Why is it important to understand the nature and chemistry of tannins to exploit their potential as nutraceuticals?

Tannins comprise a large group of polyphenols that can differ widely in chemical composition and molecular weight. The use of tannins dates back to antiquity, but it is only in recent years that their potential use as nutraceuticals associated with the human diet is beginning to be exploited. Although the biological effects of these phytocomplexes have been studied for many years, there are still several open questions regarding their chemistry and biotransformation. The vastness of the molecules that make up the class of tannins has made their characterisation, as well as their nomenclature and classification, a daunting task. This review has been written with the aim of bringing order to the chemistry of tannins by including aspects that are sometimes still overlooked or should be updated with new research in order to understand the potential of these phytocomplexes as active ingredients or technological components for nutraceutical products. Future trends in tannin research should address many questions that are still open, such as determining the exact biosynthetic pathways of all classes of tannins, the actual biological effects determined by the interaction of tannins with other molecules, their metabolization, and the best extraction methods, but with a view to market requirements.

Evaluation of Tannin-Delivery Approaches for Gut Microbiota Modulation: Comparison of Pectin-Based Microcapsules and Unencapsulated Extracts.

The aim of this study was to investigate the impact of tannins on gut microbiota composition and activity, and to evaluate the use of pectin-microencapsulation of tannins as a potential mode of tannin delivery. Thus, pectin-tannin microcapsules and unencapsulated tannin extracts were in vitro digested and fermented, and polyphenol content, antioxidant capacity, microbiota modulation, and short-chain fatty acid (SCFA) production were analyzed. Pectin microcapsules were not able to release their tannin content, keeping it trapped after the digestive process, and are therefore not recommended for tannin delivery. Unencapsulated tannin extracts were found to exert a positive effect on the human gut microbiota. The digestion step resulted to be a fundamental requirement in order to maximize tannin bioactive effects, especially with regard to condensed tannins, as the antioxidant capacity exerted and the SCFAs produced were greater when tannins were submitted to digestion prior to fermentation. Moreover, tannins interacted differently with the intestinal microbiota depending on whether they underwent prior digestion or not. Polyphenol content and antioxidant capacity correlated with SCFA production and with the abundance of several bacterial taxa.

Natural tannin extracts supplementation for COVID-19 patients (TanCOVID): a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: This research aims to study the efficacy of tannins co-supplementation on disease duration, severity and clinical symptoms, microbiota composition and inflammatory mediators in SARS-CoV2 patients. TRIAL DESIGN: This is a prospective, double-blind, randomized, placebo-controlled, parallel-group trial to evaluate the efficacy of the administration of the dietary supplement ARBOX, a molecular blend of quebracho and chestnut tannins extract and Vit B12, in patients affected by COVID-19. PARTICIPANTS: 18 years of age or older, admitted to Hospital de Clinicas Jose de San Martin, Buenos Aires University (Argentina), meeting the definition of "COVID-19 confirmed case" ( https://www.argentina.gob.ar/salud/coronavirus-COVID-19/definicion-de-caso ). Inclusion Criteria Participants are eligible to be included in the study if the following criteria apply: 1. Any gender 2. ≥18 years old 3. Informed consent for participation in the study 4. Virological diagnosis of SARS-CoV-2 infection (real-time PCR) Exclusion Criteria Participants are excluded from the study if any of the following criteria apply: 1. Pregnant and lactating patients 2. Patients who cannot take oral therapy (with severe cognitive decline, assisted ventilation, or impaired consciousness) 3. Hypersensitivity to polyphenols 4. Patients already in ICU or requiring mechanical ventilation 5. Patients already enrolled in other clinical trials 6. Decline of consent INTERVENTION AND COMPARATOR: Experimental: TREATED ARM Participants will receive a supply of 28 -- 390 mg ARBOX capsules for 14 days. Patients will be supplemented with 2 capsules of ARBOX per day. Placebo Comparator: CONTROL ARM Participants will receive placebo supply for 14 days. The placebo will be administered with the identical dose as described for the test product. All trial participants will receive standard therapy, which includes: Antipyretics or Lopinavir / Ritonavir, Azithromycin and Hydroxychloroquine, as appropriate (treatment currently recommended by the department of Infectious Diseases of the Hospital de Clínicas that could undergo to modifications). In addition, if necessary: supplemental O2, non-invasive ventilation, antibiotic therapy. MAIN OUTCOMES: Primary Outcome Measures: Time to hospital discharge, defined as the time from first dose of ARBOX to hospital discharge [ Time Frame: Throughout the Study (Day 0 to Day 28) ] Secondary Outcome Measures: 28-day all-cause mortality [ Time Frame: Throughout the Study (Day 0 to Day 28) ]-proportion Invasive ventilation on day 28 [ Time Frame: Throughout the Study (Day 0 to Day 28) ]-proportion Level of inflammation parameters and cytokines [ Time Frame: day 1-14 ] -mean difference Difference in fecal intestinal microbiota composition and intestinal permeability [ Time Frame: day 1-14 ] Negativization of COVID-PCR at day 14 [ Time Frame: day 14 ]-proportion RANDOMIZATION: Potential study participants were screened for eligibility 24 hours prior to study randomization. Patients were randomly assigned via computer-generated random numbering (1:1) to receive standard treatment coupled with tannin or standard treatment plus placebo (control group). BLINDING (MASKING): Study personnel and participants are blinded to the treatment allocation, as both ARBOX and placebo were packed in identical containers. Thus, all the used capsules had identical appearance. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Considering an alpha error of 5%, a power of 80% a sample size of 70 patients per branch was estimated. 140 patients in total. TRIAL STATUS: The protocol version is number V2, dated May 23, 2020. The first patient, first visit was on June 12, 2020; the recruitment end date was October 6, 2020. The protocol was not submitted earlier because the enrollment of some patients took place after the closure of the recruitment on the clinicaltrials platform. In fact, due to the epidemiological conditions, due to the decrease of the cases in Argentina during the summer period, the recruitment stopped t before reaching the number of 140 patients (as indicated in the webpage). However, since there was a new increase in cases, the enrolment was resumed in order to reach the number of patients initially planned in the protocol. The final participant was recruited on February 14, 2021. TRIAL REGISTRATION: ClinicalTrials.gov, number: NCT04403646 , registered on May 27th, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Pectin-Based Formulations for Controlled Release of an Ellagic Acid Salt with High Solubility Profile in Physiological Media.

Among bioactive phytochemicals, ellagic acid (EA) is one of the most controversial because its high antioxidant and cancer-preventing effects are strongly inhibited by low gastrointestinal absorption and rapid excretion. Strategies toward an increase of solubility in water and bioavailability, while preserving its structural integrity and warranting its controlled release at the physiological targets, are therefore largely pursued. In this work, EA lysine salt at 1:4 molar ratio (EALYS), exhibiting a more than 400 times increase of water solubility with respect to literature reports, was incorporated at 10% in low methoxylated (LM) and high methoxylated (HM) pectin films. The release of EA in PBS at pH 7.4 from both film preparations was comparable and reached 15% of the loaded compound over 2 h. Under simulated gastric conditions, release of EA from HM and LM pectin films was minimal at gastric pH, whereas higher concentrations-up to 300 µM, corresponding to ca. 50% of the overall content-were obtained in the case of the HM pectin film after 2 h incubation at the slightly alkaline pH of small intestine environment, with the enzyme and bile salt components enhancing the release. EALYS pectin films showed a good prebiotic activity as evaluated by determination of short chain fatty acids (SCFAs) levels following microbial fermentation, with a low but significant increase of the effects produced by the pectins themselves. Overall, these results highlight pectin films loaded with EALYS salt as a promising formulation to improve administration and controlled release of the compound.

Effects of in vitro digestion-fermentation over global antioxidant response and short chain fatty acid production of beet waste extracts in Ca(ii)-alginate beads.

The aim of the present work was to analyze the effect of in vitro gastrointestinal digestion-fermentation on antioxidant capacity, total phenols and production of short chain fatty acids (SCFAs) from biocompounds derived from beet waste (leaf and stem) encapsulated in different formulations of Ca(ii)-alginate beads. The encapsulated systems presented higher antioxidant capacity in different phases (digested and fermented) than the extracts without encapsulation, making Ca(ii)-alginate beads a suitable delivery vehicle. Levels of total phenolic compounds and antioxidant capacity of the fermented fraction were up to ten times higher than those of the digested fraction, boosted by the contribution of bioactive compounds from the by-product of beet as well as by sugars and biopolymers. Among the formulations used, those that had excipients (sugars and/or biopolymers) presented a better overall antioxidant response than the beads with just alginate. Guar gum and sucrose lead to a promising enhancement of Ca(ii)-alginate beads not only for preservation and protection but also in terms of stability under in vitro digestion-fermentation and production of SCFAs.

Natural Tannin Wood Extracts as a Potential Food Ingredient in the Food Industry.

Wood extracts are one of the most important natural sources of industrially obtained tannins. Their use in the food industry could be one of the biggest (most important) recent innovations in food science as a result of their multiple (many) possible applications. The use of tannin wood extracts (TWEs) as additives directly added in foods or in their packaging meets an ever-increasing consumer demand for innovative approaches to sustainability. The latest research is focusing on new ways to include them directly in food, to take advantage of their specific actions to prevent individual pathological conditions. The present review begins with the biology of TWEs and then explores their chemistry, specific sensorial properties, and current application in food production. Moreover, this review is intended to cover recent studies dealing with the potential use of TWEs as a starting point for novel food ingredients.

Polyphenols in dementia: From molecular basis to clinical trials.

Dementia is common in the elderly, but there are currently no effective therapies available to prevent or treat this syndrome. In the last decade, polyphenols (particularly curcumin, resveratrol and tea catechins) have been under very close scrutiny as potential therapeutic agents for neurodegenerative diseases, diabetes, inflammatory diseases and aging. Data were collected from Web of Science (ISI Web of Knowledge), Pubmed and Medline (from 2000 to 2015), by searching for the keywords "dementia" AND "curcumin", "resveratrol", "EGCG", "tea catechins". The same keywords were used to investigate the current state of clinical trials recorded in the NIH clinicaltrials.gov registry. Starting from the intrinsic properties of the compounds, we explain their specific action in patients with AD and the most common types of dementia. The pharmacological actions of curcumin, resveratrol and tea catechins have mainly been attributed to their antioxidant activity, interaction with cell signaling pathways, anti-inflammatory effect, chelation of metal ions, and neuroprotection. Evidence from in vitro and in vivo studies on polyphenols have demonstrated that they may play an integral role in preventing and treating diseases associated with neurodegeneration. Furthermore, we critically analyze the clinical trials that we found, which investigate the real pharmacological actions and the possible side effects of these compounds. This review highlights the potential role of polyphenols in the prevention/treatment of dementia and describes the current limitations of research in this field.