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Molecular Mechanisms of Bioactive Nutrients Promoting Human Health

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

Deadline for manuscript submissions: 20 August 2025 | Viewed by 14711

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Prof. Dr. Baojun Xu

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Guest Editor

Food Science and Technology Program, Department of Life Sciences, Beijing Normal-Hong Kong Baptist University, Zhuhai 519087, China
Interests: food science; phytochemicals; nutraceuticals; pharmaceuticals; functional foods; molecular nutrition; cell biology
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Dear Colleagues,

Substantial evidence has supported that cellular oxidative damage and chronic neuroinflammation are the potential mechanisms involved in the onset and development of non-communicable diseases, including obesity, diabetes, cancers, and even neurodegenerative disease. Some bioactive nutrients, such as phytochemicals, antioxidant enzymes, peptides, polysaccharides, prebiotics, probiotics, essential fatty acids, rare amino acids, minerals, and vitamins, have positive effects on human health and could reduce the likelihood of developing numerous diseases, probably attributed to their antioxidative and anti-inflammatory properties. However, the underlying mechanism of how natural bioactive components respond to chronic human disease damage is unclear. In this Special Issue, we aim to present the latest findings, including in vitro, animal, or clinical studies, relating to the health-promoting role of bioactive nutrients or their cellular signaling and molecular mechanism in response to disease prevention.

Prof. Dr. Baojun Xu
Guest Editor

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Keywords

bioactive nutrients
antioxidants
anti-inflammatory
disease prevention
molecular mechanisms

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Published Papers (8 papers)

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Research

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14 pages, 3789 KiB

Open AccessArticle

Anti-Obesity Effects of LB-GABA

by Hyein Han, Gunju Song, Jongwon Kim, Heegu Jin and Boo-Yong Lee

Int. J. Mol. Sci. 2025, 26(8), 3554; https://doi.org/10.3390/ijms26083554 - 10 Apr 2025

Viewed by 300

Abstract

Obesity is characterized by an excessive imbalance in energy metabolism and is associated with metabolic syndrome. Mammals have two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). These are key factors in regulating the energy balance. Strategies aimed at reducing obesity should encompass not only the prevention of lipid accumulation but also the stimulation of browning in both WAT and BAT, with the aim of enhancing energy expenditure. In this study, the mechanism by which Lactobacillus brevis-fermented gamma-aminobutyric acid (LB-GABA) prevents obesity was investigated, as well as whether it induces lipolysis and browning in WAT using 3T3-L1 adipocytes. The expression of proteins involved in signaling pathways regulating lipid accumulation and degradation, as well as browning, was measured using Western blotting analysis. We demonstrated that LB-GABA significantly inhibited lipid accumulation by suppressing adipogenesis and lipogenesis. In addition, the microscopic analysis of WAT demonstrated that LB-GABA reduced the adipocyte size and the number of lipid droplets. Moreover, Western blot analysis revealed that GABA increased lipolysis and activated the protein kinase A (PKA) signaling pathway, which promotes uncoupling protein 1 (UCP1)-mediated WAT browning. In conclusion, these results suggest that LB-GABA activates energy expenditure through lipid metabolism regulation and exerts anti-obesity effects. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Human Health)

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18 pages, 10541 KiB

Open AccessArticle

Enhanced Anti-Cancer Potential: Investigating the Combined Effects with Coriolus versicolor Extract and Phosphatidylinositol 3-Kinase Inhibitor (LY294002) In Vitro

by Tomasz Jędrzejewski, Justyna Sobocińska, Bartosz Maciejewski, Marcela Slovakova and Sylwia Wrotek

Int. J. Mol. Sci. 2025, 26(4), 1556; https://doi.org/10.3390/ijms26041556 - 12 Feb 2025

Viewed by 697

Abstract

Coriolus versicolor (CV), known in traditional Chinese medicine for over 2000 years, is currently used in China and Japan to reduce chemotherapy or radiotherapy side effects in cancer patients. Despite extensive research, its effects still need improvement. This study aimed to determine if combining CV extract with LY294002, an inhibitor of the phosphatidylinositol-3-kinase (PI3K) signalling pathway, enhances cancer cell treatment, potentially leading to a novel therapeutic approach. Three human cancer cell lines (MCF-7, HeLa, and A549) were treated with CV extract alone or combined with LY294002. Cell viability was assessed using MTT assays. Then, HeLa and MCF-7 cells most sensitive to the co-treatment were used to evaluate colony formation, apoptosis, cell cycle, cell migration and invasion, and phospho-PI3K expression. The results demonstrated that LY294002 enhanced the CV extract’s anti-tumour effects by reducing cell viability and colony formation. The combined treatment with CV extract and LY294002 more effectively induced G0/G1 cell cycle arrest, promoted apoptosis, reduced cell invasion and migration, and inhibited phospho-PI3K expression compared to each agent alone. This study highlights the potent cytotoxic enhancement between CV extract and LY294002 on cancer cells, primarily by inhibiting phospho-PI3K expression. These findings suggest promising avenues for developing novel combination therapies targeting cancer. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Human Health)

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14 pages, 3774 KiB

Open AccessArticle

Anti-Influenza A Potential of Tagetes erecta Linn. Extract Based on Bioinformatics Analysis and In Vitro Assays

by Minjee Kim, Aleksandra Nowakowska, Jaebum Kim and Young Bong Kim

Int. J. Mol. Sci. 2024, 25(13), 7065; https://doi.org/10.3390/ijms25137065 - 27 Jun 2024

Viewed by 1501

Abstract

Tagetes erecta Linn. (TE) is traditionally used to treat cardiovascular, renal, and gastrointestinal diseases. In this study, we investigated the active compounds and targets of TE extract that may exert antiviral effects against influenza A. Active compounds and targets of TE extract were identified using the Traditional Chinese Medicine Systems Pharmacology database (TCSMP). The influenza A-related gene set was screened using GeneCards and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein–protein interaction (PPI) network was built to establish the hub targets. Pathway and target studies were conducted using Gene Expression Omnibus (GEO). The interactions between active compounds and potential targets were assessed by molecular docking. An in vitro study was performed using antiviral and plaque reduction assays. From the compound and target search, we identified 6 active compounds and 95 potential targets. We retrieved 887 influenza-associated target genes and determined 14 intersecting core targets between TE and influenza. After constructing a compound–target network, we discovered lutein and beta-carotene to be the key compounds. Next, PPI network analysis identified the top three hub genes associated with influenza (IL-6, HIF1A, and IL-1β). Similarly, GEO analysis revealed IL-6, TGFB1, and CXCL8 to be the top three target genes. In our docking study, we identified that lutein and IL-6 had the strongest bindings. Our in vitro experimental results revealed that the TE extract exhibited therapeutic rather than prophylactic effects on influenza disease. We identified lutein as a main active compound in TE extract, and IL-6 as an important target associated with influenza, by using data mining and bioinformatics. Our in vitro findings indicated that TE extract exerted protective properties against the influenza A virus. We speculated that lutein, as a key active component in TE extract, is largely responsible for its antiviral effects. Therefore, we suggest TE extract as an alternative in the treatment of influenza. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Human Health)

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15 pages, 5587 KiB

Open AccessArticle

Assessing the Potential of an Enzymatically Liberated Salmon Oil to Support Immune Health Recovery from Acute SARS-CoV-2 Infection via Change in the Expression of Cytokine, Chemokine and Interferon-Related Genes

by Crawford Currie, Tor Åge Myklebust, Christian Bjerknes and Bomi Framroze

Int. J. Mol. Sci. 2024, 25(13), 6917; https://doi.org/10.3390/ijms25136917 - 24 Jun 2024

Viewed by 2546

Abstract

Cytokines, chemokines, and interferons are released in response to viral infection with the ultimate aim of viral clearance. However, in SARS-CoV-2 infection, there is an imbalanced immune response, with raised cytokine levels but only a limited interferon response with inefficient viral clearance. Furthermore, the inflammatory response can be exaggerated, which risks both acute and chronic sequelae. Several observational studies have suggested a reduced risk of progression to severe COVID-19 in subjects with a higher omega-3 index. However, randomized studies of omega-3 supplementation have failed to replicate this benefit. Omega-3 fats provide important anti-inflammatory effects; however, fatty fish contains many other fatty acids that provide health benefits distinct from omega-3. Therefore, the immune health benefit of whole salmon oil (SO) was assessed in adults with mild to moderate COVID-19. Eleven subjects were randomized to best supportive care (BSC) with or without a full spectrum, enzymatically liberated SO, dosed at 4g daily, for twenty-eight days. Nasal swabs were taken to measure the change in gene expression of markers of immune response and showed that the SO provided both broad inflammation-resolving effects and improved interferon response. The results also suggest improved lung barrier function and enhanced immune memory, although the clinical relevance needs to be assessed in longer-duration studies. In conclusion, the salmon oil was well tolerated and provided broad inflammation-resolving effects, indicating a potential to enhance immune health. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Human Health)

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17 pages, 2493 KiB

Open AccessArticle

Oat Beta-Glucan as a Metabolic Regulator in Early Stage of Colorectal Cancer—A Model Study on Azoxymethane-Treated Rats

by Jacek Wilczak, Adam Prostek, Katarzyna Dziendzikowska, Małgorzata Gajewska, Łukasz Kopiasz, Joanna Harasym, Michał Oczkowski and Joanna Gromadzka-Ostrowska

Int. J. Mol. Sci. 2024, 25(9), 4635; https://doi.org/10.3390/ijms25094635 - 24 Apr 2024

Cited by 1 | Viewed by 1731

Abstract

Factors that reduce the risk of developing colorectal cancer include biologically active substances. In our previous research, we demonstrated the anti-inflammatory, immunomodulatory, and antioxidant effects of oat beta-glucans in gastrointestinal disease models. The aim of this study was to investigate the effect of an 8-week consumption of a diet supplemented with low-molar-mass oat beta-glucan in two doses on the antioxidant potential, inflammatory parameters, and colonic metabolomic profile in azoxymethane(AOM)-induced early-stage colorectal cancer in the large intestine wall of rats. The results showed a statistically significant effect of AOM leading to the development of neoplastic changes in the colon. Consumption of beta-glucans induced changes in colonic antioxidant potential parameters, including an increase in total antioxidant status, a decrease in the superoxide dismutase (SOD) activity, and a reduction in thiobarbituric acid reactive substance (TBARS) concentration. In addition, beta-glucans decreased the levels of pro-inflammatory interleukins (IL-1α, IL-1β, IL-12) and C-reactive protein (CRP) while increasing the concentration of IL-10. Metabolomic studies confirmed the efficacy of oat beta-glucans in the AOM-induced early-stage colon cancer model by increasing the levels of metabolites involved in metabolic pathways, such as amino acids, purine, biotin, and folate. In conclusion, these results suggest a wide range of mechanisms involved in altering colonic metabolism during the early stage of carcinogenesis and a strong influence of low-molar-mass oat beta-glucan, administered as dietary supplement, in modulating these mechanisms. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Human Health)

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22 pages, 4661 KiB

Open AccessArticle

Chicoric Acid Effectively Mitigated Dextran Sulfate Sodium (DSS)-Induced Colitis in BALB/c Mice by Modulating the Gut Microbiota and Fecal Metabolites

by Jiani Yang, Jie Lin, Ting Gu, Quancai Sun, Weidong Xu and Ye Peng

Int. J. Mol. Sci. 2024, 25(2), 841; https://doi.org/10.3390/ijms25020841 - 10 Jan 2024

Cited by 6 | Viewed by 2858

Abstract

Chicoric acid (CA) has been reported to exhibit biological activities; it remains unclear, however, whether CA could regulate colitis via modulation of the gut microbiota and metabolites. This study aimed to assess CA’s impact on dextran sulfate sodium (DSS)-induced colitis, the gut microbiota, and metabolites. Mice were induced with 2.5% DSS to develop colitis over a 7-day period. CA was administered intragastrically one week prior to DSS treatment and continued for 14 days. The microbial composition in the stool was determined using 16S rRNA sequencing, while non-targeted metabolomics was employed to analyze the metabolic profiles of each mouse group. The results show that CA effectively alleviated colitis, as evidenced by an increased colon length, lowered disease activity index (DAI) and histological scores, and decreased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels. CA intervention restored the structure of gut microbiota. Specifically, it decreased the abundance of Bacteroidetes and Cyanobacteria at the phylum level and Bacteroides, Rosiarcus, and unclassified Xanthobacteraceae at the genus level, and increased the abundance of unclassified Lachnospiraceae at the genus level. Metabolomic analysis revealed that CA supplementation reversed the up-regulation of asymmetric dimethylarginine, N-glycolylneuraminic acid, and N-acetylneuraminic acid, as well as the down-regulation of phloroglucinol, thiamine, 4-methyl-5-thiazoleethanol, lithocholic acid, and oxymatrine induced by DSS. Our current research provides scientific evidence for developing CA into an anti-colitis functional food ingredient. Further clinical trials are warranted to elucidate the efficacy and mechanism of CA in treating human inflammatory bowel disease (IBD). Full article

(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Human Health)

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Review

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29 pages, 1588 KiB

Open AccessReview

The Potential of Superoxide Dismutase-Rich Tetraselmis chuii as a Promoter of Cellular Health

by Stuart P. Cocksedge, Lalia Mantecón, Enrique Castaño, Carlos Infante and Stephen J. Bailey

Int. J. Mol. Sci. 2025, 26(4), 1693; https://doi.org/10.3390/ijms26041693 - 16 Feb 2025

Viewed by 957

Abstract

Tetraselmis chuii (T. chuii) is a green, marine, eukaryotic, microalgae that was authorized in the European Union (EU) as a novel food for human consumption in 2014, and as a food supplement in 2017. This narrative review will provide an overview of preclinical and clinical trials assessing the efficacy of a T. chuii-derived ingredient, characterized by a high superoxide dismutase (SOD) activity (SOD-rich T. chuii), to improve various aspects of cellular health. Collectively, results from in vitro, and more importantly in vivo research, support SOD-rich T. chuii as a potential promoter of cellular health. Principally, the ingredient appears to function as an indirect antioxidant by boosting intracellular antioxidant systems. Moreover, it can positively modulate inflammatory status by up-regulating anti-inflammatory and down-regulating pro-inflammatory cytokines and factors. In addition, SOD-rich T. chuii appears to promote cellular health though protecting from DNA damage, boosting immune function, strengthening cell structure and integrity, and positively modulating cell signaling pathways. There is also some evidence to suggest that SOD-rich T. chuii may improve aspects of mitochondrial function through the up-regulation of genes linked to mitochondrial biogenesis and ATP synthesis. From the trials conducted to date, transcriptional activation of nuclear factor erythroid 2-related factor 2 (NRF2) and sirtuin 1 (SIRT1) appear to be important in mediating the effects of SOD-rich T. chuii on cellular health. These exciting preliminary observations suggest that SOD-rich T. chuii may represent a natural blue food supplement with the potential to enhance various aspects of cellular health. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Human Health)

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41 pages, 1424 KiB

Open AccessReview

Double-Edged Sword Effect of Diet and Nutrition on Carcinogenic Molecular Pathways in Breast Cancer

by Anca-Narcisa Neagu, Claudiu-Laurentiu Josan, Taniya M. Jayaweera, Krishan Weraduwage, Niyogushima Nuru and Costel C. Darie

Int. J. Mol. Sci. 2024, 25(20), 11078; https://doi.org/10.3390/ijms252011078 - 15 Oct 2024

Cited by 2 | Viewed by 2409

Abstract

Environmental exposure to a mixture of chemical xenobiotics acts as a double-edged sword, promoting or suppressing tumorigenesis and the development of breast cancer (BC). Before anything else, we are what we eat. In this review, we highlight both “the good” and “the bad” sides of the daily human diet and dietary patterns that could influence BC risk (BCR) and incidence. Thus, regularly eating new, diversified, colorful, clean, nutrient-rich, energy-boosting, and raw food, increases apoptosis and autophagy, antioxidation, cell cycle arrest, anti-inflammation, and the immune response against BC cells. Moreover, a healthy diet could lead to a reduction in or the inhibition of genomic instability, BC cell stemness, growth, proliferation, invasion, migration, and distant metastasis. We also emphasize that, in addition to beneficial compounds, our food is more and more contaminated by chemicals with harmful effects, which interact with each other and with endogenous proteins and lipids, resulting in synergistic or antagonistic effects. Thus, a healthy and diverse diet, combined with appropriate nutritional behaviors, can exert anti-carcinogenic effects and improve treatment efficacy, BC patient outcomes, and the overall quality of life of BC patients. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Human Health)

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