteration.

Grape seed proanthocyanidins (GSP) are known as condensed tannins and have been used as an anti-oxidant in various neurodegenerative diseases. In our study, GSP was used as a daily dietary supplement and the neuroprotective effects were evaluated on the retinal ganglion cells (RGCs) in the retinal tissues in glaucomatous DBA/2D (D2) mice. D2 mice and age-matched non-glaucomatous DBA/2J-Gpnmb+ (D2-Gpnmb+) mice were fed with GSP or a control diet for up to 6 months. The intraocular pressure (IOP), RGC survival, glial fibrillary acidic protein (GFAP), the levels of apoptotic proteins, and the expression of oxidative stress markers in retinal tissues were determined. In our study, the neuroprotective effects of GSP on retinal tissues were confirmed, as evidenced by (a) GSP inhibited the IOP elevation in D2 mice; (b) GSP enhanced RGC survival and mediated the apoptotic protein expression; (c) GSP suppressed GFAP expression; and (d) the oxidative stress and the levels of mitochondrial reactive oxygen species were regulated by GSP. Our findings indicate that GSP has promising potential to preserve retinal tissue functions via regulating oxidative stress and mitochondrial functions.

Grape Seed Proanthocyanidin Extract Prevents Bone Loss via Regulation of Osteoclast Differentiation, Apoptosis, and Proliferation.

Dietary procyanidin has been shown to be an important bioactive component that regulates various pharmacological activities to maintain metabolic homeostasis. In particular, grape seed proanthocyanidin extract (GSPE) is a commercially available medicine for the treatment of venous and lymphatic dysfunction. This study aimed to investigate whether GSPE protects against lipopolysaccharide (LPS)-induced bone loss in vivo and the related mechanism of action in vitro. The administration of GSPE restored the inflammatory bone loss phenotype stimulated by acute systemic injection of LPS in vivo. GSPE strongly suppressed receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation and bone resorption activity of mature osteoclasts by decreasing the RANKL-induced nuclear factor-κB transcription activity. GSPE mediates this effect through decreased phosphorylation and degradation of NF-κB inhibitor (IκB) by IκB kinaseß, subsequently inhibiting proto-oncogene cellular Fos and nuclear factor of activated T cells. Additionally, GSPE promotes osteoclast proliferation by increasing the phosphorylation of components of the Akt and mitogen-activated protein kinase signaling pathways and it also inhibits apoptosis by decreasing the activity of caspase-8, caspase-9, and caspase-3, as corroborated by a decrease in the Terminal deoxynucleotidyl transferase dUTP nick end labeling -positive cells. Our study suggests a direct effect of GSPE on the proliferation, differentiation, and apoptosis of osteoclasts and reveals the mechanism responsible for the therapeutic potential of GSPE in osteoclast-associated bone metabolism disease.

Select Polyphenol-Rich Berry Consumption to Defer or Deter Diabetes and Diabetes-Related Complications.

Berries are considered "promising functional fruits" due to their distinct and ubiquitous therapeutic contents of anthocyanins, proanthocyanidins, phenolic acids, flavonoids, flavanols, alkaloids, polysaccharides, hydroxycinnamic, ellagic acid derivatives, and organic acids. These polyphenols are part of berries and the human diet, and evidence suggests that their intake is associated with a reduced risk or the reversal of metabolic pathophysiologies related to diabetes, obesity, oxidative stress, inflammation, and hypertension. This work reviewed and summarized both clinical and non-clinical findings that the consumption of berries, berry extracts, purified compounds, juices, jams, jellies, and other berry byproducts aided in the prevention and or otherwise management of type 2 diabetes mellitus (T2DM) and related complications. The integration of berries and berries-derived byproducts into high-carbohydrate (HCD) and high-fat (HFD) diets, also reversed/reduced the HCD/HFD-induced alterations in glucose metabolism-related pathways, and markers of oxidative stress, inflammation, and lipid oxidation in healthy/obese/diabetic subjects. The berry polyphenols also modulate the intestinal microflora ecology by opposing the diabetic and obesity rendered symbolic reduction of Bacteroidetes/Firmicutes ratio, intestinal mucosal barrier dysfunction-restoring bacteria, short-chain fatty acids, and organic acid producing microflora. All studies proposed a number of potential mechanisms of action of respective berry bioactive compounds, although further mechanistic and molecular studies are warranted. The metabolic profiling of each berry is also included to provide up-to-date information regarding the potential anti-oxidative/antidiabetic constituents of each berry.

Screening active components from Rubus amabilis for pancreatic ß-cells protection.

CONTEXT: Rubus species (Rosaceae) have been used in folk medicine to treat diabetes due to their hypoglycaemic activity. OBJECTIVE: To screen the active components that act as hypoglycaemic agents in Rubus amabilis Focke and the underlying mechanisms. MATERIALS AND METHODS: Aqueous stem extract of R. amabilis was incubated with MIN6 ß-cells, PBS was used as the blank control. Then the cells were washed, cell membrane-bound components were dissociated and identified by UPLC/MS. Total procyanidins (PCs) in R. amabilis was enriched and the cytotoxicity and anti-proliferation on ß-cell were evaluated by MTT assay. PCs at 25, 50, and 75 µg/mL was applied for 24 h to determine its effects on palmitate (PA)-induced apoptosis and GSIS. Western blotting was employed to detect the protein expression of PI3K/Akt/FoxO1 signalling. The antioxidant indices were also measured. RESULTS: ß-Cell membrane-bound components were identified as three procyanidin B dimers and a C trimer. PCs showed no significant cytotoxicity up to a concentrations of 100 µg/mL. PCs treatment reversed the elevated apoptosis rate and impaired GSIS induced by PA. PCs markedly decreased the intracellular ROS and MDA production and increased the SOD activity. Moreover, PCs promoted the phosphorylation of Akt and FoxO1, and regulated Pdx-1 and Bax expression in MIN6 cells. Discussion and conclusion: The active components that act as hypoglycaemic agents in R. amabilis are procyanidins, which protected MIN6 cells against PA-induced apoptosis by activating PI3K/Akt/FoxO1 signalling. These results indicate that ß-cell extraction, combined with UPLC/MS, is a valid method for screening antidiabetic components from herbal medicines.

Administration of Apple Polyphenol Supplements for Skin Conditions in Healthy Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

This clinical study was performed to evaluate the effects of continuous apple polyphenol (AP) administration on facial skin conditions and pigmentation induced by ultraviolet (UV) irradiation in healthy women participants. Participants (n = 65, age 20-39 years) were randomized to receive tablets containing AP (300 or 600 mg/day) or placebo in a double-blinded, placebo-controlled clinical trial. Continuous administration of AP for 12 weeks significantly prevented UV irradiation induced skin pigmentation (erythema value, melanin value, L value), although a dose-dependent relationship was not clearly observed. In contrast, no significant differences were detected between the groups with regard to water content and trans-epidermal water loss. Our study demonstrated that APs and their major active compounds, procyanidins, have several health benefits. Here, we report that continuous administration of AP for 12 weeks alleviated UV irradiation induced skin pigmentation, when compared with placebo, in healthy women.

Design and Characterization of Chitosan-Graphene Oxide Nanocomposites for the Delivery of Proanthocyanidins.

INTRODUCTION: In the last years, the utilization of phytomedicines has increased given their good therapeutic activity and fewer side effects compared to allopathic medicines. However, concerns associated with the biocompatibility and toxicity of natural compounds, limit the phytochemical therapeutic action, opening the opportunity to develop new systems that will be able to effectively deliver these substances. This study has developed a nanocomposite of chitosan (CS) functionalized with graphene oxide (GO) for the delivery of proanthocyanidins (PAs), obtained from a grape seed extract (Ext.). METHODS: The GO-CS nanocomposite was covalently bonded and was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), atomic force microscopy (AFM) and by dynamic light scattering (DLS). The loading and release of Ext. from the GO-CS nanocomposite were performed in simulated physiological, and the cytotoxicity of the raw materials (GO and Ext.) and nanocomposites (GO-CS and GO-CS-Ext.) was determined using a human kidney cell line (HEK 293). RESULTS: The chemical characterization indicated that the covalent union was successfully achieved between the GO and CS, with 44 wt. % CS in the nanocomposite. The GO-CS nanocomposite was thermostable and presented an average diameter of 480 nm (by DLS). The Ext. loading capacity was approximately 20 wt. %, and under simulated physiological conditions, 28.4 wt.% Ext. (g) was released per g of the nanocomposite. GO-CS-Ext. was noncytotoxic, presenting a 97% survival rate compared with 11% for the raw extract and 48% for the GO-CS nanocomposite at a concentration of 500 µg mL-1 after 24 hrs. CONCLUSION: Due to π-π stacking and hydrophilic interactions, GO-CS was reasonably efficient in binding Ext., with high loading capacity and Ext. release from the nanocomposite. The GO-CS nanocomposite also increased the biocompatibility of PAs-rich Ext., representing a new platform for the sustained release of phytodrugs.

Wild blueberry proanthocyanidins shape distinct gut microbiota profile and influence glucose homeostasis and intestinal phenotypes in high-fat high-sucrose fed mice.

Blueberries are a rich source of polyphenols, widely studied for the prevention or attenuation of metabolic diseases. However, the health contribution and mechanisms of action of polyphenols depend on their type and structure. Here, we evaluated the effects of a wild blueberry polyphenolic extract (WBE) (Vaccinium angustifolium Aiton) on cardiometabolic parameters, gut microbiota composition and gut epithelium histology of high-fat high-sucrose (HFHS) diet-induced obese mice and determined which constitutive polyphenolic fractions (BPF) was responsible for the observed effects. To do so, the whole extract was separated in three fractions, F1) Anthocyanins and phenolic acids, F2) oligomeric proanthocyanidins (PACs), phenolic acids and flavonols (PACs degree of polymerization DP < 4), and F3) PACs polymers (PACs DP > 4) and supplied at their respective concentration in the whole extract. After 8 weeks, WBE reduced OGTT AUC by 18.3% compared to the HFHS treated rodents and the F3 fraction  contributed the most to this effect. The anthocyanin rich F1 fraction did not reproduce this response. WBE and the BPF restored the colonic mucus layer. Particularly, the polymeric PACs-rich F3 fraction increased the mucin-secreting goblet cells number. WBE caused a significant 2-fold higher proportion of Adlercreutzia equolifaciens whereas oligomeric PACs-rich F2 fraction increased by 2.5-fold the proportion of Akkermansia muciniphila. This study reveals the key role of WBE PACs in modulating the gut microbiota and restoring colonic epithelial mucus layer, providing a suitable ecological niche for mucosa-associated symbiotic bacteria, which may be crucial in triggering health effects of blueberry polyphenols.

Grape Seed Proanthocyanidin Extract Mitigates Titanium Dioxide Nanoparticle (TiO2-NPs)-Induced Hepatotoxicity Through TLR-4/NF-κB Signaling Pathway.

With the progress of nanotechnology, the adverse effects of nanoscale materials are receiving much attention. Inhibition of toll-like receptor 4 (TLR-4)/nuclear factor kappa B (NF-κB) signaling is a hallmark for downregulating the expression of many inflammatory genes implicated in oxidative stress. Therefore, the present study aimed to demonstrate the influence of grape seed proanthocyanidin extract (GSE) on the hepatic TLR-4/ NF-κB signaling pathway in TiO2-NP-induced liver damage in rats. Forty male Albino rats were divided into 4 groups (n = 10): G1 was used as a control, G2 received TiO2-NPs (500 mg/kg/day orally) from the 17th to 30th day (acute toxicity), G3 received GSE (75 mg/kg/day orally) for 30 days, and G4 pre- and co-treated with GSE (for 30 days) and TiO2-NPs (from the 17th to 30th day), with the aforementioned doses. TiO2-NPs induced severe hepatic injury that was indicated by biochemical alterations in serum liver markers (acetylcholinesterase, ALT, ALP, total proteins, albumin, and direct bilirubin), oxidative stress indicators (MDA, GSH, and catalase), and histopathological alterations as well. Moreover, TiO2-NPs triggered an inflammatory response via the upregulation of TLR-4, NF-κB, NIK, and TNF-α mRNA expressions. Pre- and co-treatments with GSE alleviated the detrimental effects of TiO2-NPs which were enforced by the histopathological improvements. These results indicated that GSE effectively protected against TiO2-NP-induced hepatotoxicity via the inhibition of TLR-4/NF-κB signaling and hence suppressed the production of pro inflammatory cytokines such as TNF-α and improved the antioxidant status of the rats.

Alleviation Effect of Grape Seed Proanthocyanidins on Neuronal Apoptosis in Rats with Iron Overload.

We aimed to evaluate the effect of grape seed proanthocyanidins (GSPCs) on neuronal apoptosis, particularly through their roles in maintaining divalent mineral element balance and resisting oxidation in rats with iron overload. A total of 40 Sprague-Dawley rats were randomly divided into control, iron overload, GSPCs, and iron overload + GSPCs groups. The iron, calcium, zinc, magnesium, and copper contents in the brain tissue of the rats were measured using inductively coupled plasma mass spectrometry. Their oxidative stress state was determined using the relevant kit. The number of apoptotic neurons was evaluated using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and synaptosome numbers were determined using the immunohistochemical approach. Fas, Bax, and Bcl-2 gene expressions in the cortex and hippocampus were detected using quantitative real-time polymerase chain reaction. After 7 weeks, compared with the control group, the zinc and magnesium contents; superoxide dismutase, glutathione peroxidase, and catalase activities; and synaptophysin and Bcl-2 gene expressions in the iron overload group were significantly decreased, whereas the iron, calcium contents, and malondialdehyde contents; TUNEL-positive cell numbers; and Fas and Bax gene expressions were significantly increased. There were no significant changes in the copper content. Conversely, the rats exhibited better recovery when GSPCs were used instead of iron alone. In summary, GSPCs protected against iron overload induced neuronal apoptosis in rats by maintaining the divalent mineral element balance, reducing oxidative stress, and regulating apoptotic genes expressions.

Long-Lasting Effects of GSPE on Ileal GLP-1R Gene Expression Are Associated with a Hypomethylation of the GLP-1R Promoter in Female Wistar Rats.

Flavonoids have been shown to modulate GLP-1 in obesity. GLP-1 induces some of its effects through the intestinal GLP-1 receptor (GLP-1R), though no data exist on how flavonoids affect this receptor. Here, we examine how a dose of grape seed proanthocyanidin extract (GSPE) with anti-obesity activity affects intestinal GLP-1R and analyze whether epigenetics play a role in the long-lasting effects of GSPE. We found that 10-day GSPE administration prior to the cafeteria diet upregulated GLP-1R mRNA in the ileum 17 weeks after the GSPE treatment. This was associated with a hypomethylation of the GLP-1R promoter near the region where the SP1 transcription factor binds. In the colon, the cafeteria diet upregulated GLP-1R without showing any GSPE effect. In conclusion, we have identified long-lasting GSPE effects on GLP-1R gene expression in the ileum that are partly mediated by hypomethylation at the gene promoter and may affect the SP1 binding factor.

Effects of Grape Seed Proanthocyanidin Extract on Vascular Endothelial Function in Participants with Prehypertension: A Randomized, Double-Blind, Placebo-Controlled Study.

This study aimed to investigate the effects of grape seed proanthocyanidin extract (GSPE) on blood pressure and vascular endothelial function in middle-aged Japanese adults with prehypertension. We conducted a randomized, double-blind, placebo-controlled study on 6 men and 24 women aged 40-64 years old. The participants were randomized to receive tablets containing either low-dose (200 mg/day) or high-dose (400 mg/day) GSPE, or placebo, for 12 weeks. Systolic and diastolic blood pressures (SBP and DBP, respectively), brachial flow-mediated dilation (FMD), and other cardiovascular parameters were measured before and after 4, 8, and 12 weeks of treatment. The mean SBP in the high-dose group significantly decreased by 13 mmHg after 12 weeks (P = 0.028), although FMD did not change. In an ad hoc analysis of non-smoking participants (n = 21), the mean SBP, DBP, stiffness parameter ß, distensibility, incremental elastic modulus (Einc), and pulse wave velocity (PWV) also significantly improved in the high-dose group after 12 weeks. Changes in Einc and PWV from baseline to 12 weeks were significantly greater in the high-dose group than in the placebo group (Einc, P = 0.023; PWV, P = 0.03). GSPE consumption could help maintain vascular elasticity and normal blood pressure in this population.

Assessment of in situ techniques to determine indigestible components in the feed and feces of cattle receiving supplemental condensed tannins1.

Reliable assessments of indigestible dietary components are required when using internal markers to estimate diet digestibility and determine the potentially digestible portion of the fiber. The lack of a standardized methodology and understanding of how antinutritional factors influence indigestible residues can result in erroneous estimates with inconsistent variation across trials and among studies. Previous studies have detailed suitable bag porosity and sample size (SS) with incubation length (IL) varying from 96 to 504 h, with many assuming that 288-h IL yields truly indigestible components. Recent studies have primarily investigated the variation that exists among feedstuffs, but most have failed to account for possible effects of secondary compounds. Using 2 similar concentrate diets, one of which contained supplemental condensed tannins (CT), we investigated the effect of bag type (BT; 10 and 25 µm), SS (20 and 40 mg/cm2), and IL (288 and 576 h) on in situ indigestible DM (iDM) and neutral detergent fiber (iNDF) residues of feed and feces, and resultant DM and NDF digestibilities. There were no 3-way interactions (P > 0.05), but 2-way interactions were present for iDM and iNDF residues with BT × SS influencing the control (no CT) ration (P < 0.01), SS × IL impacting feed containing CT (P < 0.01), and BT × IL affecting both feedstuffs (P ≤ 0.01). For the control diet, only BT × SS affected DM and NDF digestibilities. Whereas the CT diet did not demonstrate any significant interactions for digestibilities. Values of iDM were largely influenced by contamination that varied greatly based on intrinsic factors associated with the bag and incubation duration. The presence of CT influenced iDM and iNDF to varying degrees due to possible trapping of CT-substrate complexes. For the control diet, the use of 25-µm bags resulted in lower fecal recoveries relative to the 10 µm (P < 0.01). However, there appears to be a dynamic relationship among BT, SS, and IL within respective diets and sample types that can affect indigestible components and resultant digestibility estimates. Based on simulations from these data, the sample size required to attain 90% power when utilizing 2 incubation animals exceeds the triplicate and quadruplicate replications commonly utilized. Further emphasizing the necessity for a more complete understanding of incubation dynamics to design biologically and statistically valid investigations.