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The Influence of Natural Products in Neurodegenerative Disorders
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The Influence of Natural Products in Neurodegenerative Disorders

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 (30 August 2023) | Viewed by 6744

Special Issue Editor

Dr. Rosalba Siracusa

E-Mail Website
Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98122 Messina, Italy
Interests: clinical biochemistry; molecular biology; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurodegenerative diseases are among the most serious health problems affecting millions of people worldwide, and their incidence is dramatically growing together with increased lifespan. These diseases are a heterogenous group of chronic, progressive disorders characterized by the gradual loss of neurons in the central nervous system, which leads to deficits in specific brain functions. The most common neurodegenerative diseases are Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and Huntington’s disease. These multifactorial debilitating disorders share common molecular and cellular characteristics, such as oxidative stress, mitochondrial dysfunction, protein misfolding, excitotoxicity, and inflammation. Presently, there are no therapeutic approaches to cure or even halt the progression of these disorders. In this context, natural products, because of their broad spectrum of pharmacological and biological activities, are considered promising alternatives for the treatment of neurodegeneration. Natural compounds have been recognized to possess different biological activities, including antioxidant, anti-inflammatory, and antiapoptotic effects. Moreover, natural compounds have been recently shown to counteract protein misfolding and to modulate autophagy and proteasome activity.

In this Special Issue, we invite investigators to contribute original research articles, as well as review articles regarding the biological effect of natural products in preventing/counteracting neurodegeneration.

Topics include but are not limited to the following:

  • Clinical or preclinical studies investigating natural products in the treatment of neurodegenerative diseases;
  • The role of natural products in counteracting oxidative stress in neurodegeneration;
  • The role of natural products in counteracting inflammation in neurodegeneration;
  • The use of natural products in modulating autophagy and proteasome activity to counteract abnormal protein aggregation in neurodegeneration;
  • The role of natural products in modulating signalling pathways involved in neurodegeneration;
  • The use of natural products as lead compounds in drug discovery for the treatment of neurodegenerative diseases.

Dr. Rosalba Siracusa
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.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • oxidative stress
  • inflammation
  • protein misfolding
  • natural compounds
  • nutraceuticals
  • phytochemicals
  • neurodegeneration
  • Alzheimer’s disease
  • Parkinson’s disease
  • amyotrophic lateral sclerosis
  • multiple sclerosis
  • Huntington’s disease

Published Papers (4 papers)

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Research

12 pages, 1909 KiB  
Article
Combination of Secondary Plant Metabolites and Micronutrients Improves Mitochondrial Function in a Cell Model of Early Alzheimer’s Disease
by Lukas Babylon, Julia Meißner and Gunter P. Eckert
Int. J. Mol. Sci. 2023, 24(12), 10029; https://doi.org/10.3390/ijms241210029 - 12 Jun 2023
Viewed by 1072
Abstract
Alzheimer’s disease (AD) is characterized by excessive formation of beta-amyloid peptides (Aβ), mitochondrial dysfunction, enhanced production of reactive oxygen species (ROS), and altered glycolysis. Since the disease is currently not curable, preventive and supportive approaches are in the focus of science. Based on [...] Read more.
Alzheimer’s disease (AD) is characterized by excessive formation of beta-amyloid peptides (Aβ), mitochondrial dysfunction, enhanced production of reactive oxygen species (ROS), and altered glycolysis. Since the disease is currently not curable, preventive and supportive approaches are in the focus of science. Based on studies of promising single substances, the present study used a mixture (cocktail, SC) of compounds consisting of hesperetin (HstP), magnesium-orotate (MgOr), and folic acid (Fol), as well as the combination (KCC) of caffeine (Cof), kahweol (KW) and cafestol (CF). For all compounds, we showed positive results in SH-SY5Y-APP695 cells—a model of early AD. Thus, SH-SY5Y-APP695 cells were incubated with SC and the activity of the mitochondrial respiration chain complexes were measured, as well as levels of ATP, Aβ, ROS, lactate and pyruvate. Incubation of SH-SY5Y-APP695 cells with SC significantly increased the endogenous respiration of mitochondria and ATP levels, while Aβ1–40 levels were significantly decreased. Incubation with SC showed no significant effects on oxidative stress and glycolysis. In summary, this combination of compounds with proven effects on mitochondrial parameters has the potential to improve mitochondrial dysfunction in a cellular model of AD. Full article
(This article belongs to the Special Issue The Influence of Natural Products in Neurodegenerative Disorders)
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17 pages, 2527 KiB  
Article
Anti-Neuroinflammatory and Neuroprotective Effect of Intermedin B Isolated from the Curcuma longa L. via NF-κB and ROS Inhibition in BV2 Microglia and HT22 Hippocampal Cells
by Hwan Lee, Zhiming Liu, Linsha Dong, Dae Young Lee, Dahye Yoon, Hyuncheol Oh, Youn-Chul Kim, Ren-Bo An and Dong-Sung Lee
Int. J. Mol. Sci. 2023, 24(8), 7390; https://doi.org/10.3390/ijms24087390 - 17 Apr 2023
Cited by 1 | Viewed by 1389
Abstract
Compounds derived from Curcuma longa L. (C. longa) have been extensively studied and reported to be effective and safe for the prevention and treatment of various diseases, but most research has been focused on curcuminoids derived from C. longa. As [...] Read more.
Compounds derived from Curcuma longa L. (C. longa) have been extensively studied and reported to be effective and safe for the prevention and treatment of various diseases, but most research has been focused on curcuminoids derived from C. longa. As neurodegenerative diseases are associated with oxidation and inflammation, the present study aimed to isolate and identify active compounds other than curcuminoids from C. longa to develop substances to treat these diseases. Seventeen known compounds, including curcuminoids, were chromatographically isolated from the methanol extracts of C. longa, and their chemical structures were identified using 1D and 2D NMR spectroscopy. Among the isolated compounds, intermedin B exhibited the best antioxidant effect in the hippocampus and anti-inflammatory effect in microglia. Furthermore, intermedin B was confirmed to inhibit the nuclear translocation of NF-κB p-65 and IκBα, exerting anti-inflammatory effects and inhibiting the generation of reactive oxygen species, exerting neuroprotective effects. These results highlight the research value of active components other than curcuminoids in C. longa-derived compounds and suggest that intermedin B may be a promising candidate for the prevention of neurodegenerative diseases. Full article
(This article belongs to the Special Issue The Influence of Natural Products in Neurodegenerative Disorders)
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14 pages, 5337 KiB  
Article
MemophenolTM Prevents Amyloid-β Deposition and Attenuates Inflammation and Oxidative Stress in the Brain of an Alzheimer’s Disease Rat
by Daniela Impellizzeri, Mario Tomasello, Marika Cordaro, Ramona D’Amico, Roberta Fusco, Ali S. Abdelhameed, Uwe Wenzel, Rosalba Siracusa, Vittorio Calabrese, Salvatore Cuzzocrea and Rosanna Di Paola
Int. J. Mol. Sci. 2023, 24(8), 6938; https://doi.org/10.3390/ijms24086938 - 08 Apr 2023
Viewed by 1674
Abstract
Alzheimer’s disease (AD) is the most common cause of dementia, and its prevalence rises with age. Inflammation and altered antioxidant systems play essential roles in the genesis of neurodegenerative diseases. In this work, we looked at the effects of MemophenolTM, a [...] Read more.
Alzheimer’s disease (AD) is the most common cause of dementia, and its prevalence rises with age. Inflammation and altered antioxidant systems play essential roles in the genesis of neurodegenerative diseases. In this work, we looked at the effects of MemophenolTM, a compound rich in polyphenols derived from French grape (Vitis vinifera L.) and wild North American blueberry (Vaccinium angustifolium A.) extracts, in a rat model of AD. Methods: For 60 days, the animals were administered with AlCl3 (100 mg/kg, orally) and D-galactose (60 mg/kg, intraperitoneally), while from day 30, MemophenolTM (15 mg/kg) was supplied orally for 30 consecutive days. AlCl3 accumulates mainly in the hippocampus, the main part of the brain involved in memory and learning. Behavioral tests were performed the day before the sacrifice when brains were collected for analysis. Results: MemophenolTM decreased behavioral alterations and hippocampus neuronal degeneration. It also lowered phosphorylated Tau (p-Tau) levels, amyloid precursor protein (APP) overexpression, and β-amyloid (Aβ) buildup. Furthermore, MemophenolTM reduced the pro-oxidative and pro-inflammatory hippocampus changes caused by AD. Our finding, relevant to AD pathogenesis and therapeutics, suggests that MemophenolTM, by modulating oxidative and inflammatory pathways and by regulating cellular brain stress response mechanisms, protects against the behavioral and histopathological changes associated with AD. Full article
(This article belongs to the Special Issue The Influence of Natural Products in Neurodegenerative Disorders)
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23 pages, 3960 KiB  
Article
A Diet Containing Rutin Ameliorates Brain Intracellular Redox Homeostasis in a Mouse Model of Alzheimer’s Disease
by Paloma Bermejo-Bescós, Karim L. Jiménez-Aliaga, Juana Benedí and Sagrario Martín-Aragón
Int. J. Mol. Sci. 2023, 24(5), 4863; https://doi.org/10.3390/ijms24054863 - 02 Mar 2023
Cited by 5 | Viewed by 1984
Abstract
Quercetin has been studied extensively for its anti-Alzheimer’s disease (AD) and anti-aging effects. Our previous studies have found that quercetin and in its glycoside form, rutin, can modulate the proteasome function in neuroblastoma cells. We aimed to explore the effects of quercetin and [...] Read more.
Quercetin has been studied extensively for its anti-Alzheimer’s disease (AD) and anti-aging effects. Our previous studies have found that quercetin and in its glycoside form, rutin, can modulate the proteasome function in neuroblastoma cells. We aimed to explore the effects of quercetin and rutin on intracellular redox homeostasis of the brain (reduced glutathione/oxidized glutathione, GSH/GSSG), its correlation with β-site APP cleaving enzyme 1 (BACE1) activity, and amyloid precursor protein (APP) expression in transgenic TgAPP mice (bearing human Swedish mutation APP transgene, APPswe). On the basis that BACE1 protein and APP processing are regulated by the ubiquitin–proteasome pathway and that supplementation with GSH protects neurons from proteasome inhibition, we investigated whether a diet containing quercetin or rutin (30 mg/kg/day, 4 weeks) diminishes several early signs of AD. Genotyping analyses of animals were carried out by PCR. In order to determine intracellular redox homeostasis, spectrofluorometric methods were adopted to quantify GSH and GSSG levels using o-phthalaldehyde and the GSH/GSSG ratio was ascertained. Levels of TBARS were determined as a marker of lipid peroxidation. Enzyme activities of SOD, CAT, GR, and GPx were determined in the cortex and hippocampus. ΒACE1 activity was measured by a secretase-specific substrate conjugated to two reporter molecules (EDANS and DABCYL). Gene expression of the main antioxidant enzymes: APP, BACE1, a Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), caspase-3, caspase-6, and inflammatory cytokines were determined by RT-PCR. First, overexpression of APPswe in TgAPP mice decreased GSH/GSSG ratio, increased malonaldehyde (MDA) levels, and, overall, decreased the main antioxidant enzyme activities in comparison to wild-type (WT) mice. Treatment of TgAPP mice with quercetin or rutin increased GSH/GSSG, diminished MDA levels, and favored the enzyme antioxidant capacity, particularly with rutin. Secondly, both APP expression and BACE1 activity were diminished with quercetin or rutin in TgAPP mice. Regarding ADAM10, it tended to increase in TgAPP mice with rutin treatment. As for caspase-3 expression, TgAPP displayed an increase which was the opposite with rutin. Finally, the increase in expression of the inflammatory markers IL-1β and IFN-γ in TgAPP mice was lowered by both quercetin and rutin. Collectively, these findings suggest that, of the two flavonoids, rutin may be included in a day-to-day diet as a form of adjuvant therapy in AD. Full article
(This article belongs to the Special Issue The Influence of Natural Products in Neurodegenerative Disorders)
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