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Inflammatory bowel conditions can involve nearly all organ systems and induce pathological processes through increased oxidative stress, lipid peroxidation and disruption of the immune response. Patients with inflammatory bowel disease (IBD) are at high risk of having extra-intestinal manifestations, for example, in the hepatobiliary system. In 30% of patients with IBD, the blood values of liver enzymes, such as AST and ALT, are increased. Moreover, treatments for inflammatory bowel diseases may cause liver toxicity. Apple polyphenol extracts are widely acknowledged for their potential antioxidant effects, which help prevent damage from oxidative stress, reduce inflammation, provide protection to the liver, and enhance lipid metabolism. The aim of this study was to investigate whether the polyphenol apple extract from Malus domestica cv. 'Limoncella' (LAPE) may be an effective intervention for the treatment of IBD-induced hepatotoxicity. The LAPE was administrated in vivo by oral gavage (3-300 mg/kg) once a day for 3 consecutive days, starting 24 h after the induction of dinitro-benzenesulfonic acid (DNBS) colitis in mice. The results showed that LAPE significantly attenuated histological bowel injury, myeloperoxidase activity, tumor necrosis factor and interleukin (IL-1β) expressions. Furthermore, LAPE significantly improved the serum lipid peroxidation and liver injury in DNBS-induced colitis, as well as reduced the nuclear transcription factor-kappaB activation. In conclusion, these results suggest that LAPE, through its antioxidant and anti-inflammatory properties, could prevent liver damage induced by inflammatory bowel disease.

Context: Da-Yuan-Yin is a Chinese traditional prescription., Objective: This study explores the therapeutic effects of the Da-Yuan-Yin decoction polyphenol fraction (DYY-4) on acute lung injury (ALI) in mice induced by lipopolysaccharide (LPS)., Materials and Methods: The mice ( n  = 10) were orally administrated with DYY-4 (15, 30, and 60 mg/kg) or DXM (5 mg/kg), half an hour after LPS (2 mg/kg) instilled intratracheally. The protein content and the levels of inflammatory factors, the levels of complements, the mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the level of myeloperoxidase (MPO) and superoxide dismutase (SOD), the expression of the IkB kinase (IKK) and nuclear factor-kappa B (NF-κB), the lung wet-to-dry weight (W/D) ratio and lung tissue were evaluated, 24 h after LPS challenge. Network pharmacology predicted potential targets., Results: DYY-4 (30, 60 mg/kg, p  < 0.01, p  < 0.01) decreased the lung W/D ratio, total protein concentration, the levels of C3, C3c and C5a, the levels of TNF-α, IL-6, and IL-1β, while increased the levels of IL-4 and IL-10. DYY-4 (60 mg/kg) decreased the levels of C5aR1, C5b-9 and COX-2 mRNA ( p  < 0.05), the levels of MPO and iNOS mRNA, the activation of the IKK/NF-κB pathway ( p  < 0.01), and increased the levels of IL-13 and SOD ( p  < 0.01). DYY-4 (60 mg/kg) relieved the lung tissue pathological changes and reduced the C3c deposition., Discussion and Conclusions: Network pharmacology combined with animal experiments revealed the targets of DYY-4 alleviating ALI.

The current study aims to quantify HPLC-DAD polyphenolics in the crude extracts of Desmodium elegans, evaluating its cholinesterase inhibitory, antioxidant, molecular docking and protective effects against scopolamine-induced amnesia in mice. A total of 16 compounds were identified which include gallic acid (239 mg g -1 ), p-hydroxybenzoic acid (11.2 mg g -1 ), coumaric acid (10.0 mg g -1 ), chlorogenic acid (10.88 mg g -1 ), caffeic acid (13.9 mg g -1 ), p-coumaroylhexose (41.2 mg g -1 ), 3-O-caffeoylquinic acid (22.4 mg g -1 ), 4-O-caffeoylquinic acid (6.16 mg g -1 ), (+)-catechin (71.34 mg g -1 ), (-)-catechin (211.79 mg g -1 ), quercetin-3-O-glucuronide (17.9 mg g -1 ), kaempferol-7-O-glucuronide (13.2 mg g -1 ), kaempferol-7-O-rutinoside (53.67 mg g -1 ), quercetin-3-rutinoside (12.4 mg g -1 ), isorhamnetin-7-O-glucuronide (17.6 mg g -1 ) and isorhamnetin-3-O-rutinoside (15.0 mg g -1 ). In a DPPH free radical scavenging assay, the chloroform fraction showed the highest antioxidant activity, with an IC 50 value of 31.43 µg mL -1 . In an AChE inhibitory assay, the methanolic and chloroform fractions showed high inhibitory activities causing 89% and 86.5% inhibitions with IC 50 values of 62.34 and 47.32 µg mL -1 respectively. In a BChE inhibition assay, the chloroform fraction exhibited 84.36% inhibition with IC 50 values of 45.98 µg mL -1 . Furthermore, molecular docking studies revealed that quercetin-3-rutinoside and quercetin-3-O-glucuronide fit perfectly in the active sites of AChE and BChE respectively. Overall, the polyphenols identified exhibited good efficacy, which is likely as a result of the compounds' electron-donating hydroxyl groups (-OH) and electron cloud density. The administration of methanolic extract improved cognitive performance and demonstrated anxiolytic behavior among tested animals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Genus Quercus is a well-known source for its polyphenolic content and important biological activity. Plants belonging to the Quercus genus were traditionally used in asthma, inflammatory diseases, wound healing, acute diarrhea, and hemorrhoid. Our work intended to study the polyphenolic profile of the Q. coccinea (QC) leaves and to assess the protective activity of its 80% aqueous methanol extract (AME) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Together, the potential molecular mechanism was investigated. Nineteen polyphenolic compounds (1-18), including tannins, flavone, and flavonol glycosides. Phenolic acids and aglycones were purified and identified from the AME of QC leaves. Treatment with AME of QC showed an anti-inflammatory effect evidenced by a remarkable decline in the count of white blood cells and neutrophils which was in harmony with decreasing the levels of high mobility group box-1, nuclear factor kappa B, tumor necrosis factor-α, and interleukin 1 beta. In addition, the antioxidant activity of QC was documented through the significant reduction in malondialdehyde level and elevation of reduced glutathione level and superoxide dismutase activity. Furthermore, the mechanism involved in the pulmonary protective effect of QC involved the downregulation of the TLR4/MyD88 pathway. The AME of QC showed a protective effect against LPS-induced ALI through the powerful anti-inflammatory and antioxidant activities which are linked to its abundancy with polyphenols., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Sepsis is a life-threatening organ dysfunction caused by a dysregulated and unbalanced immune response to microbial infection. Restoring immune homeostasis and infection control are considered the primary strategies to manage sepsis. Natural bioactives such as polysaccharide and polyphenols from botanicals are known for their immune modulation activity. In this study, we evaluated a standardized aloe-based composition, UP360 (constitute of polysaccharides from Aloe barbadense and Poria cocos and polyphenols from Rosemary officinalis ) in lipopolysaccharide (LPS)-induced sepsis and acute inflammatory lung injury murine models. Prophylactic oral administration of UP360 for 7 days at an oral dose of 500 mg/kg improved the survival rate of mice by 62.5%, whereas all mice in the vehicle control group were deceased 82 h after LPS injection. The merit of combining these traditional herbs to yield the standardized composition UP360 was also demonstrated in this model with a mortality rate of only 30.8%, whereas 76.9%, 53.9%, and 61.5% were recorded for each individual constituents A. barbadense , P. cocos , and R. officinalis , respectively. Dose-correlated statistically significant reductions in proinflammatory cytokines and chemokine tumor necrosis factor alpha (TNF- α ), interleukin (IL)-1 β , IL-6, and cytokine-induced neutrophil chemoattractant (CINC)-3 were observed for UP360 when administered at 250 and 500 mg/kg orally for 7 days before induction of acute lung injury (ALI) model in rats. The histopathology data from lung showed statistically significant 37.9% and 37% reductions in the overall lung damage severity and pulmonary edema, respectively, for UP360-treated rats. The aloe-based composition UP360 effectively improved the survival rate of septic animals and mitigated the severity of LPS-induced ALI in vivo . These data warrant further investigation of the composition for a potential application in human as an adjunct supplement in respiratory distress and sepsis.

Green-tea-based products and their polyphenols, especially epigallocatechin-3-gallate, have attracted great attention over the years as possible nutraceuticals, due to their promising bioactivities, especially antioxidant and anti-inflammatory, which could be exploited in several diseases, including skin ailments. In this context, the present study aimed at reviewing clinical evidence about the benefits of the oral administration of green tea preparations and its polyphenols to relieve skin disorders, to point out the current knowledge, and to suggest possible novel strategies to effectively exploit the properties of green tea, also managing safety risks. To this end, a systematic review of the existing literature was carried out, using the PRISMA method. Few studies, including five focused on UV-induced erythema and skin alterations, three on photoaging, two on antioxidant skin defenses, and one on acne and genodermatosis, were retrieved. Despite several benefits, clinical evidence only supports the use of oral green tea preparations to protect skin from damage induced by ultraviolet radiation; in other cases, conflicting results and methodological limits of clinical trials do not allow one to clarify their efficacy. Therefore, their application as adjuvant or alternative sunscreen-protective interventions could be encouraged, in compliance with the safety recommendations.

Background: Type 2 diabetes mellitus (T2DM) is commonly associated with hyperglycemia, dyslipidemia, oxidative stress and inflammation which are well known cardiovascular risk factors. Pomegranate peel polyphenols have a proven hypolipemic, antioxidant and anti-inflammatory activity. However, there is a lack of clinical studies that would confirm its antioxidant and anti-inflammatory effects in diabetic patients. The potential of pomegranate peel extract (PoPEx) to counteract inflammation and oxidative stress in T2DM patients was investigated. For this purpose, a randomized, double-blind placebo-controlled study involving adult T2DM patients treated with PoPEx or placebo for eight-weeks was conducted., Methods: Patients were randomly divided into two groups: the first group (n = 30) received capsules containing PoPEx 250 mg twice daily, while the placebo group (n = 30) received placebo capsules twice daily. Plasma concentration of inflammatory factors (interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and high sensitivity C reactive protein (hsCRP)), oxidative stress biomarkers (thiobarbituric acid reactive substances (TBARS), nitrites (NO2-), superoxide anion radical (O2-), hydrogen peroxide (H2O2), total antioxidant capacity (TAC)), homocysteine and lipid profile were analyzed., Results: The PoPEx treatment showed a significant reduction of inflammatory factors (IL-6, TNF-α, hsCRP), oxidative stress biomarkers (TBARS, NO2-, O2-) and homocysteine, while the TAC was increased. Moreover, a significant improvement in lipid profile was observed in the PoPEx group. Additional analysis showed a significant inverse correlation between the decrements of all measured inflammatory markers and TAC in the PoPEx group., Conclusions: The study demonstrated that eight-week-long PoPEx administration had favorable effects on inflammatory status and oxidative stress biomarkers in diabetic patients., Competing Interests: The authors declare no conflict of interest. Vladimir Jakovljević and Dragan M Djuric are serving as Guest editors of this journal. We declare that Vladimir Jakovljević and Dragan M Djuric had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Peter A. McCullough., (© 2022 The Author(s). Published by IMR Press.)

Environmentally hazardous substances such as pesticides are gaining increasing interest in agricultural and nutritional research. This study aims to investigate the impact of these compounds on the healthspan and mitochondrial functions in an invertebrate in vivo model and in vitro in SH-SY5Y neuroblastoma cells, and to investigate the potential of polyphenolic metabolites to compensate for potential impacts. Wild-type nematodes ( Caenorhabditis elegans, N2) were treated with pesticides such as pyraclostrobin (Pyr), glyphosate (Gly), or fluopyram (Fluo). The lifespans of the nematodes under heat stress conditions (37 °C) were determined, and the chemotaxis was assayed. Energetic metabolites, including adenosine triphosphate (ATP), lactate, and pyruvate, were analyzed in lysates of nematodes and cells. Genetic expression patterns of several genes associated with lifespan determination and mitochondrial parameters were assessed via qRT-PCR. After incubation with environmentally hazardous substances, nematodes were incubated with a pre-fermented polyphenol mixture (Rechtsregulat ® Bio, RR) or protocatechuic acid (PCA) to determine heat stress resistance. Treatment with Pyr, Glyph and Fluo leads to dose-dependently decreased heat stress resistance, which was significantly improved by RR and PCA. The chemotaxes of the nematodes were not affected by pesticides. ATP levels were not significantly altered by the pesticides, except for Pyr, which increased ATP levels after 48 h leads. The gene expression of healthspan and mitochondria-associated genes were diversely affected by the pesticides, while Pyr led to an overall decrease of mRNA levels. Over time, the treatment of nematodes leads to a recovery of the nematodes on the mitochondrial level but not on stress resistance on gene expression. Fermented extracts of fruits and vegetables and phenolic metabolites such as PCA seem to have the potential to recover the vitality of C. elegans after damage caused by pesticides.

Polyphenols have long been recognized as health-promoting entities, including beneficial effects on cardiovascular disease, but their reputation has been boosted recently following a number of encouraging clinical studies in multiple chronic pathologies, that seem to validate efficacy. Health benefits of polyphenols have been linked to their well-established powerful antioxidant activity. This review aims to provide comprehensive and up-to-date knowledge on the current therapeutic status of polyphenols having sufficient heed towards the treatment of cardiovascular diseases. Furthermore, data about the safety profile of highly efficacious polyphenols has also been investigated to further enhance their role in cardiac abnormalities. Evidence is presented to support the action of phenolic derivatives against cardiovascular pathologies by following receptors and signaling pathways which ultimately cause changes in endogenous antioxidant, antiplatelet, vasodilatory, and anti-inflammatory activities. In addition, in vitro antioxidant and pre-clinical and clinical experiments on anti-inflammatory as well as immunomodulatory attributes of polyphenols have revealed their role as cardioprotective agents. However, an obvious shortage of in vivo studies related to dose selection and toxicity of polyphenols makes these compounds a suitable target for clinical investigations. Further studies are needed for the development of safe and potent herbal products against cardiovascular diseases. The novelty of this review is to provide comprehensive knowledge on polyphenols safety and their health claims. It will help researchers to identify those moieties which likely exert protective and therapeutic effects towards cardiovascular diseases., Competing Interests: The authors report no conflicts of interest for this work., (© 2021 Alotaibi et al.)

Objectives: To test the hypotheses that estimated mean pulmonary arterial pressure (MPAP) decreases and pulmonary vascular maturation, assessed by the ratio of pulmonary arterial flow acceleration time to ejection time (AT/ET ratio), increases after reversal of fetal ductus arteriosus constriction by reducing maternal intake of the causal agent (prostaglandin inhibitors, such as polyphenol-rich foods or non-steroidal anti-inflammatory drugs), and that these effects are independent of gestational age, which are inferences not yet demonstrated in the clinical setting., Methods: This was a prospective cohort study comparing Doppler echocardiographic ductal flow dynamics, MPAP and pulmonary arterial flow AT/ET ratio in third-trimester fetuses (≥ 28 weeks' gestation) with ductus arteriosus constriction, at the time of diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors either by suspending the use of pharmacological agents with potential for prostaglandin inhibition or by restricting the consumption of polyphenol-rich foods. MPAP was estimated using the Dabestani equation (MPAP = 90 - (0.62 × AT)), and pulmonary vascular maturity was assessed using the AT/ET ratio, according to reported validation studies. Student's t-test was used for comparison of variables at diagnosis with those after reversal of ductal constriction. Change in MPAP and pulmonary AT/ET ratio between the two assessments was compared with the expected change in the same gestational period in normal fetuses based on reference curves of MPAP and pulmonary AT/ET ratio constructed in normal fetuses from healthy pregnant women at 19-37 weeks' gestation, encompassing the same gestational age range as the study group (28-37 weeks)., Results: Seventy pregnancies with fetal ductus arteriosus constriction were included in the study. After 2 weeks of reduced maternal intake of prostaglandin inhibitors, normalization of mean systolic (change from 1.86 ± 0.34 m/s at diagnosis to 1.38 ± 0.41 m/s; P < 0.001) and diastolic (change from 0.41 ± 0.11 m/s to 0.21 ± 0.065 m/s; P < 0.001) ductal velocities and of mean pulsatility index (change from 1.99 ± 0.20 to 2.55 ± 0.42; P < 0.001) was demonstrated. MPAP decreased between the assessments (change from 66.7 ± 6.90 mmHg at diagnosis to 54.5 ± 6.70 mmHg after 2 weeks; P < 0.001) and mean pulmonary AT/ET ratio increased (change from 0.20 ± 0.06 to 0.33 ± 0.07; P < 0.001). Change in MPAP between diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors was -12.2 ± 0.30 mmHg, which was 5.3-times higher than that in 305 normal fetuses over 2 weeks during the same gestational period (-2.3 ± 0.19 mmHg) (P < 0.001), and change in pulmonary AT/ET ratio between the two assessments was 0.13 ± 0.08, which was 8.7-times higher than that in normal fetuses in the same gestational period (0.015 ± 0.08) (P < 0.001)., Conclusions: Resolution of fetal ductal constriction is followed by a fall in MPAP and by an increase in pulmonary vascular maturity, to a significantly greater degree than is observed in normal fetuses in the same gestational-age period. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Skeletal muscle atrophy is the decrease in muscle mass and strength caused by reduced protein synthesis/accelerated protein degradation. Various conditions, such as denervation, disuse, aging, chronic diseases, heart disease, obstructive lung disease, diabetes, renal failure, AIDS, sepsis, cancer, and steroidal medications, can cause muscle atrophy. Mechanistically, inflammation, oxidative stress, and mitochondrial dysfunction are among the major contributors to muscle atrophy, by modulating signaling pathways that regulate muscle homeostasis. To prevent muscle catabolism and enhance muscle anabolism, several natural and synthetic compounds have been investigated. Recently, polyphenols (i.e., natural phytochemicals) have received extensive attention regarding their effect on muscle atrophy because of their potent antioxidant and anti-inflammatory properties. Numerous in vitro and in vivo studies have reported polyphenols as strongly effective bioactive molecules that attenuate muscle atrophy and enhance muscle health. This review describes polyphenols as promising bioactive molecules that impede muscle atrophy induced by various proatrophic factors. The effects of each class/subclass of polyphenolic compounds regarding protection against the muscle disorders induced by various pathological/physiological factors are summarized in tabular form and discussed. Although considerable variations in antiatrophic potencies and mechanisms were observed among structurally diverse polyphenolic compounds, they are vital factors to be considered in muscle atrophy prevention strategies., Competing Interests: The authors declare no conflict of interest.

Background: The iron-chelating activities of polyphenols raise concern whether there is a risk of iron deficiency or anemia induced by polyphenol supplementation. Results from clinical trials regarding the effects of polyphenol supplementation on iron status and erythropoiesis are inconclusive., Objective: We performed a systematic review and meta-analysis of randomized controlled trials to determine the effects of polyphenol supplementation on iron status and erythropoiesis., Methods: Published articles were searched between May 1988 and 7 December, 2020. Finally, we identified 34 randomized controlled trials. Random-effects meta-analyses were performed to obtain the weighted mean difference of serum iron (SI), transferrin saturation (TS), ferritin, and hemoglobin concentration. Funnel plots and Egger's test were used to determine the risk of bias. The robustness of the effect sizes was examined by sensitivity analysis., Results: Polyphenol supplementation had an inhibitory effect on the SI concentration (-13.72 μg/dL; 95% CI: -20.74, -6.71) and TS (-3.10%; 95% CI: -4.93, -1.27), with no effect on ferritin (-9.34 ng/mL; 95% CI: -28.55, 9.87). Polyphenols increased the hemoglobin concentration (8.53 g/L; 95% CI: 3.33, 13.73). In healthy participants, polyphenol reduced the TS (-3.83%; 95% CI: -7.47, -0.19) and increased the hemoglobin concentration (12.87 g/L; 95% CI: 1.61, 24.14). Similarly, polyphenol reduced the SI concentration (-8.60 μg/dL; 95% CI: -16.10, -1.10) and increased the hemoglobin concentration (8.50 g/L; 95% CI: 0.86, 16.15) in patients with metabolic diseases. In patients with β-thalassemia, polyphenol decreased the SI concentration (-23.19 μg/dL; 95% CI: -35.84, -10.55), TS (-3.23%; 95% CI: -5.54, -0.91), and ferritin concentration (-223.62 ng/mL; 95% CI: -359.32, -87.91), but had no effect on the hemoglobin concentration., Conclusion: Healthy individuals and patients with metabolic diseases may benefit from the positive impact of polyphenols on erythropoiesis. Patients with β-thalassemia may benefit from the effect of polyphenols on reducing SI. This trial was registered at PROSPERO (International prospective register of systematic reviews) as CRD42020161983., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Prevention and treatment of non-communicable diseases (NCDs), including cardiovascular disease, diabetes, obesity, cancer, Alzheimer's and Parkinson's disease, arthritis, non-alcoholic fatty liver disease and various infectious diseases; lately most notably COVID-19 have been in the front line of research worldwide. Although targeting different organs, these pathologies have common biochemical impairments - redox disparity and, prominently, dysregulation of the inflammatory pathways. Research data have shown that diet components like polyphenols, poly-unsaturated fatty acids (PUFAs), fibres as well as lifestyle (fasting, physical exercise) are important factors influencing signalling pathways with a significant potential to improve metabolic homeostasis and immune cells' functions. In the present manuscript we have reviewed scientific data from recent publications regarding the beneficial cellular and molecular effects induced by dietary plant products, mainly polyphenolic compounds and PUFAs, and summarize the clinical outcomes expected from these types of interventions, in a search for effective long-term approaches to improve the immune system response., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Salvianolic acids (SA) has been widely used for the treatment of acute cerebral infarction (ACI) combined with basic western medicine therapy in China. This study was aimed to evaluate the efficacy and safety of SA on ACI treatment and its influence on neurological functions, activity of daily living, and cognitive functions., Methods: We retrieved related articles from PubMed, the Cochrane Center Controlled Trials Register, EMBASE, Medline, Ovid, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Database without date and language restrictions. Finally, 58 randomized controlled trials were included from 239 retrieved records. Two researchers extracted the basic information and data from included articles and assessed the quality and analysis of data by using Review Manager 5.3., Results: The administration of SA significantly increased the total clinical effective rate of ACI treatment (P < .001) and improved the National Institute of Health Stroke Scale scores, modified Rankin Scale scores, and Barthel Index scores after treatment and 3 months after ACI (P < .05). The activities of daily living scores in the SA group were significantly increased after treatment (P < .001), whereas they were remarkably decreased 3 months after ACI (P < .001) compared with that in the control group. Besides, SA profoundly promoted the recovery of Montreal Cognitive Assessment scores (P < .001). However, the use of SA increased the risk of adverse events occurrence (P = .007)., Conclusion: SA combined with basic western medicine treatment could promote neurological functions, daily living activities, and cognitive functions recovery of ACI patients. Although SA increased the risk of adverse events occurrence, these adverse events were easily controlled or disappeared spontaneously.

The health benefits of moderate wine consumption have been extensively studied during the last few decades. Some studies have demonstrated protective associations between moderate drinking and several diseases including oral cavity cancer (OCC). However, due to the various adverse effects related to ethanol content, the recommendation of moderate wine consumption has been controversial. The polyphenolic components of wine contribute to its beneficial effects with different biological pathways, including antioxidant, lipid regulating and anti-inflammatory effects. On the other hand, in the oral cavity, ethanol is oxidized to form acetaldehyde, a metabolite with genotoxic properties. This review is a critical compilation of both the beneficial and the detrimental effects of wine consumption on OCC., Competing Interests: Paula Silva and Norbert Latruffe declare no conflict of interest. Giovanni de Gaetano is a member of the International Scientific Forum on Alcohol Research, an independent organization of scientists that prepares critiques of emerging research reports on alcohol and health. The members of the Forum donate their time and effort in the review of papers and receive no financial support. The Forum itself receives no support from any organization or company in the alcoholic beverage industry. Giovanni de Gaetano was also a consultant to the Web Newsletter of Assobirra, the Italian Association of the Beer and Malt Industries and is a corresponding member of the non-profit Accademia Italiana della Vite e del Vino. He reports personal fees for given lectures at the 8th European Beer and Health Symposium (2017), Beer and Health Initiative (The Dutch Beer Institute foundation—The Brewers of Europe), outside the submitted work.

This study investigated the effect of Sinetrol-XPur on weight and body fat reduction in overweight or obese Korean participants. Among 100 overweight or obese participants enrolled in a 12-week randomized, double-blinded, controlled study, 86 participants completed the trial. Participants took either two Sinetrol-XPur tablets (450 mg per tablet) or two placebo tablets once a day. Bodyweight, body fat percentage, body mass index (BMI), body fat mass, waist circumference, and various safety parameters were measured. After the 12-week intervention, a significant reduction was observed in the body fat mass ( P  = .030) by dual-energy X-ray absorptiometry (DEXA), body weight ( P  = .002), and BMI ( P  = .002) compared to the placebo. Body fat percentage ( P  = .007) by DEXA showed a significant reduction in the Sinetrol-XPur group, but no difference compared to the control group. Abdominal metabolic risks by computed tomography and blood biochemistry analysis were significantly decreased in the Sinetrol-XPur group, but there were no differences between the Sinetrol-XPur and placebo groups. Safety profiles were not different between the two groups. These results suggested that Sinetrol-XPur significantly reduced body weight, body fat mass, and BMI in obese Korean subjects, which confirms the antiobesity effect of Sinetrol-XPur in the Korean population.

Instructions for Salvia miltiorrhiza polyphenol injections indicate abnormal liver function as an occasional adverse reaction, but the incidence of this adverse drug reaction (ADR) has increased in recent years. We assessed S. miltiorrhiza polyphenol ADRs by performing a nested case-control study(NCCS) and meta-analysis. In the NCCS, 2633 patients receiving this treatment in the First Affiliated Hospital of Bengbu Medical College were enrolled. Logistic regression models found that in 58 (2.2%) patients experiencing abnormal liver function, the risk for liver dysfunction was associated with sulfa drug allergy (OR = 7.874, 95%CI (1.280, 48.447), P = 0.026), payment methods (OR = 0.106, 95%CI (0.012, 0.934), P = 0.043), duration of administration (OR = 0.922, 95%CI (0.862, 0.986), P = 0.017), cefathiamidine (OR = 0.441, 95%CI (0.216, 0.900), P = 0.025), human serum albumin (OR = 1.958, 95%CI (1.011, 3.789), P = 0.046), Dazhu Rhodiola injection (OR = 2.599, 95%CI (1.112, 6.070), P = 0.027), or reduced glutathione (OR = 0.394, 95%CI (0.188, 0.826), P = 0.014). Meta-analysis of reports on S. miltiorrhiza polyphenol ADRs in controlled trials and other observational studies included 676 patients, of which 17 (2.17%; 95%CI (0.0105, 0.0358)) presented with liver dysfunction; associated ADR risk factors included co-administration of other drugs. Our NCCS and meta-analysis had similar ADR incidence rates, which were higher than the rate in the drug instructions. This study provides guidance for assessing liver dysfunction risks associated with S. miltiorrhiza polyphenol injections.

Objectives: Chronic prostatitis syndrome is a bothering and poorly understood condition. Many patients report genitourinary pain and Lower Urinary Tract Symptoms as a main complaint. Many different pharmacological or behavioural therapies are prescribed in daily clinical practice, but efficacy data are still lacking. The aim of our study was to test the efficacy and safety of a transrectal delivered association of Boswellia resin extract and propolis derived polyphenols for the relief of prostatitis - like symptoms., Materials and Methods: Patients affected by chronic/recurrent prostatitis - like symptoms were prospectively enrolled in our study from December, 2016 to December, 2018. Patients were screened at baseline through clinical examination and validated questionnaires administration: Chronic Prostatitis Symptom Index (CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF). Inclusion criteria were: age ≥ 18; prostatitis symptoms persisting for at least 3 of the last 6 months; CPSI pain domain score ≥ 5; previous negative Meares-Stamey test. Treatment consisted on the administration of 1 suppository containing Boswellia resin extract and propolis derived polyphenols, once a day for 20 days. The primary endpoint of the study was the improvement of quality of life after treatment, defined by a reduction of ≥ 2 points, or ≥ 25%, of mean CPSI pain domain score, compared to baseline. Secondary endpoints were the improvement of post-treatment CPSI total score and the analysis of treatment - related adverse events. All patients were re-evaluated 1 month after treatment., Results: 40 patients were enrolled in our study. Median age (Inter - Quartile Range IQR) was 51.5 (41.5-63.2) years. Mean baseline CPSI scores were: 22.15 (total score), 9.67 (pain domain), 5.15 (micturition domain) and 7.35 (quality of life domain), respectively. No significant adverse events were reported. At 1 month follow-up, CPSI scores appeared modified as follows: 16.40 (total score, p = 0.001); 6.92 (pain domain; p = 0.001; 4.02 (micturition domain, p = 0.09); 5.45 (quality of life domain, p = 0.002). Mean CPSI pain domain score reduction was -2.75 points (-28.5%). Mean CPSI total score reduction was -5.75 points (-26%)., Conclusions: The association of Boswellia resin extract and propolis derived polyphenols can reduce genitourinary pain and then improve quality of life of men affected by bothersome prostatitis - like symptoms.

Polyphenols are secondary metabolites involved in a myriad of critical processes in plants. Over recent decades, special attention has been paid to the anti-oxidative role of fruit-derived polyphenols in the human diet, with evidence supporting the contribution of polyphenols in the prevention of numerous non-communicable disease outcomes. However, due to the low concentration in biological fluids in vivo, the antioxidant properties of polyphenols seem to be related to an enhanced endogenous antioxidant capacity induced via signaling through the nuclear respiratory factor 2 pathway. Polyphenols also seem to possess anti-inflammatory and antioxidant properties and have been shown to enhance vascular function via nitric oxide mediated mechanisms. Consequently, there is rationale to support fruit-derived polyphenol supplementation to enhance exercise performance, possibly via improved muscle perfusion. Fruit-derived polyphenol supplementation in exercise studies have included a variety of fruits, e.g., New Zealand blackcurrant, pomegranate, and cherry, in the form of extracts (multicomponent or purified), juices and infusions to varying degrees of benefit. For example, research has yet to link the health-related benefits of black elderberry ( Sambucus nigra L.) ingestion to exercise performance in spite of the purported health benefits associated with black elderberry provision in vitro and in vivo models, which has been attributed to their high antioxidant capacity and polyphenol content. This review summarizes the existing evidence supporting a beneficial effect of fruit-derived polyphenols on various biological processes and outlines the potential for black elderberry ingestion to improve nitric oxide production, exercise performance, and the associated physiological responses before-, during- and post-exercise.

In recent years, the consumption of chocolate and, in particular, dark chocolate has been "rehabilitated" due to its high content of cocoa antioxidant polyphenols. Although it is recognized that regular exercise improves energy metabolism and muscle performance, excessive or unaccustomed exercise may induce cell damage and impair muscle function by triggering oxidative stress and tissue inflammation. The aim of this review was to revise the available data from literature on the effects of cocoa polyphenols on exercise-associated tissue damage and impairment of exercise performance. To this aim, PubMed and Web of Science databases were searched with the following keywords: "intervention studies", "cocoa polyphenols", "exercise training", "inflammation", "oxidative stress", and "exercise performance". We selected thirteen randomized clinical trials on cocoa ingestion that involved a total of 200 well-trained athletes. The retrieved data indicate that acute, sub-chronic, and chronic cocoa polyphenol intake may reduce exercise-induced oxidative stress but not inflammation, while mixed results are observed in terms of exercise performance and recovery. The interpretation of available results on the anti-oxidative and anti-inflammatory activities of cocoa polyphenols remains questionable, likely due to the variety of physiological networks involved. Further experimental studies are mandatory to clarify the role of cocoa polyphenol supplementation in exercise-mediated inflammation.

It is believed that apple fruits contain components with health-promoting effects, including some antidiabetic activity. One of the most known apple compounds is phloridzin, a glucoside of phloretin. Phloridzin and phloretin were reported to exert some favorable skeletal effects in estrogen-deficient rats and mice. The aim of the study was to investigate the effects of phloridzin on musculoskeletal system in rats with type 2 diabetes induced by a high-fat diet (HFD) and streptozotocin (STZ). The experiments were performed on mature female Wistar rats, divided into control rats (fed a standard laboratory diet), HFD/STZ control rats, and HFD/STZ rats receiving phloridzin (20 or 50 mg/kg/day per os) for four weeks. Serum biochemical parameters, muscle mass and strength, bone mass, density, histomorphometric parameters and mechanical properties were determined. The HFD/STZ rats developed hyperglycemia, with decreases in the muscle mass and strength and profound osteoporotic changes. Phloridzin at 20 mg/kg markedly augmented the unfavorable effects of diabetes on the muscle mass and strength and decreased growth of bones, whereas, at 50 mg/kg, it did not affect most of the investigated musculoskeletal parameters. Results of the study indicate the possibility of unfavorable effects of phloridzin on the musculoskeletal system in conditions of hyperglycemia.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. However, therapeutic options treating only its symptoms are very disappointing. Therefore there is an ongoing search for compounds capable of tackling the multi-dimensional features of PD. Recently natural polyphenols have gained great interest as potential therapeutic agents. Herein, we have attempted to summarize results obtained in different animal models demonstrating their neuroprotective effects. The in vivo findings presented below are supported by human subject data and reports regarding the ability of polyphenols to cross the blood-brain barrier. The beneficial effects of polyphenols are demonstrated by the results of behavioral examinations, mainly related to motor and cognitive capabilities, histopathological and immunohistochemical examination concerning the protection of dopaminergic neurons, analyses of dopamine and the concentration of its metabolites, as well as mechanistic studies regarding the modulation of oxidative stress, neuroinflammation, cellular iron management, proteinopathy, and additionally the regulation of signaling pathways. Importantly, data about brain distribution of the metabolic derivatives of the reviewed polyphenols are crucial for the justification of their nutritional intake in neuroprotective intervention, as well as for the identification of potential targets for a novel therapeutic approach to Parkinson's disease.

A beverage made of red wine vinegar and grape juice (Yamanashi-no-megumi™) was developed as a supplemental fluid containing polyphenols, which has been clinically shown to enhance the colonic transit. In this study, we assessed the mechanism of its prokinetic action by analyzing the effects on both the colonic phosphodiesterase activity of rats (n=4) and the isolated colonic strip preparation of guinea pigs (n=4). The 7% (v/v) solution of the beverage significantly decreased the phosphodiesterase activity by 9% (n=4). The beverage in concentrations of 0.7, 2.1 and 7% (v/v) relaxed the colonic strips pre-contracted by 1 µmol/L of carbachol in a concentration-related manner with 50, 58 and 79%, each response of which was diminished to 11, 19 and 46%, respectively in the presence of 100 µmol/L of L-nitro-arginine methyl ester. These results obtained by biochemical, functional and pharmacological analyses suggest that the beverage could relax the colon through both cAMP-associated and nitric oxide-dependent pathways, which may partly explain clinically observed prokinetic effect of the beverage.

Context: Propolis has promising biological activities. Propolis samples from the Northeast of Bahia, Brazil - sample A from Ribeira do Pombal and B, from Tucano - were investigated, with new information regarding their biological activities., Objective: This paper describes the chemical profile, antioxidant, anti-glycation and cytotoxic activities of these propolis samples., Material and Methods: Ethanol extracts of these propolis samples (EEP) and their fractions were analyzed to determine total phenolic content (TPC); antioxidant capacity through DPPH • , FRAP and lipid peroxidation; anti-glycation activity, by an in vitro glucose (10 mg/mL) bovine serum albumine (1 mg/mL) assay, during 7 d; cytotoxic activity on cancer (SF295, HCT-116, OVCAR-8, MDA-MB435, MX-1, MCF7, HL60, JURKAT, MOLT-4, K562, PC3, DU145) and normal cell lines (V79) at 0.04-25 μg/mL concentrations, for 72 h. The determination of primary phenols by ultra high-pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) and volatile organic compounds content by gas chromatography-mass spectrometry (GC-MS) were also performed., Results: The EEP polar fractions exhibited up to 90% protection against lipid peroxidation. The IC 50 value for anti-glycation activity of EEP was between 16.5 and 19.2 μg/mL, close to aminoguanidine (IC 50  = 7.7 μg/mL). The use of UHPLC-MS/MS and GC-MS allowed the identification of 12 bioactive phenols in the EEP and 24 volatile compounds, all already reported., Conclusions: The samples present good antioxidant/anti-glycation/cytotoxic activities and a plethora of biologically active compounds. These results suggest a potential role of propolis in targeting ageing and diseases associated with oxidative and carbonylic stress, aggregating value to them.

Diabetes mellitus is a chronic disease that threatens human health. The disease is caused by a metabolic disorder of the endocrine system, and long-term illness can lead to tissue and organ damage to the cardiovascular, endocrine, nervous, and urinary systems. Currently, the disease prevalence is 11.4%, the treatment rate is 48.2%, and the mortality rate is 2.7% worldwide. Comprehensive and effective control of diabetes, as well as the use of insulin, requires further study to develop additional treatment options. Here, we reviewed the current reprogramming of somatic cells using specific factors to induced pluripotent stem (iPS) cells capable of repairing islet β cell damage in diabetes patients to treat patients with type 1 diabetes mellitus. We also discuss the shortcomings associated with clinical use of iPS cells. Additionally, certain polyphenols found in spices might improve glucose homeostasis and insulin resistance in diabetes patients, thereby constituting promising options for the treatment of type 2 diabetes.

Polyphenols are a very broad group of chemicals, widely distributed in plant foods, and endowed with antioxidant activity by virtue of their numerous phenol groups. They are widely studied as putative cancer-protective agents, potentially contributing to the cancer preventive properties of fruits and vegetables. We review recent publications relating to human trials, animal experiments and cell culture, grouping them according to whether polyphenols are investigated in whole foods and drinks, in plant extracts, or as individual compounds. A variety of assays are in use to study genetic damage endpoints. Human trials, of which there are rather few, tend to show decreases in endogenous DNA damage and protection against DNA damage induced ex vivo in blood cells. Most animal experiments have investigated the effects of polyphenols (often at high doses) in combination with known DNA-damaging agents, and generally they show protection. High concentrations can themselves induce DNA damage, as demonstrated in numerous cell culture experiments; low concentrations, on the other hand, tend to decrease DNA damage., Competing Interests: The authors declare no conflict of interest.

The aim of the study was to determine whether Leonurus cardiaca L. herb extract (LCE) used at subinhibitory concentration modifies the characteristics of Staphylococcus aureus, which is important in the pathogenesis of invasive infections originating from the bloodstream, in a way favourable for the human host. Polyphenol-rich LCE, a common ingredient in pharmaceutical products used for various cardiovascular and nervous system disorders, had shown interesting antibacterial and antibiofilm properties in our previous studies. Our current findings indicate that the following S. aureus characteristics decreased, depending on the LCE concentration: (i) formation of aggregates in plasma, (ii) adherence to a fibrin-coated surface, (iii) staphylocoagulase-dependent plasma clotting, (iv) bacterial survival in whole human blood in an ex vivo model, (v) expression of cell surface protein A and (vi) synthesis of α-toxin. However, staphylococcal tolerance to exogenous hydrogen peroxide was enhanced after pre-incubation with LCE, possibly due to the increased activity of bacterial antioxidant enzymes, a possibility confirmed by the higher production of superoxide dismutase and slightly higher production of catalase. The use of LCE at sub-MIC in in vitro and ex vivo models resulted in the weakening of some important staphylococcal immunoprotective attributes but the strengthening of such virulence factors as those responsible for oxidative stress tolerance. Some of these results and the fact that LCE has direct anticoagulant properties, reflected in a reduced thrombin-dependent fibrinogen polymerization rate, suggest a risk of adverse effects, which could be important in the context of S. aureus survival in the host.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a well-characterized member of the PPAR family that is predominantly expressed in adipose tissue and plays a significant role in lipid metabolism, adipogenesis, glucose homeostasis, and insulin sensitization. Full agonists of synthetic thiazolidinediones (TZDs) have been therapeutically used in clinical practice to treat type 2 diabetes for many years. Although it can effectively lower blood glucose levels and improve insulin sensitivity, the administration of TZDs has been associated with severe side effects. Based on recent evidence obtained with plant-derived polyphenols, the present in silico study aimed at finding new selective human PPARγ (hPPARγ) modulators that are able to improve glucose homeostasis with reduced side effects compared with TZDs. Docking experiments have been used to select compounds with strong binding affinity (ΔG values ranging from -10.0±0.9 to -11.4±0.9 kcal/mol) by docking against the binding site of several X-ray structures of hPPARγ. These putative modulators present several molecular interactions with the binding site of the protein. Additionally, most of the selected compounds have favorable druggability and good ADMET properties. These results aim to pave the way for further bench-scale analysis for the discovery of new modulators of hPPARγ that do not induce any side effects.

Background: Emerging evidence from clinical and epidemiological studies suggests that dietary polyphenols play an important role in the prevention of chronic diseases, including cancer, cardiovascular disease, diabetes and neurodegenerative disorders. Although these beneficial health claims are supported by experimental data for many subpopulation groups, some studies purport that excessive polyphenol consumption may have negative health effects in other subpopulations. The ever-growing interest and public awareness surrounding the potential benefits of natural health products and polyphenols, in addition to their widespread availability and accessibility through nutritional supplements and fortified foods, has led to increased consumption throughout gestation. Therefore, understanding the implications of polyphenol intake on obstetrical health outcomes is of utmost importance with respect to safe consumption during pregnancy., Methods: Using relevant keywords, a literature search was performed to gather information regarding polyphenol pharmacology and the molecular mechanisms by which polyphenols exert their biological effects. The primary focus of this paper is to understand the relevance of these findings in the context of reproductive physiology and medicine., Results: Evidence from both in vitro experiments and in vivo studies using animals and humans demonstrates that polyphenols regulate key targets related to oxidative stress, inflammation and advanced glycation end products. Although the majority of these studies have been conducted in the context of chronic diseases, such as cancer and diabetes, several of the key targets influenced by polyphenols are also related to a variety of obstetrical complications, including pre-eclampsia, intrauterine growth restriction and preterm birth. Polyphenols have also been shown to influence fertility and sexual development, fetal health and the bioavailability of nutrients., Conclusions: Further research leading to a thorough understanding of the physiological roles and potential clinical value that polyphenol consumption may play in pregnancy is urgently needed to help inform patient safety., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Consumer use of herbal and dietary supplements has recently grown in the United States and, with increased use, reports of rare adverse reactions have emerged. One such supplement is green tea extract, containing the polyphenol epigallocatechin gallate (EGCG), which has been shown to be hepatotoxic at high doses in animal models. The Drug-Induced Liver Injury Network has identified multiple patients who have experienced liver injury ascribed to green tea extract consumption and the relationship to dose has not been straightforward, indicating that differences in sensitivity may contribute to the adverse response in susceptible people. The Diversity Outbred (DO), a genetically heterogeneous mouse population, provides a potential platform for study of interindividual toxicity responses to green tea extract. Within the DO population, an equal exposure to EGCG (50 mg/kg; daily for three days) was found to be tolerated in the majority of mice; however, a small fraction of the animals (16%; 43/272) exhibited severe hepatotoxicity (10-86.8% liver necrosis) that is analogous to the clinical cases. The data indicate that the DO mice may provide a platform for informing risk of rare, adverse reactions that may occur in consumer populations upon ingestion of concentrated herbal products., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

High blood pressure (BP) variability, which may be an important determinant of hypertensive end-organ damage, is emerging as an important predictor of cardiovascular health. Dietary antioxidants can influence BP, but their effects on variability are yet to be investigated. The aim of the present study was to assess the effects of vitamin E, vitamin C and polyphenols on the rate of daytime and night-time ambulatory BP variation. To assess these effects, two randomised, double-blind, placebo-controlled trials were performed. In the first trial (vitamin E), fifty-eight individuals with type 2 diabetes were given 500 mg/d of RRR-α-tocopherol, 500 mg/d of mixed tocopherols or placebo for 6 weeks. In the second trial (vitamin C-polyphenols), sixty-nine treated hypertensive individuals were given 500 mg/d of vitamin C, 1000 mg/d of grape-seed polyphenols, both vitamin C and polyphenols, or neither (placebo) for 6 weeks. At baseline and at the end of the 6-week intervention, 24 h ambulatory BP and rate of measurement-to-measurement BP variation were assessed. Compared with placebo, treatment with α-tocopherol, mixed tocopherols, vitamin C and polyphenols did not significantly alter the rate of daytime or night-time systolic BP, diastolic BP or pulse pressure variation (P>0·05). Treatment with the vitamin C and polyphenol combination resulted in higher BP variation: the rate of night-time systolic BP variation (P= 0·022) and pulse pressure variation (P= 0·0036) were higher and the rate of daytime systolic BP variation was higher (P= 0·056). Vitamin E, vitamin C or grape-seed polyphenols did not significantly alter the rate of BP variation. However, the increase in the rate of BP variation suggests that the combination of high doses of vitamin C and polyphenols could be detrimental to treated hypertensive individuals.

Objectives: Medications or lifestyle changes to prevent or improve hypertension often press considerable efforts on patients suffering from mild hypertension. Capsules including Umezu polyphenols (UP), polyphenols in Japanese plums, may help them to control their blood pressure (BP). The aim of this study is to evaluate the effectiveness of UP on BP and its safety., Methods: A total of 15 healthy workers without antihypertensive medication who had some concerns about their BP, preferably normal-high BP or hypertension level 1, were randomized in a double-blind manner into UP ingesting and placebo groups. Each subject was instructed to take four capsules daily for 12 weeks (daily UP dose, 800 mg for the UP ingesting group; and 0 mg for the placebo group). These subjects were followed for 12 weeks, and their BP both at home and at the examination site, as well as self-perceived quality-of-life outcomes and possible side effects, was monitored during that period. Group × time interactions on BP changes were examined., Results: All of the 15 subjects completed the 12-week intervention trial. The BP changes did not significantly differ between the UP ingesting and placebo groups, neither at the examination site nor at home. But during the study period, no adverse effects were observed., Conclusions: No remarkable effect of UP on BP was observed. However, a higher dose of UP was confirmed safe and high in adherence in this 12-week randomized controlled trial. Its effect on BP and other outcomes shall be confirmed in a larger sample.

In addition to phytate, polyphenols (PP) might contribute to low Fe bioavailability from sorghum-based foods. To investigate the inhibitory effects of sorghum PP on Fe absorption and the potential enhancing effects of ascorbic acid (AA), NaFeEDTA and the PP oxidase enzyme laccase, we carried out three Fe absorption studies in fifty young women consuming dephytinised Fe-fortified test meals based on white and brown sorghum varieties with different PP concentrations. Fe absorption was measured as the incorporation of stable Fe isotopes into erythrocytes. In study 1, Fe absorption from meals with 17 mg PP (8·5%) was higher than that from meals with 73 mg PP (3·2%) and 167 mg PP (2·7%; P< 0·001). Fe absorption from meals containing 73 and 167 mg PP did not differ (P= 0·9). In study 2, Fe absorption from NaFeEDTA-fortified meals (167 mg PP) was higher than that from the same meals fortified with FeSO₄ (4·6 v. 2·7%; P< 0·001), but still it was lower than that from FeSO₄-fortified meals with 17 mg PP (10·7%; P< 0·001). In study 3, laccase treatment decreased the levels of PP from 167 to 42 mg, but it did not improve absorption compared with that from meals with 167 mg PP (4·8 v. 4·6%; P= 0·4), whereas adding AA increased absorption to 13·6% (P< 0·001). These findings suggest that PP from brown sorghum contribute to low Fe bioavailability from sorghum foods and that AA and, to a lesser extent, NaFeEDTA, but not laccase, have the potential to overcome the inhibitory effect of PP and improve Fe absorption from sorghum foods.

Background: Resveratrol, a polyphenol from grapes and red wine has many health beneficial effects, including protection against cardiovascular and neurodegenerative diseases and cancer. However, our group and others have provided evidence for a dual cancer promoting or inhibitory role for resveratrol in breast cancer, dependent on estrogenic or antiestrogenic activities. Moreover, much of the inhibitory effects of resveratrol have been reported from studies with high non-physiological concentrations., Methods: We investigated the effects of a range of concentrations (0.5, 5, 50 mg/kg body weight) of resveratrol on mammary tumor development post-initiation, using immunocompromised mice., Results: Our findings suggest promotion of mammary tumor growth and metastasis by resveratrol at all concentrations tested in tumors derived from the low metastatic estrogen receptor (ER)α(-), ERβ(+) MDA-MB-231 and the highly metastatic ER(-) MDA-MB-435 cancer cell lines. Additionally, the activity of the migration/invasion regulator Rac, which we have previously shown to be regulated by resveratrol in vitro, was measured in tumors from resveratrol treated mice. Our results show a significant induction of tumoral Rac activity and a trend in increased expression of the Rac downstream effector PAK1 and other tumor promoting molecules following resveratrol treatment., Conclusion: Taken together, our findings implicate low concentrations of resveratrol in potential promotion of breast cancer. Therefore, this study illuminates the importance of further delineating resveratrol's concentration dependent effects, particularly in breast cancer, before it can be tested in the clinic or used as a dietary supplement for breast cancer patients.

The safety of the apple polyphenol extract EvesseEPC, which is rich in flavan-3-ols, particularly epicatechin, was evaluated. Both in a bacterial reverse mutation test and a mouse lymphoma assay, EvesseEPC showed a positive response in vitro. In vivo studies (UDS test in hepatocytes, bone marrow micronucleus test and comet assay in intestinal cells) were all negative and hence Evesse EPC is considered not to have genotoxic properties in vivo. In a 90-day study in rats, EvesseEPC was administered at dietary levels of 0%, 1.25%, 2% and 3.25%. Body weights were decreased in the high-dose group in both sexes without effects on feed or water intake. In the high-dose group, thrombocytes (males) and creatinine (both sexes) were decreased, prothrombin time (males) was increased, and liver, kidneys and spleen weights were increased (males), without histological correlates. Diffuse acinar cell hypertrophy, observed in the parotid salivary glands in all treatment groups, was not considered as adverse and presumably reflected a local, reversible and adaptive response to direct contact with EvesseEPC. The NOAEL for EvesseEPC in rats was 2% in the diet, equivalent to an overall average intake of 1.3 and 1.5 g/kg body weight/day for males and females, respectively., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A series of polyphenolic curcumin analogs were synthesized and their inhibitory effects on mushroom tyrosinase and the inhibition of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical formation were evaluated. The results indictated that the analogs possessing m-diphenols and o-diphenols exhibited more potent inhibitory activity on tyrosinase than reference compound rojic acid, and that the analogs with o-diphenols exhibited more potent inhibitory activity of DPPH free-radical formation than reference compound vitamin C. The inhibition kinetics, analyzed by Lineweaver-Burk plots, revealed that compounds B(2) and C(2) bearing o-diphenols were non-competitive inhibitors, while compounds B(11) and C(11) bearing m-diphenols were competitive inhibitors. In particular, representative compounds C(2) and B(11) showed no side effects at a dose of 2,000 mg/kg in a preliminary evaluation of acute toxicity in mice. These results suggest that such polyphenolic curcumin analogs might serve as lead compounds for further design of new potential tyrosinase inhibitors.

This paper reports the content in macronutrients, free sugars, polyphenols, and inorganic ions, known to exert any positive or negative action on microbial oral disease such as caries and gingivitis, of seven food/beverages (red chicory, mushroom, raspberry, green and black tea, cranberry juice, dark beer). Tea leaves resulted the richest material in all the detected ions, anyway tea beverages resulted the richest just in fluoride. The highest content in zinc was in chicory, raspberry and mushroom. Raspberry is the richest food in strontium and boron, beer in selenium, raspberry and mushroom in copper. Beer, cranberry juice and, especially green and black tea are very rich in polyphenols, confirming these beverages as important sources of such healthy substances. The fractionation, carried out on the basis of the molecular mass (MM), of the water soluble components occurring in raspberry, chicory, and mushroom extracts (which in microbiological assays revealed the highest potential action against oral pathogens), showed that both the high and low MM fractions are active, with the low MM fractions displaying the highest potential action for all the fractionated extracts. Our findings show that more compounds that can play a different active role occur in these foods.