Absorption Of Polyphenols Research Articles

Enhanced Preparative-Scale Extraction from Graševina Grape Pomace Using Ultrasound-Assisted Extraction and Natural Deep Eutectic Solvents

This research paper presents an advanced exploration into the utilization of ultrasound-assisted extraction (UAE) combined with natural deep eutectic solvents (NADESs) to achieve higher concentrations of polyphenols from Graševina grape pomace. Focusing on optimizing extraction parameters to maximize the yield of polyphenols, this study evaluates their potential industrial applications, particularly within the food and cosmetics sectors. The effectiveness of betaine/glucose (BGlc) NADESs in producing stable, ready-to-use extracts with enhanced bioavailability and eco-friendly attributes is underscored. The integration of UAE with BGlc NADESs has shown significant scalability and applicability for industrial use, as evidenced by the extracts’ collagenase-inhibitory effects, determined using a ninhydrin-based colorimetric assay showing the significant inhibition of gelatine degradation and scratch tests on cultured skin cells, demonstrating enhanced cell migration and wound healing, indicating their potential in anti-aging cosmetic products. Additionally, the results from PAMPA tests demonstrated that NADES extraction significantly enhances the intestinal absorption of polyphenols from grape pomace extracts compared to conventional solvents, highlighting the potential of NADESs to improve the bioavailability of these compounds and offering promising implications for their application in the food industry. Furthermore, the research highlights the practicality of directly incorporating these extracts into products, such as anti-aging creams and functional foods, supporting sustainability initiatives within the cosmetic and food industries. This work aims to provide a comprehensive guide to green extraction techniques on a preparative scale, showcasing the versatility and innovative applications of NADES-extracted compounds across various industries, thereby paving the way for the development of eco-conscious and effective products.

HPLC-UV evaluation of a microwave assisted method as an active drug loading technique for exosome-based drug delivery system

This paper evaluates the potential of a microwave radiation (MR) assisted method as an active drug loading technique for exosomes using polyphenolic nutraceuticals as model drugs (i.e. resveratrol (RV), rosmarinic acid (RA), pterostilbene (PT) and epigallocatechin gallate (EG)). MR is evaluated as a single step method and as part of a two-step method consisting of incubation (IN) followed by MR. The effect of exposure time, loading method and type of nutraceutical on the loading efficiency were investigated using high performance liquid chromatography (HPLC), X-ray diffraction (XRD) and flow cytometry. Additionally, dynamic light scattering (DLS) was used to determine the size of exosomes. Loading efficiency results indicated that MR is a promising method to be used as loading process. Results also suggested that due to different levels of hydrophobicity, related to the number of OH groups, the absorption of polyphenols into the bilayer of EVs is different for each molecule. According to XRD results, MR could not be used with any cargo drug since radiation could affect the chemical composition and the degree of crystallinity of such molecules, consequently affecting their performance. Flow cytometry results indicated that loading methods negatively affect exosome concentration.

Advanced Delivery System of Polyphenols for Effective Cancer Prevention and Therapy.

Polyphenols from plants such as fruits and vegetables are phytochemicals with physiological and pharmacological activity as potential drugs to modulate oxidative stress and inflammation associated with cardiovascular disease, chronic disease, and cancer. However, due to the limited water solubility and bioavailability of many natural compounds, their pharmacological applications have been limited. Researchers have made progress in the development of nano- and micro-carriers that can address these issues and facilitate effective drug delivery. The currently developed drug delivery systems maximize the fundamental effects in various aspects such as absorption rate, stability, cellular absorption, and bioactivity of polyphenols. This review focuses on the antioxidant and anti-inflammatory effects of polyphenols enhanced by the introduction of drug delivery systems, and ultimately discusses the inhibition of cancer cell proliferation, growth, and angiogenesis.

Enhancing Polyphenols and Tannins Concentration on Cotton Dyed with Red Tea

Natural dyes, obtained from plants, insects/animals, and minerals, are renewable and sustainable bioresource products with minimum environmental impact. However, there are still many issues to solve related to natural dyes; consequently, synthetic dyes are still wildly used. Natural dyes have a low affinity towards the substrate cotton, so a solution had to be found: mordants. Mordants can also be harmful to the environment, which is why bio-mordants are used. The mordant used in this paper is chitosan. Cotton is pre-mordanted using the pad dyeing method. By using the exhaustion method, the fabric was coloured with red Camellia sinensis (tea) extracts. The colour, absorption of polyphenols and tannins, and ultraviolet protection (UPF) were tested. A comparison study was carried out between the cotton fabric and the cotton padded with chitosan at two different concentrations. The results are impressive. Cotton pre-mordanted with chitosan can absorb more polyphenols and tannins than cotton itself, and the colour fastness and UPF, once the fabric is laundered, demonstrate there is some kind of bonding between the fibre, quitosan, and active compounds from tea. The UPF was also doubled by using chitosan and the reddish colour obtained by Camellia sinensis extracts were darker on the cotton fabric. The increase in UPF protection on mordanted fabrics is higher than the gap obtained by colour difference, which means there are active compounds that do not confer colour, but enhance UPF protection.

Fecal excretion kinetics provides further support for polyphenols targeting microbiota: An example with prebiotic-like phlorizin

The microbiota plays important roles for polyphenols exerting bioactivity, which needs support to calculate the accumulated polyphenols in the gastrointestinal tract. Taking phlorizin as an example, fecal excretion kinetics was suggested to be ingenious for achieving it. No phlorizin was excreted with feces, implying almost 100 % total availability. Combined with its 0–5 % bioavailability, more than 95 % of phlorizin quantitatively accumulated in the gastrointestinal tract. Instead, trace phloretin was excreted, and the acquired kinetic parameters were influenced by physical conditions and dietary patterns. Dosage-total-availability curves indicated different relationships among normal-diet and obese mice, resulting in critical dosages of ∼ 159 and ∼ 196 mg/kg when taking 95 % total availability by phloretin. The dietary matrix affects the intake, digestion, metabolism and absorption of polyphenols, and may alter its total availability, and fecal excretion kinetics can provide further support for polyphenol dietary supplements targeting microbiota.

Polyphenol Mechanisms against Gastric Cancer and Their Interactions with Gut Microbiota: A Review.

The lack of new drugs and resistance to existing drugs are serious problems in gastric cancer(GC) treatment. The research found polyphenols possess anti-Helicobacter pylori(Hp) and antitumor activities and may be used in the research and development of drugs for cancer prevention and treatment. However, polyphenols are affected by their chemical structures and physical properties, which leads to relatively low bioavailability and bioactivity in vivo. The intestinal flora can improve the absorption, utilization, and biological activity of polyphenols, whereas polyphenol compounds can increase the richness of the intestinal flora, reduce the activity of carcinogenic bacteria, stabilize the proportion of core flora, and maintain homeostasis of the intestinal microenvironment. Our review summarizes the gastrointestinal flora-mediated mechanisms of polyphenol against GC.

Red Wine and Health: Approaches to Improve the Phenolic Content During Winemaking.

There is ample evidence regarding the health benefits of red wine consumption due to its content of phenolic compounds, as an alternative to improve the state of health and prevent various diseases, being the implementation of procedures that allow a greater extraction and stability of phenolic compounds during the elaboration a key aspect. The first part of this review summarizes some studies, mostly at the preclinical level, on the mechanisms by which phenolic compounds act in the human organism, taking advantage of their antioxidant, anti-inflammatory, antitumor, antithrombotic, antiatherogenic, antimicrobial, antiviral, and other activities. Although the migration of grape components into the must/wine occurs during the winemaking process, the application of new technologies may contribute to increasing the content of phenolic compounds in the finished wine. Some of these technologies have been evaluated on an industrial scale, and in some cases, they have been included in the International Code of Oenological Practice by the International Organization of Vine and Wine (OIV). In this sense, the second part of this review deals with the use of these novel technologies that can increase, or at least maintain, the polyphenol content. For example, in the pre-fermentative stage, phenolic extraction can be increased by treating the berries or must with high pressures, pulsed electric fields (PEF), ultrasound (US), e-beam radiation or ozone. At fermentative level, yeasts with high production of pyranoanthocyanins and/or their precursor molecules, low polyphenol absorption, and low anthocyanin-β-glucosidase activity can be used. Whereas, at the post-fermentative level, aging-on-lees (AOL) can contribute to maintaining polyphenol levels, and therefore transmitting health benefits to the consumer.

Chemical Compounds of Berry-Derived Polyphenols and Their Effects on Gut Microbiota, Inflammation, and Cancer.

Berry-derived polyphenols are bioactive compounds synthesized and secreted by several berry fruits. These polyphenols feature a diversity of chemical compounds, including phenolic acids and flavonoids. Here, we report the beneficial health effects of berry-derived polyphenols and their therapeutical application on gut-microbiota-related diseases, including inflammation and cancer. Pharmacokinetic investigations have confirmed the absorption, availability, and metabolism of berry-derived polyphenols. In vitro and in vivo tests, as well as clinical trials, showed that berry-derived polyphenols can positively modulate the gut microbiota, inhibiting inflammation and cancer development. Indeed, these compounds inhibit the growth of pathogenic bacteria and also promote beneficial bacteria. Moreover, berry-derived polyphenols exhibit therapeutic effects against different gut-microbiota-related disorders such as inflammation, cancer, and metabolic disorders. Moreover, these polyphenols can manage the inflammation via various mechanisms, in particular the inhibition of the transcriptional factor Nf-κB. Berry-derived polyphenols have also shown remarkable effects on different types of cancer, including colorectal, breast, esophageal, and prostate cancer. Moreover, certain metabolic disorders such as diabetes and atherosclerosis were also managed by berry-derived polyphenols through different mechanisms. These data showed that polyphenols from berries are a promising source of bioactive compounds capable of modulating the intestinal microbiota, and therefore managing cancer and associated metabolic diseases. However, further investigations should be carried out to determine the mechanisms of action of berry-derived polyphenol bioactive compounds to validate their safety and examinate their clinical uses.

Pomegranate peel polyphenols interaction with intestinal flora and its metabolic transformation

1. Pomegranate peel polyphenols (PPPs) have anti-oxidation, anti-atherosclerosis, anti-obesity effect, and so on. However, few studies have been conducted on the absorption and transformation of pomegranate polyphenols in the gut and the biologically active forms that ultimately work in the body. 2. In this study, PPPs (300 mg/kg/day) were given to normal rats and relatively sterile rats by gavage respectively. The relatively sterile rats were obtained by neomycin sulfate (250 mg/kg/day) gavage to rats. The purpose of this study is to elaborate the relationship between intestinal flora and polyphenol metabolism of pomegranate peel, and to quantitatively analyze the transformation process of its metabolite urolithin in rats. 3. The results showed that decreased bacterial diversity could significantly reduce the abundance of PPPs metabolites in feces and urine in relatively sterile rats. PPPs can regulate intestinal flora structure, significantly enhance the content of Clostrida Firmicutes (P < 0.05), and effectively promote acetic acid, propionic acid, butyric acid, iso-butyric acid and valeric acid production in rat (P < 0.05 or P < 0.01 or P< 0.001). PPPs can significantly elevate the relative proportion of Ruminococcaceae (P < 0.05). Ruminococcaceae_NK4A214_group, Ruminococcaceae_UCG-014 and Ruminococcaceae_UCG-005 can promote the metabolic transformation of PPPs and make the utilization of Urolithin A more effective.

Oral delivery of decanoic acid conjugated plant protein shell incorporating hybrid nanosystem leverage intestinal absorption of polyphenols

Polyphenols are potent antioxidants, but their poor oral bioavailability owing to intrinsic insolubility and low permeability significantly hampers their effectiveness for clinical translation. Herein, upper intestinal absorptive polymer-lipid hybrid nanoparticles (PLN) was designed by exploiting the lipidic core for drug encapsulation and the decanoic acid conjugated rapeseed protein as the biopolymeric shell for gastrointestinal stability, retention and permeability. Polyphenol ellagic acid loaded core-shell PLN (EA-PLN(C/S)) was characterized of favorable physicochemical properties in simulated gastric- and intestinal fluids, including high drug loading capacity, slow drug release and prolonged stability. In Caco-2 monolayers, the cellular transport of EA-PLN(C/S) involved dual-paracellular and endocytosis pathways. Compared to drug in suspension or lipidic core nanoparticles, orally administered EA-PLN(C/S) was retained longer and more permeable via the duodenum and jejunum of upper intestine, resulting in up to 5.3-fold and 1.4-fold enhancement in the extent of drug absorption and colonic accumulation, respectively. In an acute colitis murine model, EA-PLN(C/S) at 6 mg/kg low dose markedly reduced colonic lipid peroxidation in contrast to no antioxidant effect in other EA formulations. This work suggests that integration of engineered plant protein biopolymer with lipid nanoparticles created unique oral drug delivery systems enabling intestinal site-specific absorption for effective antioxidant therapeutics.

Polyphenols-absorption and occurrence in the body system

Polyphenols are commonly present in natural plants and serve as health benefiting food compounds. The health benefits and the metabolites of polyphenols have not yet been fully investigated because of lack of information about their bioavailability. This review was based on the previously reported literature focusing on the absorption and tissue accumulation of polyphenols. Furthermore, the physiological roles and the influx/efflux route(s) of non-absorbable polyphenols in the intestinal membrane were discussed.

Determination of human FaFg of polyphenols using allometric scaling.

Certain polyphenols exhibit low permeability; precise prediction of their intestinal absorption is important for understanding internal exposure in humans. Intestinal availability, which represents the fraction of administered compounds that reach the portal blood (FaFg), is calculated by dividing bioavailability (F) by hepatic availability (Fh), and F is obtained from pharmacokinetic data from both intravenous (i.v.) and oral (p.o.) administration. However, human FaFg of polyphenols is hardly reported, as human i.v. data are extremely scarce. In this study, we developed an estimation method for FaFg of polyphenols in humans based on the extrapolation of rat clearance using allometric scaling (allometric scaling-based FaFg calculation method, AS- FaFgCM). First, for quercetin, for which human i.v. data have been reported, we compared the FaFg obtained by AS-FaFgCM with the traditional approach using human i.v. and p.o. data. Less than two-fold difference in FaFg values was observed between the two approaches. Next, we obtained FaFg of structurally diverse polyphenols (genistein, baicalein, resveratrol, and epicatechin) using AS-FaFgCM, demonstrating that all of them were poorly absorbable. Furthermore, to utilize the pharmacokinetic data of the total concentration, including aglycones and metabolites, we modified the AS-FaFgCM to focus on their excretion. The FaFg value of naringenin was obtained using modified AS-FaFgCM and was nearly equal to that of baicalein, a structural isomer of naringenin. This study provides quantitative information on the intestinal absorption of polyphenols using comprehensive estimation methods.

Determination of Percutaneous Absorption of Polyphenols from Natural Extracts by using Franz Cell

This investigation aimed to explore the bioactive compound potential in medicinal plants such as polyphenols and to test the total phenol content as well as the velocity of skin absorption and antioxidant activities of crude extracts from plants and fruits. albino rats and the Franz diffusion model was used for experimentation.Raphanus sativus proved to have the most substantial phenolic content following Beta vulgaris and Rosa indicat.Analyzed compounds led to skin permeation as Malus domestica had the highest absorbent value among all tested compounds. In addition to that, all extracts were potent DPPH radical scavengers and out of these Daucus carota oil was presented with the best antioxidant ability. The outcome of these experiments advocates for constant research and the growth of highly efficient transdermal delivery systems and aesthetic concoctions with the inherent healing from nature.

An Overview on Dietary Polyphenols and Their Biopharmaceutical Classification System (BCS).

Polyphenols are natural organic compounds produced by plants, acting as antioxidants by reacting with ROS. These compounds are widely consumed in daily diet and many studies report several benefits to human health thanks to their bioavailability in humans. However, the digestion process of phenolic compounds is still not completely clear. Moreover, bioavailability is dependent on the metabolic phase of these compounds. The LogP value can be managed as a simplified measure of the lipophilicity of a substance ingested within the human body, which affects resultant absorption. The biopharmaceutical classification system (BCS), a method used to classify drugs intended for gastrointestinal absorption, correlates the solubility and permeability of the drug with both the rate and extent of oral absorption. BCS may be helpful to measure the bioactive constituents of foods, such as polyphenols, in order to understand their nutraceutical potential. There are many literature studies that focus on permeability, absorption, and bioavailability of polyphenols and their resultant metabolic byproducts, but there is still confusion about their respective LogP values and BCS classification. This review will provide an overview of the information regarding 10 dietarypolyphenols (ferulic acid, chlorogenic acid, rutin, quercetin, apigenin, cirsimaritin, daidzein, resveratrol, ellagic acid, and curcumin) and their association with the BCS classification.

Pectin Influences the Absorption and Metabolism of Polyphenols from Blackcurrant and Green Tea in Rats.

Consumption of polyphenols and dietary fiber as part of a normal diet is beneficial to human health. In this study, we examined whether different amounts of dietary soluble fiber (pectin) affect the absorption and metabolism of polyphenols from blackcurrant and green tea in rats. After 28 days, the rats fed blackcurrant and green tea with pectin (4 or 8%) had significantly lower body weight gain and food intake compared to the rats fed a control diet. Rats fed a blackcurrant and green tea diet with 8% pectin had significantly higher fecal nitrogen output and lower protein digestibility. No polyphenols were observed in the urine, feces and plasma of rats fed the control diet. Parent catechins and flavonols were absent in urine obtained from all diet groups. Gallocatechin glucuronide was only observed in the plasma of rats fed the blackcurrant and green tea diet without pectin. Meanwhile, epicatechin and catechin gallate were present in the feces of rats fed a blackcurrant and green tea diet with and without 4% pectin. Pectin (4 or 8%) added to the blackcurrant and green tea diet increased the plasma antioxidant capacity in rats. Inclusion of pectin in the diet altered the host absorption and metabolism of polyphenols from blackcurrant and green tea.

Early-life supplementation of grape polyphenol extract promotes polyphenol absorption and modulates the intestinal microbiota in association with the increase in mRNA expression of the key intestinal barrier genes.

Early-life nutritional supplementation can dramatically influence health status. Dietary polyphenols are a widespread group of phytochemicals with potential bioactive functions. However, how polyphenol intake during early life affects health status remains largely unknown. Mice aged 3- and 6-weeks were used to investigate how grape polyphenol extract (GPE) administration during early life altered polyphenol absorption, the intestinal microbiota, and the intestinal barrier. After a 2-week GPE supplementation, there were more diverse polyphenol metabolites in the plasma of 3-week-old mice than in the plasma of 6-week-old mice. Correspondingly, GPE supplementation increased the mRNA expression of genes related to polyphenol absorption in 3-week-old mice but not 6-week-old mice. Early-life GPE administration also stimulated the key genes of the small intestinal barrier in mice. Moreover, the key genes of the small intestinal barrier were positively associated with the genes related to polyphenol absorption in the small intestine of 3-week-old mice. In addition, fecal Akkermansia and Lactobacillus were increased, as evidenced by 16S rRNA gene sequencing. As a result, the acetate and butyrate production in the large intestinal content was enhanced, and the mRNA expression of the key genes involved in the large intestinal barrier was also increased. Thus, our study demonstrates that dietary polyphenol intake in early life induces improvements in polyphenol absorption, the intestinal microbiota, and the intestinal barrier, suggesting the importance of polyphenol-rich nutritional programming during early life on health status.

Polyphenolic and Methylxanthine Bioaccessibility of Cocoa Bean Shell Functional Biscuits: Metabolomics Approach and Intestinal Permeability through Caco-2 Cell Models.

Cocoa bean shell (CBS), a by-product with considerable concentrations of bioactive compounds and proven biofunctional potential, has been demonstrated to be a suitable ingredient for high-fiber functional biscuits adapted to diabetic consumers. In this work, the in vitro bioaccessibility and intestinal absorption of polyphenols and methylxanthines contained in these biscuits were evaluated, and the effect of the food matrix was studied. Biscuits containing CBS and the CBS alone underwent in vitro digestion followed by an intestinal permeability study. The results confirmed that compounds were less bioavailable in the presence of a food matrix, although the digestion contributed to their release from this matrix, increasing the concentrations available at the intestinal level and making them capable of promoting antioxidant and antidiabetic activities. After digestion, CBS biscuits were shown to possess α-glucosidase inhibition capacity comparable to that of acarbose. Moreover, the presence of the food matrix improved the stability of polyphenols throughout the digestion process. Intestinal absorption of flavan-3-ols seemed to be limited to a maximum threshold and was therefore independent of the sample, while procyanidin was not absorbed. Methylxanthine absorption was high and was boosted by the presence of the food matrix. The results confirmed the biofunctional potential of CBS-based biscuits.

Probiotic fermented milk with high content of polyphenols: Study of viability and bioaccessibility after simulated digestion

This research evaluated the functional potential of a fermented milk made with Streptococcus thermophilus, a probiotic (Bifidobacterium animalis subsp. lactis) and pomegranate juice. Ferric‐reducing antioxidant potential, Trolox equivalent antioxidant capacity, scavenging effect on 1,1‐diphenyl‐2‐picrylhydrazyl free radical, oxygen radical absorbance capacity and Folin–Ciocalteu assays were used to estimate antioxidant activity and phenolic content. Probiotic survival, release and absorption of polyphenols were evaluated using in vitro gastrointestinal digestion. The concentration of polyphenols increased during digestion from 608 mg to 1417 gallic acid equivalents (GAE) /L. About 14% of polyphenols were found on the dialysate portion. The beverage presented high viability of probiotics with high survival rate after digestion (above 7 log cfu/mL).

Polyphenols by Generating H2O2, Affect Cell Redox Signaling, Inhibit PTPs and Activate Nrf2 Axis for Adaptation and Cell Surviving: In Vitro, In Vivo and Human Health.

Human health benefits from different polyphenols molecules consumption in the diet, derived mainly by their common activities in the gastrointestinal tract and at the level of blood micro-capillary. In the stomach, intestine and colon, polyphenols act as reducing agents preventing lipid peroxidation, generation and absorption of AGEs/ALEs (advanced glycation end products/advanced lipid oxidation end products) and postprandial oxidative stress. The low absorption of polyphenols in blood does not support their activity as antioxidants and their mechanism of activity is not fully understood. The results are from in vitro, animal and human studies, detected by relevant oxidative stress markers. The review carries evidences that polyphenols, by generating H2O2 at nM concentration, exogenous to cells and organs, act as activators of signaling factors increasing cell Eustress. When polyphenols attain high concentration in the blood system, they generate H2O2 at µM concentration, acting as cytotoxic agents and Distress. Pre-treatment of cells or organisms with polyphenols, by generating H2O2 at low levels, inhibits cellular PTPs (protein tyrosine phosphatases), inducing cell signaling through transcription of the Nrf2 (nuclear factor erythroid 2-related factor 2) axis of adaptation and protection to oxidation stress. Polyphenols ingestion at the right amount and time during the meal acts synergistically at the level of the gastrointestinal tract (GIT) and blood system, for keeping the redox homeostasis in our organism and better balancing human health.

Therapeutic Potential of Polyphenols-Loaded Polymeric Nanoparticles in Cardiovascular System.

Numerous studies document an increased production of reactive oxygen species (ROS) with a subsequent decrease in nitric oxide (NO) bioavailability in different cardiovascular diseases, including hypertension, atherosclerosis, and heart failure. Many natural polyphenols have been demonstrated to decrease ROS generation and/or to induce the endogenous antioxidant enzymatic defense system. Moreover, different polyphenolic compounds have the ability to increase the activity/expression of endothelial nitric oxide synthase (eNOS) with a subsequent enhancement of NO generation. However, as a result of low absorption and bioavailability of natural polyphenols, the beneficial effects of these substances are very limited. Recent progress in delivering polyphenols to the targeted tissues revealed new possibilities for the use of polymeric nanoparticles in increasing the efficiency and reducing the degradability of natural polyphenols. This review focuses on the effects of different natural polyphenolic substances, especially resveratrol, quercetin, curcumin, and cherry extracts, and their ability to bind to polymeric nanoparticles, and summarizes the effects of polyphenol-loaded nanoparticles, mainly in the cardiovascular system.