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Nutraceuticals, Bioactive Compounds and Functional Foods: Their Role in Chronic Diseases

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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: closed (25 April 2025) | Viewed by 11532

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Dr. María D. Navarro-Hortal

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Guest Editor

Department of Physiology, Institute of Nutrition and Food Technology "José Mataix Verdú", Biomedical Research Centre, University of Granada, 18016 Armilla, Spain
Interests: aging; natural products; neurodegenerative diseases; nutrition; redox biology

Dr. Alfonso Varela-López

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Guest Editor

Department of Physiology, Institute of Nutrition and Food Technology "José Mataix Verdú", Biomedical Research Centre, University of Granada, 18016 Armilla, Spain
Interests: aging; mitochondria; redox biology; foods; nutrition; age-related diseases; oral health
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Special Issue Information

Dear Colleagues,

In recent years, the intersection of nutrition, health, and disease prevention has garnered increasing attention from scholars and practitioners. As life expectancy increases globally, so does the burden of noncommunicable diseases, also known as chronic diseases. This underscores the urgent need to implement strategies to reduce their occurrence and negative impacts. Among the primary chronic diseases are cardiovascular diseases, cancer, diabetes, and chronic respiratory diseases.

The advent of nutraceuticals, bioactive compounds, and functional foods represents a promising frontier in combating chronic diseases. Nutraceuticals, characterized by their therapeutic properties, offer a novel approach to complementing traditional healthcare practices. Similarly, bioactive compounds found abundantly in various natural sources possess remarkable potential in modulating biological processes implicated in chronic diseases. Moreover, functional foods fortified with specific nutrients or bioactive ingredients present a convenient and accessible means of promoting health and wellbeing.

The Special Issue “Nutraceuticals, Bioactive Compounds and Functional Foods: Their Role in Chronic Diseases” of Nutrients aims to explore the multifaceted roles of bioactive compounds and foods in addressing a spectrum of chronic ailments, ranging from cardiovascular diseases and diabetes to cancer and neurodegenerative disorders. Contributions to this Special Issue, in the form of original research, both in vitro and in vivo, as well as review or meta-analysis articles are welcome.

Dr. María D. Navarro-Hortal
Dr. Alfonso Varela-López
Guest Editors

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Keywords

bioactive compounds
polyphenols
nutraceuticals
nutrition
foods
diet
chronic diseases
cardiovascular diseases
pulmonary disease chronic obstructive
autoimmune diseases
inflammatory bowel diseases
chronic kidney disease
fatty liver
neoplasms
neurodegenerative diseases
diabetes mellitus
chronic periodontitis

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Published Papers (7 papers)

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Research

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20 pages, 2369 KiB

Open AccessArticle

TOTUM-854 Human Circulating Bioactives Preserve Endothelial Cell Function

by Fabien Wauquier, Doriane Ripoche, Line Boutin-Wittrant, Yolanda F. Otero, Stéphanie Krisa, Josep Valls, Mahéva Maura, Florian Le Joubioux, Thierry Maugard, Gaëtan Bolea, Grégory Meyer, Cyril Reboul, Véronique Roux, Nicolas Macian, Gisèle Pickering, Bruno Pereira, Maxime Bargetto, Véronique Sapone, Murielle Cazaubiel, Sébastien Peltier, Pascal Sirvent and Yohann Wittrant Show full author list Hide full author list

Nutrients 2025, 17(8), 1331; https://doi.org/10.3390/nu17081331 - 11 Apr 2025

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Abstract

Background: TOTUM-854 is a patented plant extract blend characterized by its components that have previously been described for their potential health benefits in limiting hypertension onset. However, most of the literature data remain descriptive regarding the mode of action at the cellular level, especially in humans, and further investigations are required for optimized therapeutic strategies. Methods: We first demonstrated in an L-NAME mouse model that TOTUM-854 supports the prevention of hypertension in vitro and in vivo. Then, we designed an ex vivo clinical innovative approach considering the circulating metabolites produced by the digestive tract upon TOTUM-854 ingestion in humans. Human serum was collected in healthy volunteers before and after the acute intake of 3.71 g of TOTUM-854. The bioavailability of circulating metabolites was confirmed and characterized by UPLC-MS. Human serum containing TOTUM-854-derived metabolites was further processed for incubation with human endothelial cells (HUVECs), in the absence or presence of palmitate (200 µM). Results: HUVEC protection against lipotoxicity was characterized by (1) decreased ACE-1 activity (−32% p < 0.0001); (2) the inhibition of oxidative stress with decreased ROS (−12% observed by DCFDA and DHE fluorescent microscopy) and decreased Nox2 gene expression (−6.7 fold change vs. palmitate, p < 0.01); and (3) the inhibition of an inflammatory response, with a decrease in IL-1β release (−37% compared to palmitate, p < 0.001) and decreased MCP-1 and VCAM-1 gene expression (−93% p < 0.001 and −77% p < 0.001, respectively). Conclusions: Overall, this study provides insightful data regarding the protective role of TOTUM-854 in human endothelial cells. Using an innovative clinical ex vivo approach, our data support the role of TOTUM-854 circulating metabolites in vascular protection in humans. Full article

(This article belongs to the Special Issue Nutraceuticals, Bioactive Compounds and Functional Foods: Their Role in Chronic Diseases)

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18 pages, 1773 KiB

Open AccessArticle

Dose-Dependent Effects of Short-Chain Fatty Acids on 3T3-L1 Adipocyte Adipokine Secretion and Metabolic Function

by Ala Alzubi, Hannah X. Glowacki, Jessie L. Burns, Kelsey Van, Jamie L. A. Martin and Jennifer M. Monk

Nutrients 2025, 17(3), 571; https://doi.org/10.3390/nu17030571 - 4 Feb 2025

Viewed by 1197

Abstract

Background: Short-chain fatty acids (SCFAs) produced from microbial fermentation of non-digestible carbohydrates and protein have been shown to modulate adipocyte adipokine secretion and metabolic function, which has implications for mitigating dysfunction in obese adipose tissue; however, the individual effects of different SCFAs and the optimal concentration required is unknown. The purpose of this study was to dose-dependently determine the effects of individual SCFAs on adipocyte adipokine secretion and metabolic function. Methods: We recapitulated the obese adipocyte inflammatory conditions using mature 3T3-L1 adipocytes and a physiological concentration of lipopolysaccharide (LPS) ± individual SCFAs, namely acetate, propionate, and butyrate, in a dose-dependent manner (0.25 mM, 0.5 mM, and 1 mM) for 24 h. Results: SCFAs dose-dependently affected inflammatory adipokine secretion, wherein at 1 mM, all three SCFAs reduced the secretion of leptin, IL-6 and IL-1β, but only propionate and butyrate reduced MCP-1/CCL2 and MIP-1α/CCL3 compared to control (p < 0.05). Interestingly, 1 mM acetate increased RANTES/CCL5 secretion versus control, whereas propionate and butyrate decreased RANTES/CCL5 secretion, and only 1 mM propionate reduced MCP-3/CCL7 secretion (p < 0.05). At the lower 0.5 mM concentration, both propionate and butyrate reduced IL-6 and IL-1β secretion compared to control (p < 0.05), and there was no difference in adipokine secretion between groups at the 0.25 mM SCFA concentration (p > 0.05). Intracellular protein expression in the ratio of phosphorylated–to–total STAT3 was reduced by all SCFAs at 1 mM and by propionate and butyrate at 0.5 mM versus control (p < 0.05). The ratio fo phosphorylated–to–total NFκB p65 expression was reduced by propionate and butyrate at 1 mM and by butyrate alone at 0.5 mM compared to control (p < 0.05). Basal (no insulin stimulation) and insulin-stimulated glucose uptake did not differ between control and any 1 mM SCFA treatment conditions (p > 0.05). Conclusions: Individual SCFAs exert different dose-dependent effects on LPS-stimulated adipocyte function. Full article

(This article belongs to the Special Issue Nutraceuticals, Bioactive Compounds and Functional Foods: Their Role in Chronic Diseases)

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15 pages, 3522 KiB

Open AccessArticle

Resveratrol Butyrate Esters Reduce Hypertension in a Juvenile Rat Model of Chronic Kidney Disease Exacerbated by Microplastics

by Yi-Ning Huang, Chien-Ning Hsu, Chih-Yao Hou, Shin-Yu Chen and You-Lin Tain

Nutrients 2024, 16(23), 4076; https://doi.org/10.3390/nu16234076 - 27 Nov 2024

Cited by 1 | Viewed by 1259

Abstract

Background: Resveratrol is recognized as a promising nutraceutical with antihypertensive and prebiotic properties; however, its bioavailability in vivo is limited. To enhance its bioactivity, we developed resveratrol butyrate esters (RBEs). This study investigates whether RBEs can mitigate hypertension induced by chronic kidney disease (CKD) and exacerbated by microplastics (MPs) exposure in juvenile rats. Methods: Three-week-old male Sprague Dawley rats were fed either regular chow or 0.5% adenine chow for three weeks. The adenine-fed CKD rats (N = 8 per group) received either 5 μM MPs (10 mg/L) or MPs combined with RBE (25 mg/L) in their drinking water from weeks 3 to 9. Results: Our results indicate that MP exposure worsened CKD-induced hypertension, while RBE treatment resulted in a reduction in systolic BP by 15 mmHg (155 ± 2 mmHg vs. 140 ± 1 mmHg, p < 0.05). The combined exposure to adenine and MPs was associated with nitric oxide (NO) deficiency, which RBE treatment alleviated. Additionally, our findings revealed that RBE modulated both the classical and nonclassical renin–angiotensin system (RAS), contributing to its protective effects. We also observed changes in gut microbiota composition, increased butyric acid levels, and elevated renal GPR41 expression associated with RBE treatment. Conclusions: In conclusion, in this juvenile rat model of combined CKD and MP exposure, RBE demonstrates antihypertensive effects by modulating NO levels, the RAS, gut microbiota, and their metabolites. Full article

(This article belongs to the Special Issue Nutraceuticals, Bioactive Compounds and Functional Foods: Their Role in Chronic Diseases)

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Review

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23 pages, 314 KiB

Open AccessReview

Molecular Mechanisms and Therapeutic Potential of Mulberry Fruit Extract in High-Fat Diet-Induced Male Reproductive Dysfunction: A Comprehensive Review

by Kannika Adthapanyawanich, Kanyakorn Aitsarangkun Na Ayutthaya, Siriporn Kreungnium, Peter J. Mark, Hiroki Nakata, Wai Chen, Kroekkiat Chinda, Patcharada Amatyakul and Yutthapong Tongpob

Nutrients 2025, 17(2), 273; https://doi.org/10.3390/nu17020273 - 13 Jan 2025

Viewed by 1947

Abstract

High-fat diet (HFD)-induced obesity represents a significant challenge to male reproductive health, affecting approximately 13% of the global adult population. This comprehensive review synthesizes current evidence regarding mulberry (Morus alba L.) fruit extract’s therapeutic potential for HFD-induced male reproductive dysfunction. Through comprehensive analysis of the peer-reviewed literature from multiple databases (PubMed, Web of Science, Scopus, and Google Scholar; 2005–2024), we evaluated mulberry extract’s effects on testicular morphology, spermatogenesis, sperm parameters, and the underlying molecular mechanisms. Mechanistic studies reveal that standardized mulberry extract mediates protective effects through multiple pathways: enhanced antioxidant enzyme activities (SOD: +45%, Catalase: +38%, GPx: +35%), reduced inflammatory markers (TNF-α: −64%, IL-6: −58%), and modulated NF-κB signaling (−42.3%). These effects are facilitated by mulberry’s rich phytochemical profile, particularly anthocyanins (2.92–5.35 mg/g dry weight) and polyphenols (4.23–6.38 mg/g). The extract demonstrates particular efficacy in preserving seminiferous tubule integrity and maintaining blood-testis barrier function, with treated groups maintaining up to 85% of normal tubular architecture compared to HFD controls. Key molecular mechanisms include AMPK/SIRT1 pathway activation (2.3-fold increase), enhanced mitochondrial function (67% increase in mtDNA copy number), and epigenetic regulation of metabolic pathways. Temporal analysis indicates optimal therapeutic effects after 28 days of treatment, with initial improvements observable within 14 days. While current evidence is promising, limitations include predominant reliance on rodent models and lack of standardized extraction protocols. Future research priorities include well-designed human clinical trials, standardization of preparation methods, and investigation of potential synergistic effects with other therapeutic agents. This comprehensive review indicates that mulberry extract is a promising therapeutic candidate for obesity-related male infertility, warranting further clinical investigation. Full article

(This article belongs to the Special Issue Nutraceuticals, Bioactive Compounds and Functional Foods: Their Role in Chronic Diseases)

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25 pages, 1571 KiB

Open AccessReview

Renal Outcomes and Other Adverse Effects of Cannabinoid Supplementation

by Ewelina Młynarska, Natalia Kustosik, Maja Mejza, Zuzanna Łysoń, Dawid Delebis, Jakub Orliński, Jacek Rysz and Beata Franczyk

Nutrients 2025, 17(1), 59; https://doi.org/10.3390/nu17010059 - 27 Dec 2024

Viewed by 1697

Abstract

This narrative review explores the benefits and risks of cannabinoids in kidney health, particularly in individuals with pre-existing renal conditions. It discusses the roles of cannabinoid receptor ligands (phytocannabinoids, synthetic cannabinoids, and endocannabinoids) in kidney physiology. The metabolism and excretion of these substances are also highlighted, with partial elimination occurring via the kidneys. The effects of cannabinoids on kidney function are examined, emphasizing both their potential to offer nephroprotection and the risks they may pose, such as cannabinoid hyperemesis syndrome and ischemia-reperfusion injury. These complexities underscore the intricate interactions between cannabinoids and renal health. Furthermore, this review highlights the association between chronic synthetic cannabinoid use and acute kidney injury, stressing the need for further research into their mechanisms and risks. This article also highlights the growing prevalence of edible cannabis and hemp seed consumption, emphasizing their nutritional benefits, legal regulations, and challenges such as inconsistent labeling, potential health risks, and implications for kidney health. The review delves into the roles of CB1 and CB2 receptors in diabetic nephropathy, chronic kidney disease, and obesity-related kidney dysfunction, discussing the therapeutic potential of CB2 agonists and CB1 antagonists. Additionally, it examines the potential diuretic and anti-inflammatory effects of cannabinoids in preventing kidney stones, suggesting that cannabinoids could reduce crystal retention and lower the risk of stone formation. Cannabinoids’ effects on kidneys depend heavily on the characteristics of individual substances, as synthetic cannabinoids pose a major threat to the health of users. Cannabinoids offer therapeutic potential but require more research to confirm their benefits. Distinguishing between therapeutic cannabinoids and harmful synthetic variants is crucial for safe clinical application. Full article

(This article belongs to the Special Issue Nutraceuticals, Bioactive Compounds and Functional Foods: Their Role in Chronic Diseases)

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18 pages, 765 KiB

Open AccessReview

Polyphenol Intervention Ameliorates Non-Alcoholic Fatty Liver Disease: An Updated Comprehensive Systematic Review

by Yazan Ranneh, Alaa S. Bedir, Abdelghafar M. Abu-Elsaoud and Seham Al Raish

Nutrients 2024, 16(23), 4150; https://doi.org/10.3390/nu16234150 - 29 Nov 2024

Cited by 4 | Viewed by 1598

Abstract

Non-alcoholic fatty liver disease (NAFLD) has recently emerged as a challenging metabolic disorder with a strong emphasis on its prevention and management. Polyphenols, a group of naturally occurring plant compounds, have been associated with a decreased risk of various metabolic disorders related to NAFLD. The current systematic review aims to critically assess evidence about the ameliorative effect of polyphenol supplementation on NAFLD patients. A PRISMA systematic search appraisal was conducted in PubMed, Scopus, Web of Science Core Collection, and all relevant studies published prior to April 2024 and met the inclusion criteria were included. Twenty-nine randomized clinical trials (RCTs) comprised 1840 NAFLD patients. The studies primarily examined eleven phenolic compounds, including turmeric, curcumin, resveratrol, genistein, catechin, green tea extract, hesperidin, and silymarin. Turmeric and curcumin decreased liver enzymes, inflammatory cytokines, lipid profile, insulin resistance, and NAFLD score, while resveratrol did not present consistent results across all the studies. Most studies on silymarin showed a reduction in liver enzymes and lipid profile; however, no changes were observed in inflammatory cytokine levels. The dietary supplementation of hesperidin and naringenin or green tea extract caused improvements in liver enzyme, lipid profile, and inflammatory cytokine, while genistein supplementation did not modulate blood lipid profile. In conclusion, dietary supplementation of polyphenols could potentially prevent and ameliorate NAFLD. Still, the inconsistent results across the included RCTs require further clinical research to establish optimal dosage and duration. Full article

(This article belongs to the Special Issue Nutraceuticals, Bioactive Compounds and Functional Foods: Their Role in Chronic Diseases)

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35 pages, 848 KiB

Open AccessReview

Nutritional Strategies for Chronic Craniofacial Pain and Temporomandibular Disorders: Current Clinical and Preclinical Insights

by Kajita Piriyaprasath, Yoshito Kakihara, Mana Hasegawa, Yuya Iwamoto, Yoko Hasegawa, Noritaka Fujii, Kensuke Yamamura and Keiichiro Okamoto

Nutrients 2024, 16(17), 2868; https://doi.org/10.3390/nu16172868 - 27 Aug 2024

Viewed by 2863

Abstract

This narrative review provides an overview of current knowledge on the impact of nutritional strategies on chronic craniofacial pain associated with temporomandibular disorders (TMDs). Individuals experiencing painful TMDs alter their dietary habits, avoiding certain foods, possibly due to chewing difficulties, which might lead to nutrient deficiencies. Our literature investigation revealed that the causal links between nutritional changes and craniofacial pain remain unclear. However, clinical and preclinical studies suggest that nutraceuticals, including vitamins, minerals, polyphenols, omega-3 fatty acids, isoprenoids, carotenoids, lectins, polysaccharides, glucosamines, and palmitoylethanolamides, could have beneficial effects on managing TMDs. This is described in 12 clinical and 38 preclinical articles since 2000. Clinical articles discussed the roles of vitamins, minerals, glucosamine, and palmitoylethanolamides. The other nutraceuticals were assessed solely in preclinical studies, using TMD models, mostly craniofacial inflammatory rodents, with 36 of the 38 articles published since 2013. Our investigation indicates that current evidence is insufficient to assess the efficacy of these nutraceuticals. However, the existing data suggest potential for therapeutic intervention in TMDs. Further support from longitudinal and randomized controlled studies and well-designed preclinical investigations is necessary to evaluate the efficacy of each nutraceutical intervention and understand their underlying mechanisms in TMDs. Full article

(This article belongs to the Special Issue Nutraceuticals, Bioactive Compounds and Functional Foods: Their Role in Chronic Diseases)

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