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Special Issue "The Mechanism of Action of Food Components in Disease Prevention 2020"

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: 31 March 2022.

Special Issue Editor

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.

Prof. Dr. Gopinadhan Paliyath
Guest Editor

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Keywords

  • Inflammation
  • Chronic diseases
  • Diet and lifestyle
  • Nutraceuticals and function

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Published Papers (9 papers)

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Research

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Article
Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni
Int. J. Mol. Sci. 2021, 22(16), 8872; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168872 - 18 Aug 2021
Viewed by 601
Abstract
Infections by the zoonotic foodborne bacterium Campylobacter jejuni (C. jejuni) are among the most frequent causes of bacterial gastroenteritis worldwide. The aim was to evaluate the relationship between epithelial barrier disruption, mucosal immune activation, and vitamin D (VD) treatment during C. [...] Read more.
Infections by the zoonotic foodborne bacterium Campylobacter jejuni (C. jejuni) are among the most frequent causes of bacterial gastroenteritis worldwide. The aim was to evaluate the relationship between epithelial barrier disruption, mucosal immune activation, and vitamin D (VD) treatment during C. jejuni infection, using intestinal epithelial cells and mouse models focused on the interaction of C. jejuni with the VD signaling pathway and VD treatment to improve C. jejuni-induced barrier dysfunction. Our RNA-Seq data from campylobacteriosis patients demonstrate inhibition of VD receptor (VDR) downstream targets, consistent with suppression of immune function. Barrier-preserving effects of VD addition were identified in C. jejuni-infected epithelial cells and IL-10−/− mice. Furthermore, interference of C. jejuni with the VDR pathway was shown via VDR/retinoid X receptor (RXR) interaction. Paracellular leakiness of infected epithelia correlated with tight junction (TJ) protein redistribution off the TJ domain and apoptosis induction. Supplementation with VD reversed barrier impairment and prevented inhibition of the VDR pathway, as shown by restoration of transepithelial electrical resistance and fluorescein (332 Da) permeability. We conclude that VD treatment restores gut epithelial barrier functionality and decreases bacterial transmigration and might, therefore, be a promising compound for C. jejuni treatment in humans and animals. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention 2020)
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Article
Fenugreek (Trigonella Foenum-Graecum) Seed Flour and Diosgenin Preserve Endothelium-Dependent Arterial Relaxation in a Rat Model of Early-Stage Metabolic Syndrome
Int. J. Mol. Sci. 2018, 19(3), 798; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19030798 - 10 Mar 2018
Cited by 13 | Viewed by 2208
Abstract
Fenugreek is a common herb possessing several bioactive components including diosgenin. Here, dietary fenugreek seed flour and diosgenin were evaluated on a model of endothelium-dependent vasorelaxation by abdominal aortas isolated from rats receiving high-fat, high-sugar diet (HFHSD). 60 male Wistar rats were randomized [...] Read more.
Fenugreek is a common herb possessing several bioactive components including diosgenin. Here, dietary fenugreek seed flour and diosgenin were evaluated on a model of endothelium-dependent vasorelaxation by abdominal aortas isolated from rats receiving high-fat, high-sugar diet (HFHSD). 60 male Wistar rats were randomized into six groups: (i) negative control getting conventional rat feed regimen; (ii) positive control receiving HFHSD; (iii) a test group fed 2 g/kg bw/day fenugreek seed flour (containing 10 mg/kg bw/day diosgenin) + HFHSD; (iv) three test groups fed 1, 10 and 50 mg/kg bw/day diosgenin + HFHSD. Alimentary treatments were carried out for six weeks. The abdominal aortas were isolated, and 2 mm wide rings were sectioned off and mounted at a resting tension of 10 mN in organ baths containing Krebs solution (36 °C) exposed to 95% O2 and 5% CO2. After 60-min incubation, a norepinephrine concentration-response (E/c) curve was generated to determine their half-maximal effective concentration (EC50) value. After 60-min wash-out, a pre-contraction with norepinephrine EC50 was made, followed by an acetylcholine E/c curve. Plasma glutathione levels, glutathione-handling enzyme activities and blood antioxidant capacities were also determined. HFHSD significantly decreased the dilatory response to acetylcholine and increased plasma glutathione levels and these effects were significantly reversed by fenugreek seed flour, 10 and 50 mg/kg bw/day diosgenin. Both fenugreek and diosgenin treatments prevent HFHSD-induced endothelial dysfunction and redox changes. As fenugreek treatment was more effective at lower acetylcholine concentrations than diosgenin treatments, components of fenugreek other than diosgenin may contribute to the beneficial effects of dietary fenugreek seed flour. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention 2017)
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Article
Insulin-Sensitizer Effects of Fenugreek Seeds in Parallel with Changes in Plasma MCH Levels in Healthy Volunteers
Int. J. Mol. Sci. 2018, 19(3), 771; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19030771 - 08 Mar 2018
Cited by 5 | Viewed by 2485
Abstract
In developed, developing and low-income countries alike, type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases, the severity of which is substantially a consequence of multiple organ complications that occur due to long-term progression of the disease before diagnosis [...] Read more.
In developed, developing and low-income countries alike, type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases, the severity of which is substantially a consequence of multiple organ complications that occur due to long-term progression of the disease before diagnosis and treatment. Despite enormous investment into the characterization of the disease, its long-term management remains problematic, with those afflicted enduring significant degradation in quality-of-life. Current research efforts into the etiology and pathogenesis of T2DM, are focused on defining aberrations in cellular physiology that result in development of insulin resistance and strategies for increasing insulin sensitivity, along with downstream effects on T2DM pathogenesis. Ongoing use of plant-derived naturally occurring materials to delay the onset of the disease or alleviate symptoms is viewed by clinicians as particularly desirable due to well-established efficacy and minimal toxicity of such preparations, along with generally lower per-patient costs, in comparison to many modern pharmaceuticals. A particularly attractive candidate in this respect, is fenugreek, a plant that has been used as a flavouring in human diet through recorded history. The present study assessed the insulin-sensitizing effect of fenugreek seeds in a cohort of human volunteers, and tested a hypothesis that melanin-concentrating hormone (MCH) acts as a critical determinant of this effect. A test of the hypothesis was undertaken using a hyperinsulinemic euglycemic glucose clamp approach to assess insulin sensitivity in response to oral administration of a fenugreek seed preparation to healthy subjects. Outcomes of these evaluations demonstrated significant improvement in glucose tolerance, especially in patients with impaired glucose responses. Outcome data further suggested that fenugreek seed intake-mediated improvement in insulin sensitivity correlated with reduction in MCH levels. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention 2017)
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Article
Epigallocatechin Gallate Reduces Ischemia/Reperfusion Injury in Isolated Perfused Rabbit Hearts
Int. J. Mol. Sci. 2018, 19(2), 628; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19020628 - 23 Feb 2018
Cited by 8 | Viewed by 2491
Abstract
Cardioplegic arrest during heart operations is often used in cardiac surgery. During cardioplegia, the heart is subjected to a global ischemia/reperfusion-injury. (−)-epigallocatechin gallate (EGCG), one of the main ingredients of green tea, seems to be beneficial in various cardiac diseases. Therefore, the aim [...] Read more.
Cardioplegic arrest during heart operations is often used in cardiac surgery. During cardioplegia, the heart is subjected to a global ischemia/reperfusion-injury. (−)-epigallocatechin gallate (EGCG), one of the main ingredients of green tea, seems to be beneficial in various cardiac diseases. Therefore, the aim of our study was to evaluate EGCG in a rabbit model of cardioplegic arrest. Twenty four mature Chinchilla rabbits were examined. Rabbit hearts were isolated and perfused according to Langendorff. After induction of cardioplegia (without and with 20 µmol/L EGCG, n = 6 each) the hearts maintained arrested for 90-min. Thereafter, the hearts were re-perfused for 60 min. During the entire experiment hemodynamic and functional data were assessed. At the end of each experiment, left ventricular samples were processed for ATP measurements and for histological analysis. Directly after cessation of cardioplegia, all hearts showed the same decline in systolic and diastolic function. However, hearts of the EGCG-group showed a significantly faster and better hemodynamic recovery during reperfusion. In addition, tissue ATP-levels were significantly higher in the EGCG-treated hearts. Histological analysis revealed that markers of nitrosative and oxidative stress were significantly lower in the EGCG group. Thus, addition of EGCG significantly protected the cardiac muscle from ischemia/reperfusion injury. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention 2017)
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Article
Lycopene Attenuates Tulathromycin and Diclofenac Sodium-Induced Cardiotoxicity in Mice
Int. J. Mol. Sci. 2018, 19(2), 344; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19020344 - 24 Jan 2018
Cited by 30 | Viewed by 3261
Abstract
Recent experiments showed a potential cardiotoxic effect of the macrolide antibiotic (tulathromycin). This study was performed to investigate whether diclofenac sodium (DFS) potentiates the cardiotoxicity of tulathromycin and increases the cardioprotective effects of lycopene against DFS and tulathromycin. Seven groups (eight per group) [...] Read more.
Recent experiments showed a potential cardiotoxic effect of the macrolide antibiotic (tulathromycin). This study was performed to investigate whether diclofenac sodium (DFS) potentiates the cardiotoxicity of tulathromycin and increases the cardioprotective effects of lycopene against DFS and tulathromycin. Seven groups (eight per group) of adult Swiss albino mice received saline (control), tulathromycin (a single subcutaneous dose of 28 mg/kg/bw on day 14), DFS (a single oral dose of 100 mg/kg/bw on day 14), tulathromycin plus DFS, or lycopene (oral, 10 mg/kg/bw daily for 15 d) combined with tulathromycin, DFS, or both. Compared to the control group, the administration of tulathromycin or DFS (individually or in combination) caused significantly elevated (p < 0.05) serum levels of Creatine kinase-myocardial B fraction (CK-MB), lactate dehydrogenase, and cardiac-specific troponin-T and tissue levels of nitric oxide and malondialdehyde that were accompanied by significantly decreased tissue reduced glutathione content and glutathione peroxidase, superoxide dismutase, and catalase antioxidant enzyme activity. Upon histopathological and immunohistochemical examination, the mean pathology scores and the percentages of caspase-3-, Bax-, and CK-positive regions were significantly higher in the tulathromycin- and/or DFS-treated groups than in control mice. For all these parameters, the pathological changes were more significant in the tulathromycin–DFS combination group than in mice treated with either drug individually. Interestingly, co-administration of lycopene with tulathromycin and/or DFS significantly ameliorated the changes described above. In conclusion, DFS could potentiate the cardiotoxic effects of tulathromycin, whereas lycopene can serve as a cardioprotective agent against DFS and tulathromycin. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention 2017)
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Article
Spirulina maxima Extract Ameliorates Learning and Memory Impairments via Inhibiting GSK-3β Phosphorylation Induced by Intracerebroventricular Injection of Amyloid-β 1–42 in Mice
Int. J. Mol. Sci. 2017, 18(11), 2401; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18112401 - 13 Nov 2017
Cited by 18 | Viewed by 3304
Abstract
Spirulina maxima, a microalga containing high levels of protein and many polyphenols, including chlorophyll a and C-phycocyanin, has antioxidant and anti-inflammatory therapeutic effects. However, the mechanisms where by Spirulina maxima ameliorates cognitive disorders induced by amyloid-β 1–42 (Aβ1–42) are not [...] Read more.
Spirulina maxima, a microalga containing high levels of protein and many polyphenols, including chlorophyll a and C-phycocyanin, has antioxidant and anti-inflammatory therapeutic effects. However, the mechanisms where by Spirulina maxima ameliorates cognitive disorders induced by amyloid-β 1–42 (Aβ1–42) are not fully understood. In this study, we investigated whether a 70% ethanol extract of Spirulina maxima (SM70EE) ameliorated cognitive impairments induced by an intracerebroventricular injection of Aβ1–42 in mice. SM70EE increased the step-through latency time in the passive avoidance test and decreased the escape latency time in the Morris water maze test in Aβ1–42-injected mice. SM70EE reduced hippocampal Aβ1–42 levels and inhibited amyloid precursor protein processing-associated factors in Aβ1–42-injected mice. Additionally, acetylcholinesterase activity was suppressed by SM70EE in Aβ1–42-injected mice. Hippocampal glutathione levels were examined to determine the effects of SM70EE on oxidative stress in Aβ1–42-injected mice. SM70EE increased the levels of glutathione and its associated factors that were reduced in Aβ1–42-injected mice. SM70EE also promoted activation of the brain-derived neurotrophic factor/phosphatidylinositol-3 kinase/serine/threonine protein kinase signaling pathway and inhibited glycogen synthase kinase-3β phosphorylation. These findings suggested that SM70EE ameliorated Aβ1–42-induced cognitive impairments by inhibiting the increased phosphorylation of glycogen synthase kinase-3β caused by intracerebroventricular injection of Aβ1–42 in mice. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention 2017)
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Review

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Review
Gut Microbiota and Type 1 Diabetes
Int. J. Mol. Sci. 2018, 19(4), 995; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19040995 - 27 Mar 2018
Cited by 52 | Viewed by 5025
Abstract
Recently, the onset of type 1 diabetes (T1D) has increased rapidly and became a major public health concern worldwide. Various factors are associated with the development of T1D, such as diet, genome, and intestinal microbiota. The gastrointestinal (GI) tract harbors a complex and [...] Read more.
Recently, the onset of type 1 diabetes (T1D) has increased rapidly and became a major public health concern worldwide. Various factors are associated with the development of T1D, such as diet, genome, and intestinal microbiota. The gastrointestinal (GI) tract harbors a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host homeostasis and metabolic diseases. Recent evidence shows that altered gut bacterial composition (dysbiosis) is highly associated with the pathogenesis of insulin dysfunction and T1D and, thus, targeting gut microbiota may serve as a therapeutic potential for T1D patients. In this study, we updated the effect of gut microbiota on T1D and potential mechanisms were discussed. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention 2017)
Review
Dietary Plants for the Prevention and Management of Kidney Stones: Preclinical and Clinical Evidence and Molecular Mechanisms
Int. J. Mol. Sci. 2018, 19(3), 765; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19030765 - 07 Mar 2018
Cited by 53 | Viewed by 9204
Abstract
Kidney stones are one of the oldest known and common diseases in the urinary tract system. Various human studies have suggested that diets with a higher intake of vegetables and fruits play a role in the prevention of kidney stones. In this review, [...] Read more.
Kidney stones are one of the oldest known and common diseases in the urinary tract system. Various human studies have suggested that diets with a higher intake of vegetables and fruits play a role in the prevention of kidney stones. In this review, we have provided an overview of these dietary plants, their main chemical constituents, and their possible mechanisms of action. Camellia sinensis (green tea), Rubus idaeus (raspberry), Rubia cordifolia (common madder), Petroselinum crispum (parsley), Punica granatum (pomegranate), Pistacia lentiscus (mastic), Solanum xanthocarpum (yellow-fruit nightshade), Urtica dioica (stinging nettle), Dolichos biflorus (horse gram), Ammi visnaga (khella), Nigella sativa (black-cumin), Hibiscus sabdariffa (roselle), and Origanum vulgare (oregano) have received considerable interest based on scientific evidence. Beside these dietary plants, phytochemicals—such as catechin, epicatechin, epigallocatechin-3-gallate, diosmin, rutin, quercetin, hyperoside, and curcumin—as antioxidant dietary phyto-phenols were found to be effective for the prevention of urolithiasis (the process of stone formation in the urinary tract). The main underlying mechanisms of these dietary plants and their isolated phytonutrients in the management of urolithiasis include diuretic, antispasmodic, and antioxidant activity, as well as an inhibitory effect on crystallization, nucleation, and aggregation of crystals. The results as presented in this review demonstrate the promising role of dietary plants and phytophenols in the prevention and management of kidney stones. Further investigations are required to confirm the safety and efficacy of these compounds. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention 2017)
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Review
Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment
Int. J. Mol. Sci. 2017, 18(8), 1645; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18081645 - 28 Jul 2017
Cited by 37 | Viewed by 3807
Abstract
Bioactive dietary agents have been shown to regulate multiple cancer hallmark pathways. Epidemiologic studies have linked consumption of Allium vegetables, such as garlic and onions, to decreased incidence of cancer. Diallyl trisulfide (DATS), a bioactive compound derived from Allium vegetables, has been investigated [...] Read more.
Bioactive dietary agents have been shown to regulate multiple cancer hallmark pathways. Epidemiologic studies have linked consumption of Allium vegetables, such as garlic and onions, to decreased incidence of cancer. Diallyl trisulfide (DATS), a bioactive compound derived from Allium vegetables, has been investigated as an anti-cancer and chemopreventive agent. Preclinical studies provide ample evidence that DATS regulates multiple cancer hallmark pathways including cell cycle, apoptosis, angiogenesis, invasion, and metastasis. DATS has been shown to arrest cancer cells at multiple stages of the cell cycle with the G2/M arrest being the most widely reported. Additionally, increased pro-apoptotic capacity as a result of regulating intrinsic and extrinsic apoptotic pathway components has been widely reported following DATS treatment. Invasion, migration, and angiogenesis represent emerging targets of DATS and support its anti-cancer properties. This review summarizes DATS mechanisms of action as an anti-cancer and chemopreventive agent. These studies provide rationale for future investigation into its use as a cancer chemopreventive agent. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention 2017)
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