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Role of Nutraceuticals in Metabolic and Gastrointestinal Disorders

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 69168

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Special Issue Editor

Prof. Dr. Raffaele Capasso

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Guest Editor

Universita degli Studi di Napoli Federico II, Naples, Italy
Interests: role of cannabinoid, vanilloid and kappa-opioid receptors in the gastrointestinal tract; ethnopharmacological studies on medicinal plants; clinical pharmacology of herbal products; nutritional pharmacology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nutraceutics is a term derived from “nutrition” and “pharmaceutics.” The term is applied to products that are isolated from herbal products, dietary supplements (nutrients), specific diets, and processed foods such as cereals, soups, and beverages that, in addition to nutritional, are also used for medicinal purposes.

Scientific research has demonstrated a wide variety of biological properties and physiological benefits of dietary phytochemicals, highlighting their promising role in the prevention and treatment of several diseases (e.g., diabetes, infection, renal, and gastrointestinal disorders) with consequences on quality of life and longevity.

The purpose of this Special Issue is to publish original research papers and/or relevant updates of literature data, on the beneficial effects of nutraceutics in metabolic and gastrointestinal disorders

Prof. Dr. Raffaele Capasso
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Nutraceutical
Medicinal plants
Vitamins
Biological activity
Medical use
Pharmacological interactions
Metabolism
Gastrointestinal disorders
Cereals

Published Papers (12 papers)

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Research

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21 pages, 5364 KiB

Open AccessArticle

A Villin-Driven Fxr Transgene Modulates Enterohepatic Bile Acid Homeostasis and Response to an n-6-Enriched High-Fat Diet

by Spencer N. Wren, Micah G. Donovan, Ornella I. Selmin, Tom C. Doetschman and Donato F. Romagnolo

Int. J. Mol. Sci. 2020, 21(21), 7829; https://doi.org/10.3390/ijms21217829 - 22 Oct 2020

Cited by 6 | Viewed by 2723

Abstract

A diet high in n-6 polyunsaturated fatty acids (PUFAs) may contribute to inflammation and tissue damage associated with obesity and pathologies of the colon and liver. One contributing factor may be dysregulation by n-6 fatty acids of enterohepatic bile acid (BA) metabolism. The farnesoid X receptor (FXR) is a nuclear receptor that regulates BA homeostasis in the liver and intestine. This study aims to compare the effects on FXR regulation and BA metabolism of a palm oil-based diet providing 28% energy (28%E) from fat and low n-6 linoleic acid (LA, 2.5%E) (CNTL) with those of a soybean oil-based diet providing 50%E from fat and high (28%E) in LA (n-6HFD). Wild-type (WT) littermates and a transgenic mouse line overexpressing the Fxrα1 isoform under the control of the intestine-specific Villin promoter (Fxrα1^TG) were fed the CNTL or n-6HFD starting at weaning through 16 weeks of age. Compared to the CNTL diet, the n-6HFD supports higher weight gain in both WT and Fxrα^TG littermates; increases the expression of Fxrα1/2, and peroxisome proliferator-activated receptor-γ1 (Pparγ1) in the small intestine, Fxrα1/2 in the colon, and cytochrome P4507A1 (Cyp7a1) and small heterodimer protein (Shp) in the liver; and augments the levels of total BA in the liver, and primary chenodeoxycholic (CDCA), cholic (CA), and β-muricholic (βMCA) acid in the cecum. Intestinal overexpression of the Fxra1^TG augments expression of Shp and ileal bile acid-binding protein (Ibabp) in the small intestine and Ibabp in the proximal colon. Conversely, it antagonizes n-6HFD-dependent accumulation of intestinal and hepatic CDCA and CA; hepatic levels of Cyp7a1; and expression of Pparγ in the small intestine. We conclude that intestinal Fxrα1 overexpression represses hepatic de novo BA synthesis and protects against n-6HFD-induced accumulation of human-specific primary bile acids in the cecum. Full article

(This article belongs to the Special Issue Role of Nutraceuticals in Metabolic and Gastrointestinal Disorders)

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17 pages, 3423 KiB

Open AccessArticle

Food for Bone: Evidence for a Role for Delta-Tocotrienol in the Physiological Control of Osteoblast Migration

by Lavinia Casati, Francesca Pagani, Roberto Maggi, Francesco Ferrucci and Valeria Sibilia

Int. J. Mol. Sci. 2020, 21(13), 4661; https://doi.org/10.3390/ijms21134661 - 30 Jun 2020

Cited by 12 | Viewed by 2748

Abstract

Bone remodeling and repair require osteogenic cells to reach the sites that need to be rebuilt, indicating that stimulation of osteoblast migration could be a promising osteoanabolic strategy. We showed that purified δ-tocotrienol (δ-TT, 10 μg/mL), isolated from commercial palm oil (Elaeis guineensis) fraction, stimulates the migration of both MC3T3-E1 osteoblast-like cells and primary human bone marrow mesenchymal stem cells (BMSC) as detected by wound healing assay or Boyden chamber assay respectively. The ability of δ-TT to promote MC3T3-E1 cells migration is dependent on Akt phosphorylation detected by Western blotting and involves Wnt/β-catenin signalling pathway activation. In fact, δ-TT increased β-catenin transcriptional activity, measured using a Nano luciferase assay and pretreatment with procaine (2 µM), an inhibitor of the Wnt/β-catenin signalling pathway, reducing the wound healing activity of δ-TT on MC3T3-E1 cells. Moreover, δ-TT treatment increased the expression of β-catenin specific target genes, such as Osteocalcin and Bone Morphogenetic Protein-2, involved in osteoblast differentiation and migration, and increased alkaline phosphatase and collagen content, osteoblast differentiation markers. The ability of δ-TT to enhance the recruitment of BMSC, and to promote MC3T3-E1 differentiation and migratory behavior, indicates that δ-TT could be considered a promising natural anabolic compound. Full article

(This article belongs to the Special Issue Role of Nutraceuticals in Metabolic and Gastrointestinal Disorders)

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16 pages, 2357 KiB

Open AccessArticle

Pomegranate Mesocarp against Colitis-Induced Visceral Pain in Rats: Effects of a Decoction and Its Fractions

by Carmen Parisio, Elena Lucarini, Laura Micheli, Alessandra Toti, Mohamad Khatib, Nadia Mulinacci, Laura Calosi, Daniele Bani, Lorenzo Di Cesare Mannelli and Carla Ghelardini

Int. J. Mol. Sci. 2020, 21(12), 4304; https://doi.org/10.3390/ijms21124304 - 17 Jun 2020

Cited by 23 | Viewed by 3316

Abstract

The management of chronic visceral pain related to Inflammatory Bowel Diseases or Irritable Bowel Syndrome is still a clinical problem and new therapeutic strategies continue to be investigated. In the present study, the efficacy of a pomegranate decoction and of its polysaccharide and ellagitannin components in preventing the development of colitis-induced abdominal pain in rats was evaluated. After colitis induction by 2,4-dinitrobenzenesulfonic acid (DNBS), the pomegranate decoction (300 mg kg⁻¹), polysaccharides (300 mg kg⁻¹), and ellagitannins (45 mg kg⁻¹) were orally administered for 14 days. Repeated treatment with decoction reduced visceral hypersensitivity in the colitic animals both at 7 and 14 days. Similar efficacy was shown by polysaccharides, but with lower potency. Ellagitannins administered at dose equivalent to decoction content showed higher efficacy in reducing the development of visceral pain. Macroscopic and microscopic evaluations performed on the colon 14 days after the damage showed that all three preparations reduced the overall amount of mast cells, the number of degranulated mast cells, and the density of collagen fibers in the mucosal stroma. Although ellagitannins seem to be responsible for most of the beneficial effects of pomegranate on DNBS-induced colitis, the polysaccharides support and enhance its effect. Therefore, pomegranate mesocarp preparations could represent a complementary approach to conventional therapies for promoting abdominal pain relief. Full article

(This article belongs to the Special Issue Role of Nutraceuticals in Metabolic and Gastrointestinal Disorders)

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16 pages, 6189 KiB

Open AccessArticle

Celastrol Induces Necroptosis and Ameliorates Inflammation via Targeting Biglycan in Human Gastric Carcinoma

by Dandan Guo, Wei Zhang, Haijie Yang, Jiajia Bi, Yunfei Xie, Binfeng Cheng, Yan Wang and Sujuan Chen

Int. J. Mol. Sci. 2019, 20(22), 5716; https://doi.org/10.3390/ijms20225716 - 14 Nov 2019

Cited by 39 | Viewed by 4215

Abstract

Celastrol, a triterpene isolated from the root of traditional Chinese medicine Thunder of God Vine, possesses anti-cancer and anti-inflammatory activity to treat rheumatoid disease or as health product. Necroptosis is considered as a new approach to overcome chemotherapeutics resistance. However, whether celastrol exerts necroptosis leading to gastric cancer cell death is still unclear. Here, for the first time we showed that celastrol induced necroptosis in HGC27 and AGS gastric cancer cell lines. More importantly, celastrol down-regulated biglycan (BGN) protein, which is critical for gastric cancer migration and invasion. Furthermore, celastrol activated receptor-interacting protein 1 and 3 (RIP1 and RIP3) and subsequently promoted the translation of mixed-lineage kinase domain-like (MLKL) from cytoplasm to plasma membrane, leading to necroptosis of gastric cancer cell, which was blocked by over-expression BGN. In addition, celastrol suppressed the release of pro-inflammatory cytokines TNF-α and IL-8 in HGC27 and AGS cells, which was reversed by over-expression BGN. Taken together, we identified celastrol as a necroptosis inducer, activated RIP1/RIP3/MLKL pathway and suppressed the level of pro-inflammatory cytokines by down-regulating BGN in HGC-27 and AGS cells, which supported the feasibility of celastrol in gastric cancer therapy. Full article

(This article belongs to the Special Issue Role of Nutraceuticals in Metabolic and Gastrointestinal Disorders)

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Review

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17 pages, 2894 KiB

Open AccessReview

Dietary Gluten and Neurodegeneration: A Case for Preclinical Studies

by Mahesh Mohan, Chioma M. Okeoma and Karol Sestak

Int. J. Mol. Sci. 2020, 21(15), 5407; https://doi.org/10.3390/ijms21155407 - 29 Jul 2020

Cited by 18 | Viewed by 4640

Abstract

Although celiac disease (CD) is an autoimmune disease that primarily involves the intestinal tract, mounting evidence suggests that a sizeable number of patients exhibit neurological deficits. About 40% of the celiac patients with neurological manifestations have circulating antibodies against neural tissue transglutaminase-6 (tTG6). While early diagnosis and strict adherence to a gluten-free diet (GFD) have been recommended to prevent neurological dysfunction, better therapeutic strategies are needed to improve the overall quality of life. Dysregulation of the microbiota-gut-brain axis, presence of anti-tTG6 antibodies, and epigenetic mechanisms have been implicated in the pathogenesis. It is also possible that circulating or gut-derived extracellular structures and including biomolecular condensates and extracellular vesicles contribute to disease pathogenesis. There are several avenues for shaping the dysregulated gut homeostasis in individuals with CD, non-celiac gluten sensitivity (NCGS) and/or neurodegeneration. In addition to GFD and probiotics, nutraceuticals, such as phyto and synthetic cannabinoids, represent a new approach that could shape the host microbiome towards better prognostic outcomes. Finally, we provide a data-driven rationale for potential future pre-clinical research involving non-human primates (NHPs) to investigate the effect of nutraceuticals, such as phyto and synthetic cannabinoids, either alone or in combination with GFD to prevent/mitigate dietary gluten-induced neurodegeneration. Full article

(This article belongs to the Special Issue Role of Nutraceuticals in Metabolic and Gastrointestinal Disorders)

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26 pages, 1680 KiB

Open AccessReview

Gastrointestinal Disorders and Metabolic Syndrome: Dysbiosis as a Key Link and Common Bioactive Dietary Components Useful for their Treatment

by Anna De Filippis, Hammad Ullah, Alessandra Baldi, Marco Dacrema, Cristina Esposito, Emanuele Ugo Garzarella, Cristina Santarcangelo, Ariyawan Tantipongpiradet and Maria Daglia

Int. J. Mol. Sci. 2020, 21(14), 4929; https://doi.org/10.3390/ijms21144929 - 13 Jul 2020

Cited by 29 | Viewed by 5546

Abstract

Gastrointestinal (GI) diseases, which include gastrointestinal reflux disease, gastric ulceration, inflammatory bowel disease, and other functional GI disorders, have become prevalent in a large part of the world population. Metabolic syndrome (MS) is cluster of disorders including obesity, hyperglycemia, hyperlipidemia, and hypertension, and is associated with high rate of morbidity and mortality. Gut dysbiosis is one of the contributing factors to the pathogenesis of both GI disorder and MS, and restoration of normal flora can provide a potential protective approach in both these conditions. Bioactive dietary components are known to play a significant role in the maintenance of health and wellness, as they have the potential to modify risk factors for a large number of serious disorders. Different classes of functional dietary components, such as dietary fibers, probiotics, prebiotics, polyunsaturated fatty acids, polyphenols, and spices, possess positive impacts on human health and can be useful as alternative treatments for GI disorders and metabolic dysregulation, as they can modify the risk factors associated with these pathologies. Their regular intake in sufficient amounts also aids in the restoration of normal intestinal flora, resulting in positive regulation of insulin signaling, metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. This review is designed to focus on the health benefits of bioactive dietary components, with the aim of preventing the development or halting the progression of GI disorders and MS through an improvement of the most important risk factors including gut dysbiosis. Full article

(This article belongs to the Special Issue Role of Nutraceuticals in Metabolic and Gastrointestinal Disorders)

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22 pages, 495 KiB

Open AccessReview

Fatty Acid Diets: Regulation of Gut Microbiota Composition and Obesity and Its Related Metabolic Dysbiosis

by David Johane Machate, Priscila Silva Figueiredo, Gabriela Marcelino, Rita de Cássia Avellaneda Guimarães, Priscila Aiko Hiane, Danielle Bogo, Verônica Assalin Zorgetto Pinheiro, Lincoln Carlos Silva de Oliveira and Arnildo Pott

Int. J. Mol. Sci. 2020, 21(11), 4093; https://doi.org/10.3390/ijms21114093 - 08 Jun 2020

Cited by 122 | Viewed by 9080

Abstract

Long-term high-fat dietary intake plays a crucial role in the composition of gut microbiota in animal models and human subjects, which affect directly short-chain fatty acid (SCFA) production and host health. This review aims to highlight the interplay of fatty acid (FA) intake and gut microbiota composition and its interaction with hosts in health promotion and obesity prevention and its related metabolic dysbiosis. The abundance of the Bacteroidetes/Firmicutes ratio, as Actinobacteria and Proteobacteria species are associated with increased SCFA production, reported high-fat diet rich in medium-chain fatty acids (MCFAs), monounsaturated fatty acids (MUFAs), and n–3 polyunsaturated fatty acids (PUFAs) as well as low-fat diets rich in long-chain fatty acids (LCFAs). SCFAs play a key role in health promotion and prevention and, reduction and reversion of metabolic syndromes in the host. Furthermore, in this review, we discussed the type of fatty acids and their amount, including the administration time and their interplay with gut microbiota and its results about health or several metabolic dysbioses undergone by hosts. Full article

(This article belongs to the Special Issue Role of Nutraceuticals in Metabolic and Gastrointestinal Disorders)

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35 pages, 2860 KiB

Open AccessReview

Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals?

by Vicente Martínez, Amaia Iriondo De-Hond, Francesca Borrelli, Raffaele Capasso, María Dolores del Castillo and Raquel Abalo

Int. J. Mol. Sci. 2020, 21(9), 3067; https://doi.org/10.3390/ijms21093067 - 26 Apr 2020

Cited by 107 | Viewed by 14245

Abstract

Cannabis sativa is an aromatic annual flowering plant with several botanical varieties, used for different purposes, like the production of fibers, the production of oil from the seeds, and especially for recreational or medical purposes. Phytocannabinoids (terpenophenolic compounds derived from the plant), include the well-known psychoactive cannabinoid Δ⁹-tetrahydrocannabinol, and many non-psychoactive cannabinoids, like cannabidiol. The endocannabinoid system (ECS) comprises of endocannabinoid ligands, enzymes for synthesis and degradation of such ligands, and receptors. This system is widely distributed in the gastrointestinal tract, where phytocannabinoids exert potent effects, particularly under pathological (i.e., inflammatory) conditions. Herein, we will first look at the hemp plant as a possible source of new functional food ingredients and nutraceuticals that might be eventually useful to treat or even prevent gastrointestinal conditions. Subsequently, we will briefly describe the ECS and the general pharmacology of phytocannabinoids. Finally, we will revise the available data showing that non-psychoactive phytocannabinoids, particularly cannabidiol, may be useful to treat different disorders and diseases of the gastrointestinal tract. With the increasing interest in the development of functional foods for a healthy life, the non-psychoactive phytocannabinoids are hoped to find a place as nutraceuticals and food ingredients also for a healthy gastrointestinal tract function. Full article

(This article belongs to the Special Issue Role of Nutraceuticals in Metabolic and Gastrointestinal Disorders)

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24 pages, 1285 KiB

Open AccessReview

An Updated Overview on Nanonutraceuticals: Focus on Nanoprebiotics and Nanoprobiotics

by Alessandra Durazzo, Amirhossein Nazhand, Massimo Lucarini, Atanas G. Atanasov, Eliana B. Souto, Ettore Novellino, Raffaele Capasso and Antonello Santini

Int. J. Mol. Sci. 2020, 21(7), 2285; https://doi.org/10.3390/ijms21072285 - 26 Mar 2020

Cited by 67 | Viewed by 6573

Abstract

Over the last few years, the application of nanotechnology to nutraceuticals has been rapidly growing due to its ability to enhance the bioavailability of the loaded active ingredients, resulting in improved therapeutic/nutraceutical outcomes. The focus of this work is nanoprebiotics and nanoprobiotics, terms which stand for the loading of a set of compounds (e.g., prebiotics, probiotics, and synbiotics) in nanoparticles that work as absorption enhancers in the gastrointestinal tract. In this manuscript, the main features of prebiotics and probiotics are highlighted, together with the discussion of emerging applications of nanotechnologies in their formulation. Current research strategies are also discussed, in particular the promising use of nanofibers for the delivery of probiotics. Synbiotic-based nanoparticles represent an innovative trend within this area of interest. As only few experimental studies on nanoprebiotics and nanoprobiotics are available in the scientific literature, research on this prominent field is needed, covering effectiveness, bioavailability, and safety aspects. Full article

(This article belongs to the Special Issue Role of Nutraceuticals in Metabolic and Gastrointestinal Disorders)

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16 pages, 567 KiB

Open AccessReview

A Brief Review of Nutraceutical Ingredients in Gastrointestinal Disorders: Evidence and Suggestions

by Xiang Gao, Jingwen Liu, Li Li, Wei Liu and Meiyan Sun

Int. J. Mol. Sci. 2020, 21(5), 1822; https://doi.org/10.3390/ijms21051822 - 06 Mar 2020

Cited by 16 | Viewed by 10953

Abstract

The dietary effect on gut health has long been recognized through the empirical practice of soothing gastric discomfort with certain types of food, and recently the correlation between specific diets with lower incidences of several gastrointestinal diseases has been revealed. Ingredients from those considered beneficial foods have been isolated and studied, and some of them have already been put into the supplement market. In this review, we focus on latest studies of these food-derived ingredients for their proposed preventive and therapeutic roles in gastrointestinal disorders, with the attempt of drawing evidence-based suggestions on consuming these products. Full article

(This article belongs to the Special Issue Role of Nutraceuticals in Metabolic and Gastrointestinal Disorders)

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