Nutrients

Editorial

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5 pages, 202 KiB

Open AccessEditorial

Effects of Phytochemicals on Metabolic Diseases and Human Health

by María Ángeles Martín and Sonia Ramos

Nutrients 2024, 16(24), 4323; https://doi.org/10.3390/nu16244323 - 14 Dec 2024

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Abstract

Metabolic diseases constitute a worldwide health concern because of their increasing prevalence and associated mortality [...] Full article

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

Research

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12 pages, 2769 KiB

Open AccessArticle

(E)-5-hydroxy-7-methoxy-3-(2-hydroxybenzyl)-4-chromanone, a Major Homoisoflavonoid, Attenuates Free Fatty Acid-Induced Hepatic Steatosis by Activating AMPK and PPARα Pathways in HepG2 Cells

by Jae-Eun Park and Ji-Sook Han

Nutrients 2024, 16(20), 3475; https://doi.org/10.3390/nu16203475 - 14 Oct 2024

Viewed by 856

Abstract

Background: (E)-5-hydroxy-7-methoxy-3-(2-hydroxybenzyl)-4-chromanone (HMC), a homoisoflavonoid isolated from Portulaca oleracea, has significant anti-adipogenesis potential; it regulates adipogenic transcription factors. However, whether HMC improves hepatic steatosis in hepatocytes remains vague. This study investigated whether HMC ameliorates hepatic steatosis in free fatty acid-treated [...] Read more.

Background: (E)-5-hydroxy-7-methoxy-3-(2-hydroxybenzyl)-4-chromanone (HMC), a homoisoflavonoid isolated from Portulaca oleracea, has significant anti-adipogenesis potential; it regulates adipogenic transcription factors. However, whether HMC improves hepatic steatosis in hepatocytes remains vague. This study investigated whether HMC ameliorates hepatic steatosis in free fatty acid-treated human hepatocellular carcinoma (HepG2) cells, and if so, its mechanism of action was analyzed. Methods: Hepatic steatosis was induced by a free fatty acid mixture in HepG2 cells. Thereafter, different HMC concentrations (10, 30, and 50 µM) or fenofibrate (10 µM, a PPARα agonist, positive control) was treated in HepG2 cells.Results: HMC markedly decreased lipid accumulation and triglyceride content in free fatty acid-treated HepG2 cell; it (10 and 50 μM) markedly upregulated protein expressions of pAMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. HMC (10 and 50 μM) markedly inhibited the expression of sterol regulatory element-binding protein-1c, fatty acid synthase, and stearoyl-coA desaturase 1, which are the enzymes involved in lipid synthesis. Furthermore, HMC (10 and 50 μM) markedly upregulated the protein expression of peroxisome proliferator-activated receptor alpha (PPARα) and enhanced the protein expressions of carnitine palmitoyl transferase 1 and acyl-CoA oxidase 1. Conclusion: HMC inhibits lipid accumulation and promotes fatty acid oxidation by AMPK and PPARα pathways in free fatty acid-treated HepG2 cells, thereby attenuating hepatic steatosis. Full article

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

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13 pages, 2157 KiB

Open AccessArticle

1,2-Dicinnamoyl-sn-glycero-3-phosphocholine Improves Insulin Sensitivity and Upregulates mtDNA-Encoded Genes in Insulin-Resistant 3T3-L1 Adipocytes: A Preliminary Study

by Aneta Cierzniak, Anna Gliszczyńska and Małgorzata Małodobra-Mazur

Nutrients 2024, 16(18), 3163; https://doi.org/10.3390/nu16183163 - 19 Sep 2024

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Abstract

Background: Insulin resistance is a condition characterized by a reduced biological response to insulin. It is one of the most common metabolic diseases in modern civilization. Numerous natural substances have a positive effect on metabolism and energy homeostasis including restoring the proper sensitivity [...] Read more.

Background: Insulin resistance is a condition characterized by a reduced biological response to insulin. It is one of the most common metabolic diseases in modern civilization. Numerous natural substances have a positive effect on metabolism and energy homeostasis including restoring the proper sensitivity to insulin. There may be several possible mechanisms of action. In the present study, we elucidated two natural compounds with an impact on insulin signaling in IR adipocytes involving mitochondria. Methods: Mature 3T3-L1 adipocytes with artificially induced insulin resistance by palmitic acid (16:0) were used for the study. Cinnamic acid and 1,2-dicinnamoyl-sn-glycero-3-phosphocholin (1,2-diCA-PC) were tested at three concentrations: 25 μM, 50 μM, and 125 μM. The number of mitochondria and the expression of genes encoded by mtDNA were elucidated in control and experimental cells. Results: Experimental cells treated with 1,2-diCA-PC displayed increased insulin-stimulated glucose uptake in a dose-dependent manner, accompanied by an increase in mtDNA copy number. Moreover, in experimental cells treated with 1,2-diCA-PC at a concentration of 125 μM, a significant increase in the expression level of all analyzed genes encoded by mtDNA compared to control cells was observed. Our study showed a relationship between improved cellular sensitivity to insulin by 1,2-diCA-PC and an increase in the number of mitochondria and expression levels of genes encoded by mtDNA. Conclusions: To summarize, the results suggest the therapeutic potential of cinnamic acid derivative 1,2-diCA-PC to enhance the insulin sensitivity of adipocytes. Full article

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

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19 pages, 4397 KiB

Open AccessArticle

Cocoa and Carob Supplementation, Alone or in Combination with Metformin, Protects against Hepatorenal Injury in Zucker Diabetic Fatty Rats

by Esther García-Díez, María Elvira López-Oliva, Jara Pérez-Jiménez, María Ángeles Martín and Sonia Ramos

Nutrients 2024, 16(18), 3087; https://doi.org/10.3390/nu16183087 - 13 Sep 2024

Viewed by 929

Abstract

The liver and kidneys are crucial for glucose homeostasis and are seriously damaged in diabetes. Cocoa and carob possess antidiabetic activity, but their hepatorenal protective effects, especially when combined with antidiabetic drugs, are unknown. The aim of this study is to investigate the [...] Read more.

The liver and kidneys are crucial for glucose homeostasis and are seriously damaged in diabetes. Cocoa and carob possess antidiabetic activity, but their hepatorenal protective effects, especially when combined with antidiabetic drugs, are unknown. The aim of this study is to investigate the effects of a cocoa–carob-supplemented diet (CC), either alone or in combination with metformin, on liver and kidney damage in Zucker diabetic fatty (ZDF) rats, a type 2 diabetes model. Male ZDF animals received a control or CC-supplemented diet, with or without metformin, and Zucker lean rats were fed the control diet. The CC-supplemented diet improved glucose tolerance and insulin resistance and alleviated functional and structural alterations in the diabetic liver and renal cortex. The CC-supplemented diet also ameliorated oxidative stress, downregulated apoptosis, and improved insulin signalling and glucose homeostasis. The combination of CC and metformin boosted several benefits as certain parameters related to morphological and structural alterations, apoptosis, oxidative stress, glucose homeostasis, and insulin resistance, were improved in comparison to animals receiving the CC-supplemented diet or metformin alone; these include the following: apoptotic index, Bax, hepatic insulin receptor or glutathione content, among others. These results demonstrate that the CC-supplemented diet alleviates the hepatorenal damage in type 2 diabetic ZDF rats, highlighting its potential alone or as an adjuvant therapy. Full article

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

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17 pages, 3385 KiB

Open AccessArticle

Effect of a Phytochemical-Rich Olive-Derived Extract on Anthropometric, Hematological, and Metabolic Parameters

by Anna Aiello, Luana Calabrone, Douglas M. Noonan, Paola Corradino, Sara Nofri, Simone Cristoni, Giulia Accardi, Giuseppina Candore, Calogero Caruso, Angelo Zinellu and Adriana Albini

Nutrients 2024, 16(18), 3068; https://doi.org/10.3390/nu16183068 - 11 Sep 2024

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Abstract

Background: Extra virgin olive oil is a fundamental component of the Mediterranean diet. It contains several molecules that sustain human well-being by modulating cellular metabolism and exerting antioxidant, anti-inflammatory, and anti-ageing effects to protect normal tissues, and it can exert anti-angiogenic and pro-apoptotic [...] Read more.

Background: Extra virgin olive oil is a fundamental component of the Mediterranean diet. It contains several molecules that sustain human well-being by modulating cellular metabolism and exerting antioxidant, anti-inflammatory, and anti-ageing effects to protect normal tissues, and it can exert anti-angiogenic and pro-apoptotic effects on cancer cells. Metabolites found in different parts of the olive tree, including leaves, also possess properties that might help in cancer prevention and promote wellness in aging. Olive mill wastewater (OMWW), a liquid residue produced during olive oil extraction, represents an environmental issue. However, it is rich in phytochemicals with potential beneficial properties. Dietary supplements based on OMWW can be produced for nutritional supplementation with advantages to the ecology. Purpose: This work aims to measure hematochemical, anthropometric, and metabolomic parameters in volunteers taking an OMWW dietary supplement, Oliphenolia^® (OMWW-OL). Methods: The supplementation of OMWW-OL 25 mL twice daily for 30 days was tested on a pilot cohort of volunteers with characteristics close to metabolic syndrome. Hematochemical, anthropometric, serum biomarkers and serum metabolomic parameters were analyzed before the intervention, at 30 days, and 30 days after stopping consumption. Results: A total of 29 volunteers were enrolled, and 23 completed the study. The participants’ parameters at baseline were measured, and then twice daily at 30 days of treatment and 30 days after assumption discontinuation. Although treatment was with an olive derivative, their weight did not increase. Their body mass index, instead of augmenting, slightly decreased, particularly in the women. Also, hydration increased, especially in the women, while blood pressure, glycemia, and insulin decreased. Cholesterol, high-density lipoproteins, and triglycerides were stable, and LDL levels decreased, while vitamin D levels, alongside calcium, perceptibly increased. Albumin also increased. All the values were in support of an equilibrium, with no damaging effects. By mass spectrometry analysis, we also found favorable changes in the vitamin D/histamine and homocysteine/methionine ratios, an increase in a new metabolite of unknown formula, and the vitamin D/unknown metabolite ratio. Conclusions: Supplementation of OMWW-OL has no detrimental effects and might imply the beneficial modulation of several biological parameters. Although this is a small pilot study, with limited potency, it preliminarily suggests that the OMWW extract use could be potentially valuable for people at risk of metabolic syndrome. Some of these parameters could also be relevant in supporting healthy ageing and in cancer prevention. Full article

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

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26 pages, 27412 KiB

Open AccessArticle

Effects of Evodiamine on Behavior and Hippocampal Neurons through Inhibition of Angiotensin-Converting Enzyme and Modulation of the Renin Angiotensin Pathway in a Mouse Model of Post-Traumatic Stress Disorder

by Zhixing Wang, Chengcai Lai, Baoying Shen, Bowei Li, Junru Chen, Xin Shen, Zhengping Huang, Chunqi Yang and Yue Gao

Nutrients 2024, 16(12), 1957; https://doi.org/10.3390/nu16121957 - 19 Jun 2024

Viewed by 1341

Abstract

Post-traumatic stress disorder (PTSD) is a persistent psychiatric condition that arises following exposure to traumatic events such as warfare, natural disasters, or other catastrophic incidents, typically characterized by heightened anxiety, depressive symptoms, and cognitive dysfunction. In this study, animals subjected to single prolonged [...] Read more.

Post-traumatic stress disorder (PTSD) is a persistent psychiatric condition that arises following exposure to traumatic events such as warfare, natural disasters, or other catastrophic incidents, typically characterized by heightened anxiety, depressive symptoms, and cognitive dysfunction. In this study, animals subjected to single prolonged stress (SPS) were administered evodiamine (EVO) and compared to a positive control group receiving sertraline. The animals were then assessed for alterations in anxiety, depression, and cognitive function. Histological analysis was conducted to examine neuronal changes in the hippocampus. In order to predict the core targets and related mechanisms of evodiamine intervention in PTSD, network pharmacology was used. The metabolic markers pre- and post-drug administration were identified using nontargeted serum metabolomics techniques, and the intersecting Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were screened. Finally, the core targets were validated through molecular docking, enzyme-linked immunosorbent assays, and immunofluorescence staining to confirm the anti-PTSD effects and mechanisms of these targets. As well as improving cognitive impairment, evodiamine reversed anxiety- and depression-like behaviors. It also inhibited the reduction in the number of hippocampal neuronal cells and Nissl bodies in SPS mice inhibited angiotensin converting enzyme (ACE) levels in the hippocampus of SPS mice, and modulated the renin angiotensin pathway and its associated serum metabolites in brain tissue. Evodiamine shows promise as a potential candidate for alleviating the symptoms of post-traumatic stress disorder. Full article

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

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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

Cited by 3 | Viewed by 1849

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 [...] Read more.

(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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9 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

Cited by 3 | Viewed by 2837

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 [...] Read more.

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

Cited by 2 | Viewed by 1802

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 [...] Read more.

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 - 21 Dec 2023

Cited by 1 | Viewed by 1747

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 [...] Read more.

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 - 9 Dec 2023

Cited by 1 | Viewed by 2361

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 [...] Read more.

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 6 | Viewed by 5833

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, [...] Read more.

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 6 | Viewed by 6678

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 [...] Read more.

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 - 5 Jul 2023

Cited by 4 | Viewed by 2650

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 [...] Read more.

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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33 pages, 810 KiB

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Flavan-3-ols and Vascular Health: Clinical Evidence and Mechanisms of Action

by Justyna Godos, Giovanni Luca Romano, Samuele Laudani, Lucia Gozzo, Ida Guerrera, Irma Dominguez Azpíroz, Raquel Martínez Diaz, José L. Quiles, Maurizio Battino, Filippo Drago, Francesca Giampieri, Fabio Galvano and Giuseppe Grosso

Nutrients 2024, 16(15), 2471; https://doi.org/10.3390/nu16152471 - 30 Jul 2024

Cited by 3 | Viewed by 1859

Abstract

Cardiovascular diseases (CVDs) are one of the main causes of mortality and morbidity worldwide. A healthy diet rich in plant-derived compounds such as (poly)phenols appears to have a key role in improving cardiovascular health. Flavan-3-ols represent a subclass of (poly)phenols of great interest [...] Read more.

Cardiovascular diseases (CVDs) are one of the main causes of mortality and morbidity worldwide. A healthy diet rich in plant-derived compounds such as (poly)phenols appears to have a key role in improving cardiovascular health. Flavan-3-ols represent a subclass of (poly)phenols of great interest for their possible health benefits. In this review, we summarized the results of clinical studies on vascular outcomes of flavan-3-ol supplementation and we focused on the role of the microbiota in CVD. Clinical trials included in this review showed that supplementation with flavan-3-ols mostly derived from cocoa products significantly reduces blood pressure and improves endothelial function. Studies on catechins from green tea demonstrated better results when involving healthy individuals. From a mechanistic point of view, emerging evidence suggests that microbial metabolites may play a role in the observed effects. Their function extends beyond the previous belief of ROS scavenging activity and encompasses a direct impact on gene expression and protein function. Although flavan-3-ols appear to have effects on cardiovascular health, further studies are needed to clarify and confirm these potential benefits and the rising evidence of the potential involvement of the microbiota. 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

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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 6 | Viewed by 3248

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 [...] Read more.

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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