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Effects of Phytochemicals on Metabolic Disorders and Human Health

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Phytochemicals and Human Health".

Deadline for manuscript submissions: 15 August 2024 | Viewed by 16732

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Dr. María Angeles Martín

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Guest Editor

1. Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), 28040 Madrid, Spain
2. CIBER of Diabetes and Associated Metabolic Disease (CIBERDEM), ISCIII, 28029 Madrid, Spain
Interests: polyphenols; metabolic diseases; physiological functions; nutritional prevention; gut health; microbiota, oxidative stress; inflammation; signalling pathways

Dr. Sonia Ramos Rivero

E-Mail Website1 Website2
Guest Editor

1. Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), 28040 Madrid, Spain
2. CIBER of Diabetes and Associated Metabolic Disease (CIBERDEM), ISCIII, 28029 Madrid, Spain
Interests: polyphenols; metabolic diseases; nutritional prevention; oxidative stress; inflammation; signalling pathways; bioactivity

Special Issue Information

Dear Colleagues,

Phytochemicals have received rising attention for their health-promoting properties in many chronic diseases, including metabolic disorders and their associated complications (diabetes, obesity, metabolic syndrome, non-alcoholic fatty liver disease, and cardiovascular diseases). These health benefits have been related to different biological activities, such as their well-known antioxidant property, but also their anti-diabetic, anti-obesity, and anti-inflammatory actions, among others. In this regard, it is becoming apparent that phytochemicals can modulate different signalling pathways, which are responsible for these final actions and, therefore, their benefits on health. Phytochemicals are commonly found in the diet and are abundant in fruits, vegetables, olive oil, legumes, cocoa, and beverages such as tea, coffee, and wine. Indeed, because of this wide distribution and their potential effects on health, its consumption could represent a promising protective and therapeutic approach to prevent metabolic diseases and improve health and, therefore, constitutes significant research field.

This Special Issue entitled “Effects of Phytochemicals on Metabolic Diseases and Human Health” aims to highlight the most recent advances in phytochemicals, phytochemical-rich foods, their extracts, and health-promoting benefits in the context of metabolic disease. This Special Issue of Nutrients welcomes the submission of original research articles, reviews, and short communications.

Dr. María Angeles Martín
Dr. Sonia Ramos Rivero
Guest Editors

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.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

phytochemicals
type 2 diabetes
obesity
metabolic syndrome
NAFLD
cardiovascular diseases
microbiota
metabolism
oxidative stress
inflammation

Published Papers (9 papers)

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Research

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22 pages, 8353 KiB

Open AccessArticle

Nutritional and Physiological Properties of Thymbra spicata: In Vitro Study Using Fecal Fermentation and Intestinal Integrity Models

by Mohamad Khalil, Francesca Piccapane, Mirco Vacca, Giuseppe Celano, Laura Mahdi, Valeria Perniola, Carmen Aurora Apa, Alessandro Annunziato, Ilaria Iacobellis, Giuseppe Procino, Maria Calasso, Maria De Angelis, Rosa Caroppo and Piero Portincasa

Nutrients 2024, 16(5), 588; https://doi.org/10.3390/nu16050588 - 21 Feb 2024

Viewed by 859

Abstract

(Poly)phenolic-rich Mediterranean plants such as Thymbra spicata have been associated with several health-promoting effects. The nutritional value, as well as physiological interaction of T. spicata with the gastrointestinal tract, has not been investigated before. The nutritional composition of T. spicata leaves was here characterized by standard analytical methods. T. spicata leaves were subjected to ethanolic extraction, simulated gastrointestinal digestion, and anaerobic microbial gut fermentation. Phenols/flavonoid contents and radical scavenging activity were assessed by colorimetric methods. The volatile organic compounds (VOCs) were detected by gas chromatography coupled with mass spectrometry. The effect on intestinal integrity was evaluated using a Caco-2 monolayers mounted in a Ussing chamber. T. spicata contains a high amount of fiber (12.3%) and unsaturated fatty acids (76% of total fat). A positive change in VOCs including short-chain fatty acids was observed without significant change in viable microbe. T. spicata and carvacrol (main phenolic compound) enhanced ionic currents in a concentration-dependent manner without compromising the Caco-2 monolayer’s integrity. These effects were partially lost upon simulated digestion and completely abolished after colonic fermentation in line with polyphenols and carvacrol content. Conclusion: T. spicata represents a promising nutrient for the modulation of gut microbiota and the gut barrier. Further studies must better define its mechanisms of action. Full article

(This article belongs to the Special Issue Effects of Phytochemicals on Metabolic Disorders and Human Health)

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11 pages, 623 KiB

Open AccessArticle

Protective Role of Lycopene in Subjects with Liver Disease: NUTRIHEP Study

by Rossella Donghia, Angelo Campanella, Caterina Bonfiglio, Francesco Cuccaro, Rossella Tatoli and Gianluigi Giannelli

Nutrients 2024, 16(4), 562; https://doi.org/10.3390/nu16040562 - 18 Feb 2024

Viewed by 1027

Abstract

Background: Liver diseases are constantly increasing throughout the world and are often associated with other diseases, but above all they are caused by improper diet. Adherence to a diet with abundant vegetables has now been widely demonstrated to be important in combating this pathological condition. The aim of this study was to explore the protective role of lycopene (LYC) extracts from cooked and fresh tomato. Methods: The study cohort included 969 participants assessed in the NUTRIHEP cohort (2005–2006) and the associated follow-up (2014–2016), divided into two groups, based on liver condition: NAFLD, or AFLD and FLD. Results: The results indicated a statistical significance of LYC consumption, showing a protective role against liver disease, the best concentration being 9.50 mg/die, with an RR value of 0.59, p = 0.01, 0.39 to 0.90 at 95% C.I., and RRR = 0.40, p = 0.002, 0.22 to 0.71 at 95% C.I. Conclusions: The protective role of LYC extracts from tomato has not been amply demonstrated in humans. We conclude that this is one of the few papers in the literature to evaluate the protective effect of LYC against liver disease, as well as how this molecule could be used in future possible treatments. Utilizing lycopene as a supplement alone or in combination with other foods could be useful for developing treatments with reduced contraindications. Full article

(This article belongs to the Special Issue Effects of Phytochemicals on Metabolic Disorders and Human Health)

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15 pages, 8595 KiB

Open AccessArticle

Synergistic Effect of a Flavonoid-Rich Cocoa–Carob Blend and Metformin in Preserving Pancreatic Beta Cells in Zucker Diabetic Fatty Rats

by Paula Gallardo-Villanueva, Tamara Fernández-Marcelo, Laura Villamayor, Angela M. Valverde, Sonia Ramos, Elisa Fernández-Millán and María Angeles Martín

Nutrients 2024, 16(2), 273; https://doi.org/10.3390/nu16020273 - 17 Jan 2024

Viewed by 928

Abstract

The loss of functional beta-cell mass in diabetes is directly linked to the development of diabetic complications. Although dietary flavonoids have demonstrated antidiabetic properties, their potential effects on pancreatic beta-cell preservation and their synergistic benefits with antidiabetic drugs remain underexplored. We have developed a potential functional food enriched in flavonoids by combining cocoa powder and carob flour (CCB), which has shown antidiabetic effects. Here, we investigated the ability of the CCB, alone or in combination with metformin, to preserve pancreatic beta cells in an established diabetic context and their potential synergistic effect. Zucker diabetic fatty rats (ZDF) were fed a CCB-rich diet or a control diet, with or without metformin, for 12 weeks. Markers of pancreatic oxidative stress and inflammation, as well as relative beta-cell mass and beta-cell apoptosis, were analyzed. Results demonstrated that CCB feeding counteracted pancreatic oxidative stress by enhancing the antioxidant defense and reducing reactive oxygen species. Moreover, the CCB suppressed islet inflammation by preventing macrophage infiltration into islets and overproduction of pro-inflammatory cytokines, along with the inactivation of nuclear factor kappa B (NFκB). As a result, the CCB supplementation prevented beta-cell apoptosis and the loss of beta cells in ZDF diabetic animals. The observed additive effect when combining the CCB with metformin underscores its potential as an adjuvant therapy to delay the progression of type 2 diabetes. Full article

(This article belongs to the Special Issue Effects of Phytochemicals on Metabolic Disorders and Human Health)

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18 pages, 6562 KiB

Open AccessArticle

The Mechanism Underlying the Hypoglycemic Effect of Epimedin C on Mice with Type 2 Diabetes Mellitus Based on Proteomic Analysis

by Xuexue Zhou, Ziqi Liu, Xiaohua Yang, Jing Feng, Murat Sabirovich Gins, Tingyu Yan, Lei Han and Huafeng Zhang

Nutrients 2024, 16(1), 25; https://doi.org/10.3390/nu16010025 (registering DOI) - 21 Dec 2023

Viewed by 937

Abstract

Type 2 diabetes mellitus (T2DM) has become a worldwide public health problem. Epimedin C is considered one of the most important flavonoids in Epimedium, a famous edible herb in China and Southeast Asia that is traditionally used in herbal medicine to treat diabetes. In the present study, the therapeutic potential of epimedin C against T2DM was ascertained using a mouse model, and the mechanism underlying the hypoglycemic activity of epimedin C was explored using a label-free proteomic technique for the first time. Levels of fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and oral glucose tolerance, as well as contents of malondialdehyde (MDA) and low-density lipoprotein cholesterol (LDL-C) in the 30 mg·kg⁻¹ epimedin C group (EC30 group), were significantly lower than those in the model control group (MC group) (p < 0.05), while the contents of hepatic glycogen, insulin, and high-density lipoprotein cholesterol (HDL-C), as well as activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the EC30 group were notably higher than those in the MC group (p < 0.05). The structures of liver cells and tissues were greatly destroyed in the MC group, whereas the structures of cells and tissues were basically complete in the EC30 group, which were similar to those in the normal control group (NC group). A total of 92 differentially expressed proteins (DEPs) were enriched in the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In the EC30 vs. MC groups, the expression level of cytosolic phosphoenolpyruvate carboxykinase (Pck1) was down-regulated, while the expression levels of group XIIB secretory phospholipase A2-like protein (Pla2g12b), apolipoprotein B-100 (Apob), and cytochrome P450 4A14 (Cyp4a14) were up-regulated. According to the KEGG pathway assay, Pck1 participated in the gluconeogenesis and insulin signaling pathways, and Pla2g12b, Apob, and Cyp4a14 were the key proteins in the fat digestion and fatty acid degradation pathways. Pck1, Pla2g12b, Apob, and Cyp4a14 seemed to play important roles in the prevention and treatment of T2DM. In summary, epimedin C inhibited Pck1 expression to maintain FBG at a relatively stable level, promoted Pla2g12b, Apob, and Cyp4a14 expressions to alleviate liver lipotoxicity, and protected liver tissues and cells from oxidant stress possibly by its phenolic hydroxyl groups. Full article

(This article belongs to the Special Issue Effects of Phytochemicals on Metabolic Disorders and Human Health)

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26 pages, 2995 KiB

Open AccessArticle

Totum-070, a Polyphenol-Rich Plant Extract, Prevents Hypercholesterolemia in High-Fat Diet-Fed Hamsters by Inhibiting Intestinal Cholesterol Absorption

by Cédric Langhi, Marie Vallier, Yolanda F. Otero, Maheva Maura, Florian Le Joubioux, Hugo Groult, Oussama Achour, Ratna Budhi Pebriana, Martin Giera, Bruno Guigas, Thierry Maugard, Benoit Chassaing, Sébastien Peltier, Jean-Marie Bard and Pascal Sirvent

Nutrients 2023, 15(24), 5056; https://doi.org/10.3390/nu15245056 - 09 Dec 2023

Viewed by 1460

Abstract

Atherosclerotic cardiovascular disease is the leading cause of mortality worldwide, and hypercholesterolemia is a central risk factor for atherosclerosis. This study evaluated the effects of Totum-070, a plant-based polyphenol-rich supplement, in hamsters with high-fat diet (HFD)-induced dyslipidemia. The molecular mechanisms of action were explored using human Caco2 enterocytes. Totum-070 supplementation reduced the total cholesterol (−41%), non-HDL cholesterol (−47%), and triglycerides (−46%) in a dose-dependent manner, compared with HFD. HFD-induced hepatic steatosis was also significantly decreased by Totum-070, an effect associated with the reduction in various lipid and inflammatory gene expression. Upon challenging with olive oil gavage, the post-prandial triglyceride levels were strongly reduced. The sterol excretion in the feces was increased in the HFD-Totum-070 groups compared with the HFD group and associated with reduction of intestinal cholesterol absorption. These effects were confirmed in the Caco2 cells, where incubation with Totum-070 inhibited cholesterol uptake and apolipoprotein B secretion. Furthermore, a microbiota composition analysis revealed a strong effect of Totum-070 on the alpha and beta diversity of bacterial species and a significant decrease in the Firmicutes to Bacteroidetes ratio. Altogether, our findings indicate that Totum-070 lowers hypercholesterolemia by reducing intestinal cholesterol absorption, suggesting that its use as dietary supplement may be explored as a new preventive strategy for cardiovascular diseases. Full article

(This article belongs to the Special Issue Effects of Phytochemicals on Metabolic Disorders and Human Health)

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26 pages, 1450 KiB

Open AccessArticle

Novel Multi-Ingredient Supplement Facilitates Weight Loss and Improves Body Composition in Overweight and Obese Individuals: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

by Joshua P. Nederveen, Alexander J. Mastrolonardo, Donald Xhuti, Alessia Di Carlo, Katherine Manta, Matthew R. Fuda and Mark A. Tarnopolsky

Nutrients 2023, 15(17), 3693; https://doi.org/10.3390/nu15173693 - 23 Aug 2023

Cited by 1 | Viewed by 3541

Abstract

Background: Despite the growing recognition of the obesity crisis, its rates continue to rise. The current first-line therapies, such as dietary changes, energy restriction, and physical activity, are typically met with poor adherence. Novel nutritional interventions can address the root causes of obesity, including mitochondrial dysfunction, and facilitate weight loss. Objective: The objective of this study was to investigate the effects of a multi-ingredient nutritional supplement designed to facilitate mitochondrial function and metabolic health outcomes over a 12 wk period. Methods: Fifty-five overweight and/or obese participants (age (mean ± SEM): 26 ± 1; body mass index (BMI) (kg/m²): 30.5 ± 0.6) completed this double-blind, placebo-controlled clinical trial. Participants were randomized to 12 wks of daily consumption of multi-ingredient supplement (MIS; n = 28; containing 50 mg forskolin, 500 mg green coffee bean extract, 500 mg green tea extract, 500 mg beet root extract, 400 mg α-lipoic acid, 200 IU vitamin E, and 200 mg CoQ10) or control placebo (PLA, n = 27; containing microcrystalline cellulose) matched in appearance. The co-primary outcomes were bodyweight and fat mass (kg) changes. The secondary outcomes included other body composition measures, plasma markers of obesity, fatty liver disease biomarkers, resting energy metabolism, blood pressure, physical performance, and quality of life. The post-intervention differences between MIS and PLA were examined via ANCOVA which was adjusted for the respective pre-intervention variables. Results: After adjustment for pre-intervention data, there was a significant difference in weight (p < 0.001) and fat mass (p < 0.001) post-intervention between the PLA and MIS treatment arms. Post-intervention weight and fat mass were significantly lower in MIS. Significant post-intervention differences corrected for baseline were found in markers of clinical biochemistry (AST, p = 0.017; ALT, p = 0.008), molecular metabolism (GDF15, p = 0.028), and extracellular vesicle-associated miRNA species miR-122 and miR-34a in MIS (p < 0.05). Conclusions: Following the 12 wks of MIS supplementation, weight and body composition significantly improved, concomitant with improvements in molecular markers of liver health and metabolism. Full article

(This article belongs to the Special Issue Effects of Phytochemicals on Metabolic Disorders and Human Health)

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13 pages, 2407 KiB

Open AccessArticle

Antihypertensive Effects of an Optimized Aged Garlic Extract in Subjects with Grade I Hypertension and Antihypertensive Drug Therapy: A Randomized, Triple-Blind Controlled Trial

by José C. E. Serrano, Eva Castro-Boqué, Alicia García-Carrasco, María Inés Morán-Valero, Daniel González-Hedström, Marcelino Bermúdez-López, José Manuel Valdivielso, Alberto E. Espinel and Manuel Portero-Otín

Nutrients 2023, 15(17), 3691; https://doi.org/10.3390/nu15173691 - 23 Aug 2023

Cited by 1 | Viewed by 3190

Abstract

The use of garlic (Allium sativum) for treating arterial hypertension has been recognized as effective for several decades. However, tolerance to treatment is low, and several technological modifications have been developed to improve its tolerability, such as the aging process at controlled temperature and humidity. This study aims to validate the antihypertensive effects of an optimized extract of aged black garlic with low doses of s-allyl-cysteine (SAC) in a Grade I hypertensive population with drug treatment. A randomized, triple-blind, placebo-controlled parallel trial was developed, where a daily supplementation with 0.25 mg/day of SAC for 12 weeks was performed. A reduction in systolic and diastolic blood pressure of 1.8 mmHg (0.7 to 4.1 95% CI) and 1.5 mmHg (0.3 to 3.0 95% CI), respectively, was observed. Similarly, an increase in blood nitric oxide (10.3 µM, 1.1 to 19.5 95% CI) and antioxidant capacity (7 × 10⁻³ µM TE/min, (1.2 to 13 × 10⁻³ 95% CI) and a reduction in uric acid levels (−0.3 mg/dL, −0.5 to −0.001 95% CI) and ACE activity (−9.3 U/L; −18.4 to −0.4 95% CI) were observed. No changes in endothelial function and inflammatory cytokines were observed. It was concluded that low-dose SAC supplementation in an optimized black-garlic extract allows for an extra-significant reduction in blood pressure in a Grade I hypertensive population receiving drug treatment. Full article

(This article belongs to the Special Issue Effects of Phytochemicals on Metabolic Disorders and Human Health)

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20 pages, 2009 KiB

Open AccessArticle

Bile Acids and Short-Chain Fatty Acids Are Modulated after Onion and Apple Consumption in Obese Zucker Rats

by Claudia Balderas, Begoña de Ancos and Concepción Sánchez-Moreno

Nutrients 2023, 15(13), 3035; https://doi.org/10.3390/nu15133035 - 05 Jul 2023

Viewed by 1756

Abstract

Gut microorganisms are involved in the development and severity of different cardiovascular diseases, and increasing evidence has indicated that dietary fibre and polyphenols can interact with the intestinal microbiota. The study objective was to investigate the effect of onion and apple intake on the major types of microbial-derived molecules, such as short-chain fatty acids (SCFAs) and bile acids (BAs). Obese Zucker rats were randomly assigned (n = eight rats/group) to a standard diet (OC), a standard diet/10% onion (OO), or a standard diet/10% apple (OA). Lean Zucker rats fed a standard diet served as a lean control (LC) group. Faecal samples were collected at baseline, and 8 weeks later, the composition of the microbial community was measured, and BA and SCFA levels were determined using high-performance liquid chromatography–mass spectrometry (HPLC-MS) and gas chromatography–mass spectrometry (GC-MS), respectively. Rats fed onion- and apple-enriched diets had increased abundance of beneficial bacteria, such as Bifidobacterium spp. and Lactobacillus spp., enhanced SCFAs (acetic, propionic, isobutyric, and valeric acids), decreased excretion of some BAs, mainly of the primary (CA, α-MCA, and β-MCA) and secondary type (ω-MCA, HDCA, NCA, DCA, and LCA), and increased amount of taurine- and glycine-conjugated BAs compared to the OC group. The contribution of specific bioactive compounds and their metabolites in the regulation of the microbiome and the pathways linked to SCFA and BA formation and their relationship with some diseases needs further research. Full article

(This article belongs to the Special Issue Effects of Phytochemicals on Metabolic Disorders and Human Health)

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28 pages, 829 KiB

Open AccessReview

Vaccinium as Potential Therapy for Diabetes and Microvascular Complications

by Hui Huang, Yayong Luo, Qian Wang, Yihan Zhang, Zhongxia Li, Ruikun He, Xiangmei Chen and Zheyi Dong

Nutrients 2023, 15(9), 2031; https://doi.org/10.3390/nu15092031 - 23 Apr 2023

Cited by 4 | Viewed by 2330

Abstract

Diabetes mellitus is one of the most critical global health concerns, with a fast-growing prevalence. The incidence of diabetic vascular complications is also rapidly increasing, exacerbating the burden on individuals with diabetes and the consumption of public medical resources. Despite the overall improvements in the prevention, diagnosis, and treatment of diabetic microvascular complications in recent years, safe and effective alternative or adjunctive therapies are urgently needed. The mechanisms underlying diabetic vascular complications are complex, with hyperglycemia-induced oxidative stress and inflammation being the leading causes. Therefore, glycemic control, antioxidation, and anti-inflammation are considered the main targets for the treatment of diabetes and its vascular comorbidities. Vaccinium L. (Ericaceae) is a genus of plants enriched with polyphenolic compounds in their leaves and fruits. Vaccinium and its extracts have demonstrated good bioactivity in reducing blood glucose, oxidative stress, and inflammation, making them excellent candidates for the management of diabetes and diabetic vascular complications. Here, we review recent preclinical and clinical studies on the potential effect of Vaccinium on ameliorating diabetes and diabetic complications, particularly diabetic kidney disease and diabetic retinopathy. Full article

(This article belongs to the Special Issue Effects of Phytochemicals on Metabolic Disorders and Human Health)

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