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.

Regulation of Enteric Infection and Immunity by Dietary Proanthocyanidins.

The role of dietary components in immune function has acquired considerable attention in recent years. An important focus area is to unravel the role of bioactive dietary compounds in relation to enteric disease and their impact on gut mucosal immunity. Proanthocyanidins (PAC) are among the most common and most consumed dietary polyphenols, and are characterised by their variable molecular structures and diverse bioactivities. In particular, their anti-oxidative effects and ability to modulate gut microbiota have been widely described. However, there is limited evidence on the mechanism of action of PAC on the immune system, nor is it clearly established how PAC may influence susceptibility to enteric infections. Establishing the sites of action of PAC and their metabolites within the gut environment is fundamental to determine the applicability of PAC against enteric pathogens. Some mechanistic studies have shown that PAC have direct modulatory effects on immune cell signalling, isolated pathogens, and gut mucosal barrier integrity. Boosting the recruitment of immune cells and suppressing the amount of pro-inflammatory cytokines are modulating factors regulated by PAC, and can either be beneficial or detrimental in the course of re-establishing gut homeostasis. Herein, we review how PAC may alter distinct immune responses towards enteric bacterial, viral and parasitic infections, and how the modulation of gut microbiota may act as a mediating factor. Furthermore, we discuss how future studies could help unravel the role of PAC in preventing and/or alleviating intestinal inflammation and dysbiosis caused by enteric disease.

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.

Procyanidin B2 Promotes Intestinal Injury Repair and Attenuates Colitis-Associated Tumorigenesis via Suppression of Oxidative Stress in Mice.

Aims: Intact intestinal epithelium is essential to maintain normal intestinal physiological function. Irradiation-induced gastrointestinal syndrome or inflammatory bowel disease occurred when epithelial integrity was impaired. This study aims at exploring the mechanism of procyanidin B2 (PB2) administration to promote intestinal injury repair in mice. Results: PB2 treatment reduces reactive oxygen species (ROS) accumulation and protects the intestine damage from irradiation. Mechanistic studies reveal that PB2 could effectively slow down the degradation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and it significantly triggers Nrf2 into the nucleus, which leads to subsequent antioxidant enzyme expression. However, knockdown of Nrf2 attenuates PB2-induced protection in the intestine. More importantly, PB2 also promotes leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5)-positive intestinal stem cells (Lgr5+ ISCs) driven regeneration via enhancing Wnt/ß-catenin signaling, which depends on, at least in part, activation of the Nrf2 signal. Evidence from an injury model of intestinal organoids is similar with in vivo results. Correspondingly, results from flow cytometric analysis and luciferase reporter assay reveal that PB2 also inhibits the level of ROS and promotes Lgr5 expression in vitro. Finally, PB2 alleviates the severity of experimental colitis and colitis-associated cancer in a long-term inflammatory model via inhibiting nuclear localization of p65. Innovation: This study, for the first time, reveals a role of PB2 for intestinal regeneration and repair after radiation or dextran sulfate sodium-induced injury in mice. Conclusion: Our results indicate that PB2 can repress oxidative stress via Nrf2/ARE signaling and then promote intestinal injury repair.

Influence of dietary inclusion of tannin extracts from mimosa, chestnut and tara on volatile compounds and flavour in lamb meat.

Tannins are compounds able to form complexes with proteins limiting their ruminal degradation and thus the synthesis of some odour-active compounds may be inhibited. Tannins are broadly divided in condensed tannins (CT) and hydrolysable tannins (HT). The study aimed to assess the influence of dietary inclusion of three commercial tannin extracts, namely mimosa (Acacia mearnsii; CT), chestnut (Castanea sativa; HT) or tara (Caesalpinia spinosa; HT) on volatile profile and flavour of meat and kidney fat from lambs. Comisana male lambs were divided into four groups (n = 9 each) and fed for 75 days with a concentrate-based diet (CON) or CON supplemented with 4% of one of the tannin extracts. Tannins reduced "pastoral" odour in perirenal fat of lambs the meat of which was characterized by a very low perception of this attribute. It may be assumed that p-cresol and 8-methylnonanoic acid mostly contributed to "pastoral" odour expression in the diet without condensed or hydrolysable tannins.

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.

Cinnamtannin D1 Protects Pancreatic ß-Cells from Glucolipotoxicity-Induced Apoptosis by Enhancement of Autophagy In Vitro and In Vivo.

In our previous study, cinnamtannin D1 (CD-1), one of the A-type procyanidin oligomers isolated from Cinnamomum tamala, was reported to have the activity of antiapoptosis in palmitic acid-treated pancreatic ß cells via alleviating oxidative stress in vitro. In this study, the aim was to further disclose its protective effect and underlying mechanisms against glucolipotoxicity-induced ß-cells apoptosis in vitro and in vivo. We found that CD-1 was able to dose-dependently and time-dependently activate autophagy in INS-1 pancreatic ß-cells. High glucose and palmitic acid (HG/PA)-induced apoptosis and autophagy impairment could be attenuated by CD-1 in INS-1 cells as well as primary cultured murine islets. We also demonstrated that CD-1-induced autophagy was through AMPK/mTOR/ULK1 pathway. Moreover, it was shown that the effects of CD-1 on activation of Keap1/Nrf2 antioxidant signaling pathway and the amelioration of inflammation, endoplasmic reticulum stress, and apoptosis were through autophagy induction in HG/PA-treated INS-1 cells. These protective effects in vivo and hypoglycemic activity of CD-1 were also observed in diabetic db/db mice. These findings have great significance in revealing the antidiabetic mechanisms of procyanidin oligomers and paving the way for their application in the treatment of diabetes.

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.

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.

Procyanidin B2 Improves Oocyte Maturation and Subsequent Development in Type 1 Diabetic Mice by Promoting Mitochondrial Function.

Type 1 diabetes (T1D) results in decreased oocyte quality and compromised early embryonic development. Procyanidin B2 (PB2) is a natural compound extracted from grape seeds and has strong antioxidant activity in vivo. This study evaluated the effect of PB2 on oocyte maturation in diabetic mice. Diabetic mice were induced by streptozotocin (STZ) injection. PB2 was supplemented in the in vitro maturation medium, and the ratio of germinal vesicle breakdown (GVBD) and polar body extrusion (PBE), reactive oxygen species (ROS) levels, mitochondrial function, developmental ability, as well as crotonylation at H4K5 were determined in oocytes. PB2 can promote the extrusion of PBE (88.34% vs. 75.02%, P < 0.05); reduce the generation of ROS (1.12 vs. 1.96, P < 0.05); and improve the level of mitochondrial membrane potential (0.87 vs. 0.79 Δφm, P < 0.05), ATP level (1.31 vs. 0.71 pmol, P < 0.05), and mitochondria temperature (618.25 vs. 697.39 pixels, P < 0.05). The addition of PB2 also improved the level of oocyte crotonylation at H4K5 (crH4K5) (47.26 vs. 59.68 pixels, P < 0.05) and increased the blastocyst rate (61.51% vs. 36.07%, P < 0.05) after parthenogenetic activation. Our results are the first to reveal a role for PB2 in promoting the viability of oocytes by regulating the mitochondrial function. Moreover, we uncover that PB2 can improve the level of crH4K5, which provides a new strategy to combat the decline in oocyte quality of diabetic.

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.

Proanthocyanidin promotes functional recovery of spinal cord injury via inhibiting ferroptosis.

Improving the microenvironment of lesioned spinal cord to minimize the secondary injury is one important strategy to treat spinal cord injury (SCI). The ensuing hemorrhage after SCI has tight connection with ferroptosis. This study investigated the effects of proanthocyanidins (PACs) on SCI repair and the underlying mechanisms. Adult female mice were divided into four groups, including sham, SCI, PACs5 and PACs10 (i.p. 5 and 10 mg/kg PACs after SCI respectively). The impacts of SCI and PACs treatment on redox parameters (iron contents, TBARS, GSH, and GPX activities) and ferroptosis essential factors such as ACSL4, LPCAT3, Alox15B, Nrf2, HO-1, GPX4 were investigated. The results demonstrated that PACs treatment significantly decreased the levels of iron, TBARS, ACSL4, and Alox15B, while increased the levels of GSH, GPX4, Nrf2, and HO-1 in traumatic spinal cords. Above all, PACs improved the locomotive function of SCI mice. These results suggest that PACs might be potential therapeutics for SCI repair by inhibiting ferroptosis in SCI.

Protective Effect of Procyanidin B2 on Acute Liver Injury Induced by Aflatoxin B 1 in Rats.

OBJECTIVE: This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B 1 (AFB 1) in rats. METHODS: Forty Sprague Dawley rats were randomly divided into control, AFB 1, AFB 1 + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB 1 groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB 1 and AFB 1 + PCB2 groups were intraperitoneally injected with AFB 1 (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured. RESULTS: AFB 1 significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB 1. CONCLUSION: Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB 1.

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.