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Nutraceuticals in the Prevention and Treatment of Inflammatory Diseases

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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: closed (31 January 2023) | Viewed by 28130

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Special Issue Editor

Prof. Dr. Dipak Ramji

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Guest Editor

Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK
Interests: inflammation; cytokines; cell signaling; atherosclerosis; macrophages; foam cells; nutraceuticals; gene expression
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammatory diseases include a vast range of conditions and disorders that are orchestrated by chronic inflammation. Examples of inflammatory diseases include atherosclerosis, diabetes, obesity, rheumatoid arthritis and cancer. Such inflammatory diseases are responsible for most global deaths and therefore represent an enormous economic burden. Although pharmaceutical therapies have recently reduced morbidity and mortality from such inflammatory diseases, they are not fully effective and are associated with adverse side effects in some cases, thereby necessitating further research on alternative therapeutic avenues. Nutraceuticals, food products with health benefits beyond their nutritional values, represent promising alternatives for the prevention and treatment of inflammatory disorders. Studies aimed at underpinning the molecular mechanisms underlying nutraceutical actions together with large clinical trials are essential to fully realise their potential as preventative and therapeutic agents against inflammatory disorders.

This Special Issue is focused on nutraceuticals in the prevention and treatment of inflammatory diseases and will include original articles and reviews on mechanism-based in vitro and in vivo studies aimed at understanding the molecular mechanisms that underpin nutraceutical actions together with human studies aimed at delineating their efficacy as preventative and therapeutic agents. Potential topics include, but are not limited to, nutraceutical actions in cultured cells, animal models of inflammatory disorders and human subjects addressing aspects such as cellular responses, signal transduction, gene expression, intracellular targets, biomarkers and disease severity, bioavailability and several others.

Prof. Dr. Dipak Ramji
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

nutraceuticals
natural products
inflammatory diseases
cardiovascular disease
atherosclerosis
diabetes
obesity
rheumatoid arthritis
cancer
cellular processes
mechanisms
signaling
gene expression
prevention
treatment

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Published Papers (6 papers)

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Research

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18 pages, 2399 KiB

Open AccessArticle

Assessment of Lab4P Probiotic Effects on Cognition in 3xTg-AD Alzheimer’s Disease Model Mice and the SH-SY5Y Neuronal Cell Line

by Thomas S. Webberley, Ryan J. Bevan, Joshua Kerry-Smith, Jordanna Dally, Daryn R. Michael, Sophie Thomas, Meg Rees, James E. Morgan, Julian R. Marchesi, Mark A. Good, Sue F. Plummer, Duolao Wang and Timothy R. Hughes

Int. J. Mol. Sci. 2023, 24(5), 4683; https://doi.org/10.3390/ijms24054683 - 28 Feb 2023

Cited by 11 | Viewed by 3699

Abstract

Aging and metabolic syndrome are associated with neurodegenerative pathologies including Alzheimer’s disease (AD) and there is growing interest in the prophylactic potential of probiotic bacteria in this area. In this study, we assessed the neuroprotective potential of the Lab4P probiotic consortium in both age and metabolically challenged 3xTg-AD mice and in human SH-SY5Y cell culture models of neurodegeneration. In mice, supplementation prevented disease-associated deteriorations in novel object recognition, hippocampal neurone spine density (particularly thin spines) and mRNA expression in hippocampal tissue implying an anti-inflammatory impact of the probiotic, more notably in the metabolically challenged setting. In differentiated human SH-SY5Y neurones challenged with β-Amyloid, probiotic metabolites elicited a neuroprotective capability. Taken together, the results highlight Lab4P as a potential neuroprotective agent and provide compelling support for additional studies in animal models of other neurodegenerative conditions and human studies. Full article

(This article belongs to the Special Issue Nutraceuticals in the Prevention and Treatment of Inflammatory Diseases)

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13 pages, 1608 KiB

Open AccessArticle

Anti-Atherogenic Actions of the Lab4b Consortium of Probiotics In Vitro

by Victoria L. O’Morain, Jing Chen, Sue F. Plummer, Daryn R. Michael and Dipak P. Ramji

Int. J. Mol. Sci. 2023, 24(4), 3639; https://doi.org/10.3390/ijms24043639 - 11 Feb 2023

Cited by 2 | Viewed by 2089

Abstract

Probiotic bacteria have many protective effects against inflammatory disorders, though the mechanisms underlying their actions are poorly understood. The Lab4b consortium of probiotics contains four strains of lactic acid bacteria and bifidobacteria that are reflective of the gut of newborn babies and infants. The effect of Lab4b on atherosclerosis, an inflammatory disorder of the vasculature, has not yet been determined and was investigated on key processes associated with this disease in human monocytes/macrophages and vascular smooth muscle cells in vitro. The Lab4b conditioned medium (CM) attenuated chemokine-driven monocytic migration, monocyte/macrophage proliferation, uptake of modified LDL and macropinocytosis in macrophages together with the proliferation and platelet-derived growth factor-induced migration of vascular smooth muscle cells. The Lab4b CM also induced phagocytosis in macrophages and cholesterol efflux from macrophage-derived foam cells. The effect of Lab4b CM on macrophage foam cell formation was associated with a decrease in the expression of several key genes implicated in the uptake of modified LDL and induced expression of those involved in cholesterol efflux. These studies reveal, for the first time, several anti-atherogenic actions of Lab4b and strongly implicate further studies in mouse models of the disease in vivo and in clinical trials. Full article

(This article belongs to the Special Issue Nutraceuticals in the Prevention and Treatment of Inflammatory Diseases)

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16 pages, 28637 KiB

Open AccessArticle

Anti-Inflammatory Activity and Mechanism of Sweet Corn Extract on Il-1β-Induced Inflammation in a Human Retinal Pigment Epithelial Cell Line (ARPE-19)

by Inthra Koraneeyakijkulchai, Rianthong Phumsuay, Parunya Thiyajai, Siriporn Tuntipopipat and Chawanphat Muangnoi

Int. J. Mol. Sci. 2023, 24(3), 2462; https://doi.org/10.3390/ijms24032462 - 27 Jan 2023

Cited by 7 | Viewed by 7456

Abstract

Age-related macular degeneration (AMD) is an eye disease associated with aging. Development of AMD is related to degeneration and dysfunction of the retinal pigment epithelium (RPE) caused by low-grade chronic inflammation in aged RPE cells leading to visual loss and blindness. Sweet corn is a good source of lutein and zeaxanthin, which were reported to exert various biological activities, including anti-inflammatory activity. The present study aims to investigate the anti-inflammatory activity and mechanisms of SCE to inhibit the production of inflammatory biomarkers related to AMD development. Cells were pretreated with SCE for 1 h followed by stimulation with IL-1β for another 24 h. The results demonstrated that SCE attenuated IL-1β-induced production of IL-6, IL-8, and MCP-1 and the expression of ICAM-1 and iNOS in a dose-dependent manner. In addition, SCE suppressed the phosphorylation of ERK1/2, SAPK/JNK, p38, and NF-κB (p65) in IL-1β-stimulated ARPE-19 cells. These results proved that SCE protected ARPE-19 cells from IL-1β-induced inflammation by inhibiting inflammatory markers partly via suppressing the activation of MAPK and NF-κB signaling pathways. Overall, SCE is a potential agent for the prevention of AMD development, which should be further evaluated in animals. Full article

(This article belongs to the Special Issue Nutraceuticals in the Prevention and Treatment of Inflammatory Diseases)

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12 pages, 2391 KiB

Open AccessArticle

Conjugated Linoleic Acids Have Anti-Inflammatory Effects in Cultured Endothelial Cells

by Carina A. Valenzuela, Ella J. Baker, Elizabeth A. Miles and Philip C. Calder

Int. J. Mol. Sci. 2023, 24(1), 874; https://doi.org/10.3390/ijms24010874 - 3 Jan 2023

Cited by 12 | Viewed by 2823

Abstract

Conjugated linoleic acid (CLA) isomers may have a role in preventing atherosclerosis through the modulation of inflammation, particularly of the endothelium. However, whether low concentrations of CLAs are able to affect basal unstimulated endothelial cell (EC) responses is not clear. The aim of this study was to evaluate the effects of two CLAs (cis-9, trans-11 (CLA9,11) and trans-10, cis-12 (CLA10,12)) on the basal inflammatory responses by ECs. EA.hy926 cells (HUVEC lineage) were cultured under standard conditions and exposed to individual CLAs for 48 h. Both CLAs were incorporated into ECs in a dose-dependent manner. CLA9,11 (1 μM) significantly decreased concentrations of MCP-1 (p < 0.05), IL-6 (p < 0.05), IL-8 (p < 0.01) and RANTES (p < 0.05) in the culture medium. CLA10,12 (10 μM) decreased the concentrations of MCP-1 (p < 0.05) and RANTES (p < 0.05) but increased the concentration of IL-6 (p < 0.001). At 10 μM both CLAs increased the relative expression of the NFκβ subunit 1 gene (p < 0.01 and p < 0.05, respectively), while decreasing the relative expression of PPARα (p < 0.0001), COX-2 (p < 0.0001) and IL-6 (p < 0.0001) genes. CLA10,12 increased the relative expression of the gene encoding IκK-β at 10 μM compared with CLA9,11 (p < 0.05) and increased the relative expression of the gene encoding IκBα at 1 and 10 μM compared with linoleic acid (both p < 0.05). Neither CLA affected the adhesion of monocytes to ECs. These results suggest that low concentrations of both CLA9,11 and CLA10,12 have modest anti-inflammatory effects in ECs. Thus, CLAs may influence endothelial function and the risk of vascular disease. Nevertheless, at these low CLA concentrations some pro-inflammatory genes are upregulated while others are downregulated, suggesting complex effects of CLAs on inflammatory pathways. Full article

(This article belongs to the Special Issue Nutraceuticals in the Prevention and Treatment of Inflammatory Diseases)

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Review

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32 pages, 1544 KiB

Open AccessReview

Polyunsaturated Fatty Acids: Conversion to Lipid Mediators, Roles in Inflammatory Diseases and Dietary Sources

by John L. Harwood

Int. J. Mol. Sci. 2023, 24(10), 8838; https://doi.org/10.3390/ijms24108838 - 16 May 2023

Cited by 46 | Viewed by 4657

Abstract

Polyunsaturated fatty acids (PUFAs) are important components of the diet of mammals. Their role was first established when the essential fatty acids (EFAs) linoleic acid and α-linolenic acid were discovered nearly a century ago. However, most of the biochemical and physiological actions of PUFAs rely on their conversion to 20C or 22C acids and subsequent metabolism to lipid mediators. As a generalisation, lipid mediators formed from n-6 PUFAs are pro-inflammatory while those from n-3 PUFAs are anti-inflammatory or neutral. Apart from the actions of the classic eicosanoids or docosanoids, many newly discovered compounds are described as Specialised Pro-resolving Mediators (SPMs) which have been proposed to have a role in resolving inflammatory conditions such as infections and preventing them from becoming chronic. In addition, a large group of molecules, termed isoprostanes, can be generated by free radical reactions and these too have powerful properties towards inflammation. The ultimate source of n-3 and n-6 PUFAs are photosynthetic organisms which contain Δ-12 and Δ-15 desaturases, which are almost exclusively absent from animals. Moreover, the EFAs consumed from plant food are in competition with each other for conversion to lipid mediators. Thus, the relative amounts of n-3 and n-6 PUFAs in the diet are important. Furthermore, the conversion of the EFAs to 20C and 22C PUFAs in mammals is rather poor. Thus, there has been much interest recently in the use of algae, many of which make substantial quantities of long-chain PUFAs or in manipulating oil crops to make such acids. This is especially important because fish oils, which are their main source in human diets, are becoming limited. In this review, the metabolic conversion of PUFAs into different lipid mediators is described. Then, the biological roles and molecular mechanisms of such mediators in inflammatory diseases are outlined. Finally, natural sources of PUFAs (including 20 or 22 carbon compounds) are detailed, as well as recent efforts to increase their production. Full article

(This article belongs to the Special Issue Nutraceuticals in the Prevention and Treatment of Inflammatory Diseases)

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25 pages, 1511 KiB

Open AccessReview

The Beneficial Effects of Pine Nuts and Its Major Fatty Acid, Pinolenic Acid, on Inflammation and Metabolic Perturbations in Inflammatory Disorders

by Rabaa Takala, Dipak P. Ramji and Ernest Choy

Int. J. Mol. Sci. 2023, 24(2), 1171; https://doi.org/10.3390/ijms24021171 - 6 Jan 2023

Cited by 9 | Viewed by 6335

Abstract

Inflammatory disorders such as atherosclerosis, diabetes and rheumatoid arthritis are regulated by cytokines and other inflammatory mediators. Current treatments for these conditions are associated with significant side effects and do not completely suppress inflammation. The benefits of diet, especially the role of specific components, are poorly understood. Polyunsaturated fatty acids (PUFAs) have several beneficial health effects. The majority of studies on PUFAs have been on omega-3 fatty acids. This review will focus on a less studied fatty acid, pinolenic acid (PNLA) from pine nuts, which typically constitutes up to 20% of its total fatty acids. PNLA is emerging as a dietary PUFA and a promising supplement in the prevention of inflammatory disorders or as an alternative therapy. Some studies have shown the health implications of pine nuts oil (PNO) and PNLA in weight reduction, lipid-lowering and anti-diabetic actions as well as in suppression of cell invasiveness and motility in cancer. However, few reviews have specifically focused on the biological and anti-inflammatory effects of PNLA. Furthermore, in recent bioinformatic studies on human samples, the expression of many mRNAs and microRNAs was regulated by PNLA indicating potential transcriptional and post-transcriptional regulation of inflammatory and metabolic processes. The aim of this review is to summarize, highlight, and evaluate research findings on PNO and PNLA in relation to potential anti-inflammatory benefits and beneficial metabolic changes. In this context, the focus of the review is on the potential actions of PNLA on inflammation along with modulation of lipid metabolism and oxidative stress based on data from both in vitro and in vivo experiments, and human findings, including gene expression analysis. Full article

(This article belongs to the Special Issue Nutraceuticals in the Prevention and Treatment of Inflammatory Diseases)

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