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The Mechanism of Action of Food Components in Disease Prevention 2022

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 (15 October 2023) | Viewed by 16702

Special Issue Editors


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Guest Editor
Institute of Food Science, Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), Jose Antonio Novais 10, 28040 Madrid, Spain
Interests: grains; peptides; phenolic compounds; nutritional characterization; protein quality and digestibility; bioavailability of food compounds; bioactivity; germination; fermentation; enzymatic treatments
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Guest Editor
Department of Bioactivity and Food Analysis, Institute of Food Science Research (CIAL, CSIC-UAM, CEI UAM+CSIC), Nicolás Cabrera 9, 28049 Madrid, Spain
Interests: bioactive peptides; food proteins; multifuncionality; digestion; bioavailability; inflammation-associated diseases; chemopreventive activity; peptidomics; antioxidant activity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chronic degenerative diseases continue to increase around the world, despite increased nutrition awareness. Obesity and type II diabetes have reached epidemic proportions in some countries. Despite increasing survival rates, cancer continues to be a social malady and an economic burden. Cancer impacts/has impacted most families in one way or another, and is a tremendous burden on the patient, the family, and society. The increase in cancer is being correlated with alterations in the environment, food habits, and lifestyles. The adoption of a healthy lifestyle can reduce the incidences of cancer development. Cancer has been claimed to be a preventable disease, as ~90% of cancer cases have a lifestyle or environmental related cause for origin, while only 5%–10% have impaired genetics as a causative factor. A diet enriched in fruits, vegetables, and their processed products is known to reduce the incidences of chronic diseases affecting several sites. Similarly, cardiovascular and cerebrovascular diseases can be prevented through an appropriate diet and lifestyle. Diet is a major source for several essential molecules that act in conjunction with antioxidant enzymes, providing protection from deleterious reactive oxygen species (ROS). Examples of these bioactives include vitamins, such as C, E; carotenoids, such as b-carotene (a precursor for vitamin A), lycopene, and xanthophylls; polyphenols (flavonoids, such as quercetin, catechin, naringenin, and anthocyanins, which include sugar derivatives of cyanidin, pelargonidin, petunidin, peonidin, and malvidin); and essential minerals, such as selenium and zinc (that act as cofactors for essential host pathway enzymes). However, a detailed understanding on the mechanism of action of nutraceuticals leading to disease prevention is needed.

Inflammation is being recognized as the initiation point for several forms of cancer and chronic diseases. Diet- and lifestyle-related risk factors, such as obesity, smoking, environmental pollutants, alcohol, irradiation, and a high fat diet, are known to be risk factors for cancer. A major link between risk factors and cancer is inflammation. The activation of major inflammatory pathways involving Nf-kB (nuclear factor kappa B), STAT3, etc., is associated with most cancers. In addition to the modulation of inflammation-related cytokine signaling and gene expression, nutraceuticals act through epigenetic mechanisms, including inhibition of histone deacetylases, micro RNAs, and the modulation of the CpG methylation of genes related to cancer development. MicroRNAs have become particularly attractive in oncology, as they are simple, stable molecules that are easy to detect in tissues and blood circulation. Increasing evidence suggests that miRNAs are involved in broad genomic processes, including the regulation of the expression of oncogenic and tumor-suppressive genes. As they are widely deregulated in cancer, miRNAs are therapeutic targets and promising diagnostic and prognostic markers of cellular growth, apoptosis, and inflammation. The greatest potential for miRNAs is their use as minimally invasive circulating biomarkers, alone or in combination with other molecules, promising to significantly improve the diagnostic and prognostic accuracy of cancer treatments and prevention. Inflammatory genes and miRNAs have causative roles in carcinogenesis, and together, they are ideal candidates as therapeutic and prevention targets. Plant polyphenols may deliver positive effects on health by regulating specific miRNA expression. The mechanism of regulation of selective miRNAs by polyphenols needs to be explored further. The up-regulation of miR-22 expression by curcumin suppresses the expression of the miR-22 target genes Sp1 and estrogen receptor 1 in human pancreatic cancer cells. Curcumin also reduces the miR-21 promoter activity and expression in primary colon cancer. Epigallocatechin gallate (EGCG) is a major green tea polyphenol that acts on cancer miR-16 to mediate apoptotic effects. Resveratrol modulates the levels of multiple miRNAs targeting genes of the TGFβ signaling pathway in SW480 colon cancer cells.

Polyphenols in the diet act in multiple ways, which include direct antioxidant action to scavenge cancer initiating free radicals, activation of the transcription of cytoprotective enzymes involved in the detoxification of xenobiotics, and the modulation of signal transduction systems. Antioxidants can activate the Keap1/Nrf2/ARE (Kelch ECH associating protein 1 /NF-E2-related factor 2/antioxidant response elements) pathway, resulting in an increased expression of phase 2 detoxification enzymes and antioxidant enzymes. Sulphoraphane in broccoli causes cytotoxicity and G2/M arrest in HT-29 colon cancer cells and MCF-7 breast cancer cells. The induction of apoptosis in cancer cells by sulphoraphane involves the activation of Bcl2 proteins Bax and Bak. Sulphoraphane causes inhibition of tubulin polymerization, activation of G2/M kinases and histone deacetylation resulting in cell cycle arrest and apoptosis. These mechanisms may enable sulphoraphane to inhibit carcinogenesis even after initiation. Thus, dietary antioxidants are compelling candidates for use as nutraceuticals in order to enhance the function of the antioxidant defense system during normal living conditions, thus preventing inflammation and decreasing the chances of developing chronic diseases.

Dr. Cristina Martínez-Villaluenga
Dr. Blanca Hernández-Ledesma
Guest Editors

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Keywords

  • inflammation
  • chronic diseases
  • diet and lifestyle
  • nutraceuticals and function

Published Papers (3 papers)

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Research

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22 pages, 2854 KiB  
Article
Antioxidant, Immunostimulatory, and Anticancer Properties of Hydrolyzed Wheat Bran Mediated through Macrophages Stimulation
by Irene Tomé-Sánchez, Cristina Martínez-Villaluenga, Ana Belén Martín-Diana, Daniel Rico, Iván Jiménez-Pulido, Juana Frias and Vermont P. Dia
Int. J. Mol. Sci. 2023, 24(8), 7436; https://doi.org/10.3390/ijms24087436 - 18 Apr 2023
Cited by 2 | Viewed by 1682
Abstract
Previous studies demonstrated that enzymatic hydrolysis enhances wheat bran (WB) biological properties. This study evaluated the immunostimulatory effect of a WB hydrolysate (HYD) and a mousse enriched with HYD (MH) before and after in vitro digestion on murine and human macrophages. The antiproliferative [...] Read more.
Previous studies demonstrated that enzymatic hydrolysis enhances wheat bran (WB) biological properties. This study evaluated the immunostimulatory effect of a WB hydrolysate (HYD) and a mousse enriched with HYD (MH) before and after in vitro digestion on murine and human macrophages. The antiproliferative activity of the harvested macrophage supernatant on colorectal cancer (CRC) cells was also analyzed. MH showed significantly higher content than control mousse (M) in soluble poly- and oligosaccharides (OLSC), as well as total soluble phenolic compounds (TSPC). Although in vitro gastrointestinal digestion slightly reduced the TSPC bioaccessibility of MH, ferulic acid (FA) levels remained stable. HYD showed the highest antioxidant activity followed by MH, which demonstrated a greater antioxidant activity before and after digestion as compared with M. RAW264.7 and THP-1 cells released the highest amounts of pro-inflammatory cytokines after being treated with 0.5 mg/mL of digested WB samples. Treatment with digested HYD-stimulated RAW264.7 supernatant for 96 h showed the most anticancer effect, and spent medium reduced cancer cell colonies more than direct WB sample treatments. Although a lack of inner mitochondrial membrane potential alteration was found, increased Bax:Bcl-2 ratio and caspase-3 expression suggested activation of the mitochondrial apoptotic pathway when CRC cells were treated with macrophage supernatants. Intracellular reactive oxygen species (ROS) were positively correlated with the cell viability in CRC cells exposed to RAW264.7 supernatants (r = 0.78, p < 0.05) but was not correlated in CRC cells treated with THP-1 conditioned media. Supernatant from WB-stimulated THP-1 cells may be able to stimulate ROS production in HT-29 cells, leading to a decrease of viable cells in a time-dependent manner. Therefore, our present study revealed a novel anti-tumour mechanism of HYD through the stimulation of cytokine production in macrophages and the indirect inhibition of cell proliferation, colony formation, and activation of pro-apoptotic proteins expression in CRC cells. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention 2022)
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13 pages, 742 KiB  
Article
Sourdough Fermentation Improves the Antioxidant, Antihypertensive, and Anti-Inflammatory Properties of Triticum dicoccum
by Morena Gabriele, Nafiou Arouna, Július Árvay, Vincenzo Longo and Laura Pucci
Int. J. Mol. Sci. 2023, 24(7), 6283; https://doi.org/10.3390/ijms24076283 - 27 Mar 2023
Cited by 7 | Viewed by 2924
Abstract
The fermentation process has been widely used to improve plant-based foods’ nutritional and nutraceutical properties. This study aimed to investigate and compare the impact of sourdough fermentation on the bioactive content and profile, antioxidant and antihypertensive activities, as well as the anti-inflammatory properties [...] Read more.
The fermentation process has been widely used to improve plant-based foods’ nutritional and nutraceutical properties. This study aimed to investigate and compare the impact of sourdough fermentation on the bioactive content and profile, antioxidant and antihypertensive activities, as well as the anti-inflammatory properties of fermented (FS) and non-fermented (NFS) flour from Tuscan Triticum dicoccum wheat (spelt) on tumor necrosis factor-alpha (TNF-α)-inflamed human intestinal epithelial cells (HT-29). FS showed significantly higher total phenolic and flavonoid content, in vitro and ex vivo antioxidant activities, and ACE-inhibitory activities than NFS. Gallic acid was identified by HPLC-DAD as the most representative polyphenol, followed by rutin, trans-ferulic acid, iso-quercitrin, and quercetin, in the fermented spelt sample. Instead, rutin and gallic acid were identified as the predominant compounds in the non-fermented ones. Moreover, FS exhibited a better protective effect on inflamed HT-29 cells by significantly counteracting the TNFα-induced alterations, lowering the expression of IL-8, COX-2, and ICAM-1 inflammatory mediator while enhancing antioxidant enzyme HO-1 gene expression. In conclusion, sourdough fermentation positively affected the nutraceutical and functional properties of spelt, which may represent a valuable ingredient for the formulation of functional foods and a key product for managing hypertension and inflammatory intestinal diseases. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention 2022)
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28 pages, 912 KiB  
Review
From Cocoa to Chocolate: Effect of Processing on Flavanols and Methylxanthines and Their Mechanisms of Action
by Luis Goya, John Edem Kongor and Sonia de Pascual-Teresa
Int. J. Mol. Sci. 2022, 23(22), 14365; https://doi.org/10.3390/ijms232214365 - 18 Nov 2022
Cited by 27 | Viewed by 11434
Abstract
Despite the health benefits associated with the ingestion of the bioactive compounds in cocoa, the high concentrations of polyphenols and methylxanthines in the raw cocoa beans negatively influence the taste, confer the astringency and bitterness, and affect the stability and digestibility of the [...] Read more.
Despite the health benefits associated with the ingestion of the bioactive compounds in cocoa, the high concentrations of polyphenols and methylxanthines in the raw cocoa beans negatively influence the taste, confer the astringency and bitterness, and affect the stability and digestibility of the cocoa products. It is, therefore, necessary to process cocoa beans to develop the characteristic color, taste, and flavor, and reduce the astringency and bitterness, which are desirable in cocoa products. Processing, however, affects the composition and quantities of the bioactive compounds, resulting in the modification of the health-promoting properties of cocoa beans and chocolate. In this advanced review, we sought to better understand the effect of cocoa’s transformational process into chocolate on polyphenols and methylxanthine and the mechanism of action of the original flavanols and methylxanthines. More data on the cocoa processing effect on cocoa bioactives are still needed for better understanding the effect of each processing step on the final polyphenolic and methylxanthine composition of chocolate and other cocoa products. Regarding the mechanisms of action, theobromine acts through the modulation of the fatty acid metabolism, mitochondrial function, and energy metabolism pathways, while flavanols mainly act though the protein kinases and antioxidant pathways. Both flavanols and theobromine seem to be involved in the nitric oxide and neurotrophin regulation. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention 2022)
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