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Abstract

Hydrolysable tannins are phenolic phytochemicals that show high antioxidant and free-radical scavenging activities. For this reason their potential effects preventing oxidative related diseases, such as cardiovascular diseases, have been largely studied. In vitro studies show that ellagitannins, at concentrations in the range 10-100 μM, show some relevant anti-atherogenic, anti-thrombotic, anti-inflammatory and anti-angiogenic effects, supporting the molecular mechanisms for the vascular health benefits. While there is good evidence supporting the vascular effects in vitro, the evidence on animal models or humans is much scarcer. The in vitro results often do not match the findings in the in vivo studies. This could be explained by the low bioavailability of the antioxidant ellagitannins and ellagic acid. The main ellagitannin metabolites circulating in plasma are ellagic acid microbiota metabolites known as urolithins, and they have lost their free-radical scavenging activity. They are present in plasma as glucuronide or sulphate conjugates, at concentrations in the nM range. Future studies should focus in the bioavailable metabolites, urolithins, and in the form (conjugated with glucuronic acid or sulphate) and concentrations (nM range) in which they are found in plasma. In this review we critically discuss the role of ellagitannins and ellagic acid on vascular health.

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... Since the late 90s, EA benefits have been reviewed by many authors [1,2,7,8] and both in vitro and in vivo studies have been carried out in an attempt to define the molecular and cellular events rationalizing the biological activities that EA and/or its derivatives exert in pathological conditions. In vitro, EA showed considerable health effects including anti-carcinogenic [1,2,9,[10][11][12], antiatherogenic [13], anti-thrombotic [14,15], anti-angiogenic [16], anti-neurodegenerative [9,17-20] properties, as well as the capability to prevent obesity [21]. ...
... Since the late 90s, EA benefits have been reviewed by many authors [1,2,7,8] and both in vitro and in vivo studies have been carried out in an attempt to define the molecular and cellular events rationalizing the biological activities that EA and/or its derivatives exert in pathological conditions. In vitro, EA showed considerable health effects including anti-carcinogenic [1,2,9,[10][11][12], antiatherogenic [13], anti-thrombotic [14,15], anti-angiogenic [16], anti-neurodegenerative [9,17-20] properties, as well as the capability to prevent obesity [21]. ...
... Many factors dictate for ETs poor bioavailability, such as their large size ranging between 634 and 3740 Da, their relatively high polarity, the presence of a C-C linkage, and their probable binding to some proteins in saliva, that limits their further metabolism and causes astringency [31]. While some ETs are even resistant to acid and basic hydrolysis and can reach the large intestine almost intact [9,32], most are sensitive to acidic and basic pH and are promptly metabolized in stomach and duodenum, respectively, releasing free EA [1,2,9,33]. ...
Article
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Oxidative stress (OS), triggered by overproduction of reactive oxygen and nitrogen species, is the main mechanism responsible for several human diseases. The available one-target drugs often face such illnesses, by softening symptoms without eradicating the cause. Differently, natural polyphenols from fruits and vegetables possess multi-target abilities for counteracting OS, thus representing promising therapeutic alternatives and adjuvants. Although in several in vitro experiments, ellagitannins (ETs), ellagic acid (EA), and its metabolites urolithins (UROs) have shown similar great potential for the treatment of OS-mediated human diseases, only UROs have demonstrated in vivo the ability to reach tissues to a greater extent, thus appearing as the main molecules responsible for beneficial activities. Unfortunately, UROs production depends on individual metabotypes, and the consequent extreme variability limits their potentiality as novel therapeutics, as well as dietary assumption of EA, EA-enriched functional foods, and food supplements. This review focuses on the pathophysiology of OS; on EA and UROs chemical features and on the mechanisms of their antioxidant activity. A discussion on the clinical applicability of the debated UROs in place of EA and on the effectiveness of EA-enriched products is also included.
... In clinical studies, dietary phenols such as ellagitannins have been considered as supplements for the treatment of cardiovascular diseases and certain pathological changes [139]. The main metabolites of ellagitannins in the systemic circulation are urolithins, which are beneficial for vascular health [140]. It has been found that PE can improve endothelium-dependent vasodilatation of aortic rings from hyperglycemic rats, alleviate NO synthesis disorders, and suppress the phosphorylation of Akt and downstream transcriptional targets of Wnt/β-catenin signaling. ...
... Therefore, the prevention and control effect of PE on DC may bring some hope to them. PE can, for example, improve the utilization of Anti-atherogenic, anti-thrombotic, anti-inflammatory and anti-angiogenic effects; NO radical scavenging; inhibition of platelet aggregation [136,140,144] Urolithin (EA metabolites) Alleviate NO synthesis disorders, suppress the phosphorylation of Akt and downstream transcriptional targets of Wnt/β-catenin signaling [140] ...
... Therefore, the prevention and control effect of PE on DC may bring some hope to them. PE can, for example, improve the utilization of Anti-atherogenic, anti-thrombotic, anti-inflammatory and anti-angiogenic effects; NO radical scavenging; inhibition of platelet aggregation [136,140,144] Urolithin (EA metabolites) Alleviate NO synthesis disorders, suppress the phosphorylation of Akt and downstream transcriptional targets of Wnt/β-catenin signaling [140] ...
Article
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Phyllanthus emblica is a fruit widely consumed in subtropical areas, which is rich in polyphenols and other nutrients. There are increasing evidences that as a daily and nutritious fruit, it may have a positive role in controlling diabetic complications. According to the new study, its mechanisms include enhancing the functioning of insulin, reducing insulin resistance, activating the insulin-signaling pathway, protecting β-cells, scavenging free radicals, alleviating inflammatory reactions, and reducing the accumulation of advanced glycation end products. Owing to its few side effects, and low price, it should be easily accepted by patients and has potential for preventing diabetes. Taken together, Phyllanthus emblica may be an ideal fruit for controlling diabetic complications. This review highlights the latest findings of the role of Phyllanthus emblica in anti-diabetes and its complications, especially clarifies the molecular mechanism of the chemical components related to this effect, and prospects some existing problems and future research directions.
... As urolithin metabolites exhibit distinctive UV spectra, they can be detected and identified by HPLC coupled with UV/DAD, with lambda max ranging from 246 to 367 nm [119]. Animal studies have shown that the formation of these metabolites is initiated in the small intestine, suggesting that the anaerobic bacteria is responsible for this biotransformation [121]. It has been suggested that the production of urolithins stems from the removal of either one or two lactone groups after the lactonase and decarboxylase activity and the subsequent loss of hydroxyl group catalysed by a dehydroxylase [118,122]. ...
... After their production, urolithins are initially present in faeces as glucuronides and can be absorbed and circulated in plasma prior to their accumulation in urine as glucuronide and sulphate conjugates [124,125]. Urolithin A and B aglycones are conjugated in the liver or intestinal cells, through the action of uridine 5'-diphospho (UDP)-glucuronosyltransferases, which enhance their solubility and therefore excretion in urine [40,121]. The high bioactivity of these compounds has been also confirmed as they were present in urine even after seven days post-ingestion. ...
... These authors also reasoned the comparatively lower hydrophobicity of urolithins C, D, M5, hexahydroxydiphenyl, and ellagic acid derivatives compared to urolithins A and B was the main reason for their low bioavailability in the intestinal lumen [39]. Differences in the production of urolithins by humans had been reported in an earlier study, wherein the authors indicated the action of different gut microorganisms influence the urolithin production [121]. After assessing human breast milk samples, Zhang et al. [85] revealed that urolithins were the most significant metabolites identified among them. ...
Article
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Berries have been widely assessed for their beneficial health effects, predominately due to their high (poly)phenol content of anthocyanins and ellagitannins. After ellagitannins and ellagic acid are metabolized by the gut microbiome, a class of compounds known as urolithins are produced, which exert potential advantageous health effects. Anthocyanins, on the other hand, undergo a complex metabolic pathway after their interaction with microbial and endogenous enzymes, forming a broad range of metabolites and catabolic products. In most cases, in vitro models and cell lines are used to generate metabolites, whereas their assessment in vivo is currently limited. Thus far, several analytical methods have been developed for the qualitative and quantitative analysis of phenolic metabolites in berries, including liquid chromatography, mass spectrometry, and other hyphenated techniques, and have been undoubtedly valuable tools for the detailed metabolite characterization and profiling. In this review, a compilation of studies providing information on the qualitative and quantitative analysis of (poly)phenol metabolites in blackberries and raspberries after the utilization of in vitro and in vivo methods is presented. The different analytical techniques employed are assessed, focusing on the fate of the produced metabolic compounds in order to provide evidence on their characteristics, formation, and beneficial effects.
... Pomegranate ellagitannins have been reported to possess several biological properties. In fact, they are considered as the major antioxidant in vitro of pomegranate juice and their gut microbiota metabolites, urolithins, have displayed a broad array of chemopreventive properties (Clifford and Scalbert 2000;González-Sarrías et al. 2009b;Larrosa et al. 2010a). ...
... In the same way, anti-atherosclerotic benefits of pomegranate should be due to the concerted action of a combination of phytochemicals and other pomegranate nutrients, rather than the sole effects of a unique compound. Moreover, both anthocyanins and ellagitannins, main pomegranate phenolics, have demonstrated possessing large cardiovascular health-promoting effects as it has been previously reviewed (de Pascual-Teresa et al. 2010;Larrosa et al. 2010a). The superior anti-proliferative and anti-atherogenic activity of pomegranate juice above pomegranate extracts and purified phenolics have already been reported Aviram et al. 2008). ...
Article
The role of pomegranate on folk medicine has been largely established and in recent years a notable increase of scientific support has occurred. However, what is real? Evidence suggests that phenolic phytochemicals of pomegranate fruit, mainly anthocyanins and ellagitannins, could exert multiple therapeutic properties on health management as playing an essential role in oxidative stress balance, preventing important cardiovascular diseases, and fighting as chemoprotective agent against several kinds of cancer. In addition, pomegranate antioxidant bioactives also could possess a role as neuroprotectors in some neurological disorders just as broad antimicrobial activities among other beneficial implications. Regarding promising prospects of pomegranate phenolics, this review summarizes the available scientific information related to health promotion features of pomegranate-derived products and underlines the influence of multiple constituents on the observed biological actions, pointing out pomegranate juice as an interesting source to obtain health benefits.
... Gut bacteria are crucial in the conversion of both ellagitannins and ellagic acid to urolithin A and its glucuronide conjugate, urolithin B and its glucuronide conjugate, isourolithin A, and its glucuronide conjugate, which are anticarcinogenic and anti-inflammatory metabolites. These metabolites are highly bioavailable [27][28][29]. ...
... Metabolism of ellagitannin/ellagic acid by human gut microbiota. Population genotypes have a significant influence on the metabolic pathway[28][29][30]. ...
Chapter
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Several phytochemicals have been developed as medicinal compounds. Extensive research has recently been conducted on phytochemicals such as curcumin, resveratrol, catechin, gallic acid, humulone, quercetin, rutin, diosgenin, allicin, gingerenone-A, caffeic acid, ellagic acid, kaempferol, isorhamnetin, chlorogenic acid, and others. All of these phytochemicals are metabolized in the biological system. To study the metabolic pathways of phytochemicals, studies are done using both in vitro and in vivo techniques. Metabolism is critical in determining phytochemical bioavailability, pharmacokinetics, and effectiveness. Metabolism can occur in organs such as the intestine, liver, gut, and spleen. The metabolic process is aided by a variety of enzymes, including cytochrome P450 enzymes found in the organs. This study outlines a few phytochemicals metabolic pathways. Tannic acid, ellagic acid, curcumin, quercetin, and resveratrol are selected and explained as examples.
... Ellagitannins and ellagic acid with anti-inflammatory and vasculoprotective effects are transformed by the gut microbiota to produce urolithins, bioavailable metabolites [17,18] (Figure 2). There is, however, a large variability in health effects and can be associated with the different polyphenol glucuronide metabolic profiles. ...
Chapter
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Pomegranate (Punica granatum L.) is one of the oldest edible fruits in the Mediterranean area and has been used extensively in the folk medicine. Popularity of pomegranate has increased especially in the last decade because of the health effects of the fruit. Polyphenols, represent the predominant class of phytochemicals of pomegranate, mainly consisting of hydrolysable tannins and ellagic acid. Pomegranate is a rich source of the ellagitannin punicalagin, which has aroused considerable interest in pomegranate fruit as a new therapeutic agent in recent years. Most studies on the effects of pomegranate juice have focused on its ability to cure diabetes and atherosclerosis. The present review summarizes some recent studies on the vasculoprotective and neuroprotective effect of various parts of pomegranate and its main compounds especially hydrolysable tannins ellagitannins, ellagic acid and their metabolites. The in vitro and in vivo studies, showed that the whole parts of pomegranate as well as its main components had a positive influence on blood glucose, lipid levels, oxidation stress and neuro/inflammatory biomarkers. They could be used as a future therapeutic agent towards several vascular and neurodegenerative disorders such as hypertension, coronary heart disease and Alzheimer.
... After initial in vitro reports suggested antiatherogenic, antithrombotic, anti-inflammatory, and antiangiogenic effects of ellagitannins, the in vivo metabolites of ellagitannins were established to be beneficial in the context of cardiovascular health. 31 The metabolism of dietary ellagitannins is now known to proceed from ellagic acid through decomposition by gut bacteria into the bioactive metabolites urolithin A, B, and C. 32 At least one bacterial species present in the human gut microflora specifically involved in this reaction was identified. 33 Urolithins A, B, and C refer to the 3-mono-, 3,8-di-, and 3,8,9-tri-hydroxyurolithins, respectively, depicted in Figure 2. ...
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Since ancient times, oak wood polyphenols are consumed concomitantly with beverages that are stored and aged in oak wood barrels. Among these polyphenols are roburins, which belong to the class of ellagitannins and only occur in oak. To date, water-extracted standardized French Quercus robur wood extract, commercially known as Robuvit®, has been investigated in 1172 subjects in over 20 published clinical trials. The results of the clinical studies are consistent with reported effects of urolithins regarding increased mitophagy, pointing to enhanced energy capacity. The Robuvit metabolite urolithin A, B, and C levels and the number of urolithin producers were found to be increased after intake of the extract. Mitophagy is a process, which assigns energy inefficient mitochondria to disassembly, followed by reconstruction to new and more efficient replacements. This effect of Robuvit was observed in different study groups. Supplementation of Robuvit is ascribed to aid chronically fatigued or burnt-out individuals to regain higher energy and activity levels. Robuvit has been further shown to improve conditions such as renal insufficiency, liver insufficiency, mild heart failure, posttraumatic stress disorder and fatigue after surgery and facilitate recovery from mild health impairments such as flu or hangover. There are also indications that Robuvit helps improve erectile function and general loss of vigor in elderly men. Ex vivo gene expression experiments using metabolites collected from Robuvit consumers point to increased ribosomal biogenesis in endothelial, neuronal, and keratinocyte cells. Higher ribosome density accelerates the peptide production to meet protein demand, making Robuvit a potential enhancer of physical endurance and performance. A study with recreational athletes, supplemented with Robuvit daily, reported significantly increased performance in triathlon.
... Previous studies also showed that ellagitannins, and derivates of ellagic acid being a large part of the polyphenolic fraction in pomegranate juice (Sentandreu et al., 2013;Gómez-Caravaca et al., 2013;Akhavan et al., 2015). Ellagitannins, such as ellagic acid and punicalgin, largely contribute to pomegranate juice functionality through biological activities such as antioxidant function, estrogenic and/or anti-estrogenic effects, anti-inflammatory effects, and antimicrobial and prebiotic effects (Landete, 2011;Larrosa et al., 2010). Among ellagitannins, punicalagin is unique to pomegranate and reported to be responsible for more than half the potent antioxidant activity of the juice (Gil et al., 2000). ...
Article
The utilization of pomegranate (P. granatum L.) in various industries has recently increased. The consumption of pomegranate juice is highly recommended because of bioactive compounds that have a pro-health effect on the human body. The main aim of this study is phytochemical screening and comparison of pomegranate juices available at the Montenegrin market, prepared from whole fruits and arils of wild pomegranate. Besides the determination of basic juice parameters (pH, EC, TTA, and TSS), the quantification of sugars, organic acids, vitamin C, and phenolics was performed by high-performance liquid chromatography. It was found that juice is a rich, good source of flavan-3-ols (2650―9820 mg L⁻¹), ellagitannins (2010–6420 mg L⁻¹), and hydroxybenzoic acids (720―3390 mg L⁻¹). The juices prepared from whole fruits in comparison to the ones from arils have lower pH and higher content of numerous phenolics. The ratio between certain parameters was very high, especially for: punicalin derivative 1 (8.8), ellagic acid, ellagic acid dihexoside, digalloyl-hexoside 1, gallagyl ester 1, gallic acid, ellagic acid galloyl hexoside, ellagitannin 5, digalloyl hexoside 2, ellagitannin 4 (4.4). A significant difference in the content was not found for some acids, sugars, and all anthocyanins, i.e., exactly for 39 compounds.
... The processing of lactones, phenolic acids, and aromatics with different side chain lengths and hydroxylation, depending on the precursor structures (phenylvaleric acids, phenylacetic acids, phenylvalerolactones, hippuric acids, phenylpropionic acids, benzoic acids, etc.) take place consecutively (28,29). Besides, in the most recent decade, researchers also studied the transformation of non-flavonoid polymeric molecules called ellagitannins (or hydrolyzable tannins) (30,31). Tannin structures are exposed to hydrolysis in the intestinal lumen, delivering free ellagic acid, after using ellagitanninrich foods, such as strawberries and raspberries, pecans, pomegranates, and oaked wines. ...
Article
Full-text available
Polyphenols are natural plant compounds and are the most abundant antioxidants in the human diet. As the gastrointestinal tract is the primary organ provided to diet sections, the diet may be regarded as one of the essential factors in the functionality, integrity, and composition of intestinal microbiota. In the gastrointestinal tract, many polyphenols remain unabsorbed and may accumulate in the large intestine, where the intestinal microbiota are most widely metabolized. When assuming primary roles for promoting host well-being, this intestinal health environment is presented to the effect of external influences, including dietary patterns. A few different methodologies have been developed to increase solvency and transport across the gastrointestinal tract and move it to targeted intestinal regions to resolve dietary polyphenols at low bioavailability. Polyphenols form a fascinating community among the different nutritional substances, as some of them have been found to have critical biological activities that include antioxidant, antimicrobial, or anticarcinogenic activities. Besides, it affects the metabolism and immunity of the intestines and has anti-inflammatory properties. The well-being status of subjects can also benefit from the development of bioactive polyphenol-determined metabolites, although the mechanisms have not been identified. Even though the incredible variety of health-advancing activities of dietary polyphenols has been widely studied, their effect on intestinal biology adaptation and the two-way relationship between polyphenols and microbiota is still poorly understood. We focused on the results of polyphenols in diet with biological activities, gut ecology, and the influence of their proportional links on human well-being and disease in this study.
... Conversely, the % of ellagic acid was significantly (p < 0.05) increased in the intestinal fractions of the non-fermented and fermented puree compared to their undigested samples. The observed increase in ellagic acid concentration could be due to the hydrolysis of ellagitannins from the food matrix to ellagic acid due to the mild alkaline pH (7.5) at the intestinal phase [56]. The highest % bioaccessibility of ellagic acid was in the W64*D7 (200.0%) ...
Article
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This study describes the impact of utilising different strains of lactic acid bacteria (LAB) for the fermentation of papaya puree and their effect on the quality parameters and bioaccessibility of phenolic compounds during simulated in vitro gastrointestinal digestion. Papaya was processed into puree; pasteurised and fermented at 37 °C for 2 days; and stored for 7 days at 4 °C using LAB strains Lactiplantibacillus plantarum 75 (L75*D2; L75*D7), Weissella cibaria64 (W64*D2; W64*D7) and Leuconostoc pseudomesenteroides 56 (L56*D2; L56*D7), respectively. Non-fermented samples at 0 (PPD0), 2 (PPD2) and 7 days (PPD7) served as controls. pH was reduced with fermentation and was lowest in L56*D2 (3.03) and L75*D2 (3.16) after storage. The colour change (ΔE) increased with the fermentation and storage of purees; L75*D7 showed the highest ΔE (13.8), and its sourness reduced with storage. The fermentation by W64*D7 and L75*D7 increased the % recovery of chlorogenic, vanillic, syringic, ellagic, ferulic acids, catechin, epicatechin and quercetin in the intestinal fraction compared to the L56*D7 and PPD7. Fermentation by W64*D7 and L75*D7 significantly improved the antioxidant capacity of the dialysed fraction compared to the L56*D7 or PPD7. L56*D7-fermented papaya puree showed the highest inhibitory effect of α-glucosidase activity followed by L75*D7. L75*D7 had a significantly higher survival rate. LAB fermentation affected the bioacessibilities of phenolics and was strain dependent. This study recommends the use of Lpb. plantarum 75 for fermenting papaya puree.
... Ruangtong et al. [10] has synthesized a nano material by ZnO and banana peel extract applied in cancer treatment, thanks to the available bio-compounds. Pomegranate peels have been demonstrated as a valuable source of antioxidant compounds, with a high amount of ellagic acid and flavonoids [11]. In addition, pomelo peel essential oil has been widely used in traditional medicine. ...
Article
Full-text available
The purpose of this study was to evaluate the antioxidant, antibacterial, and anti-UVB of three kinds of fermented fruit peel extracts by pectinase enzyme, including pomegranate, pomelo, and banana peel. The antioxidant was evaluated by the DPPH (2,2-Diphenyl-1-picrylhydrazyl) free radical scavenging method. Antibacterial activity against Escherichia coli and Staphylococcus aureus was assessed by disk diffusion assay, and the photoprotective activity was measured using a photospectrometric method. The results revealed that pomegranate peel extract at 3000 IU/g peel exhibited potent free radical scavenging property against DPPH, with the smallest IC50 value at 0.18%, which was better than that of pomelo peel extract at 55.79%. Furthermore, the results suggested that the pomegranate peel extract also exhibited antibacterial activity against E. coli better than pomelo peel extract, but none of the three samples shows the antibacterial capacity against S. aureus. Moreover, 10% pomegranate peel extract also expressed the strongest anti-UVB activity, with an SPF value of 36.582. The research demonstrates pomegranate peel’s bioactivity potential for further experiments.
... These findings of the mechanism of action of the bioactive compounds provide evidence of the antidiabetic role of pomegranate. In fact, the ellagitannins contained in pomegranate might induce the activation of eNOS synthase (with a cardiovascular protection role) in the endothelial cells of human arteries [27]. In 2020, Guerrero-Solano et al. (2020) determined that pomegranate and its secondary metabolites can be considered in the treatment of inflammatory pain, nociceptive pain and neuropathic pain [28]. ...
Article
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The aim of this study was to develop films based on β–glucans in association with pomegranate juice for its potential in metabolic disorders such as diabetes due to plenty of bioactive compounds from the film composition. Initially, a Box-Behnken design was generated by varying the level of β–glucan content (0.5, 1, 1.5 g), sodium alginate (0.2, 0.4, 0.6 g) and pomegranate juice (10, 20, 30 mL) for development of films. Subsequently, glycerin was added as 25% of the total dry matter. The optimization of the films prepared by the solvent casting method was conducted based on the different responses such as: water vapor transmission rate (WVTR), water vapor permeability (WVP), thickness, density, moisture content, solubility, film opacity and color. The water activity profile and FT–IR analysis were performed in all tests. The model was used to determine the optimal experimental values considering that the optimal film will make a sustained contribution to diabetes. The optimal values of the film sample made of β–glucans, sodium alginate, pomegranate juice and glycerin make it befitting for packaging dry powdered pharmaceuticals. Finally, antimicrobial activity against Gram-negative and Gram-positive bacteria, UV barrier properties and microcrack and pore detections through SEM were also investigated for the optimal film sample.
... The processing of lactones, phenolic acids, and aromatics with different side chain lengths and hydroxylation, depending on the precursor structures (phenylvaleric acids, phenylacetic acids, phenylvalerolactones, hippuric acids, phenylpropionic acids, benzoic acids, etc.) take place consecutively (28,29). Besides, in the most recent decade, researchers also studied the transformation of non-flavonoid polymeric molecules called ellagitannins (or hydrolyzable tannins) (30,31). Tannin structures are exposed to hydrolysis in the intestinal lumen, delivering free ellagic acid, after using ellagitanninrich foods, such as strawberries and raspberries, pecans, pomegranates, and oaked wines. ...
Article
Full-text available
Polyphenols are natural plant compounds and are the most abundant antioxidants in the human diet. As the gastrointestinal tract is the primary organ provided to diet sections, the diet may be regarded as one of the essential factors in the functionality, integrity, and composition of intestinal microbiota. In the gastrointestinal tract, many polyphenols remain unabsorbed and may accumulate in the large intestine, where the intestinal microbiota are most widely metabolized. When assuming primary roles for promoting host well-being, this intestinal health environment is presented to the effect of external influences, including dietary patterns. A few different methodologies have been developed to increase solvency and transport across the gastrointestinal tract and move it to targeted intestinal regions to resolve dietary polyphenols at low bioavailability. Polyphenols form a fascinating community among the different nutritional substances, as some of them have been found to have critical biological activities that include antioxidant, antimicrobial, or anticarcinogenic activities. Besides, it affects the metabolism and immunity of the intestines and has anti-inflammatory properties. The well-being status of subjects can also benefit from the development of bioactive polyphenol-determined metabolites, although the mechanisms have not been identified. Even though the incredible variety of health-advancing activities of dietary polyphenols has been widely studied, their effect on intestinal biology adaptation and the two-way relationship between polyphenols and microbiota is still poorly understood. We focused on results of polyphenols in diet with biological activities, gut ecology, and the influence of their proportional links on human well-being and disease in this study.
... Ellagic acid is present in oak species such as Quercus alba and Quercus robus, and can be extracted from mushroom Phellinus linteus. Mostly, in nature, they exist as complexes called ellagitannins and geranilins, which usually undergo hydrolysis in the gastrointestinal tract to form ellagic acid [93]. Subsequent studies proved its anti-diabetic [94] anti-inflammatory [95], anti-neoplastic [96] property. ...
Article
IntroductionProtein kinase C (PKC) is a promising drug target for various therapeutic areas. Natural products derived from plants, animals, microorganisms, and marine organisms have been used by humans as medicine from prehistoric times. Recently, several compounds derived from plants have been found to modulate PKC activities through competitive binding with ATP binding site, and other allosteric regions of PKC. As a result fresh race has been started in academia and pharmaceutical companies to develop an effective naturally derived small-molecule inhibitor to target PKC activities. Herein, in this review, we have discussed several natural products and their derivatives, which are reported to have an impact on PKC signaling cascade.Methods All information presented in this review article regarding the regulation of PKC by natural products has been acquired by a systematic search of various electronic databases, including ScienceDirect, Scopus, Google Scholar, Web of science, ResearchGate, and PubMed. The keywords PKC, natural products, curcumin, rottlerin, quercetin, ellagic acid, epigallocatechin-3 gallate, ingenol 3 angelate, resveratrol, protocatechuic acid, tannic acid, PKC modulators from marine organism, bryostatin, staurosporine, midostaurin, sangivamycin, and other relevant key words were explored.ResultsThe natural products and their derivatives including curcumin, rottlerin, quercetin, ellagic acid, epigallocatechin-3 gallate, ingenol 3 angelate, resveratrol, bryostatin, staurosporine, and midostaurin play a major role in the management of PKC activity during various disease progression.Conclusion Based on the comprehensive literature survey, it could be concluded that various natural products can regulate PKC activity during disease progression. However, extensive research is needed to circumvent the challenge of isoform specific regulation of PKC by natural products.
... Vitamin C sodium ascorbate salt possesses a strong apoptotic activity on neuroblastoma (NB) cells, while ellagitannins (ETs) have shown activities against several degenerative diseases, such as cardiovascular, cancer, and central-nervous-system-disabling disorders, including Parkinson's disease, Alzheimer, multiple sclerosis, and amyotrophic lateral sclerosis. The same effects were displayed by gallic and ellagic acids (GA and EA), which are ETs' metabolites, in both in vitro studies and animal models [22][23][24][25][26][27]. Since it was established that most human diseases are produced by oxidative stress (OS) caused by an uncontrolled accumulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), the BACs benefit for human health mainly depends on their free radical scavenging activity, their capability to inhibit the assembly of microtubule and microfilament, to chelate metals and to inhibit protease [28][29][30]. ...
Article
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Numerous foods, plants, and their bioactive constituents (BACs), named nutraceuticals and phytochemicals by experts, have shown many beneficial effects including antifungal, antiviral, anti-inflammatory, antibacterial, antiulcer, anti-cholesterol, hypoglycemic, immunomodulatory, and antioxidant activities. Producers, consumers, and the market of food- and plant-related compounds are increasingly attracted by health-promoting foods and plants, thus requiring a wider and more fruitful exploitation of the healthy properties of their BACs. The demand for new BACs and for the development of novel functional foods and BACs-based food additives is pressing from various sectors. Unfortunately, low stability, poor water solubility, opsonization, and fast metabolism in vivo hinder the effective exploitation of the potential of BACs. To overcome these issues, researchers have engineered nanomaterials, obtaining food-grade delivery systems, and edible food- and plant-related nanoparticles (NPs) acting as color, flavor, and preservative additives and natural therapeutics. Here, we have reviewed the nanotechnological transformations of several BACs implemented to increase their bioavailability, to mask any unpleasant taste and flavors, to be included as active ingredients in food or food packaging, to improve food appearance, quality, and resistance to deterioration due to storage. The pending issue regarding the possible toxic effect of NPs, whose knowledge is still limited, has also been discussed.
... Ellagitannins (ETs) are secondary plant metabolites belonging to the group of hydrolysable tannins (Feldman et al. 2003;Dai and Mumper 2010). They exhibit beneficial health properties, including antioxidant, antibacterial, antiviral, and anti-inflammatory activity (Sangiovanni et al. 2013;Kahkonen et al. 2012;Larrosa et al. 2010;Puljula et al. 2020;Marquez -Lopez et al. 2020). The health-promoting activity of ETs has been demonstrated both in vitro and in vivo. ...
Article
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The paper presents the kinetics of two-step ellagitannin (ET) extraction with an aqueous acetone solution from two technological types of pomace from selected berry fruits of the Rosaceae family. ETs were identified and quantified using HPLC–MS and HPLC–DAD. The results revealed the extraction kinetics of total ETs, their high and low molecular weight fractions (≤ 1569 Da and > 1569 Da), and individual ETs characteristic of the examined fruits. ET extraction proceeded at a faster rate in the first step, regardless of the tested pomace. For all pomace variants, the mean extraction half time t 1/2 was 48 min in the first step and 70 min in the second step. The fruit species and the technological type of pomace were not found to exert a definite effect on the kinetics of ET extraction. Statistical analysis demonstrated that the molecular weight of ETs did not influence the kinetics of their extraction, either. It was shown that the technological type of pomace had a significant impact on the extraction rate of both low molecular weight (LMW) and high molecular weight (HMW) ETs in the first extraction step, with the mean t 1/2 being 44 min for pomace from juice production and 63 min for pomace from puree production.
... Contents of these compounds in pomegranate fruits include ellagitannins are found 2020-2660 mg/L in wonderful variety [34]. ...
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Punica granatum (pomegranate) is a high-polyphenol, high-bioavailability fruit that is often regarded as a superfood. The fruits have long been employed in the prevention and treatment of many malignant illnesses, and their involvement in pathophysiological processes has been documented in both scientific and non-science literature. The medicinal potential of pomegranate fruit is extensively mentioned in the ancient literature and also used in different system of medicines. These fruits are known for major bioactive compounds such as quercetin, ellagic acid, punicalagin, pedunculagin, tannic acid, anthocyanins, rutin, catechin and polyphenols. These compounds are well known for their antioxidant, neuroprotective, anti-inflammatory, anti-angiogenic, anticancerous, anti-mutagenic, cytoprotective, cardiovascular protective, anti-diabetic, anti-ulcerogenic, hepatoprotective, antibacterial and antifungal potentials. The present review highlights the beneficial effects of pomegranate on human health and also represents the mechanisms involved in its action. [Peel extracts (rind), seed extract, juice and whole fruit on the selected bacteria and fungi activity]. The review will be extended to anti�microbial, wound healing activities and anti-cancerous activity. The pomegranate genotypes have an important value in health and nutrition of the human. The pomegranate peels could be utilized by the food industry and pharma/nutraceutical’s industry (Pomegranate peel extract-based nanoparticles by chemical complication method). Pomegranate contains secondary metabolites such as alkaloids, flavonoids, steroids, phenolic, terpenes and volatile oils. This review will focus the areas for which pomegranate has shown therapeutic properties in different mechanisms. This review article presents the recently published findings on different aspects of this plant, with a focus on its bioactive compound properties. The pomegranate peel is an inexhaustible resource with many potential functions in numerous industries; added exploration of the fruit peel infected, premature and damaged fruit peel due to natural calamities may lead to new and novel ways of creating wealth from waste
... In fact, tannins and ellagitannins, once ingested, provide pharmacological effects both locally and systemically (Serrano, Puupponen-Pimia, Dauer, Aura, & Saura-Calixto, 2009). In the small intestines, ellagitannins are hydrolyzed and partly absorbed (Espin et al., 2013) and reach the colon where they are metabolized by the microbiota (Marin, Miguelez, Villar, & Lombo, 2015) to urolithins (Larrosa et al., 2010). Urolithins enter the enterohepatic circulation system and may be recovered in blood, urine, and tissues (Cerda, Espin, Parra, Martinez, & Tomas-Barberan, 2004). ...
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Ellagitannins may have a beneficial impact in cardiovascular diseases. The aim of the study was to evaluate the effect of high‐fat diet (HFD) and the efficacy of Castanea sativa Mill. bark extract (ENC) on cardiac and vascular parameters. Rats were fed with regular diet, (RD, n = 15), HFD (n = 15), RD + ENC (20 mg/kg/day by gavage, n = 15), and HFD + ENC (same dose, n = 15) and the effects on body weight, biochemical serum parameters, and inflammatory cytokines determined. Cardiac functional parameters and aorta contractility were also assessed on isolated atria and aorta. Results showed that ENC reduced weight gain and serum lipids induced by HFD. In in vitro assays, HFD decreased the contraction force of left atrium, increased right atrium chronotropy, and decreased aorta K⁺‐induced contraction; ENC induced transient positive inotropic and negative chronotropic effects on isolated atria from RD and HFD rats and a spasmolytic effect on aorta. In ex vivo experiments, ENC reverted inotropic and chronotropic changes induced by HFD and enhanced Nifedipine effect more on aorta than on heart. In conclusion, ENC restores metabolic dysfunction and cardiac cholinergic muscarinic receptor function, and exerts spasmolytic effect on aorta in HFD rats, highlighting its potential as nutraceutical tool in obesity.
... In addition, thanks to gammatocopherol, a type of vitamin E, and other elements, the elements play an important role in cleaning the environment of the heart, especially cholesterol, and reducing the risk of cardiovascular disease by reducing insulin resistance, cholesterol concentrations, lipid peroxidation and oxidative (Rim et al., 1993;Kris-Etherton, et al., 1999;Anderson, et al., 2001;Albert, 2002;Spaccarotella, et al., 2008;Banel et al., 2009;Ros, 2009;Bernsteine, et al., 2010;Kendall et al., 2010;Ros, 2010;Sabate et al., 2010;Estruch et al., 2013;Guasch-Ferré, et al., 2013;Aune et al., 2016;Ros ve ark., 2018). However, some researchers have reported in recent studies on walnuts that ellagitannins in walnuts have protective effects in relation to cardiovascular diseases (Papoutsi et al., 2008;Spaccarotella et al., 2008;Larrosa et al., 2010;Vadivel et al., 2012;Nergiz-Unal et al., 2013;Sánchez-González, et al., 2017). There is growing evidence and studies are ongoing regarding the role of walnut consumption in reducing the risk of coronary heart disease. ...
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The history of using plants to treat human health and many diseases is as old as human history; such that it has a history of several thousand years in many countrie. In the past centuries, natural remedies, especially medicinal plants, were accepted as the basis of treatment. In the last decade, it has been shown that there is a great tendency and willingness to accept natural treatments in developed and developing countries (Delaviz et al., 2017). The use of plants in traditional medicine for many diseases has become widespread in the world. In many studies conducted over the last 30 years; They found that there is a relationship between people's eating habits and diseases. While investigating the relationships between some well-known diseases and nutrition, the most questioned food component/food item was fats. The walnut which has a history of thousands of years, is the oldest tree known to man and is used in the treatment of different diseases. Almost all parts of this plant such as bark, kernel (seed), flower, leaf, green bark, septum, oil have unique food, cosmetic pharmaceutical industries and medicinal properties
... Discovered by Henri Braconnot in 1831, EA is a polyphenolic active compound with high nutritional and therapeutic beneficial effects for human health [5,6]. It is widely distributed in many tropical and mediterranean plant species such as Adenium obesum (Apocynaceae), Terminalia chebula (Combretaceae), Rosa rugosa (Rosaceae) and Punica granatum (Lythraceae) [7][8][9]. In plants, EA is found in free form or linked to sugars or polyols, forming ellagitannins or hydrolysable tannins [10]. ...
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... Different health benefits and biological activities are attributed to these natural products being based on the dietary and clinical prospective and retrospective studies [1]. The impaired health conditions in which ellagitannin-containing products were shown to express preventive or curative effects are in particular diseases with the inflammatory background such as cardiovascular diseases and intestinal inflammations [2][3][4][5]. Despite the effectiveness of these products has been unambiguously confirmed in clinical and epidemiological studies, due to the low bioavailability of ellagitannins, this group of compounds cannot be directly considered as factors, which trigger the biological effects at the systemic level. ...
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... Ellagic acid in combination with the sugar moiety is a constituent unit of ellagitannins, which are known for their cardiovascular benefits [47]. Ellagic acid, as a constituent and metabolite of ellagitannins, has been shown to have considerable vasorelaxant effects in in vitro animal models via an endothelial-dependent mechanism [48]. ...
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Alchemilla viridiflora Rothm., Rosaceae is a herbaceous plant widespread in central Greece, Bulgaria, North Macedonia and Serbia with Kosovo. Liquid chromatography-mass spectrometry analysis leads to the identification of 20 compounds in methanol extract, mainly ellagitannins and flavonoid glycosides. Given that various plant extracts have traditionally been used to treat hypertension and that some of the analyzed methanol extract constituents have beneficial cardiovascular effects, we hypothesized that some of these effects are achieved by inhibiting angiotensin I-converting enzyme (ACE). The dose-dependent ACE inhibitory activities of A. viridiflora and miquelianin were observed with an IC50 of 2.51 ± 0.00 µg/mL of A. viridiflora extract compared to the IC50 of 5.4139 ± 0.00 µM for miquelianin. The contribution of the single compounds to the tested activity was further analyzed through the in silico experimental approach. Computational docking results showed that tiliroside, ellagic acid pentose and galloyl-hexahydroxydiphenoyl-glucose exhibited even better binding affinity for the ACE active site than miquelianin, for which ACE activity was confirmed by an in vitro assay.
... In recent decades, EA is attracting great attention due to its pronounced antioxidant [15][16][17][18][19][20][21][22][23], anti-inflammatory [24][25][26][27][28][29], antimutagenic [30][31][32][33], and antiproliferative properties [34][35][36][37][38][39] and its therapeutic potential in the treatment of several human diseases. Numerous studies have shown that EA may be involved in regulating a spectrum of cellular signaling pathways to prevent, mitigate, or slow down the progression of chronic disorders, including cardiovascular [40][41][42][43] and neurodegenerative diseases [44][45][46][47], diabetes [48][49][50][51], and cancer [38,[52][53][54]. This compound has also been shown to exhibit neuroprotective [55][56][57][58][59], hepatoprotective [60][61][62][63][64][65][66][67][68], nephroprotective [69,70], cardioprotective [71][72][73], antifibrotic [74], antiatherosclerotic [75,76], antiallergic [77][78][79], antinociceptive [80][81][82], antiestrogenic [83], skin-protecting [84][85][86][87], wound-healing [88][89][90], osteogenic [91][92][93], antimicrobial [20,37,94], antiviral [19,[95][96][97], and antiparasitic [98][99][100] effects. ...
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Ellagic acid (EA) is a bioactive polyphenolic compound naturally occurring as secondary metabolite in many plant taxa. EA content is considerable in pomegranate (Punica granatum L.) and in wood and bark of some tree species. Structurally, EA is a dilactone of hexahydroxydiphenic acid (HHDP), a dimeric gallic acid derivative, produced mainly by hydrolysis of ellagitannins, a widely distributed group of secondary metabolites. EA is attracting attention due to its antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties. EA displayed pharmacological effects in various in vitro and in vivo model systems. Furthermore, EA has also been well documented for its antiallergic, antiatherosclerotic, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties. This review reports on the health-promoting effects of EA, along with possible mechanisms of its action in maintaining the health status, by summarizing the literature related to the therapeutic potential of this polyphenolic in the treatment of several human diseases.
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Andean blackberry is a fruit recognized by its health benefits associated with its high content of bioactive compounds. However, it is also one of the most perishable fruits because it does not have a protective cuticle, and it shows high respiration and ethylene production rates. Furthermore, it is susceptible to microbiological attacks. During harvest and commercialization, the highest percentage of losses is caused by factors such as the maturity stage, harvest practices and containers, and marketing packages. The current work aims at studying the effect of the package on fruit quality, for which the harvested fruits were placed in clamshells, traditional wooden and plastic crates with a capacity of 7 kg. The quality of the fruit was evaluated by counting in situ, damage by bruising, cuts, deformations, microbiological attacks, missing of the peduncle, and non-uniform pollination. Damage analysis included the evaluation of different regression models considering information criteria and significant parameters (P 0.05). The use of traditional packages led to higher damage from cuts and bruises. Although in clamshells there was a higher probability of finding healthy fruits, a proposal for its redesign is proposed to guarantee a better quality and shelf life of the Andean blackberry fruits.
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Foods-derived multifunctional compounds, such as carotenoids, vitamins, phytosterols, polyunsaturated lipids, curcuminoids, flavonoids and polyphenols, in addition to the basic nutritional value, own extra health benefits and are considered “pharmaceutical-grade nutrients” better known as “nutraceuticals”. Similarly, phytochemicals from plants, characterized by analogous chemical structures, can be considered “pharmaceutical-grade molecules”. They could provide both diseases preventive actions and remarkable therapeutic benefits but, the efforts for identifying their mode of action and for applying them into food industry with health-promoting purposes, are often unsuccessful. Solubility is essential for a good absorption in the gastrointestinal tract and to achieve the systemic concentration necessary for an effective therapeutic activity, but the majority of these compounds are water-insoluble. Consequently, when ingested, they encounter many difficulties in crossing the diverse barriers to reach the bloodstream and to distribute to cells and tissues. Their absorption at gastric or intestinal level is troubled and in addition, they suffer from early degradation or fast metabolism, so rarely they manage to reach the site of action in therapeutically effective concentration and their clinical applications result strongly limited. Toxic excipients and harmful solubilizing agents were and are extensively used for solubilizing and delivering non-soluble bioactive chemicals (BACs) despite the resulting unpleasant side effects complained of by patients. During last decades, several new techniques, often resorting to nanotechnology, aiming at enhancing BACs solubility, at solving their pharmacokinetics drawbacks, at avoiding their early inactivation or fast metabolism, have been developed. On this background, the following chapter provides an overview concerning nanotechnology contribute and its technological advancements in “manufacturing” nutraceuticals and phytochemicals in more bioavailable nanoparticles. In addition, it is reviewed the involvement of nanoscience in developing and enhancing food-grade solid nanosized materials to be used as BACs “containers” and “vehicles” either for their safe and effective oral administration, in the frame of medical treatments, or for achieving smart food ingredients to improve the quality and shelf life of nourishments.
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Scope We aimed at evaluating the effect of dietary ellagic acid (EA) and its microbial metabolite urolithin A (UA) on glucose metabolism and insulin resistance (IR) in mice with diet‐induced IR. Methods and results DBA2J mice were fed a high fat/high sucrose diet (HF/HS) for 8 weeks to induce IR and then 0.1% EA, UA, or EA and UA combined (EA+UA) were added to the HF/HS‐diet for another 8 weeks. UA significantly decreased fasting glucose and increased serum adiponectin compared with HF/HS‐controls. During intraperitoneal insulin tolerance test, EA+UA significantly improved insulin‐mediated glucose lowering effects at 15 and 120 min and reduced blood triglycerides compared with HF/HS‐controls. Serum free fatty acids were significantly decreased by EA, UA and EA+UA. We observed differential expression of genes related to mitochondrial function by EA, UA and EA+UA in liver and skeletal muscle. Primary hepatocytes from IR‐mice had higher proton leak, basal and ATP‐linked oxygen consumption rates compared with healthy controls. EA and EA+UA but not UA reduced the proton leak in hepatocytes from IR‐mice. Conclusion EA and UA induced different metabolic benefits in HF/HS diet induced IR mice. The effects of EA and UA on mitochondrial function suggest a potentially novel mechanism modulating metabolism. This article is protected by copyright. All rights reserved
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Ethnopharmacological relevance Pomegranate, Punica granatum L., has been used in traditional medicine in China and several regions of the world including Ayurveda, Islamic, and Persian for the treatment of atherosclerosis, diabetes, hypertension, hyperlipidemia, and several types of cancer, as well as for peptic ulcer and oral diseases for hundreds of years. Presently, pomegranate is treated as both a “medicine food homology” herbal medicine and a healthy food supplemental product. Aim of the study The aim of this work is to develop an overview of pomegranate in the context of the status of its traditional medicine theories, the spread along the Silk Road, ethnopharmacological uses, chemical compositions, pharmacological activities, toxicology, and the involved pathways. Materials and Methods Information on P. granatum L. was acquired from published materials, including monographs on medicinal plants, ancient and modern recorded classical texts; and pharmacopoeias and electronic databases (PubMed, Science Direct, Web of Science, Google Scholar, CNKI, and Wanfang Data). Results Pomegranate has been used in many traditional medical systems throughout history. It is widely cultivated in Central Asia and spread throughout China along the Silk Road. Many phytochemicals, such as tannins, organic acids, flavonoids, alkaloids, and volatile oils have been identified from different parts of pomegranate, these compounds have a wide range of activities, including antioxidant, antimicrobial, and anti-oncogenic properties, as well as conferring resistance to cerebrovascular disease. Furthermore, A summary of the four promising pharmacological pathways is provided. Conclusions The traditional uses, chemical compositions, pharmacological activities, and signaling pathways of pomegranate are summarized comprehensively in the review. It can be treated as a guidance for the future clinical and basic research. The information provided in this review will be very useful for further studies to develop novel therapeutic directions for application of pomegranate.
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The maternal−infant transmission of several urolithins through breast milk and the gut colonization of infants by the urolithin-producing bacterium Gordonibacter during their first year of life were explored. Two trials (proof-of-concept study: n = 11; validation study: n = 30) were conducted, where breastfeeding mothers consumed walnuts as a dietary source of urolithin precursors. An analytical method was developed and validated to characterize the urolithin profile in breast milk. Total urolithins ranged from 8.5 to 176.9 nM, while they were not detected in breast milk of three mothers. The mothers' urolithin metabotypes governed the urolithin profile in breast milk, which might have biological significance on infants. A specific quantitative polymerase chain reaction method allowed monitoring the gut colonization of infants by Gordonibacter during their first year of life, and neither breastfeeding nor vaginal delivery was essential for this. The pattern of Gordonibacter establishment in babies was conditioned by their mother's urolithin metabotype, probably because of mother−baby close contact.
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Type 2 diabetes has a series of metabolic aberrations accompanied by chronic hyperglycemia, along with various comorbidities. In recent reports, punicalagin from pomegranate has been reported to exert hypoglycemic effects against diabetes. The goal of the current research was to investigate the therapeutic effectiveness and elucidate the mechanisms of punicalagin underlying type 2 diabetes. Type 2 diabetes was induced by a high-fat diet (HFD) combined with streptozotocin (STZ) injection in C57BL/6J mice. Punicalagin was administered daily by oral gavage for 4 weeks. The results indicated that high FBG (fasting blood glucose), dyslipidemia and associated islet, liver and kidney injury were observed in the model group mice. Through metabolomics analysis, it was found that the administration of punicalagin could regulate 24 potential biomarkers and their related metabolic pathways. Moreover, the pathological changes in the liver and kidney were mainly mediated by reducing gluconeogenesis and increasing glycogenesis via stimulation of the PI3K/AKT signaling pathway and regulation of the HMGB-1/TLR4/NF-κB signaling pathway, which simultaneously interrelated to ten main pathological pathways. In addition, we confirmed the positive role of punicalagin in glucosamine-induced HepG2 cells and HG-induced HK-2 cells through related mechanistic studies in vitro. In conclusion, these findings suggested that the multi-effect and multi-target action mode of punicalagin had a significant hypoglycemic effect and a protective effect on diabetes mellitus. Punicalagin might serve as an alternative functional food or as a clinical supplemental therapy for the diabetic population to ameliorate metabolic syndrome.
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The possible action of polyphenolic compounds in the reduction of reactive oxygen species (ROS) and mitochondrial toxicity may suggest them as putative agents for the treatment of drug-induced mitochondrial dysfunction and cardiotoxicity. This study was designed to explore protective effect of ellagic acid (EA) against celecoxib-induced cellular and mitochondrial toxicity in cardiomyocytes and their isolated mitochondria. In order to do this, isolated cardiomyocytes and mitochondria were pretreated with 3 different concentrations of EA (10, 50 and 100 µM), after which celecoxib (16 µg/ml) was added to promote deleterious effects on cells and mitochondria. Using flow cytometry and biochemical methods, the parameters of cellular and mitochondrial toxicity were investigated. Our results showed that celecoxib (16 µg/ml) caused a significant decrease in cell viability, mitochondrial membrane potential (MMP), glutathione (GSH) in intact cardiomyocytes and succinate dehydrogenase (SDH) activity, MMP collapse, and mitochondrial swelling, and a significant increase in reactive oxygen species (ROS) formation, lipid peroxidation (LP) and oxidative stress in isolated mitochondria. Also, our results revealed that co-administration of EA (50 and 100 µM) with celecoxib significantly attenuated the cellular and mitochondrial toxicity effects. In this study, we showed that simultaneous treatment with of EA ameliorated the cellular and mitochondrial toxicity induced by celecoxib, with cardiomyocytes presenting normal activity compared to the control group, and mitochondria retaining their normal activity.
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In Costa Rica, two species of Psidium fruits, P. guajava and P. friedrichsthalianum, are widely consumed as food and used in folk medicine. Although studies have revealed the health effects of these fruits, there has been little research showing the antiplatelet activity of these species. This work evaluated the antiplatelet potential of aqueous extracts made from leaves and fruits of pink guava and Costa Rican guava. Platelet aggregation was induced by the platelet agonists ADP, TRAP-6, collagen and PMA. Platelet activation and secretion were studied using flow cytometry. The chemical profiles of the four extracts were characterized using UPLC-DAD-ESI-QTOF-MS. The studies revealed that the aqueous extracts of leaves and fruits of P. guajava and P. friedrichsthalianum inhibited platelet aggregation induced by ADP (4 µM), TRAP-6 (5 µM), collagen (1 µg mL- 1) and PMA (100 nM),and the effect was dependent on the extract concentration. Extracts of leaves and fruits of pink guava and Costa Rican guava reduced secretion of P-selectin and activation of GP IIb/IIIa. The extracts of leaves and fruits of pink guava and Costa Rican guava proved to be a rich source of phenolic compounds, mainly quercetin aglycones and proanthocyanidins derived from (epi) catechin units. Other compounds such as ellagitannins, and benzophenones were also putatively identified. This research showed that P. guajava and P. friedrichsthalianum could potentially be used for the prevention of thrombotic events.
Chapter
Sweet chestnut (Castanea sativa) is one of the most interesting foods in the modern world offering a great diversity in cultural values, production, consumption, functions, economy and environmental aspects particularly of the developed countries. After having originated from the Mediterranean regions, sweet chestnut was brought into Europe by the Romans. The chestnut production has been increasing over the years with China leading the global production. In the present times, sweet chestnut is considered a prized food and vital in sustainable agroforestry. The deciduous tree has a strong and expanded root system working in a symbiotic mycorrhizal association. Flowering of the monoecious tree occurs from the mid of May to June. The green cupule around the flowers forms the chestnut bur that ultimately encases the dark brown nuts. Sweet chestnut mainly comprises of moisture (48.64–54.26%), starch (42.68–73.35%), protein (2.71–7.47%), fibre (2.06–2.79%), fat (0.80–3.80%) and ash (0.77–2.40%). Sweet chestnut and its by-products including bark, leaves, catkin and peel contain nutraceutical compounds (vitamin C, vitamin E, ellagic acid, gallic acid, hydrolysable ellagitannins and gallotannins) having vital health implications. These compounds have antioxidant activities, anti-carcinogenic activities, cardioprotective activities and antimicrobial activities. As such, sweet chestnut and its by-products could be a great prospect for exploitation as medical foods.
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This review combined scientific data regarding the use of genus Eugenia plants for the management of diabetes. Diabetes mellitus is a chronic metabolic disease mainly characterized by hyperglycaemia, which can lead to serious health complications. Scientists have been seeking therapeutic compounds in plants, reporting the species of the genus Eugenia as a potential source of phytochemicals with antidiabetic properties. In vitro and in vivo studies have proved that the bioactive compounds in the genus Eugenia can positively affect the biomarkers of diabetes. We discussed the phytochemical profile of the genus Eugenia and its mechanism of action on diabetes, which could modulate carbohydrate metabolism, glucose homeostasis, and insulin secretion, inhibit carbohydrases and reduce oxidative stress, suppressing the formation of advanced glycation end-products and protecting/regenerating pancreatic β-cells. Therefore, plants of the genus Eugenia showed therapeutic potential to be used in the treatment of diabetes and its comorbidities.
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Alkaline earth stannates with perovskite structure (ASnO3, A = Ca, Sr, Ba) have been studied for a long time due to their unique structure and physicochemical properties, but few works in literature have been devoted to their thin films. The technology of thin films makes structuring materials in fettered dimensions very simple, making them useful in electronic devices. Moreover, the possibility of oriented and epitaxial growth allows a better understanding of the surface and interface properties of the films to tailor their functionalities. In this chapter, recent findings on photoluminescent properties of ASnO3-type perovskites are discussed and results on polycrystalline and epitaxial thin films deposited using a physical deposition method (pulsed laser deposition, PLD) and a chemical one (chemical solution deposition, CSD) are presented. In this context, two different series were carefully investigated considering the Sr-site substitution in SrSnO3 perovskite to form the Ca1−xSrxSnO3 solid solution, and the Sn-site substitution giving origin to SrSn1−xTixO3 (x = 0, 0.25, 0.5, 0.75 and 1). The structural and microstructural characteristics of all films are first presented. Then, discussion about the influence of composition, method of deposition, type of growth and short-range order/disorder related to photoluminescence properties are shown.
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During the 20th century processed and ready-to-eat foods became routinely consumed resulting in a sharp rise of fat, salt, and sugar intake in people’s diets. Currently, the global incidence of obesity, raised blood lipids, hypertension, and diabetes in an increasingly aged population contributes to the rise of atherothrombotic events and cardiovascular diseases (CVD) mortality. Drug-based therapies are valuable strategies to tackle and help manage the socio-economic impact of atherothrombotic disorders though not without adverse side effects. The inclusion of fresh fruits and vegetables rich in flavonoids to human diets, as recommended by WHO offers a valuable nutritional strategy, alternative to drug-based therapies, to be explored in the prevention and management of atherothrombotic diseases at early stages. Though polyphenols are mostly associated to color and taste in foods, food flavonoids are emerging as modulators of cholesterol biosynthesis, appetite and food intake, blood pressure, platelet function, clot formation, and anti-inflammatory signaling, supporting the health-promoting effects of polyphenol-rich diets in mitigating the impact of risk factors in atherothrombotic disorders and CVD events. Here we overview the current knowledge on the effect of polyphenols particularly of flavonoid intake on the atherothrombotic risk factors and discuss the caveats and challenges involved with current experimental cell-based designs.
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Myrciaria cauliflora (jabuticaba) is a Brazilian native species of the Atlantic forest region that produces fruits enriched with outstanding antioxidant content, such as anthocyanins, polyphenols, tannins and flavonoids. It additionally is known that jabuticaba fruits are attractive sources of bioactive molecules that drive phytotechnological research worldwide. Several works with jabuticaba were developed in last years covering mainly the agricultural, pharmaceutical and food science fields. However, there is still a gap regarding technological development. Here, we make an approach over the technological products obtained form jabuticaba fruits, their biological potential, the drug-like properties of chemical markers and the main techniques that would be employed in future development of other products with commercial value.
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Parkinson’s Disease (PD) is a neurodegenerative disease that causes damage to the cognitive and motor system due to the death of dopaminergic neurons, which are responsible for the synthesis of the neurotransmitter dopamine. The study aimed to compare the monoamine oxidase B (MAO-B) inhibitory activity of natural molecules described in the literature with Selegiline, as potential drugs for the treatment of PD through molecular modeling, molecular docking and prediction of ADME/Tox properties. Thus, it was found the structure of the four natural molecules, Amburoside A, Harman, Harmaline and Harmalol, showed antiparkinsonian biological activity. Maps Electrostatic Potential showed similar regions between the molecules, except for Amburoside A, and Harmaline had a greater similarity in the positive potential with Selegiline. Molecular docking demonstrated that the studied molecules interact with 4–6 amino acids from the active site of the MAO-B enzyme, indicating that it has an inhibitory action on the enzyme, through hydrogen bonding and hydrophobic interactions. For ADME property predictions, most of the molecules showed good human oral absorption, all showed average permeability in Caco-2 cells, most showed average permeability in MDCK cells, showed low binding to plasma proteins, and for permeability in the blood-brain barrier, they were between good and medium. Overall, Harmaline has more properties similar to Selegiline. For toxicological properties, all molecules including Selegiline showed a positive result for the possibility of mutagenicity, whereas for the parameter of carcinogenicity in rats only the molecules Harmaline and Harmalol were positive, but no molecule was positive for carcinogenicity in mice. Therefore, the molecule that presented the best results was Harmaline, opening perspectives for the execution of in vitro studies.
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Herein, we integrate boronate-affinity controllable-oriented ellagic acid-imprinted magnetic nanoparticles (BCEMN) and boronic acid-modified / polyethylene glycol-coated allochroic-graphene oxide (BPAO) for specific and ultrasensitive detection of ellagic acid (EA). The novel detection method depends on a dual boronate-affinity sandwich strategy. The symmetric EA is first specifically captured by the BCEMN based on the boronate-affinity-related molecularly imprinted recognition, and then labeled with BPAO due to the boronate-affinity recognition. The BPAO, which is functionalized with 2,6-difluoro-4-formyl-phenylboronic acid, loaded with a large amount of pH-sensitive thymol phthalide and coated with hydrophilic polyethylene glycol, can specifically recognize the cis-diol of EA at physiological condition (pH 7.4) and perform signal amplification and readout through pH-triggered allochroism. Furthermore, the signal readout of allochroism is linear with the logarithm of EA concentration over the range between 0.02 ng mL⁻¹ to 10⁴ ng mL⁻¹ with a good correlation coefficient (R² = 0.993), and the limit of detection (LOD) is 2.96 pg mL⁻¹. Finally, the BCEMN linked BPAO (BCBP) strategy has also been successfully applied in the detection of EA concentration in spiked strawberry sample with recovery and relative standard deviation in the range of 84.9%–110.2% and 3.9%–6.1%, respectively.
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An integrated biorefinery has been developed using winery wastes (grape pomace-GP, stalks-GS, wine lees-WL). Bacterial cellulose was produced from GP extracted free sugars. Grape-seed oil and polyphenols were extracted from GP. Experimental design was employed to optimize lignin removal (50.8%) from mixtures of remaining GP solids and GS via NaOH (1.19% w/v) treatment at 70°C for 30 min. Delignification liquid contained condensed tannins with 76% Stiasny number. Enzymatic hydrolysis produced a sugar-rich hydrolysate (40.2 g/L sugars). Ethanol, antioxidants, tartaric acid and nutrient-rich hydrolysate were produced from WL. The crude hydrolysates were used in fed-batch Actinobacillus succinogenes cultures for 37.2 g/L succinic acid production. The biorefinery produces 42.65 g bacterial cellulose, 24.3 g oil, 40.3 g phenolic-rich extract with 1.41 Antioxidant Activity Index, 80.2 g ethanol, 624.8 g crude tannin extract, 20.03 g tartaric acid and 157.8 g succinic acid from 1 kg of either waste stream.
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Previous studies have reported the anti-inflammatory properties of pomegranate extracts, suggesting that ellagitannins (ET) and ellagic acid (EA) are the main anti-inflammatory compounds. However, both ET and EA are metabolised in vivo by the gut microbiota to yield urolithins (Uro) which can be found in the gut and in systemic bloodstream. The present study was carried out to evaluate the individual effect of EA and their microbiota-derived metabolites Uro on colon fibroblasts upon IL-1beta treatment as an in vitro inflammation model. Uro-A and Uro-B (10 microm) inhibited PGE2 production (85 and 40 %, respectively) after IL-1beta stimulation, whereas EA did not show any effect. Uro-A, but not Uro-B, down-regulated cyclo-oxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) mRNA expression and protein levels. Both Uro inhibited NF-kappaB translocation to nucleus. Slight but significant effects were found in the activation of mitogen-activated protein kinase (MAPK) pathways. Uro-A lowered c-Jun N-terminal kinase phosphorylation state, and both Uro inhibited p38 activation. No metabolites derived from Uro or EA were found in the cell media upon incubation of EA or Uro with the cells, and only traces of the compounds were found inside the cells. The present results suggest that Uro, mainly Uro-A, are the main compounds that are responsible for the pomegranate anti-inflammatory properties. The mechanism of action implicated seems to be via the inhibition of activation of NF-kappaB and MAPK, down-regulation of COX-2 and mPGES-1 expressions, and consequently,via the reduction of PGE2 production. Taking into account that Uro did not enter the cells, a competitive binding for IL-1beta membrane receptor cannot be discarded.
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The fate of anthocyanins, ellagic acid, and ellagitannins was studied following the consumption of 300 g of raspberries by healthy human volunteers and subjects with an ileostomy. Postingestion plasma and urine from the former and ileal fluid and urine from the latter group were collected and analyzed by HPLC-PDA-MS(2). Plasma from the healthy volunteers did not contain detectable quantities of either the native raspberry polyphenolics or their metabolites. The three main raspberry anthocyanins were excreted in urine in both healthy and ileostomy volunteers 0-7 h after ingestion, in quantities corresponding to <0.1% of intake. This indicates a low level of absorption in the small intestine. With ileostomy volunteers 40% of anthocyanins and 23% of the ellagitannin sanguiin H-6 were recovered in ileal fluid with the main excretion period being the first 4 h after raspberry consumption. The recovery of ellagic acid in ileal fluid was 241%, indicating hydrolysis of ellagitannins in the stomach and/or the small intestine. Urinary excretion of ellagic acid and an ellagic acid-O-glucuronide was <1% of intake. No intact or conjugated forms of ellagitannins were detected in urine from either healthy subjects or ileostomy volunteers. However, in healthy subjects, but not the ileostomists, ellagitannins were catabolized with the appearance of urolithin A-O-glucuronide, two of its isomers, and urolithin B-O-glucuronide in urine collected 7-48 h after raspberry consumption. There was marked variation in the urolithin profile of individual volunteers, indicating differences in the colonic microflora responsible for ellagitannin degradation.
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Type 2 diabetes is the most prevalent and serious metabolic disease all over the world, and its hallmarks are pancreatic beta-cell dysfunction and insulin resistance. Under diabetic conditions, chronic hyperglycemia and subsequent augmentation of reactive oxygen species (ROS) deteriorate beta-cell function and increase insulin resistance which leads to the aggravation of type 2 diabetes. In addition, chronic hyperglycemia and ROS are also involved in the development of atherosclerosis which is often observed under diabetic conditions. Taken together, it is likely that ROS play an important role in the development of type 2 diabetes and atherosclerosis.
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Strawberries are known to contain antioxidants, but the significance of ingesting antioxidant-rich fruits remains to be established. In order to determine whether the consumption of strawberries impacted measures of in vivo antioxidant capacity, frozen strawberries (250 g) were administered daily for 3 weeks to 21 healthy female volunteers. Compliance was confirmed by quantitating pelargonidin-glucuronide, urolithin A-glucuronide, and 2,5-dimethyl-4-hydroxy-3-[(2)H]furanone-glucuronide in plasma and urine by liquid chromatography-mass spectrometry and antioxidant capacity in serum measured by the increase in lag phase of low-density lipoprotein after copper sulfate exposure, DNA strand breaks in lymphocytes, and activity of phase II enzymes. Among these measures lipid peroxidation lag time increased by 20% (P < .01), whereas other measures did not change significantly. The potent antioxidant defenses in humans make determination of changes due to dietary ingestion in healthy individuals difficult. In summary, daily consumption of strawberries resulted in a modest but significant increase in antioxidant capacity in a healthy population.
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The occurrence of ellagitannins in common foodstuffs is limited to a few fruit and nut species. Dietary intake of ellagitannins is largely explained by the consumption of strawberries, raspberries and blackberries. No reliable figures are available for the ellagitannin burden, but it will probably not exceed 5 mg day⁻¹. Their bioavailability is not well defined. A fraction of the ellagitannins ingested is hydrolysed in the gut and the resulting ellagic acid absorbed and metabolised, but whether intact ellagitannins are absorbed is not clear. There are apparently conflicting claims for beneficial and toxic effects caused by ellagitannins, ellagic acid or ellagitannin‐containing extracts in various animal species including rodents and ruminants. It seems unlikely that normal consumption can cause toxic effects in man, but any attempt to increase the intake significantly in pursuit of the suggested benefits should be resisted until the metabolism and pharmacokinetics are better understood. © 2000 Society of Chemical Industry
Book
While one may not find ancient studies that substantiate the pomegranate’s curative and preventive qualities, the exalted status of this fruit goes back as far as the history of agriculture itself. Allusions to the pomegranate are readily found in the oldest cultures of the Indus Valley, ancient China, and classical Greece, as well as in the Old Testament. To modern scientists, the biochemistry of the pomegranate is as equally fascinating as its storied place in literature and religion. Providing an unprecedented compilation of scientific information, Pomegranates: Ancient Roots to Modern Medicine offers an exploration of the biochemistry, health effects, and cultivation of the pomegranate that is as authoritative as it is unparalleled. Featuring the contributions of a multidisciplinary and international team of prominent researchers, it presents the latest findings on the potential human health benefits of this exceptionally polyphenol-rich fruit. As the research indicates, the physiological effects of pomegranate juice constituents are remarkable in their preventive potential against two of the major chronic diseases of aging - heart disease and cancer. Many of the pioneering researchers responsible for initiating our newfound fascination with pomegranates discuss its biochemistry, detailing the location and action of the phytochemicals found in the fruit’s flesh, peels and seeds. They present evidence of the pomegranate’s impact on heart disease, including its ability to enhance nitric oxide production in endothelial cells. They also reveal the significant antiproliferative and proapoptotic effects attributed to the pomegranate in battling several different types of cancer cells, as well as its ability to retard tumor growth in animals. Recognizing that the pomegranate is only as valuable as it is available, the editors include a substantial section on commercialization and another on plant growth and improvement. These additions make this text as uniquely essential for botanists and agriculturists as it is for nutritionists, cancer researchers, natural product chemists, botanical supplement producers and consumers, and pharmacognosists seeking to evaluate both the pomegranate’s legacy and future as a powerful natural healing agent.
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Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases is emerging. Bioavailability differs greatly from one polyphenol to another, so that the most abundant polyphenols in our diet are not necessarily those leading to the highest concentrations of active metabolites in target tissues. Mean values for the maximal plasma concentration, the time to reach the maximal plasma concentration, the area under the plasma concentration-time curve, the elimination half-life, and the relative urinary excretion were calculated for 18 major polyphenols. We used data from 97 studies that investigated the kinetics and extent of polyphenol absorption among adults, after ingestion of a single dose of polyphenol provided as pure compound, plant extract, or whole food/beverage. The metabolites present in blood, resulting from digestive and hepatic activity, usually differ from the native compounds. The nature of the known metabolites is described when data are available. The plasma concentrations of total metabolites ranged from 0 to 4 mumol/L with an intake of 50 mg aglycone equivalents, and the relative urinary excretion ranged from 0.3% to 43% of the ingested dose, depending on the polyphenol. Gallic acid and isoflavones are the most well-absorbed polyphenols, followed by catechins, flavanones, and quercetin glucosides, but with different kinetics. The least well-absorbed polyphenols are the proanthocyanidins, the galloylated tea catechins, and the anthocyanins. Data are still too limited for assessment of hydroxycinnamic acids and other polyphenols. These data may be useful for the design and interpretation of intervention studies investigating the health effects of polyphenols.
Chapter
Ellagitannins are hydrolyzable tannins that release ellagic acid upon hydrolysis. They exhibit various biological activities in vitro that have been associated with pharmacological (ellagitannin-containing medicinal plants) and nutritional (ellagitannin-containing foods) effects in vivo. The potential health effects are mainly related to the prevention of cardiovascular diseases and cancer. In vivo biological effects may be due partially to the potent free-radical scavenging activity that these compounds exert in vitro. It is, however, necessary to take into account the fate of ellagitannins in the gastrointestinal tract, their bioaccessibility, bioavailability, metabolism, and tissue distribution of the corresponding metabolites to understand the efcacy and the physiological role of dietary and medicinal ellagitannins. In the present chapter, we review the current knowledge regarding the bioavailability and metabolism of ellagitannins and point out various unresolved issues within these processes in humans that require further research.
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Background—Epidemiological studies suggest that nut intake decreases coronary artery disease (CAD) risk. Nuts have a cholesterol-lowering effect that partly explains this benefit. Endothelial dysfunction is associated with CAD and its risk factors and is reversed by antioxidants and marine n-3 fatty acids. Walnuts are a rich source of both antioxidants and-linolenic acid, a plant n-3 fatty acid. Methods and Results—To test the hypothesis that walnut intake will reverse endothelial dysfunction, we randomized in a crossover design 21 hypercholesterolemic men and women to a cholesterol-lowering Mediterranean diet and a diet of similar energy and fat content in which walnuts replaced 32% of the energy from monounsaturated fat. Participants followed each diet for 4 weeks. After each intervention, we obtained fasting blood and performed ultrasound measurements of brachial artery vasomotor function. Eighteen subjects completing the protocol had suitable ultrasound studies. Compared with the Mediterranean diet, the walnut diet improved endothelium-dependent vasodilation and reduced levels of vascular cell adhesion molecule-1 (P0.05 for both). Endothelium-independent vasodilation and levels of intercellular adhesion molecule-1, C-reactive protein, homocysteine, and oxidation biomarkers were similar after each diet. The walnut diet significantly reduced total cholesterol (4.47.4%) and LDL cholesterol (6.410.0%) (P0.05 for both). Cholesterol reductions correlated with increases of both dietary-linolenic acid and LDL-tocopherol content, and changes of endothelium-dependent vasodilation correlated with those of cholesterol-to-HDL ratios (P0.05 for all). Conclusions—Substituting walnuts for monounsaturated fat in a Mediterranean diet improves endothelium-dependent vasodilation in hypercholesterolemic subjects. This finding might explain the cardioprotective effect of nut intake beyond cholesterol lowering.
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Peroxisome proliferator-activated receptor (PPAR)-{gamma} activators are widely used in the treatment of type 2 diabetes because they improve the sensitivity of insulin receptors. Punica granatum flower (PGF) has been used as an anti-diabetic medicine in Unani medicinal literature. The mechanism of actions is, however, unknown. In the current study, we demonstrated that 6-week oral administration of methanol extract from PGF (500 mg/kg, daily) inhibited glucose loading-induced increase of plasma glucose levels in Zucker diabetic fatty rats (ZDF), a genetic animal model for type 2 diabetes, whereas it did not inhibit the increase in Zucker lean rats (ZL). The treatment did not lower the plasma glucose levels in fasted ZDF and ZL rats. Furthermore, RT-PCR results demonstrated that the PGF extract treatment in ZDF rats enhanced cardiac PPAR-{gamma} mRNA expression and restored the down-regulated cardiac glucose transporter (GLUT)-4 (the insulin-dependent isoform of GLUTs) mRNA. These results suggest that the anti-diabetic activity of PGF extract may result from improved sensitivity of the insulin receptor. From the in vitro studies, we demonstrated that the PGF extract enhanced PPAR-{gamma} mRNA and protein expression and increased PPAR-{gamma}-dependent mRNA expression and activity of lipoprotein lipase in human THP-1-differentiated macrophage cells. Phytochemical investigation demonstrated that gallic acid in PGF extract is mostly responsible for this activity. Thus, our findings indicate that PPAR-{gamma} is a molecular target for PGF extract and its prominent component gallic acid, and provide a better understanding of the potential mechanism of the anti-diabetic action of PGF.
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The success of green tea as a cancer preventive is based on evidence that green tea contains tannins and antioxidants, does not show toxicity in humans and has long traditional use in Asia. In the light of this, herbal medicines are now also attracting attention as potential sources of cancer preventive agents. Using the inhibition of TNF-a release assay, we studied Acer nikoense (Megusurino-ki in Japanese), one of the herbal medicines. The inhibitory activity of TNF-a release was found in the leaf extract rather than the bark extract, and the main active constituents were identified as geraniin and corilagin, which are present in another Japanese traditional herb, Geranium thunbergii (Genno-shoko). The IC50 values of TNF-alpha release inhibition were 43 muM for geraniin and 76 muM for corilagin, whereas that for (-)-epigallocatechin gallate (EGCG) was 26 muM. Treatment with geraniin prior to application of okadaic acid, a tumor promoter on mouse skin initiated with 7,12-dimethylbenz(a)anthracene, reduced the percentage of tumor-bearing mice from 80.0 to 40.0% and the average numbers of tumor per mouse from 3.8 to 1.1 in week 20. Thus, geraniin has slightly weaker inhibitory activity than EGCG. Since geraniin and corilagin have been well investigated as representative tannins, we discuss here the new possibility of classical herbal medicine in the development of preventive agents for cancer and other life-style related diseases.
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Flavonoids have been reported to demonstrate their benefits in lowering oxidative stress and beneficial effects on cardiovascular and chronic inflammatory diseases. Common phenolic compounds, including phenolic acids, flavonols, isoflavones, and anthocyanins, present in fruits, vegetables, and grains were investigated for their effects on the production of tumor necrosis factor alpha (TNF-alpha) in LPS/IFN-gamma-activated RAW 264.7 macrophages. Gallic acid and (+)-catechin showed small but significant effects, whereas chlorogenic acid had no effect on TNF-alpha production. The flavonol quercetin inhibited TNF-alpha production, but kaempferol and myricetin induced the secretion of TNF-a. The isoflavone genistein was an inhibitor of TNF-alpha, whereas daidzein induced TNF-alpha production. Glycosylation of genistein changed its inhibitory effects to TNF-alpha induction, and glycosylation of daidzein had no effect on its activity. Anthocyanidins/anthocyanins and anthocyanin-rich extracts induced TNF-alpha production and acted as modulators of the immune response in activated macrophages. This is the first study to report the effects of anthocyanins and berry extracts on TNF-alpha production.