Polyphenol-Rich Extract from 'Limoncella' Apple Variety Ameliorates Dinitrobenzene Sulfonic Acid-Induced Colitis and Linked Liver Damage.

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-1ß) 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.

Polyphenol-enriched Desmodium elegans DC. ameliorate scopolamine-induced amnesia in animal model of Alzheimer's disease: In Vitro, In Vivo and In Silico approaches.

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 IC50 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 IC50 values of 62.34 and 47.32 µg mL-1 respectively. In a BChE inhibition assay, the chloroform fraction exhibited 84.36% inhibition with IC50 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.

UP360, a Standardized Composition from Extracts of Aloe barbadense, Poria cocos, and Rosemary officinalis Protected Against Sepsis and Mitigated Acute Lung Injury in Murine Models.

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)-1ß, 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.

Quercus coccinea Münchh leaves polyphenols: Appraisal acute lung injury induced by lipopolysaccharide in mice.

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.

Da-Yuan-Yin decoction polyphenol fraction attenuates acute lung injury induced by lipopolysaccharide.

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-1ß, 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.

Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background: Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD. Methods: The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis. Results: The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients. Conclusion: Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.

Efficacy and Safety of Oral Green Tea Preparations in Skin Ailments: A Systematic Review of Clinical Studies.

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.

Antihyperglycemic, Antihyperlipidemic, and Antioxidant Effects of Salvia tingitana in Streptozotocin-Induced Diabetic Rats.

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.

Supplementation of polyphenol-rich grapes attenuates colitis, colitis-associated colon cancer, and disease-associated dysbiosis in mice, but fails to mitigate colitis in antibiotic-treated mice.

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.

Advances in Nanoformulated Polyphenols for Protection Against Cardiovascular Diseases.

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).

Effect of Pulicaria mauritanica on Glucose Metabolism and Glycogen Content in Streptozotocin-Induced Diabetic Rats.

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.

A prospective, randomized, double-blind, placebo-controlled trial of polyphenols on the outcomes of inflammatory factors and oxidative stress in patients with type 2 diabetes mellitus.

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.

Potential neuroprotective of trans resveratrol a promising agent tempeh and soybean seed coats-derived against betaamyloid neurotoxicity on primary culture of nerve cells induced by 2-methoxyethanol / Potencial neuroprotetor do agente trans-resveratrol em cascas de sementes de soja e tempê derivadas da neurotoxicidade beta-amiloide na cultura primária de células nervosas induzidas pelo 2-metoxietanol

Resveratrol, a natural polyphenol found in tempeh, has not been investigated especially in vitro as a neuroprotective agent against 2-methoxyethanol (2-ME)-induced beta-amyloid cytotoxicity. Beta amyloid peptides (Aβ) could initiate neurotoxic events and neuron-inflammatory response via microglial activation. However, it remains unknown whether the neurotoxic effect of beta-amyloid and/or associated with the potential of 2-ME to induce neurotoxic effects on primary culture of nerve cells induced by 2-ME. This study investigated potential neuroprotective of trans-resveratrol a promising agent tempeh and soybean seed coats-derived against beta amyloid cytotoxicity on primary culture of nerve cells induced by 2-methoxyethanol. Biotium and MTT assays were used to analyze neurons, which were isolated from the cerebral cortex of fetal mice at gestation day 19 (GD-19). A standard solution of 2-methoxyethanol was dosed at 10 μL. The cultured cells were randomly divided into the following groups: (1) 2-ME group + resveratrol standard, (2) 2-ME group + resveratrol isolated from tempeh, (3) 2-ME group + resveratrol isolated from soybean seed coats, and (4) the control group, without the addition of either 2-ME or resveratrol. Exposure of the primary cortical neuron cells to beta-amyloid monoclonal antibody pre-incubated for 24 h with 10 µL of 4.2 µg/mL resveratrol and 7.5 mmol/l 2-methoxy-ethanol additions. Here, we report that the addition of 2-ME and resveratrol (standard and isolated from tempeh) of cell culture at concentrations of 1.4, 2.8 and 4.2 µg/mL showed that the majority of neurons grew well. In contrast, after exposure to 2-ME and Beta-amyloid, showed that glial activated. These findings demonstrate a role for resveratrol in neuroprotective-neurorescuing action.

O resveratrol, um polifenol natural encontrado em tempê, não foi investigado apenas in vitro como agente neuroprotetor contra a citotoxicidade beta-amiloide induzida por 2-metoxietanol (2-ME). Os peptídeos beta amiloides (Aβ) podem iniciar eventos neurotóxicos e resposta inflamatória dos neurônios via ativação microglial. No entanto, permanece desconhecido se o efeito neurotóxico do peptídeo beta-amiloide associado ao potencial do 2-ME causa efeitos neurotóxicos na cultura primária de células nervosas induzidas pelo 2-ME. Este estudo investigou o potencial neuroprotetor do agente trans-resveratrol em cascas de sementes de soja e tempê derivadas da citotoxicidade beta-amiloide na cultura primária de células nervosas induzidas pelo 2-metoxietanol. Ensaios de biotium e MTT foram utilizados para analisar os neurônios isolados do córtex cerebral de camundongos fetais no dia da gestação 19 (GD-19). As células cultivadas foram divididas aleatoriamente nos seguintes grupos: (1) grupo 2-ME + padrão de resveratrol; (2) grupo 2-ME + resveratrol isolado de tempê; (3) grupo 2-ME + resveratrol isolado de cascas de sementes de soja; e (4) grupo controle, sem a adição de 2-ME ou resveratrol. Houve exposição das células primárias dos neurônios corticais ao anticorpo monoclonal beta-amiloide pré-incubado por 24 horas, com 10 µL de 4,2 µg/mL de resveratrol, e adições de 7,5 mmol/l de 2-metoxietanol. A adição de 2-ME e resveratrol (padrão e isolado do tempê) da cultura de células nas concentrações de 1,4, 2,8 e 4,2 µg/mL mostrou que a maioria dos neurônios cresceu bem. Por outro lado, após a exposição ao 2-ME e beta-amiloide, a glia foi ativada. Esses achados demonstram um papel do resveratrol na ação neuroprotetora e de neurorresgate.

Therapeutic Effects and Safe Uses of Plant-Derived Polyphenolic Compounds in Cardiovascular Diseases: A Review.

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.

Effects of Pesticides on Longevity and Bioenergetics in Invertebrates-The Impact of Polyphenolic Metabolites.

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 and Their Effects on Muscle Atrophy and Muscle Health.

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.

Efficacy and Safety of Polyphenols for Osteoarthritis Treatment: A Meta-Analysis.

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 I2 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.

Effects of dietary polyphenol supplementation on iron status and erythropoiesis: a systematic review and meta-analysis of randomized controlled trials.

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 ß-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 ß-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.

Improvement in fetal pulmonary hypertension and maturity after reversal of ductal constriction: prospective cohort study.

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.

Analysis of the intricate effects of polyunsaturated fatty acids and polyphenols on inflammatory pathways in health and disease.

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.