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Molecular Mechanisms of Anti-inflammatory Phytochemicals 2.0

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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 (18 May 2023) | Viewed by 13130

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Prof. Dr. Natália Cruz-Martins

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Guest Editor

1. Faculty of Medicine, University of Porto, 4099-002 Porto, Portugal
2. Institute for Research and Innovation in Health (i3S), University of Porto, 4099-002 Porto, Portugal
3. Institute of Research and Advanced Training in Health Sciences and Technologies, CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal
4. TOXRUN - Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, Portugal
Interests: evidence-based medicine; phytochemistry; phytopharmacology; drug discovery; natural products biochemistry; bioactive molecules; functional foods; nutraceuticals
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Dear Colleagues,

Inflammation is a normal biological process characterized by the activation of immune and non-immune cells to provide defense against infection and promote tissue repair. However, it is becoming increasingly clear that inflammation also plays a crucial role in the development and progression of many chronic diseases, including cancer, diabetes, cardiovascular diseases, arthritis, asthma, neurodegenerative disorders, and autoimmune diseases. This provides the rationale to develop agents that can target inflammation for the prevention and treatment of chronic diseases.

Phytochemicals are non-nutritive plant-derived compounds that represent a large library of bioactive molecules. Due to their diverse structures and cellular targets, phytochemicals provide broad therapeutic opportunities. Recent studies have discovered the potential of phytochemicals to block key steps in the pathogenesis of inflammatory diseases.

This Special Issue, “Molecular Mechanisms of Anti-Inflammatory Phytochemicals 2.0” will include in vitro, in vivo, and clinical studies on the anti-inflammatory effects and molecular mechanisms of phytochemicals, including therapeutic applications in chronic diseases, modes of action, target identification, structure-activity relationships, and identification and quantification of phytochemicals from new sources. Original research articles or reviews in this field are welcome.

Prof. Dr. Natália Cruz-Martins
Guest Editor

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Keywords

phytochemicals
inflammation
molecular mechanism
chronic diseases
inflammatory diseases
cell signaling
bioactivity

Published Papers (7 papers)

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Editorial

Jump to: Research, Review

3 pages, 204 KiB

Open AccessEditorial

Molecular Mechanisms of Anti-Inflammatory Phytochemicals 2.0

by Natália Cruz-Martins

Int. J. Mol. Sci. 2023, 24(24), 17443; https://doi.org/10.3390/ijms242417443 - 13 Dec 2023

Viewed by 534

Abstract

Inflammation is currently the most investigated cell response, not only for the frequency with which it occurs but essentially due to the growing incidence of inflammatory diseases, increasingly labeled as characteristics of modern society [...] Full article

(This article belongs to the Special Issue Molecular Mechanisms of Anti-inflammatory Phytochemicals 2.0)

Research

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14 pages, 5956 KiB

Open AccessArticle

Hypolipidemic and Anti-Inflammatory Effects of Curcuma longa-Derived Bisacurone in High-Fat Diet-Fed Mice

by Chaoqi He, Taiki Miyazawa, Chizumi Abe, Takahiro Ueno, Mikiko Suzuki, Masashi Mizukami, Kazue Kurihara and Masako Toda

Int. J. Mol. Sci. 2023, 24(11), 9366; https://doi.org/10.3390/ijms24119366 - 27 May 2023

Cited by 1 | Viewed by 1678

Abstract

Turmeric (Curcuma longa) contains various compounds that potentially improve health. Bisacurone is a turmeric-derived compound but has been less studied compared to other compounds, such as curcumin. In this study, we aimed to evaluate the anti-inflammatory and lipid-lowering effects of bisacurone in high-fat diet (HFD)-fed mice. Mice were fed HFD to induce lipidemia and orally administered bisacurone daily for two weeks. Bisacurone reduced liver weight, serum cholesterol and triglyceride levels, and blood viscosity in mice. Splenocytes from bisacurone-treated mice produced lower levels of the pro-inflammatory cytokines IL-6 and TNF-α upon stimulation with a toll-like receptor (TLR) 4 ligand, lipopolysaccharide (LPS), and TLR1/2 ligand, Pam3CSK4, than those from untreated mice. Bisacurone also inhibited LPS-induced IL-6 and TNF-α production in the murine macrophage cell line, RAW264.7. Western blot analysis revealed that bisacurone inhibited the phosphorylation of IKKα/β and NF-κB p65 subunit, but not of the mitogen-activated protein kinases, p38 kinase and p42/44 kinases, and c-Jun N-terminal kinase in the cells. Collectively, these results suggest that bisacurone has the potential to reduce serum lipid levels and blood viscosity in mice with high-fat diet-induced lipidemia and modulate inflammation via inhibition of NF-κB-mediated pathways. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Anti-inflammatory Phytochemicals 2.0)

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20 pages, 3444 KiB

Open AccessArticle

In Vitro Study of the Therapeutic Potential of Brown Crude Fucoidans in Osteoarthritis Treatment

by Carlos Vaamonde-García, Emma Capelo-Mera, Noelia Flórez-Fernández, María Dolores Torres, Beatriz Rivas-Murias, Rosa Mejide-Faílde, Francisco J. Blanco and Herminia Domínguez

Int. J. Mol. Sci. 2022, 23(22), 14236; https://doi.org/10.3390/ijms232214236 - 17 Nov 2022

Cited by 4 | Viewed by 1934

Abstract

Osteoarthritis, one of the most common joint degenerative pathologies, still has no cure, and current treatments, such as nonsteroidal anti-inflammatory drugs, can cause serious adverse effects when taken for a long time. Brown seaweed crude fucoidans are used for the clinical treatment of several pathologies. In this study, the therapeutical potential of these biocompounds was analyzed in primary chondrocytes and the 260TT human chondrocyte cell line. Crude fucoidan from Undaria pinnatifida (Up) and Sargassum muticum (Sm) was obtained by different extraction techniques (microwave-assisted extraction, pressurized hot-water extraction, ultrasound-assisted extraction) and chemically and structurally characterized by Fourier transform infrared spectroscopy, high-performance size-exclusion chromatography, proton nuclear magnetic resonance, and scanning electron microscopy. Once cell viability was confirmed in chondrocytes treated with crude fucoidans, we evaluated their anti-inflammatory effects, observing a significant reduction in IL-6 production stimulated by IL-1β. Findings were confirmed by analysis of IL-6 and IL-8 gene expression, although only fucoidans from Up achieved a statistically significant reduction. Besides this, the antioxidant capacity of crude fucoidans was observed through the upregulation of Nrf-2 levels and the expression of its transcriptional target genes HO-1 and SOD-2, with compounds from Up again showing a more consistent effect. However, no evidence was found that crude fucoidans modulate senescence, as they failed to reduced β-galactosidase activity, cell proliferation, or IL-6 production in chondrocytes stimulated with etoposide. Thus, the findings of this research seem to indicate that the tested crude fucoidans are capable of partially alleviating OA-associated inflammation and oxidative stress, but fail to attenuate chondrocyte senescence. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Anti-inflammatory Phytochemicals 2.0)

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23 pages, 3646 KiB

Open AccessArticle

Reprograming of Gene Expression of Key Inflammatory Signaling Pathways in Human Peripheral Blood Mononuclear Cells by Soybean Lectin and Resveratrol

by Nilofer Qureshi, Julia Desousa, Adeela Z. Siddiqui, David C. Morrison and Asaf A. Qureshi

Int. J. Mol. Sci. 2022, 23(21), 12946; https://doi.org/10.3390/ijms232112946 - 26 Oct 2022

Cited by 1 | Viewed by 1728

Abstract

Inflammation is linked to several human diseases like microbial infections, cancer, heart disease, asthma, diabetes, and neurological disorders. We have shown that the prototype inflammatory agonist LPS modulates the activity of Ubiquitin-Proteasome System (UPS) and regulates transcription factors such as NF-κB, leading to inflammation, tolerance, hypoxia, autophagy, and apoptosis of cells. We hypothesized that proteasome modulators resveratrol and soybean lectin would alter the gene expression of mediators involved in inflammation-induced signaling pathways, when administered ex vivo to human peripheral blood mononuclear blood cells (PBMCs) obtained from normal healthy controls. To test this hypothesis, analysis of RNA derived from LPS-treated human PBMCs, with or without resveratrol and soybean lectin, was carried out using Next Generation Sequencing (NGS). Collectively, the findings described herein suggest that proteasome modulators, resveratrol (proteasome inhibitor) and lectins (proteasome activator), have a profound capacity to modulate cytokine expression in response to proteasome modulators, as well as expression of mediators in multiple signaling pathways in PBMCs of control subjects. We show for the first-time that resveratrol downregulates expression of mediators involved in several key signaling pathways IFN-γ, IL-4, PSMB8 (LMP7), and a subset of LPS-induced genes, while lectins induced IFN-γ, IL-4, PSMB8, and many of the same genes as LPS that are important for innate and adaptive immunity. These findings suggest that inflammation may be influenced by common dietary components and this knowledge may be used to prevent or reverse inflammation-based diseases. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Anti-inflammatory Phytochemicals 2.0)

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13 pages, 2616 KiB

Open AccessArticle

Inhibition of Borrelia Burgdorferi-Induced TLR2-NFκB Canonical Signaling by Gallic Acid through Targeting the CD14+ Adaptor Protein and p65 Molecule

by Anna Goc, Matthias Rath and Aleksandra Niedzwiecki

Int. J. Mol. Sci. 2022, 23(19), 10987; https://doi.org/10.3390/ijms231910987 - 20 Sep 2022

Cited by 1 | Viewed by 1985

Abstract

The cases of Lyme disease caused by Borrelia burgdorferi infection have been increasing throughout Northern America and Europe. This pathogen, if not treated in a timely manner with antibiotics, can cause persisting and debilitating health outcomes. In the search for novel agents against B. burgdorferi, we investigated a phenolic compound—gallic acid—for its anti-Borrelia and anti-inflammatory effects. Our results showed its biocidal effect starting from 100 μg/mL against active spirochetes, persisters/round-shaped bodies, and biofilm like aggregates of B. burgdorferi sensu stricto. Activation of macrophages by live B. burgdorferi also resulted in a robust NFκB-dependent proinflammatory responses seen in increased production of cytokines. Using human CD14+ macrophages in vitro, we showed that CD14+ adaptor and phosphorylated p65 molecule are impeded at nonbiocidal and noncytotoxic concentrations of gallic acid, resulting in the inhibition of both expression and secretion of cytokines IL1β, IL6, and TNFα. Our findings demonstrate efficacy of gallic acid against B. burgdorferi and provide potential mechanistic insight into its TLR2/CD14+-NFκB mediated mode of action. Further studies on the potential of gallic acid as a safe and effective compound against Borrelia-caused infection are warranted. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Anti-inflammatory Phytochemicals 2.0)

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Review

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21 pages, 1490 KiB

Open AccessReview

Preventive Effect of Pharmaceutical Phytochemicals Targeting the Src Family of Protein Tyrosine Kinases and Aryl Hydrocarbon Receptor on Environmental Stress-Induced Skin Disease

by So Jeong Paik, Dong Joon Kim and Sung Keun Jung

Int. J. Mol. Sci. 2023, 24(6), 5953; https://doi.org/10.3390/ijms24065953 - 21 Mar 2023

Cited by 1 | Viewed by 1990

Abstract

The skin protects our body; however, it is directly exposed to the environment and is stimulated by various external factors. Among the various environmental factors that can threaten skin health, the effects of ultraviolet (UV) and particulate matter (PM) are considered the most notable. Repetitive exposure to ultraviolet and particulate matter can cause chronic skin diseases such as skin inflammation, photoaging, and skin cancer. The abnormal activation of the Src family of protein tyrosine kinases (SFKs) and the aryl hydrocarbon receptor (AhR) in response to UV and/or PM exposure are involved in the development and aggravation of skin diseases. Phytochemicals, chemical compounds of natural plants, exert preventive effects on skin diseases through the regulation of various signaling pathways. Therefore, this review aims to highlight the efficacy of phytochemicals as potential nutraceuticals and pharmaceutical materials for the treatment of skin diseases, primarily by targeting SFK and AhR, and to explore the underlying mechanisms of action. Future studies are essential to validate the clinical potential for the prevention and treatment of skin diseases. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Anti-inflammatory Phytochemicals 2.0)

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15 pages, 1665 KiB

Open AccessReview

Zingiber officinale Rosc. in the Treatment of Metabolic Syndrome Disorders—A Review of In Vivo Studies

by Ewelina Gumbarewicz, Agata Jarząb, Andrzej Stepulak and Wirginia Kukula-Koch

Int. J. Mol. Sci. 2022, 23(24), 15545; https://doi.org/10.3390/ijms232415545 - 08 Dec 2022

Cited by 2 | Viewed by 2290

Abstract

Inflammation is a protective reaction of the innate immune system as a response to imbalances caused by a specific stimulus, a disease or a pathogen. A prolonged inflammatory condition may lead to the development of metabolic syndrome, which affects more than one-fourth of the world’s population. This condition leads to the development of multi-organ disorders based on disrupted blood lipid and sugar levels, hypertension and oxidative stress. The review aims to present Zingiber officinale Rosc. as a plant that exhibits a variety of healing properties and restores the organism’s equilibrium. Ginger (GI) rhizomes have been commonly used in traditional medicine to treat arthritis, stomach ache, nonalcoholic fatty liver disease, rheumatism, nervous system syndromes, asthma, diabetes and nausea caused by pregnancy or chemotherapy. This review gathers together data from in vivo experiments related to the application of ginger for the treatment of inflammatory conditions, obesity, diabetes and other related disorders as a consequence of metabolic syndrome, including the confirmed molecular mechanisms of action. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Anti-inflammatory Phytochemicals 2.0)

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