Polyphenols in the Treatment for Neuroinflammation-Induced Neurodegenerative Disease

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: 25 June 2024 | Viewed by 6203

Special Issue Editors


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Guest Editor
Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, Viale Morgagni 50, 50134 Florence, Italy
Interests: amyloid aggregation; autophagy; natural polyphenols; neurodegenerative diseases
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Guest Editor
Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy
Interests: bioactive natural products; inflammation; oxidative stress; polyphenols; cell migration; autophagy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neuroinflammation is defined as an inflammatory response within the brain or spinal cord. This inflammation is mediated by the production of cytokines, chemokines, reactive oxygen species, and secondary messengers. These mediators are produced by resident CNS glia (microglia and astrocytes), endothelial cells, and peripherally derived immune cells. There are immune, physiological, biochemical, and psychological consequences of these neuroinflammatory responses. Moreover, the degree of neuroinflammation depends on the context, duration, and course of the primary stimulus or insult. In recent years, neuroinflammation has attracted particular interest, and genetic variants of molecules associated with ‘‘microgliopathies’’ result in increased risk of developing neurodegenerative disorders and cognitive decline. Current therapies for neurodegenerative disorders treat symptoms and final manifestations, including aggregate build-up, memory loss, behavioral changes, and sleep deficits; however, this strategy is not a sustainable approach to appropriate management of disease onset or progression. One of the more promising approaches considers the inhibition of amyloid formation by small-molecule inhibitors; however, multiple failures of clinical therapeutic approaches indicate that the current strategies must be modulated and emphasize the importance of targeting pre-symptomatic signs as oxidative stress and inflammation. Both oxidative stress and neuroinflammation preside over the symptomology of neurodegenerative disorders, and each promotes neurotoxic environments associated with neurodegeneration.

In this scenario, polyphenols represent a promising starting point for new preventive and therapeutic approaches, since they target effectively and simultaneously inflammatory and oxidative pathways, and amyloid aggregation. These molecules have worldwide availability, low cost, and low toxicity. Improved knowledge of these topics is mandatory to promote the use of natural polyphenols well beyond their known antioxidant, antidiabetic, and antilipidemic effects. Increased information in this sense could be exploited to enrich, from a commercial and nutraceutical point of view, the alimentary and healthy value of natural compounds.

Dr. Manuela Leri
Dr. Marzia Vasarri
Guest Editors

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Published Papers (3 papers)

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Research

19 pages, 5973 KiB  
Article
EVOO Polyphenols Exert Anti-Inflammatory Effects on the Microglia Cell through TREM2 Signaling Pathway
by Manuela Leri, Marzia Vasarri, Federica Carnemolla, Francesco Oriente, Serena Cabaro, Maria Stio, Donatella Degl’Innocenti, Massimo Stefani and Monica Bucciantini
Pharmaceuticals 2023, 16(7), 933; https://doi.org/10.3390/ph16070933 - 27 Jun 2023
Cited by 8 | Viewed by 1569
Abstract
In Alzheimer’s disease (AD), microglia, brain resident immune cells, become chronically inflammatory and neurotoxic. In recent years, neuroinflammation has attracted particular interest in the scientific community. The genetic variants of molecules associated with ‘‘microgliopathies’’, including the triggering receptor expressed in myeloid cells-2 (TREM2), [...] Read more.
In Alzheimer’s disease (AD), microglia, brain resident immune cells, become chronically inflammatory and neurotoxic. In recent years, neuroinflammation has attracted particular interest in the scientific community. The genetic variants of molecules associated with ‘‘microgliopathies’’, including the triggering receptor expressed in myeloid cells-2 (TREM2), result in increased risk of developing AD and cognitive decline. We performed a set of in vitro assays using human neuronal (SH-SY5Y) and microglial (BV2 and C13NJ) cell models. Cells were differentially treated with extra virgin olive oil (EVOO) polyphenols, oleuropein aglycone (OleA) and hydroxytyrosol (HT) before adding LPS. We evaluated the protective effects of these EVOO products by a set of biochemical and cell biology assays, including ELISA, MTT, ROS detection, Western blotting and immunofluorescence. Our results provide an integrated understanding of the neuroprotection exerted by polyphenols in terms of: (i) reduction of pro-inflammatory cytokines release (IL-6, IL-8, IP-10 and RANTES); (ii) activation of the TREM2-dependent anti-inflammatory pathway; (iii) enhancement of protective microglial activity favoring the M2 polarization phenotype. Such findings provide new and important insights into the mechanisms by which the dietary olive polyphenols exert beneficial properties against neuroinflammation and neuronal impairment. Full article
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19 pages, 1794 KiB  
Article
Development of Novel Fluorinated Polyphenols as Selective Inhibitors of DYRK1A/B Kinase for Treatment of Neuroinflammatory Diseases including Parkinson’s Disease
by Gian Luca Araldi and Yu-Wen Hwang
Pharmaceuticals 2023, 16(3), 443; https://doi.org/10.3390/ph16030443 - 15 Mar 2023
Cited by 4 | Viewed by 1836
Abstract
Natural polyphenol derivatives such as those found in green tea have been known for a long time for their useful therapeutic activity. Starting from EGCG, we have discovered a new fluorinated polyphenol derivative (1c) characterized by improved inhibitory activity against DYRK1A/B [...] Read more.
Natural polyphenol derivatives such as those found in green tea have been known for a long time for their useful therapeutic activity. Starting from EGCG, we have discovered a new fluorinated polyphenol derivative (1c) characterized by improved inhibitory activity against DYRK1A/B enzymes and by considerably improved bioavailability and selectivity. DYRK1A is an enzyme that has been implicated as an important drug target in various therapeutic areas, including neurological disorders (Down syndrome and Alzheimer’s disease), oncology, and type 2 diabetes (pancreatic β-cell expansion). Systematic structure–activity relationship (SAR) on trans-GCG led to the discovery that the introduction of a fluoro atom in the D ring and methylation of the hydroxy group from para to the fluoro atom provide a molecule (1c) with more desirable drug-like properties. Owing to its good ADMET properties, compound 1c showed excellent activity in two in vivo models, namely the lipopolysaccharide (LPS)-induced inflammation model and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model for Parkinson’s disease. Full article
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21 pages, 17683 KiB  
Article
In Vitro Antiviral Effect and Potential Neuroprotection of Salvadora persica L. Stem Bark Extract against Lipopolysaccharides-Induced Neuroinflammation in Mice: LC-ESI-MS/MS Analysis of the Methanol Extract
by Reem Binsuwaidan, Walaa A. Negm, Engy Elekhnawy, Nashwah G. M. Attallah, Eman Ahmed, Sameh Magdeldin, Ehssan Moglad, Sally Abdallah Mostafa and Suzy A. El-Sherbeni
Pharmaceuticals 2023, 16(3), 398; https://doi.org/10.3390/ph16030398 - 6 Mar 2023
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Abstract
Neuroinflammation is a serious immunomodulatory complex disorder that causes neurological and somatic ailments. The treatment of brain inflammation with new drugs derived from natural sources is a significant therapeutic goal. Utilizing LC-ESI-MS/MS analysis, the active constituents of Salvadora persica extract (SPE) were identified [...] Read more.
Neuroinflammation is a serious immunomodulatory complex disorder that causes neurological and somatic ailments. The treatment of brain inflammation with new drugs derived from natural sources is a significant therapeutic goal. Utilizing LC-ESI-MS/MS analysis, the active constituents of Salvadora persica extract (SPE) were identified tentatively as exerting antioxidant and anti-inflammatory effects in natural medicine. Herein, we determined the antiviral potential of SPE against herpes simplex virus type 2 (HSV-2) using the plaque assay. HSV-2 is a neurotropic virus that can cause neurological diseases. SPE exhibited promising antiviral potential with a half-maximal cytotoxic concentration (CC50) of 185.960 ± 0.1 µg/mL and a half-maximal inhibitory concentration (IC50) of 8.946 ± 0.02 µg/mL. The in vivo study of the SPE impact against lipopolysaccharide (LPS)-induced neuroinflammation was performed using 42 mice divided into seven groups. All groups were administered LPS (0.25 mg/kg) intraperitoneally, except for the normal and SPE groups 1 and 2. Groups 5, 6, and 7 received 100, 200, and 300 mg/kg SPE. It was revealed that SPE inhibited acetylcholinesterase in the brain. It increased superoxide dismutase and catalase while decreasing malondialdehyde, which explains its antioxidative stress activity. SPE downregulated the gene expression of the inducible nitric oxide synthase, as well as the apoptotic markers (caspase-3 and c-Jun). In addition, it decreased the expression of the proinflammatory cytokines (interleukin-6 and tumor necrosis factor-alpha). Mice administered SPE (300 mg/kg) with LPS exhibited normal neurons in the cerebral cortices, hippocampus pyramidal layer, and cerebellum, as determined by the histopathological analysis. Therefore, using S. persica to prevent and treat neurodegeneration could be a promising new therapeutic strategy to be explored. Full article
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