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Bioactive Compounds and Small Molecules with Neuroprotective and Anti-Inflammatory Functions
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Bioactive Compounds and Small Molecules with Neuroprotective and Anti-Inflammatory Functions

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 1999

Special Issue Editor

Prof. Dr. Chiara Porro

E-Mail Website
Guest Editor
Department of Clinical and Experimental Medicine, University of Foggia, 71121 Foggia, Italy
Interests: extracellular vesicle; microglia; bioactive foods; neuroprotection; neurodegenerative diseases; ageing; anti-inflammatory molecules; curcumin; resveratrol; vitamins
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Most neurodegenerative diseases are defined as complex multifactorial disorders, with genetic and environmental factors greatly contributing to their onset.

The relevance of lifestyle, including diet and exercise, has been associated with improved learning and memory capacity, delayed age-related cognitive decline, and a reduced risk of neurodegeneration.

The bioactive compounds and small molecules found in food exhibit beneficial effects, such as antioxidant, anti-inflammatory, and neuroprotective.

There is evidence that the consumption of certain food components, such as omega-3 fatty acids, carotenoids, flavonoids, polyphenols, etc., can reduce the risk of neurodegeneration and inflammatory diseases.

Supplementation with bioactive compounds is a valuable tool for strengthening neuroprotection and preventing inflammatory diseases. Therefore, there is increasing interest in identifying nutrients or dietary treatments that are neuroprotective and anti-inflammatory.

This Special Issue, entitled “Bioactive Compounds and Small Molecules with Neuroprotective and Anti-Inflammatory Functions”, welcomes the submission of both original research manuscripts and reviews concerning the in vitro and in vivo biological effects of bioactive foods and small molecules and their potential therapeutic applications in neuroprotection and inflammatory diseases.

Prof. Dr. Chiara Porro
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. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • bioactive foods
  • small molecules
  • neuroprotection
  • anti-inflammatory
  • inflammasome
  • neurodegeneration

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Published Papers (3 papers)

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Research

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18 pages, 2563 KiB  
Article
The Potential Anti-Cancer Effects of Polish Ethanolic Extract of Propolis and Quercetin on Glioma Cells Under Hypoxic Conditions
by Małgorzata Kłósek, Anna Kurek-Górecka, Radosław Balwierz, Grażyna Pietsz and Zenon P. Czuba
Molecules 2025, 30(14), 3008; https://doi.org/10.3390/molecules30143008 - 17 Jul 2025
Viewed by 403
Abstract
Tissue hypoxia is commonly observed in head cancers and contributes to both molecular and functional changes in tumour cells. It is known to stimulate erythropoiesis, angiogenesis, and metabolic alterations within tumour cells. Glioblastoma, a type of brain tumour, is characterized by rapid proliferation [...] Read more.
Tissue hypoxia is commonly observed in head cancers and contributes to both molecular and functional changes in tumour cells. It is known to stimulate erythropoiesis, angiogenesis, and metabolic alterations within tumour cells. Glioblastoma, a type of brain tumour, is characterized by rapid proliferation and aggressive growth. Recent studies have indicated that natural products may hold potential as components of cancer therapy. Among these, Polish propolis and its active compound, quercetin, have demonstrated promising anti-cancer properties. The aim of this study was to evaluate the concentrations of selected cytokines—specifically IL-6, IL-9, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1)—produced by astrocytes of the CCF-STTG1 cell line. The cytotoxic effects of ethanolic extract of propolis (EEP) and quercetin were assessed using the MTT assay. Astrocytes were stimulated with lipopolysaccharide (LPS, 200 ng/mL) and/or IFN-α (100 U/mL), followed by treatment with EEP or quercetin (25–50 µg/mL) under hypoxic conditions for two hours. Cytokine concentrations were measured using the xMAP Luminex Multiplex Immunoassay and the Multiplex Bead-Based Cytokine Kit. Our study demonstrated that Polish propolis and its component quercetin modulate the tumour microenvironment in vitro, primarily by altering the levels of specific cytokines. The HCA analysis revealed that IL-6 and MCP-1 formed a distinct cluster at the highest linkage distance (approximately 100% of Dmax), suggesting that their expression patterns are significantly different from those of the other cytokines and that they are more similar to each other than to the rest. PCA analysis showed that EEP-PL (50 μg/mL) with IFN-α and EEP-PL (50 μg/mL) with LPS exert similar activities on cytokine secretion by astrocytes. Similar effects were demonstrated for EEP-PL 50 μg/mL + LPS + IFN-α, EEP-PL 25 μg/mL + IFN-α and EEP-PL 25 μg/mL + LPS + IFN-α. Our findings suggest that Polish propolis and quercetin may serve as promising natural agents to support the treatment of stage IV malignant astrocytoma. Nonetheless, further research is needed to confirm these results. Full article
(This article belongs to the Special Issue Bioactive Compounds and Small Molecules with Neuroprotective and Anti-Inflammatory Functions)
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Review

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19 pages, 753 KiB  
Review
Neuroprotective Role of Omega-3 Fatty Acids: Fighting Alzheimer’s Disease
by Mervin Chávez-Castillo, María Paula Gotera, Pablo Duran, María P. Díaz, Manuel Nava, Clímaco Cano, Edgar Díaz-Camargo, Gabriel Cano, Raquel Cano, Diego Rivera-Porras and Valmore Bermúdez
Molecules 2025, 30(15), 3057; https://doi.org/10.3390/molecules30153057 - 22 Jul 2025
Abstract
Alzheimer’s disease (AD) is one of the main causes of dementia, with an exponential increment in its incidence as years go by. However, since pathophysiological mechanisms are complex and multifactorial, therapeutic strategies remain inconclusive and only provide symptomatic relief to patients. In order [...] Read more.
Alzheimer’s disease (AD) is one of the main causes of dementia, with an exponential increment in its incidence as years go by. However, since pathophysiological mechanisms are complex and multifactorial, therapeutic strategies remain inconclusive and only provide symptomatic relief to patients. In order to solve this problem, new strategies have been investigated over recent years for AD treatment. This field has been reborn due to epidemiological and preclinical findings that demonstrate the fact that omega-3 polyunsaturated fatty acids (ω-3 PUFAs) can be promising therapeutic agents because of their anti-inflammatory, antioxidant, and neurogenic-promoting activities, thus allowing us to classify these molecules as neuroprotectors. Similarly, ω-3 PUFAs perform important actions in the formation of characteristic AD lesions, amyloid-β plaques (Aβ) and neurofibrillary tangles, reducing the development of these structures. Altogether, the aforementioned actions hinder cognitive decline and possibly reduce AD development. In addition, ω-3 PUFAs modulate the inflammatory response by inhibiting the production of pro-inflammatory molecules and promoting the synthesis of specialised pro-resolving mediators. Consequently, the present review assesses the mechanisms by which ω-3 PUFAs can act as therapeutic molecules and the effectiveness of their use in patients. Clinical evidence so far has shown promising results on ω-3 PUFA effects, both in animal and epidemiological studies, but remains contradictory in clinical trials. More research on these molecules and their neuroprotective effects in AD is needed, as well as the establishment of future guidelines to obtain more reproducible results on this matter. Full article
(This article belongs to the Special Issue Bioactive Compounds and Small Molecules with Neuroprotective and Anti-Inflammatory Functions)
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29 pages, 1368 KiB  
Review
Specialized Pro-Resolving Lipid Mediators in Pulmonary Diseases: Molecular and Therapeutic Implications
by Ángel Ortega, Pablo Duran, Bermary Garrido, Alexander Manzano, Carolina Navarro, Aljadis Silva, Milagros Rojas, Juan Bautista De Sanctis, Danuta Radzioch, Diego Rivera-Porras, Carlos Silva Paredes and Valmore Bermúdez
Molecules 2025, 30(10), 2212; https://doi.org/10.3390/molecules30102212 - 19 May 2025
Viewed by 1248
Abstract
Inflammatory lung diseases (ILDs) represent a global public health crisis characterized by escalating prevalence, significant morbidity, and substantial mortality. In response to the complex immunopathogenic mechanisms driving these conditions, novel pharmacological strategies targeting resolution pathways have emerged throughout the discovery of specialized pro-resolving [...] Read more.
Inflammatory lung diseases (ILDs) represent a global public health crisis characterized by escalating prevalence, significant morbidity, and substantial mortality. In response to the complex immunopathogenic mechanisms driving these conditions, novel pharmacological strategies targeting resolution pathways have emerged throughout the discovery of specialized pro-resolving lipid mediator (SPM; resolvins, maresins, and protectins) dysregulation across the ILD spectra, positioning these endogenous molecules as promising therapeutic candidates for modulating maladaptive inflammation and promoting tissue repair. Over the past decade, this paradigm has catalyzed extensive translational research into SPM-based interventions as precision therapeutics for respiratory inflammation. In asthma, they reduce mucus hypersecretion, bronchial hyperreactivity, and airway inflammation, with prenatal SPM exposure potentially lowering offspring disease risk. In COPD, SPMs attenuate amyloid A-driven inflammation, normalizing cytokine/chemokine imbalances and oxidative stress and mitigating COVID-19-associated cytokine storm, enhancing survival. This review synthesizes SPMs’ pharmacotherapeutic mechanisms in ILDs and evaluates current preclinical and clinical evidence. Full article
(This article belongs to the Special Issue Bioactive Compounds and Small Molecules with Neuroprotective and Anti-Inflammatory Functions)
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