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5 pages, 186 KiB

Open AccessEditorial

Nutraceuticals in Immune Function

by Soo-Liang Ooi and Sok-Cheon Pak

Molecules 2021, 26(17), 5310; https://doi.org/10.3390/molecules26175310 - 1 Sep 2021

Cited by 9 | Viewed by 3259

Abstract

Nutraceutical, a term derived from ‘nutrition’ and ‘pharmaceutical’, refers to any product isolated from herbs, nutrients, specific diets, processed foods, and beverages used not only for nutritional but also for medicinal purposes [...] Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

Research

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16 pages, 2350 KiB

Open AccessArticle

In Vitro Effects of Sulforaphane on Interferon-Driven Inflammation and Exploratory Evaluation in Two Healthy Volunteers

by Elena Genova, Maura Apollonio, Giuliana Decorti, Alessandra Tesser, Alberto Tommasini and Gabriele Stocco

Molecules 2021, 26(12), 3602; https://doi.org/10.3390/molecules26123602 - 12 Jun 2021

Cited by 3 | Viewed by 2439

Abstract

Interferonopathies are rare genetic conditions defined by systemic inflammatory episodes caused by innate immune system activation in the absence of pathogens. Currently, no targeted drugs are authorized for clinical use in these diseases. In this work, we studied the contribution of sulforaphane (SFN), [...] Read more.

Interferonopathies are rare genetic conditions defined by systemic inflammatory episodes caused by innate immune system activation in the absence of pathogens. Currently, no targeted drugs are authorized for clinical use in these diseases. In this work, we studied the contribution of sulforaphane (SFN), a cruciferous-derived bioactive molecule, in the modulation of interferon-driven inflammation in an immortalized human hepatocytes (IHH) line and in two healthy volunteers, focusing on STING, a key-component player in interferon pathway, interferon signature modulation, and GSTM1 expression and genotype, which contributes to SFN metabolism and excretion. In vitro, SFN exposure reduced STING expression as well as interferon signature in the presence of the pro-inflammatory stimulus cGAMP (cGAMP 3 h vs. SFN+cGAMP 3 h p value < 0.0001; cGAMP 6 h vs. SFN+cGAMP 6 h p < 0.001, one way ANOVA), restoring STING expression to the level of unstimulated cells. In preliminary experiments on healthy volunteers, no appreciable variations in interferon signature were identified after SFN assumption, while only in one of them, presenting the GSTM1 wild type genotype related to reduced SFN excretion, could a downregulation of STING be recorded. This study confirmed that SFN inhibits STING-mediated inflammation and interferon-stimulated genes expression in vitro. However, only a trend towards the downregulation of STING could be reproduced in vivo. Results obtained have to be confirmed in a larger group of healthy individuals and in patients with type I interferonopathies to define if the assumption of SFN could be useful as supportive therapy. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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16 pages, 1646 KiB

Open AccessArticle

Lycopene Inhibits Toll-Like Receptor 4-Mediated Expression of Inflammatory Cytokines in House Dust Mite-Stimulated Respiratory Epithelial Cells

by Jiyeon Choi, Joo Weon Lim and Hyeyoung Kim

Molecules 2021, 26(11), 3127; https://doi.org/10.3390/molecules26113127 - 24 May 2021

Cited by 12 | Viewed by 2556

Abstract

House dust mites (HDM) are critical factors in airway inflammation. They activate respiratory epithelial cells to produce reactive oxygen species (ROS) and activate Toll-like receptor 4 (TLR4). ROS induce the expression of inflammatory cytokines in respiratory epithelial cells. Lycopene is a potent antioxidant [...] Read more.

House dust mites (HDM) are critical factors in airway inflammation. They activate respiratory epithelial cells to produce reactive oxygen species (ROS) and activate Toll-like receptor 4 (TLR4). ROS induce the expression of inflammatory cytokines in respiratory epithelial cells. Lycopene is a potent antioxidant nutrient with anti-inflammatory activity. The present study aimed to investigate whether HDM induce intracellular and mitochondrial ROS production, TLR4 activation, and pro-inflammatory cytokine expression (IL-6 and IL-8) in respiratory epithelial A549 cells. Additionally, we examined whether lycopene inhibits HDM-induced alterations in A549 cells. The treatment of A549 cells with HDM activated TLR4, induced the expression of IL-6 and IL-8, and increased intracellular and mitochondrial ROS levels. TAK242, a TLR4 inhibitor, suppressed both HDM-induced ROS production and cytokine expression. Furthermore, lycopene inhibited the HDM-induced TLR4 activation and cytokine expression, along with reducing the intracellular and mitochondrial ROS levels in HDM-treated cells. These results collectively indicated that the HDM induced TLR4 activation and increased intracellular and mitochondrial ROS levels, thus resulting in the induction of cytokine expression in respiratory epithelial cells. The antioxidant lycopene could inhibit HDM-induced cytokine expression, possibly by suppressing TLR4 activation and reducing the intracellular and mitochondrial ROS levels in respiratory epithelial cells. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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11 pages, 2280 KiB

Open AccessArticle

Effect of Korean Red Ginseng and Rg3 on Asian Sand Dust-Induced MUC5AC, MUC5B, and MUC8 Expression in Bronchial Epithelial Cells

by Seung-Heon Shin, Mi-Kyung Ye, Dong-Won Lee, Byung-Jun Kang and Mi-Hyun Chae

Molecules 2021, 26(7), 2002; https://doi.org/10.3390/molecules26072002 - 1 Apr 2021

Cited by 6 | Viewed by 2467

Abstract

Korean Red ginseng (KRG), commonly used in traditional medicine, has anti-inflammatory, anti- oxidative, and anti-tumorigenic properties. Asian sand dust (ASD) is known to aggravate upper and lower airway inflammatory responses. BEAS-2B cells were exposed to ASD with or without KRG or ginsenoside Rg3. [...] Read more.

Korean Red ginseng (KRG), commonly used in traditional medicine, has anti-inflammatory, anti- oxidative, and anti-tumorigenic properties. Asian sand dust (ASD) is known to aggravate upper and lower airway inflammatory responses. BEAS-2B cells were exposed to ASD with or without KRG or ginsenoside Rg3. Mucin 5AC (MUC5AC), MUC5B, and MUC8 mRNA and protein expression levels were determined using quantitative RT-PCR and enzyme-linked immunosorbent assay. Nuclear factor kappa B (NF-κB), activator protein 1, and mitogen-activated protein kinase expression and activity were determined using western blot analysis. ASD induced MUC5AC, MUC5B, and MUC8 mRNA and protein expression in BEAS-2B cells, which was significantly inhibited by KRG and Rg3. Although ASD-induced mucin expression was associated with NF-κB and p38 mitogen-activated protein kinase (MAPK) activity, KRG and Rg3 significantly suppressed only ASD-induced NF-κB expression and activity. KRG and Rg3 inhibited ASD-induced mucin gene expression and protein production from bronchial epithelial cells. These results suggest that KRG and Rg3 have potential for treating mucus-producing airway inflammatory diseases. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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15 pages, 2648 KiB

Open AccessArticle

β-Carotene Inhibits Expression of Matrix Metalloproteinase-10 and Invasion in Helicobacter pylori-Infected Gastric Epithelial Cells

by Suji Bae, Joo Weon Lim and Hyeyoung Kim

Molecules 2021, 26(6), 1567; https://doi.org/10.3390/molecules26061567 - 12 Mar 2021

Cited by 24 | Viewed by 2639

Abstract

Matrix metalloproteinases (MMPs), key molecules of cancer invasion and metastasis, degrade the extracellular matrix and cell–cell adhesion molecules. MMP-10 plays a crucial role in Helicobacter pylori-induced cell-invasion. The mitogen-activated protein kinase (MAPK) signaling pathway, which activates activator protein-1 (AP-1), is known to [...] Read more.

Matrix metalloproteinases (MMPs), key molecules of cancer invasion and metastasis, degrade the extracellular matrix and cell–cell adhesion molecules. MMP-10 plays a crucial role in Helicobacter pylori-induced cell-invasion. The mitogen-activated protein kinase (MAPK) signaling pathway, which activates activator protein-1 (AP-1), is known to mediate MMP expression. Infection with H. pylori, a Gram-negative bacterium, is associated with gastric cancer development. A toxic factor induced by H. pylori infection is reactive oxygen species (ROS), which activate MAPK signaling in gastric epithelial cells. Peroxisome proliferator-activated receptor γ (PPAR-γ) mediates the expression of antioxidant enzymes including catalase. β-Carotene, a red-orange pigment, exerts antioxidant and anti-inflammatory properties. We aimed to investigate whether β-carotene inhibits H. pylori-induced MMP expression and cell invasion in gastric epithelial AGS (gastric adenocarcinoma) cells. We found that H. pylori induced MMP-10 expression and increased cell invasion via the activation of MAPKs and AP-1 in gastric epithelial cells. Specific inhibitors of MAPKs suppressed H. pylori-induced MMP-10 expression, suggesting that H. pylori induces MMP-10 expression through MAPKs. β-Carotene inhibited the H. pylori-induced activation of MAPKs and AP-1, expression of MMP-10, and cell invasion. Additionally, it promoted the expression of PPAR-γ and catalase, which reduced ROS levels in H. pylori-infected cells. In conclusion, β-carotene exerts an inhibitory effect on MAPK-mediated MMP-10 expression and cell invasion by increasing PPAR-γ-mediated catalase expression and reducing ROS levels in H. pylori-infected gastric epithelial cells. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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14 pages, 3280 KiB

Open AccessArticle

Resveratrol Promotes Hypertrophy in Wildtype Skeletal Muscle and Reduces Muscle Necrosis and Gene Expression of Inflammatory Markers in Mdx Mice

by Keryn G. Woodman, Chantal A. Coles, Shireen R. Lamandé and Jason D. White

Molecules 2021, 26(4), 853; https://doi.org/10.3390/molecules26040853 - 6 Feb 2021

Cited by 9 | Viewed by 3509

Abstract

Duchenne muscular dystrophy (DMD) is a progressive fatal neuromuscular disorder with no cure. Therapies to restore dystrophin deficiency have been approved in some jurisdictions but long-term effectiveness is yet to be established. There is a need to develop alternative strategies to treat DMD. [...] Read more.

Duchenne muscular dystrophy (DMD) is a progressive fatal neuromuscular disorder with no cure. Therapies to restore dystrophin deficiency have been approved in some jurisdictions but long-term effectiveness is yet to be established. There is a need to develop alternative strategies to treat DMD. Resveratrol is a nutraceutical with anti-inflammatory properties. Previous studies have shown high doses (100–400 mg/kg bodyweight/day) benefit mdx mice. We treated 4-week-old mdx and wildtype mice with a lower dose of resveratrol (5 mg/kg bodyweight/day) for 15 weeks. Voluntary exercise was used to test if a lower dosage than previously tested could reduce exercise-induced damage where a greater inflammatory infiltrate is present. We found resveratrol promoted skeletal muscle hypertrophy in wildtype mice. In dystrophic muscle, resveratrol reduced exercise-induced muscle necrosis. Gene expression of immune cell markers, CD86 and CD163 were reduced; however, signalling targets associated with resveratrol’s mechanism of action including Sirt1 and NF-κB were unchanged. In conclusion, a lower dose of resveratrol compared to the dosage used by other studies reduced necrosis and gene expression of inflammatory cell markers in dystrophic muscle suggesting it as a therapeutic candidate for treating DMD. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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12 pages, 2288 KiB

Open AccessArticle

Micellar Casein and Whey Powder Hold a TGF-β Activity and Regulate ID Genes In Vitro

by Layla Panahipour, Selma Husejnovic, Jila Nasirzade, Stephan Semelmayer and Reinhard Gruber

Molecules 2021, 26(2), 507; https://doi.org/10.3390/molecules26020507 - 19 Jan 2021

Cited by 6 | Viewed by 3184

Abstract

Casein and whey being food supplements have been considered to be used in oral health care products. However, the response of oral cells to micellar casein and whey powder remains unclear. Considering that milk contains the growth factor TGF-β, and lactoperoxidase was recently [...] Read more.

Casein and whey being food supplements have been considered to be used in oral health care products. However, the response of oral cells to micellar casein and whey powder remains unclear. Considering that milk contains the growth factor TGF-β, and lactoperoxidase was recently reported to decrease the expression of inhibitor of DNA-binding (ID) proteins, there is a rationale to assume that casein and whey can also provoke these responses in oral cells. To examine the TGF-β activity, gingival fibroblasts were exposed to reconstituted casein and whey powder from food supplement before the expression of TGF-β target genes were analyzed by reverse transcription-quantitative polymerase chain reaction. Immunoassays were performed for interleukin11 (IL11) in the cell culture supernatant and for TGF-β in the reconstituted casein and whey. We blocked TGF-β by neutralizing the antibody and the TGF-β receptor type I kinase with the inhibitor SB431542. We also showed smad3 phosphorylation and smad2/3 nuclear translocation by Western blot and immunostaining, respectively. Moreover, with reconstituted casein and whey powder, ID1 and ID3 expression analysis was evaluated in HSC2 human oral squamous carcinoma cells. We report here that casein and whey powder caused a robust increase of TGF-β target genes interleukin11 (IL11), NADPH oxidase 4 (NOX4) and proteoglycan4 (PRG4) in gingival fibroblasts that was blocked by SB431542 and the neutralizing antibody. Moreover, casein and whey powder increased the phosphorylation of smad3 and nuclear translocation of smad2/3. No changes of proliferation markers Ki67 and cyclinD1 were observed. Furthermore, reconstituted casein and whey powder decreased ID1 and ID3 expression in the HSC2 oral squamous carcinoma cells. These findings suggest that the processing of milk into casein and whey powder maintains the TGF-β activity and its capacity to regulate ID1 and ID3 genes in oral fibroblasts and oral squamous carcinoma cells, respectively. These data increase the scientific knowledge on the biological activity of casein and whey with a special emphasis on oral health. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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21 pages, 9708 KiB

Open AccessArticle

Effect of Vitamin B Complex Treatment on Macrophages to Schwann Cells Association during Neuroinflammation after Peripheral Nerve Injury

by Adil Ehmedah, Predrag Nedeljkovic, Sanja Dacic, Jelena Repac, Biljana Draskovic-Pavlovic, Dragana Vučević, Sanja Pekovic and Biljana Bozic Nedeljkovic

Molecules 2020, 25(22), 5426; https://doi.org/10.3390/molecules25225426 - 19 Nov 2020

Cited by 20 | Viewed by 4071

Abstract

Peripheral nerve injury (PNI) triggers a complex multi-cellular response involving the injured neurons, Schwann cells (SCs), and immune cells, often resulting in poor functional recovery. The aim of this study was to investigate the effects of the treatment with vitamin B (B1, B2, [...] Read more.

Peripheral nerve injury (PNI) triggers a complex multi-cellular response involving the injured neurons, Schwann cells (SCs), and immune cells, often resulting in poor functional recovery. The aim of this study was to investigate the effects of the treatment with vitamin B (B1, B2, B3, B5, B6, and B12) complex on the interaction between macrophages and SCs during the recovery period after PNI. Transection of the motor branch of the femoral nerve followed by reconstruction by termino-terminal anastomosis was used as an experimental model. Isolated nerves from the sham (S), operated (O), and operated groups treated with the B vitamins (OT group) were used for immunofluorescence analysis. The obtained data indicated that PNI modulates interactions between macrophages and SCs in a time-dependent manner. The treatment with B vitamins complex promoted the M1-to M2-macrophage polarization and accelerated the transition from the non-myelin to myelin-forming SCs, an indicative of SCs maturation. The effect of B vitamins complex on both cell types was accompanied with an increase in macrophage/SC interactions, all of which correlated with the regeneration of the injured nerve. Clearly, the capacity of B vitamins to modulate macrophages-SCs interaction may be promising for the treatment of PNI. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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12 pages, 2381 KiB

Open AccessArticle

Glucosamine Enhancement of BDNF Expression and Animal Cognitive Function

by Lien-Yu Chou, Yu-Ming Chao, Yen-Chun Peng, Hui-Ching Lin and Yuh-Lin Wu

Molecules 2020, 25(16), 3667; https://doi.org/10.3390/molecules25163667 - 12 Aug 2020

Cited by 13 | Viewed by 3681

Abstract

Brain-derived neurotrophic factor (BDNF) is an important factor for memory consolidation and cognitive function. Protein kinase A (PKA) signaling interacts significantly with BDNF-provoked downstream signaling. Glucosamine (GLN), a common dietary supplement, has been demonstrated to perform a variety of beneficial physiological functions. In [...] Read more.

Brain-derived neurotrophic factor (BDNF) is an important factor for memory consolidation and cognitive function. Protein kinase A (PKA) signaling interacts significantly with BDNF-provoked downstream signaling. Glucosamine (GLN), a common dietary supplement, has been demonstrated to perform a variety of beneficial physiological functions. In the current study, an in vivo model of 7-week-old C57BL/6 mice receiving daily intraperitoneal injection of GLN (0, 3, 10 and 30 mg/animal) was subjected to the novel object recognition test in order to determine cognitive performance. GLN significantly increased cognitive function. In the hippocampus GLN elevated tissue cAMP concentrations and CREB phosphorylation, and upregulated the expression of BDNF, CREB5 and the BDNF receptor TrkB, but it reduced PDE4B expression. With the in vitro model in the HT22 hippocampal cell line, GLN exposure significantly increased protein and mRNA levels of BDNF and CREB5 and induced cAMP responsive element (CRE) reporter activity; the GLN-mediated BDNF expression and CRE reporter induction were suppressed by PKA inhibitor H89. Our current findings suggest that GLN can exert a cognition-enhancing function and this may act at least in part by upregulating the BDNF levels via a cAMP/PKA/CREB-dependent pathway. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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12 pages, 3293 KiB

Open AccessArticle

In Vitro Hormetic Effect Investigation of Thymol on Human Fibroblast and Gastric Adenocarcinoma Cells

by Ayse Günes-Bayir, Abdurrahim Kocyigit, Eray Metin Guler and Agnes Dadak

Molecules 2020, 25(14), 3270; https://doi.org/10.3390/molecules25143270 - 17 Jul 2020

Cited by 25 | Viewed by 3036

Abstract

The concept of hormesis includes a biphasic cellular dose-response to a xenobiotic stimulus defined by low dose beneficial and high dose inhibitory or toxic effects. In the present study, an attempt has been made to help elucidate the beneficial and detrimental effects of [...] Read more.

The concept of hormesis includes a biphasic cellular dose-response to a xenobiotic stimulus defined by low dose beneficial and high dose inhibitory or toxic effects. In the present study, an attempt has been made to help elucidate the beneficial and detrimental effects of thymol on different cell types by evaluating and comparing the impact of various thymol doses on cancerous (AGS) and healthy (WS-1) cells. Cytotoxic, genotoxic, and apoptotic effects, as well as levels of reactive oxygen species and glutathione were studied in both cell lines exposed to thymol (0–600 µM) for 24 h. The results showed significant differences in cell viability of AGS compared to WS-1 cells exposed to thymol. The differences observed were statistically significant at all doses applied (P ≤ 0.001) and revealed hormetic thymol effects on WS-1 cells, whereas toxic effects on AGS cells were detectable at all thymol concentrations. Thymol at low concentrations provides antioxidative protection to WS-1 cells in vitro while already inducing toxic effects in AGS cells. In that sense, the findings of the present study suggest that thymol exerts a dose-dependent hormetic impact on different cell types, thereby providing crucial information for future in vivo studies investigating the therapeutic potential of thymol. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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Review

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21 pages, 1871 KiB

Open AccessReview

Nutraceuticals and Enteric Glial Cells

by Laura López-Gómez, Agata Szymaszkiewicz, Marta Zielińska and Raquel Abalo

Molecules 2021, 26(12), 3762; https://doi.org/10.3390/molecules26123762 - 21 Jun 2021

Cited by 10 | Viewed by 4115

Abstract

Until recently, glia were considered to be a structural support for neurons, however further investigations showed that glial cells are equally as important as neurons. Among many different types of glia, enteric glial cells (EGCs) found in the gastrointestinal tract, have been significantly [...] Read more.

Until recently, glia were considered to be a structural support for neurons, however further investigations showed that glial cells are equally as important as neurons. Among many different types of glia, enteric glial cells (EGCs) found in the gastrointestinal tract, have been significantly underestimated, but proved to play an essential role in neuroprotection, immune system modulation and many other functions. They are also said to be remarkably altered in different physiopathological conditions. A nutraceutical is defined as any food substance or part of a food that provides medical or health benefits, including prevention and treatment of the disease. Following the description of these interesting peripheral glial cells and highlighting their role in physiological and pathological changes, this article reviews all the studies on the effects of nutraceuticals as modulators of their functions. Currently there are only a few studies available concerning the effects of nutraceuticals on EGCs. Most of them evaluated molecules with antioxidant properties in systemic conditions, whereas only a few studies have been performed using models of gastrointestinal disorders. Despite the scarcity of studies on the topic, all agree that nutraceuticals have the potential to be an interesting alternative in the prevention and/or treatment of enteric gliopathies (of systemic or local etiology) and their associated gastrointestinal conditions. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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28 pages, 458 KiB

Open AccessReview

Nutraceuticals: Transformation of Conventional Foods into Health Promoters/Disease Preventers and Safety Considerations

by Mudhi AlAli, Maream Alqubaisy, Mariam Nasser Aljaafari, Asma Obaid AlAli, Laila Baqais, Aidin Molouki, Aisha Abushelaibi, Kok-Song Lai and Swee-Hua Erin Lim

Molecules 2021, 26(9), 2540; https://doi.org/10.3390/molecules26092540 - 27 Apr 2021

Cited by 100 | Viewed by 16262

Abstract

Nutraceuticals are essential food constituents that provide nutritional benefits as well as medicinal effects. The benefits of these foods are due to the presence of active compounds such as carotenoids, collagen hydrolysate, and dietary fibers. Nutraceuticals have been found to positively affect cardiovascular [...] Read more.

Nutraceuticals are essential food constituents that provide nutritional benefits as well as medicinal effects. The benefits of these foods are due to the presence of active compounds such as carotenoids, collagen hydrolysate, and dietary fibers. Nutraceuticals have been found to positively affect cardiovascular and immune system health and have a role in infection and cancer prevention. Nutraceuticals can be categorized into different classes based on their nature and mode of action. In this review, different classifications of nutraceuticals and their potential therapeutic activity, such as anti-cancer, antioxidant, anti-inflammatory and anti-lipid activity in disease will be reviewed. Moreover, the different mechanisms of action of these products, applications, and safety upon consumers including current trends and future prospect of nutraceuticals will be included. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

17 pages, 2079 KiB

Open AccessReview

The Health-Promoting Properties and Clinical Applications of Rice Bran Arabinoxylan Modified with Shiitake Mushroom Enzyme—A Narrative Review

by Soo Liang Ooi, Sok Cheon Pak, Peter S. Micalos, Emily Schupfer, Catherine Lockley, Mi Houn Park and Sung-Joo Hwang

Molecules 2021, 26(9), 2539; https://doi.org/10.3390/molecules26092539 - 27 Apr 2021

Cited by 16 | Viewed by 7115

Abstract

Rice bran arabinoxylan compound (RBAC) is derived from defatted rice bran hydrolyzed with Lentinus edodes mycelial enzyme. It has been marketed as a functional food and a nutraceutical with health-promoting properties. Some research has demonstrated this rice bran derivative to be a potent [...] Read more.

Rice bran arabinoxylan compound (RBAC) is derived from defatted rice bran hydrolyzed with Lentinus edodes mycelial enzyme. It has been marketed as a functional food and a nutraceutical with health-promoting properties. Some research has demonstrated this rice bran derivative to be a potent immunomodulator, which also possesses anti-inflammatory, antioxidant, and anti-angiogenic properties. To date, research on RBAC has predominantly focused on its immunomodulatory action and application as a complementary therapy for cancer. Nonetheless, the clinical applications of RBAC can extend beyond cancer therapy. This article is a narrative review of the research on the potential benefits of RBAC for cancer and other health conditions based on the available literature. RBAC research has shown it to be useful as a complementary treatment for cancer and human immunodeficiency virus infection. It can positively modulate serum glucose, lipid and protein metabolism in diabetic patients. Additionally, RBAC has been shown to ameliorate irritable bowel syndrome and protect against liver injury caused by hepatitis or nonalcoholic fatty liver disease. It can potentially ease symptoms in chronic fatigue syndrome and prevent the common cold. RBAC is safe to consume and has no known side effects at the typical dosage of 2–3 g/day. Nevertheless, further research in both basic studies and human clinical trials are required to investigate the clinical applications, mechanisms, and effects of RBAC. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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15 pages, 1609 KiB

Open AccessReview

Anti-Inflammatory Action and Mechanisms of Resveratrol

by Tiantian Meng, Dingfu Xiao, Arowolo Muhammed, Juying Deng, Liang Chen and Jianhua He

Molecules 2021, 26(1), 229; https://doi.org/10.3390/molecules26010229 - 5 Jan 2021

Cited by 356 | Viewed by 19685

Abstract

Resveratrol (3,4′,5-trihy- droxystilbene), a natural phytoalexin polyphenol, exhibits anti-oxidant, anti-inflammatory, and anti-carcinogenic properties. This phytoalexin is well-absorbed and rapidly and extensively metabolized in the body. Inflammation is an adaptive response, which could be triggered by various danger signals, such as invasion by microorganisms [...] Read more.

Resveratrol (3,4′,5-trihy- droxystilbene), a natural phytoalexin polyphenol, exhibits anti-oxidant, anti-inflammatory, and anti-carcinogenic properties. This phytoalexin is well-absorbed and rapidly and extensively metabolized in the body. Inflammation is an adaptive response, which could be triggered by various danger signals, such as invasion by microorganisms or tissue injury. In this review, the anti-inflammatory activity and the mechanism of resveratrol modulates the inflammatory response are examined. Multiple experimental studies that illustrate regulatory mechanisms and the immunomodulatory function of resveratrol both in vivo and in vitro. The data acquired from those studies are discussed. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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11 pages, 1678 KiB

Open AccessReview

Microbiota-Mediated Immune Regulation in Atherosclerosis

by Sahar Eshghjoo, Arul Jayaraman, Yuxiang Sun and Robert C. Alaniz

Molecules 2021, 26(1), 179; https://doi.org/10.3390/molecules26010179 - 1 Jan 2021

Cited by 14 | Viewed by 6394

Abstract

There is a high level of interest in identifying metabolites of endogenously produced or dietary compounds generated by the gastrointestinal (GI) tract microbiota, and determining the functions of these metabolites in health and disease. There is a wealth of compelling evidence that the [...] Read more.

There is a high level of interest in identifying metabolites of endogenously produced or dietary compounds generated by the gastrointestinal (GI) tract microbiota, and determining the functions of these metabolites in health and disease. There is a wealth of compelling evidence that the microbiota is linked with many complex chronic inflammatory diseases, including atherosclerosis. Macrophages are key target immune cells in atherosclerosis. A hallmark of atherosclerosis is the accumulation of pro-inflammatory macrophages in coronary arteries that respond to pro-atherogenic stimuli and failure of digesting lipids that contribute to foam cell formation in atherosclerotic plaques. This review illustrates the role of tryptophan-derived microbiota metabolites as an aryl hydrocarbon receptor (AhR) ligand that has immunomodulatory properties. Also, microbiota-dependent trimethylamine-N-oxide (TMAO) metabolite production is associated with a deleterious effect that promotes atherosclerosis, and metabolite indoxyl sulfate has been shown to exacerbate atherosclerosis. Our objective in this review is to discuss the role of microbiota-derived metabolites in atherosclerosis, specifically the consequences of microbiota-induced effects of innate immunity in response to atherogenic stimuli, and how specific beneficial/detrimental metabolites impact the development of atherosclerosis by regulating chronic endotoxemic and lipotoxic inflammation. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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12 pages, 296 KiB

Open AccessReview

The Role of Vitamin C, Vitamin D, and Selenium in Immune System against COVID-19

by Minkyung Bae and Hyeyoung Kim

Molecules 2020, 25(22), 5346; https://doi.org/10.3390/molecules25225346 - 16 Nov 2020

Cited by 194 | Viewed by 34332

Abstract

Low levels of micronutrients have been associated with adverse clinical outcomes during viral infections. Therefore, to maximize the nutritional defense against infections, a daily allowance of vitamins and trace elements for malnourished patients at risk of or diagnosed with coronavirus disease 2019 (COVID-19) [...] Read more.

Low levels of micronutrients have been associated with adverse clinical outcomes during viral infections. Therefore, to maximize the nutritional defense against infections, a daily allowance of vitamins and trace elements for malnourished patients at risk of or diagnosed with coronavirus disease 2019 (COVID-19) may be beneficial. Recent studies on COVID-19 patients have shown that vitamin D and selenium deficiencies are evident in patients with acute respiratory tract infections. Vitamin D improves the physical barrier against viruses and stimulates the production of antimicrobial peptides. It may prevent cytokine storms by decreasing the production of inflammatory cytokines. Selenium enhances the function of cytotoxic effector cells. Furthermore, selenium is important for maintaining T cell maturation and functions, as well as for T cell-dependent antibody production. Vitamin C is considered an antiviral agent as it increases immunity. Administration of vitamin C increased the survival rate of COVID-19 patients by attenuating excessive activation of the immune response. Vitamin C increases antiviral cytokines and free radical formation, decreasing viral yield. It also attenuates excessive inflammatory responses and hyperactivation of immune cells. In this mini-review, the roles of vitamin C, vitamin D, and selenium in the immune system are discussed in relation to COVID-19. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

14 pages, 1016 KiB

Open AccessReview

Astaxanthin and its Effects in Inflammatory Responses and Inflammation-Associated Diseases: Recent Advances and Future Directions

by Ming Xian Chang and Fan Xiong

Molecules 2020, 25(22), 5342; https://doi.org/10.3390/molecules25225342 - 16 Nov 2020

Cited by 139 | Viewed by 13058

Abstract

Astaxanthin is a natural lipid-soluble and red-orange carotenoid. Due to its strong antioxidant property, anti-inflammatory, anti-apoptotic, and immune modulation, astaxanthin has gained growing interest as a multi-target pharmacological agent against various diseases. In the current review, the anti-inflammation mechanisms of astaxanthin involved in [...] Read more.

Astaxanthin is a natural lipid-soluble and red-orange carotenoid. Due to its strong antioxidant property, anti-inflammatory, anti-apoptotic, and immune modulation, astaxanthin has gained growing interest as a multi-target pharmacological agent against various diseases. In the current review, the anti-inflammation mechanisms of astaxanthin involved in targeting for inflammatory biomarkers and multiple signaling pathways, including PI3K/AKT, Nrf2, NF-κB, ERK1/2, JNK, p38 MAPK, and JAK-2/STAT-3, have been described. Furthermore, the applications of anti-inflammatory effects of astaxanthin in neurological diseases, diabetes, gastrointestinal diseases, hepatic and renal diseases, eye and skin disorders, are highlighted. In addition to the protective effects of astaxanthin in various chronic and acute diseases, we also summarize recent advances for the inconsistent roles of astaxanthin in infectious diseases, and give our view that the exact function of astaxanthin in response to different pathogen infection and the potential protective effects of astaxanthin in viral infectious diseases should be important research directions in the future. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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30 pages, 747 KiB

Open AccessReview

Mast Cell Regulation and Irritable Bowel Syndrome: Effects of Food Components with Potential Nutraceutical Use

by José Antonio Uranga, Vicente Martínez and Raquel Abalo

Molecules 2020, 25(18), 4314; https://doi.org/10.3390/molecules25184314 - 20 Sep 2020

Cited by 41 | Viewed by 12921

Abstract

Mast cells are key actors in inflammatory reactions. Upon activation, they release histamine, heparin and nerve growth factor, among many other mediators that modulate immune response and neuron sensitization. One important feature of mast cells is that their population is usually increased in [...] Read more.

Mast cells are key actors in inflammatory reactions. Upon activation, they release histamine, heparin and nerve growth factor, among many other mediators that modulate immune response and neuron sensitization. One important feature of mast cells is that their population is usually increased in animal models and biopsies from patients with irritable bowel syndrome (IBS). Therefore, mast cells and mast cell mediators are regarded as key components in IBS pathophysiology. IBS is a common functional gastrointestinal disorder affecting the quality of life of up to 20% of the population worldwide. It is characterized by abdominal pain and altered bowel habits, with heterogeneous phenotypes ranging from constipation to diarrhea, with a mixed subtype and even an unclassified form. Nutrient intake is one of the triggering factors of IBS. In this respect, certain components of the daily food, such as fatty acids, amino acids or plant-derived substances like flavonoids, have been described to modulate mast cells’ activity. In this review, we will focus on the effect of these molecules, either stimulatory or inhibitory, on mast cell degranulation, looking for a nutraceutical capable of decreasing IBS symptoms. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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49 pages, 13389 KiB

Open AccessReview

Hormesis and Ginseng: Ginseng Mixtures and Individual Constituents Commonly Display Hormesis Dose Responses, Especially for Neuroprotective Effects

by Edward J. Calabrese

Molecules 2020, 25(11), 2719; https://doi.org/10.3390/molecules25112719 - 11 Jun 2020

Cited by 21 | Viewed by 5243

Abstract

This paper demonstrates that ginseng mixtures and individual ginseng chemical constituents commonly induce hormetic dose responses in numerous biological models for endpoints of biomedical and clinical relevance, typically providing a mechanistic framework. The principal focus of ginseng hormesis-related research has been directed toward [...] Read more.

This paper demonstrates that ginseng mixtures and individual ginseng chemical constituents commonly induce hormetic dose responses in numerous biological models for endpoints of biomedical and clinical relevance, typically providing a mechanistic framework. The principal focus of ginseng hormesis-related research has been directed toward enhancing neuroprotection against conditions such as Alzheimer’s and Parkinson’s Diseases, stroke damage, as well as enhancing spinal cord and peripheral neuronal damage repair and reducing pain. Ginseng was also shown to reduce symptoms of diabetes, prevent cardiovascular system damage, protect the kidney from toxicities due to immune suppressant drugs, and prevent corneal damage, amongst other examples. These findings complement similar hormetic-based chemoprotective reports for other widely used dietary-type supplements such as curcumin, ginkgo biloba, and green tea. These findings, which provide further support for the generality of the hormetic dose response in the biomedical literature, have potentially important public health and clinical implications. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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26 pages, 3151 KiB

Open AccessReview

Therapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties

by Sahu Henamayee, Kishore Banik, Bethsebie Lalduhsaki Sailo, Bano Shabnam, Choudhary Harsha, Satti Srilakshmi, Naidu VGM, Seung Ho Baek, Kwang Seok Ahn and Ajaikumar B Kunnumakkara

Molecules 2020, 25(10), 2278; https://doi.org/10.3390/molecules25102278 - 12 May 2020

Cited by 101 | Viewed by 6903

Abstract

According to the World Health Organization (WHO), cancer is the second-highest cause of mortality in the world, and it kills nearly 9.6 million people annually. Besides the fatality of the disease, poor prognosis, cost of conventional therapies, and associated side-effects add more burden [...] Read more.

According to the World Health Organization (WHO), cancer is the second-highest cause of mortality in the world, and it kills nearly 9.6 million people annually. Besides the fatality of the disease, poor prognosis, cost of conventional therapies, and associated side-effects add more burden to patients, post-diagnosis. Therefore, the search for alternatives for the treatment of cancer that are safe, multi-targeted, effective, and cost-effective has compelled us to go back to ancient systems of medicine. Natural herbs and plant formulations are laden with a variety of phytochemicals. One such compound is rhein, which is an anthraquinone derived from the roots of Rheum spp. and Polygonum multiflorum. In ethnomedicine, these plants are used for the treatment of inflammation, osteoarthritis, diabetes, and bacterial and helminthic infections. Increasing evidence suggests that this compound can suppress breast cancer, cervical cancer, colon cancer, lung cancer, ovarian cancer, etc. in both in vitro and in vivo settings. Recent studies have reported that this compound modulates different signaling cascades in cancer cells and can prevent angiogenesis and progression of different types of cancers. The present review highlights the cancer-preventing and therapeutic properties of rhein based on the available literature, which will help to extend further research to establish the chemoprotective and therapeutic roles of rhein compared to other conventional drugs. Future pharmacokinetic and toxicological studies could support this compound as an effective anticancer agent. Full article

(This article belongs to the Special Issue Nutraceuticals in Immune Function)

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