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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.)

Purpose of Review: Polycystic ovarian syndrome (PCOS) is a common endocrine disease characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology and causing various reproductive, metabolic, cardiovascular, oncological, and psychological complications. Recent meta-analyses and systemic reviews showed that PCOS increases the risk factor for various cardio-metabolic complications like insulin resistance, type II diabetes mellitus, dyslipidemia, metabolic syndrome, hypertension, and endothelial dysfunction. In addition to these, it was suggested that chronic low-grade inflammation and oxidative stress are the underlying mechanisms of PCOS-mediated metabolic consequences and might trigger cardio-metabolic risk in women with PCOS. At this point, there is substantial evidence to suggest that various non-nutrient food components modulate cardio-metabolic health together with inflammation and oxidative stress., Recent Findings: Increasing the intake of dietary polyphenols might reduce oxidative stress and inflammation and thus alleviate the risk of metabolic, endothelial, and cardiovascular disorders. Nowadays, there are an increasing number of studies related to the effects of dietary polyphenols on PCOS and its accompanying cardio-metabolic disturbances. Currently, there is a cumulative number of studies connected to the effects of dietary polyphenols on PCOS and accompanying cardio-metabolic disturbances. However, there is a lack of knowledge in combining the probable mechanisms of dietary polyphenols on PCOS and related cardio-metabolic consequences. Thus, the effects of dietary polyphenols on PCOS and accompanying cardio-metabolic disturbances need to be discussed and evaluated with underlying mechanisms. Consequently, this review was written to reveal the potential effects of dietary polyphenols on PCOS and related metabolic and cardiovascular risk factors in all their aspects., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Abstract: In the past decade, a plethora of research has revealed numerous biological effects of polyphenols, most significantly anticancer and antimicrobial. These versatile, naturally occurring compounds have attracted growing interest among researchers owing to their crucial role in modifying disease progression associated with almost all the body's vital systems, including cardiovascular, neurological, and gastrointestinal systems. However, poor water solubility and rapid metabolism result in low bioavailability, which is a critical limitation to their clinical use. Nanotechnology is one promising approach that has served to maximize the therapeutic potential of polyphenols. Incorporation of sensitive polyphenolic compounds into nanocarriers protects them from physiological degradation, facilitates prolonged release, improves bioavailability, and allows targeted drug delivery. There is emerging evidence that nanomedicine could provide a solution to the poor pharmacokinetics of polyphenols and enhance their treatment efficacy. This review focuses on the various nanoparticle-based delivery systems that have been developed for the entrapment of these hydrophobic molecules and circumvent the pitfalls of poor systemic availability with an emphasis on their application in cardiovascular disorders. It elucidates recent developments in nanotechnology that could not only be imperative to cardiovascular disease alleviation but also in resolving issues of safety and specificity associated with these molecules. It also highlights the improved physicochemical properties and possible molecular mechanisms of some major polyphenols administered as nanoformulations and describes the results of in vitro and in vivo studies performed in animal models of cardiovascular diseases (CVDs)., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Polyphenols are known to interact with gut microbes that play key roles in maintaining gut health, but the role of gut microbiota modulation by polyphenols in mitigating colonic diseases is not fully established. We hypothesize that the interaction of polyphenols with the gut microbiota contributes to the attenuation of colitis and colitis-associated colon cancer (CAC). To test this hypothesis, we examined the effects of dietary supplementation of polyphenol-rich grape powder (GP) on azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced colitis, CAC, and the gut microbiota in mice (study 1), and further compared anti-colitis effects of GP in regular and antibiotic-treated mice (study 2). Compared to the control diet that has matched non-polyphenol contents, 10% GP, but not 3% GP, attenuated AOM-DSS-induced colitis and tumor multiplicity by 29% (P<.05). Ten percent GP increased gut bacterial evenness and counteracted CAC-induced decrease of bacterial evenness and changes in microbial composition. Remarkably, the estimated gut bacterial functional profiles of healthy mice and diseased mice fed 10% GP were similar, and both were significantly different from those of diseased mice fed the control diet. Furthermore, 10% GP increased the relative abundance of butyrate-producing bacteria in the Lachnospiraceae family and enhanced the concentrations of fecal butyrate. Additionally, 10% GP mitigated DSS-induced colitis in conventional mice, but not the antibiotic-treated, gut microbe-depleted mice. Collectively, our studies demonstrate that grape polyphenols alleviate colonic diseases and prevent disease-associated dysbiosis, and their interaction with the gut microbiota may play a causative role in the protection of gut health., (Copyright © 2022. Published by Elsevier Inc.)

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.)

Aims: The study aimed to assess the antidiabetic effect of Salvia tingitana (S. tingitana)., Background: S. tingitana is an aromatic plant that belongs to the Lamiaceae family. Phytochemical analysis of the aerial parts of S. tingitana revealed the existence of terpenoids and flavonoids. In addition, S. tingitana possesses antimicrobial activity., Objective: The goal of the study was to obtain information about the antihyperglycemic, antihyperlipidemic, antioxidant abilities of S. tingitana aqueous extract., Methods: The effect of an acute and sub-chronic administration of S. tingitana aqueous extract (AEST) at the doses of 60 and 80 mg/kg on glucose, lipid profile, and lipoprotein profile was examined in normoglycemic and hyperglycemic rats. Additionally, a preliminary phytochemical screening and the antioxidant activity using DPPH assay were carried out., Results: Rats treated with AEST at a dose of 60 mg/kg showed a significant decrease in the serum glucose levels during the single oral administration at the 4th and 6th hour of treatment in both normal and streptozotocin(STZ)-induced hyperglycemic rats. Interestingly, a dose of 80 mg/kg AEST produced a significant lowering effect on blood glucose levels at the 2nd, 4th, and 6th hour of treatment after a single oral administration in both diabetic and normal rats. Both doses of AEST (60 and 80 mg/kg) revealed a significant amelioration of lipid and lipoprotein profile. In addition, the qualitative and quantitative phytochemical analysis proved the presence of polyphenols compounds, flavonoids, and tannins. Results suggest that S. tingitana contains some secondary metabolites like alkaloids, phenols, flavonoids, and saponins. Importantly, the study revealed that the aqueous extract of S. tingitana has a very interesting antioxidant activity (IC50 = 553.21 μg/ml)., Conclusion: The study illustrates the beneficial action of the aqueous extract of S. tingitana as an antihyperglycemic and antihyperlipidemic agent., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: The study aimed to assess the antihyperglycemic activity of Pulicaria mauritanica., Background: Pulicaria mauritanica is a medicinal and aromatic plant used for the treatment of many diseases such as inflammation, diabetes, and intestinal disorders., Objective: The main goals of this present paper were to confirm the antihyperglycemic capacity of aqueous extract from Pulicaria mauritanica in normoglycemic and diabetic rats over a period of time (7 days of treatment)., Methods: The effect of the aqueous extract of Pulicaria mauritanica from aerial parts (AEPM) on glucose and lipid metabolism was tested using an acute test (single dose during 6 hours) and subchronic assay (repeated oral administration for seven days) at a dose of 60 mg/kg and the serum glucose levels were measured in normoglycemic and streptozotocin(STZ)-induced diabetic rats. In addition, the glycogen content in the liver, extensor digitorum longus (EDL), and soleus was evaluated. The antioxidant activity, phytochemical screening, and quantification of some secondary metabolites of this extract were also performed., Results: AEPM at a dose of 60 mg/kg reduced the plasma glucose concentrations significantly in STZ-induced diabetic rats after a single oral administration (p<0.05). This lowering effect became more significant during the repeated oral administration in hyperglycemic rats (p<0.0001). Also, the findings showed that this plant exhibited a significant increase in liver and skeletal soleus muscle glycogen content in diabetic rats. AEPM revealed a remarkable antioxidant activity in addition to the presence of polyphenol compounds such as flavonoids, tannins, saponins, sterols, glucides, terpenoids, quinones, anthraquinones, and mucilage., Conclusion: The study shows that AEPM exhibits antihyperglycemic activity in diabetic rats, and it increases liver and muscle glycogen content., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.)

Purpose: Osteoarthritis (OA) is a chronic and degenerative disorder associated with joint pain and loss of joint function. It is reported that polyphenols could yield articular benefits in patients with OA through the inhabitation of key inflammatory pathways. This meta-analysis was conducted to assess the efficacy and safety of polyphenol products for OA treatment., Methods: This study included searches of PubMed, EMBASE, and the Cochrane Library databases from inception to November 6, 2019. Randomized controlled trials (RCTs) comparing polyphenols versus NSAIDs or placebo for human OA were included. Standardized mean differences (SMD) or risk ratios (RRs) were calculated for all relevant outcomes. Meta-analyses were conducted by using random effect models, and heterogeneity was assessed by using the I 2 statistic., Findings: A total of 18 RCTs (N = 1724) were eligible for analysis. Polyphenol products showed a significant advantage over placebo on pain relief (SMD, -1.11; 95% CI, -1.35 to -0.87) and functional improvement (SMD, -1.14; 95% CI, -1.38 to -0.90). No differences in safety outcomes were detected between polyphenols and placebo. There were no differences in efficacy outcomes between polyphenols and NSAIDs, although patients receiving polyphenols had a lower but nonsignificant risk of experiencing gastrointestinal dysfunction compared with those treated with NSAIDs. Polyphenols and NSAIDs in combination yielded more significant benefits in efficacy than NSAIDs alone., Implications: The results of our study suggest that polyphenols may be a promising alternative for OA by relieving symptoms while reducing safety risks. However, the generalizability of our results may be limited by the quality and sample size of the available research, as well as the heterogeneity between RCTs. High-quality clinical trials are needed to make meaningful clinical practice recommendations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.

Aim: A large body of evidence supports a role of polyphenols in the prevention of chronic diseases, i.e. type 2 diabetes (DMT2), cardiovascular diseases and some types of cancer. In the present manuscript, the effect of polyphenol/phenolic compounds on the main cardio-metabolic risk factors (body weight, blood pressure, blood glucose concentrations, plasma lipids, inflammation and oxidative stress) in humans will be discussed., Data Synthesis: Epidemiological evidence supports the beneficial effects of polyphenol-rich diets in the prevention of T2D risk. However, the available evidence from randomized controlled clinical trials did not allow the identification of specific phenolic compounds or polyphenol-rich foods that effectively improve cardio-metabolic risk factors. The most promising results in terms of the management of cardio-metabolic risk factors derive from RCTs based on a long-term intake of polyphenol-rich foods and beverages. Therefore, future studies should focus on a diet containing different classes of polyphenols rather than a specific food or phenolic compound. The hypothesis is that a polyphenol-rich diet may have a pleiotropic effect on cardiometabolic risk factors thanks to the specific action of different polyphenol subclasses., Conclusion: The lack of conclusive evidence on the effectiveness of polyphenols in the management of cardio-metabolic risk factors does not allow recommendation of their use as supplements to reduce T2D and CVD risk. However, the daily consumption of naturally polyphenol-rich foods and beverages might be advised according to the current nutritional dietary recommendation., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

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.

Dietary polyphenols, a natural component in many kinds of foods such as fruits and vegetables, play essential roles in a wide range of plant functions. Importantly, the discovery of the functions of polyphenols including anti-oxidant, anti-carcinogenic and anti-inflammatory has been appealing to researchers' attentions. Dietary polyphenols have shown protective effects on chronic degenerative diseases (CDD) such as cardiovascular diseases, cancers, and neurodegenerative diseases by regulating gene expression. Dietary polyphenols also affect the composition and activity of gut microbiota, in reverse, gut microbiota influences the bioavailability and physiological activity of dietary polyphenols. However, not all kinds of dietary polyphenols are beneficial for human health. The potential deleterious effects of several dietary polyphenols have been reported by inducing DNA damage and gene mutants. This review summarizes the potential therapeutic effects of dietary polyphenols on chronic degeneration diseases, the polyphenols-gut microbiota interactions, and the potential dangers of individual dietary polyphenols on human health.

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.

Antimicrobial chemotherapy based on ultraviolet-A (UVA) irradiation of polyphenol solution has been proposed as an adjunctive treatment for dental caries. However, the safety of this treatment has not been thoroughly evaluated. Therefore, the aim of the present study was to assess the influence of this treatment on the oral mucosa in hamsters and wounded skin in rats. An oral mucosal irritation test was performed in hamsters. The cheek pouch was everted and treated with UVA irradiation (wavelength: 365 nm) of pure water, 1 mg/mL of caffeic acid, or 1 mg/mL of grape seed extract using a light-emitting diode at an irradiance of 275 mW/cm 2 . Each treatment was performed for 2 or 5 min and repeated three times. Macroscopic and histological evaluations were performed 24 h after the last treatment. We also examined the effects of the treatment on the healing process of skin wounds in rats. Full-thickness skin wounds created on the back of the rats were treated for 2 min as described above, but only once. The wound area was then assessed daily for 9 days. The results demonstrated that the treatment induced oral mucosal irritation depending on the irradiation time; however, it did not influence the wound healing process. The oral mucosal irritation potential of three treatment sessions performed for 2 and 5 min was minimal and mild to moderate, respectively, according to histological analysis. These findings suggest that the duration of treatment based on UVA irradiation of polyphenols in the oral cavity should be as short as possible, considering the clinical efficacy of the antimicrobial effects and the irritation potential., (Copyright © 2018 Elsevier B.V. All rights reserved.)

About 12% of world population is affected by different forms of urolithiasis of which the recurrence rate in female is 47-60% and in male is 70-80%. Standard therapeutic agents (allopurinol, citrate, cystone and thiazide diuretics) are used to prevent and treat urolithiasis but these are not universally-effective due to common kidney stone relapse and other side effects. Surgical treatment causes long-term renal damage, hypertension and stone recurrence. Polyphenols, the plant-derived bioactive molecules, have showed protection against cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases, among a number of other ailments. The role of these phytochemicals in urolithiasis management is emerging. Hence, the present review discusses peer-reviewed published literature till date on this aspect and highlights that polyphenols could effectively inhibit the formation of calcium oxalate urinary stones (most common renal stone), correlating with their antioxidant, anti-inflammatory, diuretic and angiotensin-converting enzyme (ACE) inhibition. Further, we have proposed the prospects and challenges in developing the plant polyphenols into drugs against kidney stone prevention. This review might be a stepping stone for further investigation into the clinical implications of the polyphenols in urolithiasis remediation., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Adverse drug reactions of Danshen injection mainly manifested as pseudoallergic reactions. In the present study, salvianolic acid A and a pair of geometric isomers (isosalvianolic acid C and salvianolic acid C) were identified as pseudoallergic components in Danshen injection by a high-expression Mas-related G protein coupled receptor X2 cell membrane chromatography coupled online with high-performance liquid chromatography with electrospray ionization tandem mass spectrometry. Their pseudoallergic activities were evaluated by in vitro assay, which were consistent with the retention times on the cell membrane chromatography column. Salvianolic acid C, the most outstanding compound, was further found to induce pseudoallergic reaction through Mas-related G protein coupled receptor X2. All the results above indicated that the system developed in this study is an effective method for simultaneously analyzing pseudoallergic components, even those with similar structures and the microcomponents in complex samples (salvianolic acid C in Danshen injection)., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

Paracetamol (acetaminophen or N-acetyl-p-aminophenol) is considered a safe analgesic and antipyretic nonsteroidal antiinflammatory drug commonly used during pediatric ages and during pregnancy. We report on a term neonate with closed ductus arteriosus, severe cardiomyopathy, right ventricular dysfunction, and functional stenosis of pulmonary arteries at birth after maternal self-medication with paracetamol and consumption of polyphenol-rich foods in late pregnancy. This drug, especially when associated with other vasoconstrictors (such as polyphenols), interferes with prostaglandin metabolism, which seriously accentuates the intrauterine ductus arteriosus constriction and leads to pharmacologic adverse events. We suggest maternal educational programs to avoid risky self-medications and provide training for the best diets., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

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.

Neurodegenerative disease is an incurable disease which involves the degeneration or death of the nerve cells. Alzheimer's Disease (AD) is a neurodegenerative disease discovered in 1906 by Alois Alzheimer, a German clinical psychiatrist and neuroanatomist. The main pathological hallmarks of this disease are the formation of extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangle (NFT). The accumulation of the amyloid protein aggregates in the brain of AD patients leads to oxidative stress and inflammation. Other postulated reasons for the development of this disease are cholinergic depletion and excessive glutamatergic neurotransmission. The current drugs approved and marketed for the treatment of AD are cholinesterase inhibitors (ChEIs) and N-methyl-Daspartate (NMDA) receptor antagonists. The function of ChEIs is to avoid cholinergic depletion; whereas the function of NMDA receptor antagonist is to block excessive glutamatergic neurotransmission. Unfortunately, the current drugs prescribed for AD show only modest improvement in terms of symptomatic relief and delay the progression of the disease. This review will discuss about several polyphenolic compounds as potential natural treatment options for AD. Three compounds are highlighted in this review - Curcumin (Cur), Resveratrol (Rsv) and Epigallocatechin-3- gallate (EGCG). These compounds have huge potential for AD treatment, especially due to their low frequency of adverse events. However, the current conventional pharmaceutical drugs remain as the mainstay of treatment for AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

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.

This work evaluates chronic safety in middle-aged ovariectomized rats supplemented with different dosages of green tea polyphenols (GTP) in drinking water. The experiment used 6-mo-old sham (n = 39) and ovariectomized (OVX, n = 143) female rats. All sham (n = 39) and 39 of the OVX animals received no GTP treatment and their samples were collected for outcome measures at baseline, 3 mo, and 6 mo (n = 13 per group for each). The remaining OVX animals were randomized into 4 groups receiving 0.15%, 0.5%, 1%, and 1.5% (n = 26 for each) of GTP (wt/vol), respectively, in drinking water for 3 and 6 mo. No mortality or abnormal treatment-related findings in clinical observations or ophthalmologic examinations were noted. No treatment-related macroscopic or microscopic findings were noted for animals administered 1.5% GTP supplementation. Throughout the study, there was no difference in the body weight among all OVX groups. In all OVX groups, feed intake and water consumption significantly decreased with GTP dose throughout the study period. At 6 mo, GTP intake did not affect hematology, clinical chemistry, and urinalysis, except for phosphorus and blood urea nitrogen (increased), total cholesterol, lactate dehydrogenase, and urine pH (decreased). This study reveals that the no-observed-adverse-effect level (NOAEL) of GTP is 1.5% (wt/vol) in drinking water, the highest dose used in this study., (© 2017 Institute of Food Technologists®.)

This review aimed to investigate possible protective or deleterious effects of polyphenol-rich foods (PRF) on chronic diseases, e.g. cardiovascular, and in pregnant women, along with their antioxidant and anti-inflammatory action. A great variety of foods and beverages, such as herbal teas, grape and orange derivatives, dark chocolate, and many others contain high concentrations of flavonoids and are freely consumed by the general population. In humans, PRF consumption reduces lipid peroxidation, and several studies have shown a positive correlation between an increased consumption of PRF and a decrease in the incidence of cardiovascular disease. On the other hand, current studies have suggested that maternal ingestion of PRF, especially during the third trimester of pregnancy, could be associated to fetal ductal constriction (DC). Fetuses exposed to this type of diet show higher ductal velocities and lower pulsatility indexes, as well as larger right ventricles than those exposed to minimal amounts of these substances. The underlying mechanism involved in these conditions has not been entirely elucidated, but it seems to be a result of the antioxidant and anti-inflammatory effects of polyphenols by some pathway. Furthermore, taking into account the deleterious effect in late-pregnancy against the numerous positive effects associated to polyphenols, this dual behavior deserves attention particularly to control the dietary ingestion of PRF during gestation. In this line, same PRF, natural constituents of human diet, may represent risk to fetal in late pregnancy compared to the use of nonsteroidal anti-inflammatory drugs.

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease characterized by excess lipid deposition in the hepatic tissue and subsequent oxidative and inflammatory damage. Curcumin is a dietary polyphenol with lipid-modifying, antioxidant and anti-inflammatory properties. This study aimed to evaluate the efficacy and safety of supplementation with phytosomal curcumin in subjects with NAFLD.Patients diagnosed with NAFLD (grades 1-3 according to liver ultrasonography) were randomly assigned to the curcumin (phytosomal form; 1 000 mg/day in 2 divided doses) (n=50) or placebo group (n=52) for a period of 8 weeks. All patients received dietary and lifestyle advises before the start of trial. Anthropometric measurements, hepatic enzymes, and liver ultrasonography were assessed at baseline and after 8 weeks of follow-up.87 subjects (n=44 and 43 in the curcumin and control group, respectively) completed the trial. Supplementation with curcumin was associated with a reduction in body mass index (-0.99±1.25 vs.  - 0.15±1.31 in the curcumin and placebo groups, respectively; p=0.003) and waist circumference (-1.74±2.58 vs. -0.23±3.49 in the curcumin and placebo groups, respectively; p=0.024). Ultrasonographic findings were improved in 75.0% of subjects in the curcumin group, while the rate of improvement in the control group was 4.7% (p<0.001). Serum levels of aspartate aminotransferase and alanine aminotransferase were reduced by the end of trial in the curcumin group (p<0.001) but elevated in the control group (p<0.001). Curcumin was safe and well tolerated during the course of trial.Short-term supplementation with curcumin improves liver fat and transaminase levels in patients with NAFLD., (© Georg Thieme Verlag KG Stuttgart · New York.)

The objective of this study was to assess the underlying mechanisms of mango polyphenol decreased cell proliferation and tumor volume in ductal carcinoma in situ breast cancer. We hypothesized that mango polyphenols suppress signaling along the AKT/mTOR axis while up-regulating AMPK. To test this hypothesis, mango polyphenols (0.8 mg gallic acid equivalents per day) and pyrogallol (0.2 mg/day) were administered for 4 weeks to mice xenografted with MCF10DCIS.com cells subcutaneously (n=10 per group). Tumor volumes were significantly decreased, both mango and pyrogallol groups displayed greater than 50% decreased volume compared to control. There was a significant reduction of phosphorylated protein levels of IR, IRS1, IGF-1R, and mTOR by mango; while pyrogallol significantly reduced the phosphorylation levels of IR, IRS1, IGF-1R, p70S6K, and ERK. The protein levels of Sestrin2, which is involved in AMPK-signaling, were significantly elevated in both groups. Also, mango significantly elevated AMPK phosphorylation and pyrogallol significantly elevated LKB1 protein levels. In an in vitro model, mango and pyrogallol increased reactive oxygen species (ROS) generation and arrested cells in S phase. In silico modeling indicates that pyrogallol has the potential to bind directly to the allosteric binding site of AMPK, inducing activation. When AMPK expression was down-regulated using siRNA in vitro, pyrogallol reversed the reduced expression of AMPK. This indicates that pyrogallol not only activates AMPK, but also increases constitutive protein expression. These results suggest that mango polyphenols and their major microbial metabolite, pyrogallol, inhibit proliferation of breast cancer cells through ROS-dependent up-regulation of AMPK and down-regulation of the AKT/mTOR pathway., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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 need to protect human spermatozoa from oxidative stress during assisted reproductive technology, has prompted a detailed analysis of the impacts of phenolic compounds on the functional integrity of these cells. Investigation of 16 individual compounds revealed a surprising variety of negative effects including: (i) a loss of mitochondrial membrane potential (Δψm) via mechanisms that were not related to opening of the permeability transition pore but associated with a reduction in thiol expression, (ii) a decline in intracellular reduced glutathione, (iii) the stimulation of pro-oxidant activity including the induction of ROS generation from mitochondrial and non-mitochondrial sources, (iv) stimulation of lipid peroxidation, (v) the generation of oxidative DNA damage, and (vi) impaired sperm motility. For most of the polyphenolic compounds examined, the loss of motility was gradual and highly correlated with the induction of lipid peroxidation (r=0.889). The exception was gossypol, which induced a rapid loss of motility due to its inherent alkylating activity; one consequence of which was a marked reduction in carboxymethyl lysine expression on the sperm tail; a post-translational modification that is known to play a key role in the regulation of sperm movement. The only polyphenols that did not appear to have adverse effects on spermatozoa were resveratrol, genistein and THP at doses below 100μM. These compounds could, therefore, have some therapeutic potential in a clinical setting., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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.

Angiogenesis, the formation of new blood-vessel, is crucial in the pathogenesis of several diseases, and thus represents a druggable target for the prevention and treatment of different disorders. It is nowadays well kwon how diet can control cancer development and progression, and how the use of certain diet components can prevent cancer development. Several studies, also from our lab, now indicate that natural plant products including nutraceuticals modulate tumor angiogenesis. In this review, it is reported how phytochemicals, comprising hydroxytyrosol, resveratrol, genistein, curcumin, and the green tea component epigallocatechin-3-gallate among the others, negatively regulate angiogenesis. A single plant-derived compound may affect both endothelial and tumor cells, with the common denominator of anti-inflammatory and radical scavenger activities. Beside these positive features, documented in cellular and animal models, a series of critical issues should be considered from a pharmacological point of view as: what is the best source of bioactive compounds: food and beverages, extracted phytocomplexes, isolated nutraceuticals or synthetic analogues? How is the bioavailability of the compounds of interest in relation to the above source? Is there any biological activity by circulating metabolic derivatives? What is the best formulation, administration route and posology? How safe are in humans? How strong and reliable are the clinical trials designed for their use alone or in combination with conventional chemotherapy? After a dissertation of these critical points, the conclusion can be drawn that novel and effective strategies should be optimized to improve their bioavailability and efficacy, considering their exploitation as chemopreventive and/or curative approaches., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In recent years, the intake of functional foods containing high-doses of green tea polyphenols (GP) has been increasing. In this study, the long-term safety of high-dose GP was assessed from a pharmacokinetic point of view by focusing on the drug-metabolizing enzyme, cytochrome P450 (CYP). Mice were fed a diet containing 3% GP for 4weeks, and the CYP expression levels and activity were determined. The GP-treated group showed a significant decrease in the hepatic CYP3A and an increase in the hepatic CYP2C expression compared with the control group. CYP1A, CYP2D, and CYP2E expression were not different between the GP-treated and the control groups. In the small intestine, there were no differences in the CYP3A protein levels between the groups. The increase in the plasma triazolam concentration in the GP-treated group was observed. Although no changes were found in the hepatic CYP3A levels in mice receiving a diet containing 0.1% GP for 4weeks, a significant decrease was seen in the hepatic CYP3A level in mice receiving a diet containing 3% GP for only 1week. This study revealed that the intake of a high-dose GP results in a liver-specific decrease in the CYP3A expression level. The results also indicated that the effects of GP on CYP3A were not observed following the intake of a low-dose GP. In the future, caution should be taken in cases when functional foods containing a high-dose GP are concomitantly consumed with a CYP3A substrate drug., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A large evidence-based review on the effects of a moderate consumption of beer on human health has been conducted by an international panel of experts who reached a full consensus on the present document. Low-moderate (up to 1 drink per day in women, up to 2 in men), non-bingeing beer consumption, reduces the risk of cardiovascular disease. This effect is similar to that of wine, at comparable alcohol amounts. Epidemiological studies suggest that moderate consumption of either beer or wine may confer greater cardiovascular protection than spirits. Although specific data on beer are not conclusive, observational studies seem to indicate that low-moderate alcohol consumption is associated with a reduced risk of developing neurodegenerative disease. There is no evidence that beer drinking is different from other types of alcoholic beverages in respect to risk for some cancers. Evidence consistently suggests a J-shaped relationship between alcohol consumption (including beer) and all-cause mortality, with lower risk for moderate alcohol consumers than for abstainers or heavy drinkers. Unless they are at high risk for alcohol-related cancers or alcohol dependency, there is no reason to discourage healthy adults who are already regular light-moderate beer consumers from continuing. Consumption of beer, at any dosage, is not recommended for children, adolescents, pregnant women, individuals at risk to develop alcoholism, those with cardiomyopathy, cardiac arrhythmias, depression, liver and pancreatic diseases, or anyone engaged in actions that require concentration, skill or coordination. In conclusion, although heavy and excessive beer consumption exerts deleterious effects on the human body, with increased disease risks on many organs and is associated to significant social problems such as addiction, accidents, violence and crime, data reported in this document show evidence for no harm of moderate beer consumption for major chronic conditions and some benefit against cardiovascular disease., (Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)