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Phytochemistry, Human Health and Molecular Mechanisms
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Phytochemistry, Human Health and Molecular Mechanisms

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

Deadline for manuscript submissions: 30 September 2025 | Viewed by 9873

Special Issue Editors

Prof. Dr. Valeria Naponelli

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy
Interests: autophagy; cancer; epigallocatechin gallate; polyphenol; flavanols; White Tea; antioxidant; extract
Prof. Dr. Elena Ferrari

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
Interests: allergenic proteins; protein structure; metabolomics; metabolism in health and disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleague,

The Section of Molecules entitled “Phytochemistry, Human Health and Molecular Mechanisms” aims to publish high-quality scientific contributions that provide novel insights into the impact of plant components, also known as phytochemicals, on human health. We welcome submissions with novel data on phytochemical bioaccessibility, bioavailability, absorption, metabolism, and bioactivity. Additionally, we are interested in stimulating debate on (facilitating conversations about) their effects on microbiota, their mechanisms of action, their improved formulation, and their safety of use as a food ingredient or additive. We will give special consideration to studies on the role of phytochemicals in key physiological functions and in the pathogenesis of human diseases. In addition, epidemiological studies that seek to identify the relationship between dietary intake of phytochemicals and the risk of disease also fall within the scope of this Section.

Both original research articles and comprehensive reviews are eligible for inclusion.

Prof. Dr. Valeria Naponelli
Prof. Dr. Elena Ferrari
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 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 compounds
  • bioavailability
  • extraction methods
  • biological activities
  • functional applications
  • nutraceuticals
  • human metabolism
  • toxicity
  • bioactive-gut microbiota relationships

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Published Papers (7 papers)

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Research

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13 pages, 1963 KiB  
Article
Supplementing Freezing Medium with Crocin Exerts a Protective Effect on Bovine Spermatozoa Through the Modulation of a Heat Shock-Mediated Apoptotic Pathway
by Vasiliki Sapanidou, Maria P. Tsantarliotou, Konstantinos Feidantsis, Eleni E. Tzekaki, Georgios Kourousekos and Sophia N. Lavrentiadou
Molecules 2025, 30(6), 1329; https://doi.org/10.3390/molecules30061329 - 16 Mar 2025
Viewed by 708
Abstract
The supplementation of freezing medium with crocin results in an amelioration of post-thawing sperm quality, as determined by motility and viability. This study aimed to examine the molecular mechanisms underlying the ameliorative effect of crocin. Bovine spermatozoa were cryopreserved in a freezing medium [...] Read more.
The supplementation of freezing medium with crocin results in an amelioration of post-thawing sperm quality, as determined by motility and viability. This study aimed to examine the molecular mechanisms underlying the ameliorative effect of crocin. Bovine spermatozoa were cryopreserved in a freezing medium supplemented with 0, 0.5, or 1 mM of crocin. Sperm lysates were evaluated for their redox status and the expression of proteins implicated in the heat stress response (HSR) and apoptosis. Crocin protected spermatozoa from the accumulation of superoxide anion and ameliorated their post-thawing antioxidant capacity in terms of ROS scavenging activity and glutathione content. Moreover, crocin decreased the levels of inducible nitric oxide synthase (iNOS), while it increased superoxide dimsutase-1 (SOD-1) levels. These effects were associated with an inhibition of apoptosis, as evidenced by a decreased Bax/Bcl-2 protein ratio and decreased levels of caspase-cleaved substrates. Finally, crocin affected the heat shock response of spermatozoa, since it upregulated the levels of heat shock proteins (Hsp) 60, 70, and 90. In conclusion, the addition of crocin to the freezing medium ensured controlled amounts of ROS, enhanced the antioxidant capacity of spermatozoa, and upregulated the anti-apoptotic proteins and Hsps, thus contributing to the maintenance of cellular homeostasis. Full article
(This article belongs to the Special Issue Phytochemistry, Human Health and Molecular Mechanisms)
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21 pages, 4568 KiB  
Article
From “Maraschino” to Cell Cultures: A Deep Study on Prunus cerasus L. Cell Culture Juices
by Vanessa Dalla Costa, Anna Piovan, Ina Varfaj, Maria Carla Marcotullio, Paola Brun and Raffaella Filippini
Molecules 2025, 30(5), 1089; https://doi.org/10.3390/molecules30051089 - 27 Feb 2025
Viewed by 359
Abstract
Prunus cerasus var. Marasca (Rosaceae) is an important Croatian cultivar, known wordwide for the production of Luxardo maraschino liqueur, which occurs in the eastern Po Valley of Italy. Besides liqueur, Marasca is attractive for its beneficial effects on human health and well-being. The [...] Read more.
Prunus cerasus var. Marasca (Rosaceae) is an important Croatian cultivar, known wordwide for the production of Luxardo maraschino liqueur, which occurs in the eastern Po Valley of Italy. Besides liqueur, Marasca is attractive for its beneficial effects on human health and well-being. The undifferentiated in vitro cell cultures of Marasca were investigated as a source of healthy products. The in vitro conditions for obtaining callus and suspension cultures under photoperiod were defined. The cell lines were evaluated for growth rate, total phenol and proanthocyanidin contents, and antioxidant activities via colorimetric assays. The best cell lines were also subcultured in darkness, studying the importance of the light parameter in the possible industrial scaling-up. The juices extracted from the obtained biomasses were analyzed by LC-DAD-MS and six flavanone derivatives, among which naringenin and its glucoside were identified. The quantitative analysis, pursued during the cell growth cycle, revealed that the flavanone content was higher at the end of the growth cycle (28th day) and that the total content of identified flavanone compounds varied from 17.22 to 79.22 μg/mL of juice. The results of the antioxidant and anti-inflammatory activities on Caco-2 cells support the potential applications of this material in human health. Full article
(This article belongs to the Special Issue Phytochemistry, Human Health and Molecular Mechanisms)
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18 pages, 3217 KiB  
Article
The Biflavonoid Agathisflavone Regulates Microglial and Astrocytic Inflammatory Profiles via Glucocorticoid Receptor
by Áurea Maria Alves Nunes Almeida, Cleonice Creusa dos Santos, Daniele Takahashi, Larissa Pereira da Silva, Verônica Moreira de Sousa, Monique Reis de Santana, Ana Elisa Del Arco, Balbino Lino dos Santos, Jorge Mauricio David, Victor Diogenes Amaral da Silva, Suzana Braga-de-Souza and Silvia Lima Costa
Molecules 2025, 30(5), 1014; https://doi.org/10.3390/molecules30051014 - 22 Feb 2025
Viewed by 512
Abstract
Nuclear receptors such as glucocorticoid receptors (GRs) are transcription factors with prominent regulatory effects on neuroinflammation. Agathisflavone is a biflavonoid that demonstrates neurogenic, neuroprotective, anti-inflammatory, antioxidant, and pro-myelinogenic effects in vitro. This study investigated whether the control of glial reactivity by agathisflavone is [...] Read more.
Nuclear receptors such as glucocorticoid receptors (GRs) are transcription factors with prominent regulatory effects on neuroinflammation. Agathisflavone is a biflavonoid that demonstrates neurogenic, neuroprotective, anti-inflammatory, antioxidant, and pro-myelinogenic effects in vitro. This study investigated whether the control of glial reactivity by agathisflavone is mediated by GRs. Primary cultures of astrocytes and microglia were induced to neuroinflammation by lipopolysaccharides (LPSs) and exposed to agathisflavone or not in the presence or absence of mifepristone, a GR antagonist. The microglia morphology and reactivity were evaluated by immunofluorescence against calcium-binding ionized adapter (Iba-1) and CD68. The astrocyte morphology and reactivity were evaluated by immunofluorescence against glial fibrillary acidic protein (GFAP). The inflammatory profile was evaluated by RT-qPCR. Molecular docking was performed to characterize agathisflavone and GR interactions. Microglial branching was increased in response to agathisflavone, an effect that was inhibited by mifepristone. CD68 and GFAP expression was decreased by agathisflavone but not in the presence of mifepristone. Agathisflavone decreased the expression of the pro-inflammatory cytokine IL-1β and increased the expression of the regulatory cytokine IL-10. The increase in IL-10 mRNA was inhibited by the GR antagonist. The in silico analysis showed that agathisflavone binds to a pocket at the glucocorticoid receptor. These interactions were stronger than mifepristone, dexamethasone, and the agathisflavone monomer apigenin. These results indicate that the GR is involved in the regulatory effects of agathisflavone on microglia and astrocyte inflammation, contributing to the elucidation of the molecular mechanisms of agathisflavone’s effects in the nervous system. Full article
(This article belongs to the Special Issue Phytochemistry, Human Health and Molecular Mechanisms)
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14 pages, 3056 KiB  
Article
Comparative Studies of Bioactivities and Chemical Components in Fresh and Black Garlics
by Kanako Matsuse, Sho Hirata, Mostafa Abdelrahman, Tetsuya Nakajima, Yoshihito Iuchi, Satoshi Kambayashi, Masaru Okuda, Kimiko Kazumura, Benya Manochai and Masayoshi Shigyo
Molecules 2024, 29(10), 2258; https://doi.org/10.3390/molecules29102258 - 11 May 2024
Cited by 5 | Viewed by 3462
Abstract
To investigate the bioactivities of fresh garlic and its processed product, black garlic, we conducted comparative analyses of antioxidant, anti-inflammatory, innate immune activation, and anti-cancer activities in addition to the chemical composition (sugar, amino acid, and polyphenol contents) of these materials. Simultaneous assay [...] Read more.
To investigate the bioactivities of fresh garlic and its processed product, black garlic, we conducted comparative analyses of antioxidant, anti-inflammatory, innate immune activation, and anti-cancer activities in addition to the chemical composition (sugar, amino acid, and polyphenol contents) of these materials. Simultaneous assay using neutrophil-like cells showed that fresh garlic exhibited antioxidant and innate immunostimulatory activities, whereas black garlic displayed a potent anti-inflammatory effect. The antioxidant activity index was correlated with phenol and flavonoid contents, while the innate immunostimulatory activity was correlated with fructan content. Furthermore, some black garlics with low fructose content were found to inhibit the proliferation of UM-UC-3 cancer cells, while other black garlics rich in fructose increased UM-UC-3 cell proliferation. It was shown that the processing of fresh garlic could change the composition of sugars, antioxidants, and amino acids, which have different effects on neutrophil-like cells and UM-UC-3 cells, as well as on bioactivities. Full article
(This article belongs to the Special Issue Phytochemistry, Human Health and Molecular Mechanisms)
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13 pages, 1440 KiB  
Article
Chemical Constituents and α-Glucosidase Inhibitory, Antioxidant and Hepatoprotective Activities of Ampelopsis grossedentata
by Qu-Jing Luo, Wen-Chao Zhou, Xin-Yi Liu, Ya-Jie Li, Qing-Ling Xie, Bin Wang, Chao Liu, Wen-Mao Wang, Wei Wang and Xu-Dong Zhou
Molecules 2023, 28(24), 7956; https://doi.org/10.3390/molecules28247956 - 5 Dec 2023
Cited by 6 | Viewed by 1844
Abstract
Ampelopsis grossedentata is a valuable medicinal and edible plant, which is often used as a traditional tea by the Tujia people in China. A. grossedentata has numerous biological activities and is now widely used in the pharmaceutical and food industries. In this study, [...] Read more.
Ampelopsis grossedentata is a valuable medicinal and edible plant, which is often used as a traditional tea by the Tujia people in China. A. grossedentata has numerous biological activities and is now widely used in the pharmaceutical and food industries. In this study, two new flavonoids (1–2) and seventeen known compounds (3–19) were isolated and identified from the dried stems and leaves of A. grossedentata. These isolated compounds were characterized by various spectroscopic data including mass spectrometry and nuclear magnetic resonance spectroscopy. All isolates were assessed for their α-glucosidase inhibitory, antioxidant, and hepatoprotective activities, and their structure–activity relationships were further discussed. The results indicated that compound 1 exhibited effective inhibitory activity against α-glucosidase, with an IC50 value of 0.21 μM. In addition, compounds 1–2 demonstrated not only potent antioxidant activities but also superior hepatoprotective properties. The findings of this study could serve as a reference for the development of A. grossedentata-derived products or drugs aimed at realizing their antidiabetic, antioxidant, and hepatoprotective functions. Full article
(This article belongs to the Special Issue Phytochemistry, Human Health and Molecular Mechanisms)
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Review

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22 pages, 3808 KiB  
Review
Natural and Designed Cyclic Peptides as Potential Antiviral Drugs to Combat Future Coronavirus Outbreaks
by Hilarie Uwamahoro, Willard E. Collier, Toufic O. Nashar, Jesse M. Jaynes, Desmond G. Mortley, Cheryl G. Davis, Getrude G. Kanyairita, Eslam F. Abdelazim, Jean Francois Regis Igiramaboko, Concorde Habineza, Devotha Tumushimiyimana, Umuraza Noella Rutayisire, Yasmin A. Davis and Kamora L. Renard
Molecules 2025, 30(8), 1651; https://doi.org/10.3390/molecules30081651 - 8 Apr 2025
Viewed by 562
Abstract
The COVID-19 pandemic has underscored the need for effective and affordable antiviral drugs. Anthropogenic activities have increased interactions among humans, animals, and wildlife, contributing to the emergence of new and re-emerging viral diseases. RNA viruses pose significant challenges due to their rapid mutation [...] Read more.
The COVID-19 pandemic has underscored the need for effective and affordable antiviral drugs. Anthropogenic activities have increased interactions among humans, animals, and wildlife, contributing to the emergence of new and re-emerging viral diseases. RNA viruses pose significant challenges due to their rapid mutation rates, high transmissibility, and ability to adapt to host immune responses and antiviral treatments. The World Health Organization has identified several diseases (COVID-19, Ebola, Marburg, Zika, and others), all caused by RNA viruses, designated as being of priority concern as potential causes of future pandemics. Despite advances in antiviral treatments, many viruses lack specific therapeutic options, and more importantly, there is a paucity of broad-spectrum antiviral drugs. Additionally, the high costs of current treatments such as Remdesivir and Paxlovid highlight the need for more affordable antiviral drugs. Cyclic peptides from natural sources or designed through molecular modeling have shown promise as antiviral drugs with stability, low toxicity, high target specificity, and low antiviral resistance properties. This review emphasizes the urgent need to develop specific and broad-spectrum antiviral drugs and highlights cyclic peptides as a sustainable solution to combat future pandemics. Further research into these compounds could provide a new weapon to combat RNA viruses and address the gaps in current antiviral drug development. Full article
(This article belongs to the Special Issue Phytochemistry, Human Health and Molecular Mechanisms)
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16 pages, 262 KiB  
Review
The Chemical Residues in Secondary Beekeeping Products of Environmental Origin
by Joanna Wojtacka
Molecules 2024, 29(16), 3968; https://doi.org/10.3390/molecules29163968 - 22 Aug 2024
Viewed by 1361
Abstract
Natural products of bee origin, despite their complex composition and difficulties in standardization, have been of high interest among scientists representing various disciplines from basic sciences to industrial and practical implementation. As long as their use is monitored and they do not impact [...] Read more.
Natural products of bee origin, despite their complex composition and difficulties in standardization, have been of high interest among scientists representing various disciplines from basic sciences to industrial and practical implementation. As long as their use is monitored and they do not impact human health, they can be considered valuable sources of many chemical compounds and are potentially useful in medicine, food processing, nutrition, etc. However, apart from honey, the general turnover of bee products lacks precise and detailed legal requirements ensuring their quality. The different residues in these products constitute a problem, which has been reported in numerous studies. All products derived from beekeeping are made by bees, but they are also influenced by the environment. Such a dual pathway requires detailed surveillance of hazards stemming from outside and inside the apiary. This should be ensured via harmonized requirements arising from the binding legal acts, especially in international and intercontinental trade zones. Full article
(This article belongs to the Special Issue Phytochemistry, Human Health and Molecular Mechanisms)
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