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The Role of Phytochemicals in Aging and Aging-Related Diseases, 2nd...
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The Role of Phytochemicals in Aging and Aging-Related Diseases, 2nd Edition

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

Deadline for manuscript submissions: 25 October 2026 | Viewed by 2275

Special Issue Editors

Prof. Dr. Giovanni Scapagnini

E-Mail Website
Guest Editor
Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
Interests: phytochemicals; dietary supplementation; nutrition; natural compounds; antioxidants; aging
Special Issues, Collections and Topics in MDPI journals
Dr. Sergio Davinelli

E-Mail Website
Guest Editor
Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
Interests: nutrition and dietetics; health promotion; aging; functional foods; food phytochemicals; dietary polyphenols
Special Issues, Collections and Topics in MDPI journals
Dr. Alessandro Medoro

E-Mail Website
Guest Editor
Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
Interests: phytochemicals; plant-based diet; dietary supplementation; pharma-nutrition; aging; nutrition; aging-related diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Aging is an inevitable process influenced by genetic, lifestyle, and environmental factors. Recent non-pharmacological approaches toward achieving improvements in the aging process, as well as those toward potentially reversing/delaying it,, shed new light on this topic. Among the variegated class of anti-aging molecules, phytochemicals and their metabolites have been suggested to improve aging and aging-related diseases. They comprise a large family of plant-derived metabolites with highly diverse chemical structures that are not directly involved in the growth and development of plants but are synthesized to increase their survival fitness. A growing body of evidence suggests that phytochemicals can not only act as simple antioxidant agents that neutralize free radicals, but that they can also modulate one or more cellular pathways associated with lifespan, aging, and disease prevention. Indeed, these bioactive molecules exert anti-aging effects via different mechanisms, such as the inhibition of cell senescence and mitochondrial dysfunction and the reduction in telomere shortening, epigenetic alterations, and genomic instability. Finally, phytochemicals’ excellent safety profile and large structural diversity make them particularly attractive for drug discovery processes.

This Special Issue will include publications on topics including (but not limited to) the following:

  • Biological effects of phytochemicals associated with aging-related pathways and diseases;
  • Molecular pharmacology techniques to identify potential anti-aging phytochemicals;
  • The Bioavailability of dietary phytochemicals (e.g., gut microbiota, additive/synergistic effects) in the context of aging;
  • Dietary phytochemicals and the design of new drugs/derivatives to target aging-related mechanisms;
  • Dietary phytochemicals and human intervention trials against aging-related disease.

Prof. Dr. Giovanni Scapagnini
Dr. Sergio Davinelli
Dr. Alessandro Medoro
Guest Editors

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 250 words) can be sent to the Editorial Office for assessment.

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. Pharmaceuticals is an international peer-reviewed open access monthly 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 2900 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

  • phytochemicals
  • plant-based diet
  • dietary supplementation
  • pharma-nutrition
  • aging
  • aging-related diseases
  • prevention

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Related Special Issue

Published Papers (3 papers)

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Research

17 pages, 1709 KB  
Article
A Lecithin-Based Delivery Form of Quercetin Promotes Stress Resistance and Longevity in Caenorhabditis elegans
by Margherita Romeo, Maria Monica Barzago, Claudia Fracasso, Manuel Nettis, Antonella Riva, Marco Gobbi, Serena Tongiani and Luisa Diomede
Pharmaceuticals 2026, 19(4), 525; https://doi.org/10.3390/ph19040525 - 24 Mar 2026
Viewed by 573
Abstract
Background/Objectives: The flavonoid quercetin (Q) has recently been suggested as a natural anti-aging and senolytic agent. However, its low stability and poor oral bioavailability may limit its efficacy. To address this, we investigated whether a lecithin-based formulation of Q, Quercefit™ (QF), enhances [...] Read more.
Background/Objectives: The flavonoid quercetin (Q) has recently been suggested as a natural anti-aging and senolytic agent. However, its low stability and poor oral bioavailability may limit its efficacy. To address this, we investigated whether a lecithin-based formulation of Q, Quercefit™ (QF), enhances stress resistance and delays aging in vivo. Methods: The nematode Caenorhabditis elegans was used as an animal model to evaluate the effects of QF under physiological and stress conditions. Unformulated Q was administered as a control. Worm survival, healthspan, resistance to thermal and oxidative stress, and expression of stress- and longevity-related genes were assessed. All the experiments were conducted at least in triplicate, each including a minimum of 15 worms. The data were analyzed using Student’s t-test, one-way or two-way ANOVA, and Bonferroni’s post hoc test. Results: One hundred micromolar Q administered in QF was more effective than equimolar unformulated Q in increasing the worms’ ability to resist acute thermal stress at 35 °C (tested on 75 worms/group) and oxidative stress caused by 0.5 mM hydrogen peroxide (tested on 75 worms/group). In this last case, the protective effect of QF was similar to that of N-acetylcysteine and ascorbic acid. Under experimental conditions mimicking the long-term consequences of thermal stress, QF, like Q, increased the worms’ lifespan and healthspan by approximately 50%, counteracting the age-related decline associated with stress (120 worms/group). These benefits are supported by QF’s capacity to act as a reactive oxygen species scavenger; suppress heat-shock element gene transcription activated by thermal stress, such as hsp-16.2 and hsp-70, and stimulate the sod-3 and gst-4 genes that are involved in antioxidant and detoxification responses. Conclusions: These findings suggest that Q, when administered in the QF formulation, can act at the transcriptional level to protect against aging induced by stressful conditions. Full article
(This article belongs to the Special Issue The Role of Phytochemicals in Aging and Aging-Related Diseases, 2nd Edition)
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40 pages, 17948 KB  
Article
Yixin Yangshen Granules Target HIF−1 Signaling to Modulate the Neuroimmune Microenvironment in Alzheimer’s Disease: Insights from Integrative Multi-Omics and Deep Learning
by Zhihao Wang, Linshuang Wang, Yusheng Zhang, Sixia Yang, Bo Shi, Dasheng Liu, Han Zhang, Wan Xiao, Junying Zhang, Xuejie Han and Dongfeng Wei
Pharmaceuticals 2026, 19(3), 502; https://doi.org/10.3390/ph19030502 - 18 Mar 2026
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Abstract
Background/Objectives: Alzheimer’s disease (AD) involves amyloid and tau pathology with neuroimmune dysregulation, and Yixin Yangshen Granules (YXYS) shows neuroprotective promise, though mechanisms remain unclear. This study aimed to elucidate the multi-target mechanisms of YXYS in AD. Methods: The study began by [...] Read more.
Background/Objectives: Alzheimer’s disease (AD) involves amyloid and tau pathology with neuroimmune dysregulation, and Yixin Yangshen Granules (YXYS) shows neuroprotective promise, though mechanisms remain unclear. This study aimed to elucidate the multi-target mechanisms of YXYS in AD. Methods: The study began by analyzing a public human AD hippocampal snRNA-seq dataset to identify cell-type-specific pathological pathways and profiled YXYS constituents by UPLC-QTOF-MS. In vitro, YXYS cytoprotection against mitochondrial dysfunction and oxidative stress was tested in Aβ25–35-challenged HT22 cells; in vivo efficacy was assessed in Aβ1–42-induced mice via behavioral and histopathological analyses. Integrated transcriptomic and proteomic profiling of brain tissue, with ELISA, qRT-PCR, and Western blot validation, confirmed pathway targets. Using the intersection of transcriptomic and proteomic targets as biological input, the DTIAM deep learning framework was employed to prioritize active YXYS constituents. Finally, molecular docking and 100-ns dynamics simulations demonstrated direct binding of Ganosporelactone A to HIF−1α. Results: AD snRNA-seq analysis highlighted HIF−1 and AGE-RAGE signaling as prominent pathways in the AD hippocampus, particularly enriched in brain microvascular endothelial cells, implicating neurovascular hypoxic and inflammatory stress. In Aβ-induced mice, YXYS improved cognition, reduced Aβ pathology, suppressed neuroinflammation, and promoted neuronal survival, consistent with in vitro evidence of restored mitochondrial function. Multi-omics confirmed convergence on HIF−1 and AGE-RAGE pathways, with YXYS rebalancing the neuroimmune microenvironment by reducing pro-inflammatory M0 macrophages. Screening against these consensus signaling hubs, deep learning analysis prioritized Ganosporelactone A as the top-ranked modulator, and molecular further demonstrated the stable binding of Ganosporelactone A to HIF−1α, linking YXYS to mitigation of hypoxic stress. Conclusions: Guided by multi-omics and deep learning, our findings suggest that YXYS may alleviate AD-related phenotypes through multi-target modulation of the HIF−1 and AGE-RAGE pathways, with associated improvements in neuro-immune homeostasis and reductions in oxidative stress, neuroinflammation, and hypoxia. Full article
(This article belongs to the Special Issue The Role of Phytochemicals in Aging and Aging-Related Diseases, 2nd Edition)
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15 pages, 3803 KB  
Article
Differential Impact of Olive Leaf Extract and Its Secoiridoid Components, Oleuropein Aglycone and Oleacin, on Adipogenic Differentiation and Proliferation of Bone Marrow Mesenchymal Stem Cells
by Chiara Giordani, Angelica Giuliani, Silvia Di Valerio, Tatiana Spadoni, Laura Graciotti, Sonia Bonacci, Antonio Domenico Procopio, Antonio Procopio and Maria Rita Rippo
Pharmaceuticals 2026, 19(3), 353; https://doi.org/10.3390/ph19030353 - 25 Feb 2026
Viewed by 581
Abstract
Background/Objectives: Bone marrow adipose tissue (BMAT) serves multiple physiological roles but accumulates with age, compromising skeletal health. This expansion is largely driven by an adipogenic drift of bone marrow mesenchymal stromal cells (BMSCs), shifting attention toward stromal cell fate regulation as a [...] Read more.
Background/Objectives: Bone marrow adipose tissue (BMAT) serves multiple physiological roles but accumulates with age, compromising skeletal health. This expansion is largely driven by an adipogenic drift of bone marrow mesenchymal stromal cells (BMSCs), shifting attention toward stromal cell fate regulation as a target to preserve bone marrow homeostasis. Preventing adipogenic commitment may be as relevant as directly inducing osteogenesis for maintaining a bone-permissive marrow microenvironment. Here, we investigated whether olive leaf extract (OLE) and its purified secoiridoid components, oleacin (OC) and oleuropein aglycone (OA), modulate the adipogenic differentiation and proliferative capacity of human BMSCs. Methods: Human BMSCs were induced to undergo adipogenic differentiation and treated with OLE, OC, or OA. Intracellular lipid accumulation and the expression of key adipogenic regulators were assessed. Proliferative capacity was evaluated under both maintenance and adipogenic conditions. Results: Under adipogenic conditions, OLE markedly reduced intracellular lipid accumulation and induced a coordinated downregulation of PPARγ, PLIN1, FABP4, ADIPOQ, LEP and the adipogenesis-associated miR-422a. In contrast, OC and OA exerted more selective and specific effects on biomarkers, indicating the partial and complementary modulation of adipogenic programs. Notably, OLE also increased BMSC proliferation under both maintenance and adipogenic conditions, suggesting the preservation of a less committed stromal cell pool. Although the relative contribution of enhanced proliferation versus the direct inhibition of adipogenic pathways cannot be fully disentangled, the combined molecular and functional data support a dual action of OLE on stromal cell fate. Conclusions: OLE limits adipogenic commitment while maintaining stromal cell proliferative competence, processes that are critically involved in BMAT expansion and bone marrow dysfunction. OC and OA contribute to OLE bioactivity deserving further investigation, particularly in combination, as potential modulators of BMAT expansion. Full article
(This article belongs to the Special Issue The Role of Phytochemicals in Aging and Aging-Related Diseases, 2nd Edition)
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