Molecules

32 pages, 1896 KB

Open AccessArticle

Effects of Aronia melanocarpa Tannins on Oxidative Stress and Immune Dysfunction

by Kseniya Bushmeleva, Alexandra Vyshtakalyuk, Dmitriy Terenzhev, Timur Belov, Kamila Kazimova and Vladimir Zobov

Molecules 2025, 30(22), 4338; https://doi.org/10.3390/molecules30224338 (registering DOI) - 8 Nov 2025

Abstract

Natural polyphenols, particularly tannins, are of interest due to their complex composition and multi-target biological activities. A highly purified tannin fraction was isolated from Aronia melanocarpa fruits, and its composition was characterized by HPLC-MS and IR spectroscopy. The Aronia tannin fraction exhibited comprehensive [...] Read more.

Natural polyphenols, particularly tannins, are of interest due to their complex composition and multi-target biological activities. A highly purified tannin fraction was isolated from Aronia melanocarpa fruits, and its composition was characterized by HPLC-MS and IR spectroscopy. The Aronia tannin fraction exhibited comprehensive antioxidant properties, demonstrating superior DPPH radical scavenging activity compared to quercetin and a membrane-protective effect exceeding reference antioxidants. In vivo, Aronia tannins showed a delayed but potent antioxidant effect against cyclophosphamide (CP)-induced oxidative stress, significantly reducing malondialdehyde (MDA) levels, with the maximum effect observed at days 14–21. The immunomodulatory effect involved a complex regulation of the phagocytic system: selective activation of the monocytic arm with simultaneous modulation of neutrophilic activity. Crucially, a high phagocytic completion rate was maintained, indicating support for both bacterial uptake and intracellular killing. Tannins accelerated recovery post-CP, restoring leukocyte and platelet counts. Modulation of neutrophil oxidative metabolism, measured by chemiluminescence, indicates an ability to balance defense activation with prevention of excessive oxidative stress. These findings confirm the potential of the Aronia melanocarpa tannin fraction for correcting oxidative stress and immune dysfunction. Full article

(This article belongs to the Special Issue Natural Products with Pharmaceutical Activities, 2nd Edition)

► Show Figures

Figure 1

20 pages, 3312 KB

Open AccessArticle

Application of VHH-Immobilized Cryogel-Based Immunoaffinity Chromatography for Isolation of Extracellular Vesicles

by Jovana Terzić, Lidija Filipović, Ninoslav Mitić, Sanja Stevanović, Jugoslav Krstić, Ario de Marco, Julie Courraud and Milica Popović

Molecules 2025, 30(22), 4337; https://doi.org/10.3390/molecules30224337 (registering DOI) - 8 Nov 2025

Abstract

Extracellular vesicles (EVs) are nanosized structures involved in intercellular communication that have high potential as disease biomarkers and for the delivery of therapeutic cargos. However, translation to the clinic is hampered by time-consuming, low-yield, and poorly reproducible EV isolation methods. We describe a [...] Read more.

Extracellular vesicles (EVs) are nanosized structures involved in intercellular communication that have high potential as disease biomarkers and for the delivery of therapeutic cargos. However, translation to the clinic is hampered by time-consuming, low-yield, and poorly reproducible EV isolation methods. We describe a cryogel-based immunoaffinity chromatography system that exploits single-domain VHH antibodies as capture elements for the selective isolation of EVs from human plasma. Supermacroporous cryogels functionalized with five unique anti-EV VHHs (total immobilization capacity ~500 µg/g) were prepared, yielding a highly permeable and hydrophilic support. They were captured and eluted under mild conditions, and their morphology and identity were confirmed by SEM, AFM, NTA, and flow cytometry. Proteomic profiling of the isolated samples identified 234 proteins, of which 63% were ExoCarta-listed exosomal proteins; contaminants such as albumin and apolipoproteins were also identified. The purification method provided samples with ~2 × 10⁹ EVs/mL, with EV median size of 135 nm and consistent protein-to-lipid ratio across three independent isolations (CV < 10%). This study demonstrates that VHH-functionalized cryogels (VHH-SMC) are a rapid and reproducible EV purification method that represents a promising alternative to conventional ultracentrifugation- or precipitation-based protocols. While optimization of nanobody density and reduction in plasma protein carryover are still necessary, the platform holds potential for scalable EV enrichment, a condition that can significantly speed up biomarker research and clinical diagnostics. Full article

(This article belongs to the Section Chemical Biology)

► Show Figures

Figure 1

14 pages, 2296 KB

Open AccessArticle

A Potential Pathway for the Synthesis of Biomass-Based Polyamide Monomer 2,5-Bis(aminomethyl)furan from 2,5-Furandicarboxylic Acid

by Cong Wang, Xin Li, Junqi Zhao, Bin Sun, Enquan Wang, Xuhong Mu and Xiaoxin Zhang

Molecules 2025, 30(22), 4336; https://doi.org/10.3390/molecules30224336 (registering DOI) - 8 Nov 2025

Abstract

In this study, the transformation of 2,5-furandicarboxylic acid (FDCA) to 2,5-bis(aminomethyl)furan (BAMF) is proposed and investigated for the first time. Using FDCA as the substrate, the process involves two key steps: first, converting FDCA to 2,5-dicyanofuran (DCF) via carboxy-cyanation, followed by the heterogeneous [...] Read more.

In this study, the transformation of 2,5-furandicarboxylic acid (FDCA) to 2,5-bis(aminomethyl)furan (BAMF) is proposed and investigated for the first time. Using FDCA as the substrate, the process involves two key steps: first, converting FDCA to 2,5-dicyanofuran (DCF) via carboxy-cyanation, followed by the heterogeneous catalytic hydrogenation of DCF to produce BAMF. For the carboxy-cyanation, two ammoniation routes were compared, including the molten ammoniated dehydration route and the moderate ammoniated dehydration route. The difference between the ammoniation of bio-based cyclic dicarboxylic acid and that of petroleum-based aliphatic dicarboxylic acid was discovered. A moderate ammoniated dehydration route that is more suitable for bio-based cyclic dicarboxylic acid has been developed. SOCl₂ was found to effectively activate the stable carboxyl group and act as a dehydrating agent, facilitating the dehydration of the intermediate 2,5-furandicarboxamide (FDAM) to DCF with higher efficiency. For the hydrogenation reaction of DCF, Raney Co exhibited excellent catalytic performance, achieving a 94.5% yield of BAMF from DCF. Based on industrial practice, this research represents the first exploration of the pathway from bio-based FDCA to BAMF, which opens a new line for the sustainable production of bio-based diamines. Full article

(This article belongs to the Special Issue 5th Anniversary of the "Applied Chemistry" Section)

► Show Figures

Figure 1

22 pages, 1144 KB

Open AccessArticle

Momordica charantia L. (Cucurbitaceae) Leaf Extract from Phytochemical Characterization and Toxicity Evaluation to Modulation of Pro-Inflammatory Cytokines and MAPK/NFκB Pathways

by Maria Lúcia de Azevedo Oliveira, Rubiamara Mauricio de Sousa, Eder Alves Barbosa, Ony Araújo Galdino, Duanny Lorena Aires Dantas, Ingrid Reale Alves, Raphaelle Sousa Borges, Nayara Costa de Melo Castelo Branco, Artemis Socorro do Nascimento Rodrigues, Gisele Custódio de Souza, Saulo Victor e Silva, Gabriel Araujo-Silva, Jefferson Romáryo Duarte da Luz and Maria das Graças Almeida

Molecules 2025, 30(22), 4335; https://doi.org/10.3390/molecules30224335 (registering DOI) - 7 Nov 2025

Abstract

Momordica charantia L. (Cucurbitaceae) has been widely recognized for its pharmacological potential, although studies on its leaves remain scarce. In this study, the hydroethanolic leaf extract (MCHLE) was chemically characterized by LC–MS/MS, revealing the presence of octopamine, ferulate, vitexin-2-O-rhamnoside, and other bioactive phenolics. [...] Read more.

Momordica charantia L. (Cucurbitaceae) has been widely recognized for its pharmacological potential, although studies on its leaves remain scarce. In this study, the hydroethanolic leaf extract (MCHLE) was chemically characterized by LC–MS/MS, revealing the presence of octopamine, ferulate, vitexin-2-O-rhamnoside, and other bioactive phenolics. Toxicological evaluation in Wistar rats demonstrated that both acute (2000 mg/kg) and repeated oral administration (up to 400 mg/kg for 28 days) caused no clinical or behavioral signs of toxicity. Notably, treatment significantly reduced glucose and cholesterol levels, in addition to attenuating lipid peroxidation and enhancing antioxidant defenses. In vivo, MCHLE inhibited leukocyte and neutrophil infiltration in the LPS-induced peritonitis model, with efficacy comparable to dexamethasone. It also reduced TNF-α secretion and nitric oxide generation in peritoneal fluids. In vitro assays with LPS-stimulated RAW 264.7 macrophages confirmed these effects, showing dose-dependent inhibition of TNF-α, IL-1β, and NO production. Gene expression analysis further demonstrated downregulation of TNF-α and MAPK, with marked suppression of NF-κB transcripts. Collectively, these results suggest that MCHLE exerts anti-inflammatory activity by targeting both mediator release and upstream signaling pathways, while maintaining a favorable safety profile, supporting its potential for further investigation as a promising source of bioactive compounds. Full article

(This article belongs to the Special Issue Natural Compounds for Disease and Health, 3rd Edition)

19 pages, 3043 KB

Open AccessArticle

Dawson- and Lindqvist-Type Hybrid Polyoxometalates: Synthesis, Characterization and Ca²⁺-ATPase Inhibition Potential

by Islem Meskini, Frédéric Capet, Gil Fraqueza, Necmi Dege, Muhammad Nawaz Tahir, Brahim Ayed and Manuel Aureliano

Molecules 2025, 30(22), 4334; https://doi.org/10.3390/molecules30224334 (registering DOI) - 7 Nov 2025

Abstract

Polyoxometalates (POMs) represent a broad class of anionic inorganic (V, Mo, W) clusters with versatile structures of chemical and physical properties. POMs are inhibitors of many enzymes, including P-type ATPases, well-known to be a target of several approved drugs. Herein, two new hybrid [...] Read more.

Polyoxometalates (POMs) represent a broad class of anionic inorganic (V, Mo, W) clusters with versatile structures of chemical and physical properties. POMs are inhibitors of many enzymes, including P-type ATPases, well-known to be a target of several approved drugs. Herein, two new hybrid POMs with Mo and mixed V/W, namely (C₂H₈N₁)₆[V₂Mo₁₈O₆₂].3H₂O (1) and (C₄H₁₆N₃)₄[V₂W₄O₁₉]₃.12H₂O (2), were synthesized via wet chemical methods in aqueous solution, and their purity was confirmed and characterized by single X-ray diffraction and infrared spectroscopy. The cations are dimethylammonium ((C₂H₈N)⁺) and diethylenetriammonium ((C₄H₁₆N₃)³⁺), respectively. POMs biological activities were investigated, specifically their inhibitory potential against Ca²⁺-ATPase. The sarcoplasmic reticulum Ca²⁺-ATPase activities were measured spectrophotometrically using the coupled enzyme pyruvate kinase/lactate dehydrogenase assay. For the Ca²⁺-ATPase activity, Dawson (1) showed an IC₅₀ value of 3.4 μM, whereas Lindqvist (2) displayed a value of 45.1 μM. The Ca²⁺-ATPase inhibitory potential of these POMs can be correlated with the net charge (namely 6- and 4-) and the charge density (namely 0.33 and 0.67). A structure–activity-relationship was established for a series of 17 POMs Ca²⁺-ATPase inhibitors correlating IC₅₀ values and POMs net charge and POMs charge density. The described features make Dawson (1) and Lindqvist (2) attractive POMs in a wide range of chemistry fields as well as in biomedical applications. Full article

(This article belongs to the Special Issue Synthesis and Biological Evaluation of Coordination Compounds)

► Show Figures

Figure 1

18 pages, 669 KB

Open AccessArticle

Titanium Dioxide Solar Photocatalytic Microbial Inactivation Assessment Utilizing Viability Tests and a Novel Triplex qPCR Assay for Nucleic Acid Degradation Determination

by Ioannis Paspaltsis, Eirini Kanata, Sotirios Sotiriadis, Chrysanthi Berberidou, Sophia Tsoumachidou, Athanasios Arsenakis, Konstantinos Xanthopoulos, Dimitra Dafou, Ioannis Poulios and Theodoros Sklaviadis

Molecules 2025, 30(22), 4333; https://doi.org/10.3390/molecules30224333 (registering DOI) - 7 Nov 2025

Abstract

Photocatalytic oxidation of microorganisms is a powerful alternative to established disinfection approaches, applicable to a variety of water matrices. Bacterial vegetative cells, spores, fungi, and viruses, represent potential biopathogens and photocatalysis targets. Inactivation efficiency is usually evaluated by assessing viability through culture. However, [...] Read more.

Photocatalytic oxidation of microorganisms is a powerful alternative to established disinfection approaches, applicable to a variety of water matrices. Bacterial vegetative cells, spores, fungi, and viruses, represent potential biopathogens and photocatalysis targets. Inactivation efficiency is usually evaluated by assessing viability through culture. However, additional inactivation assessment approaches are needed, as some microbes, despite being unculturable, remain metabolically active and pathogenic. Nucleic acid quantification approaches (qPCR) can assess nucleic acid release and degradation during photocatalysis. We developed a novel multiplex qPCR assay for simultaneous detection/quantification of genomic DNA from different bacterial and fungal species and of MS2 bacteriophage load. Following small-scale solar titanium dioxide photocatalysis on a microbial suspension mixture containing different biopathogen classes, we assessed photocatalytic efficiency by conventional microbiological assays (culture) and our novel molecular assay. Microbiological assays show a significant reduction in microbe viability within one hour of processing, following previously reported patterns of microbial species resistance. Molecular analysis data show that nucleic acids released in solution due to microbial oxidative damage were significantly reduced due to oxidative degradation within six hours. Through targeting different biopathogen classes, our assay could be a useful tool for assessment of photocatalytic microbe inactivation both in laboratory and real-wastewater applications. Full article

(This article belongs to the Topic Advanced Oxidation Processes for Wastewater Purification)

39 pages, 4000 KB

Open AccessReview

Aptamer-Based Biosensors for Rapid Detection and Early Warning of Food Contaminants: From Selection to Field Applications

by Cong Wang, Mengyu Ye, Ximeng Zhang, Xin Chai, Huijuan Yu, Boshi Liu, Chengyu Zhang and Yuefei Wang

Molecules 2025, 30(22), 4332; https://doi.org/10.3390/molecules30224332 - 7 Nov 2025

Abstract

Aptamer-based biosensors have emerged as an important and promising technology for applications in food safety, environmental monitoring, and pharmaceutical analysis. Obtained via Systematic evolution of ligands by exponential enrichment (SELEX) screening, these recognition elements exhibit antibody-comparable affinity and specificity, alongside superior chemical stability, [...] Read more.

Aptamer-based biosensors have emerged as an important and promising technology for applications in food safety, environmental monitoring, and pharmaceutical analysis. Obtained via Systematic evolution of ligands by exponential enrichment (SELEX) screening, these recognition elements exhibit antibody-comparable affinity and specificity, alongside superior chemical stability, easy synthesis, and broad target adaptability. Substantial advances in the field have been marked by the systematic development of food contaminant-specific aptamers, elucidation of their binding mechanisms, and construction of versatile biosensing platforms. The integration of these aptamers with conventional electrochemical and optical sensors has substantially enhanced detection sensitivity and lowered detection limits, particularly for trace-level analytes in complex food matrices. Furthermore, the integration of aptamer technology with novel nanomaterials has facilitated the development of high-performance detection platforms for a wide range of food contaminants, including heavy metals, antibiotics, foodborne pathogens, mycotoxins, pesticides, and food additives. This review systematically summarizes recent advances in SELEX techniques for aptamer screening, highlights the application of aptamer-based biosensors in detecting these contaminants, and discusses current challenges and future prospects in the field of food safety, which establishes a comprehensive framework to advance aptamer-based biosensing technologies for rapid detection and early warning in food safety monitoring. Full article

(This article belongs to the Special Issue New Insights into Protein and Biomolecule Interactions)

18 pages, 875 KB

Open AccessArticle

Ultrasound-Assisted Extraction: Unlocking the Antibacterial Potential of Coptis chinensis Franch. Against ESBL-Producing Enterobacterales

by Ching Ching Hui, Fred Wang Fat Lee, Wesley Chin Ho Lung, Kai Chung Fan, Ivan Tak Fai Wong, Gilman Kit Hang Siu, Yeuk Lung Chow, Ping Lung Chan, Siu-Mui Ng, Ling Shi, Sai Wang Seto, Franklin Wang Ngai Chow and Emily Wan Ting Tam

Molecules 2025, 30(22), 4331; https://doi.org/10.3390/molecules30224331 (registering DOI) - 7 Nov 2025

Abstract

The global rise of multidrug-resistant Extended Spectrum β-Lactamase Producing-Enterobacterales (ESBL-PE) poses a critical threat to public health, driving the urgent need for alternative therapeutic approaches. This study evaluates the antimicrobial properties of 20 Chinese medicinal herbs against 14 ESBL-PE strains from seven [...] Read more.

The global rise of multidrug-resistant Extended Spectrum β-Lactamase Producing-Enterobacterales (ESBL-PE) poses a critical threat to public health, driving the urgent need for alternative therapeutic approaches. This study evaluates the antimicrobial properties of 20 Chinese medicinal herbs against 14 ESBL-PE strains from seven bacterial species, utilizing three extraction methods: traditional water decoction, 80% ethanol maceration, and 50% ethanol with ultrasound-assisted extraction (UAE). Among the herbs tested, Coptis chinensis Franch. demonstrated the most potent anti-ESBL-PE activity, effectively inhibiting multiple strains, including Escherichia coli, Klebsiella pneumoniae, Hafnia alvei, Citrobacter freundii and Proteus hauseri. C. chinensis extracts obtained via UAE exhibited superior antibacterial activity to the other two extraction methods, attributed to enhanced extraction efficiency and improved bioactive compound yields. Specifically, UAE increased the extraction yield of alkaloids in C. chinensis by 80.9%, compared to the ethanol maceration method, and the increase in berberine, the key antimicrobial compound, was 75.4%. Berberine demonstrated significant antibacterial effects against ESBL-PE strains, while other phytochemicals in C. chinensis extracts have an additional effect with berberine, further amplifying the overall antimicrobial activity. These findings highlight that the UAE is a promising method for enhancing the therapeutic potential of C. chinensis and other Chinese medicinal herbs against multidrug-resistant bacteria. Full article

(This article belongs to the Special Issue Extraction, Chromatography, and Mass Spectrometry Analysis of Food and Plant Biomolecules)

► Show Figures

Figure 1

27 pages, 888 KB

Open AccessArticle

The Impact of Production Technology on the Quality of Potato Spirit

by Maria Balcerek, Rafał Mielczarek, Urszula Dziekońska, Katarzyna Pielech-Przybylska and Andrea Patelski

Molecules 2025, 30(22), 4330; https://doi.org/10.3390/molecules30224330 - 7 Nov 2025

Abstract

Spirit drink, known in Central and Eastern Europe as ‘okowita’ (its official designation is ‘spirit’), is obtained by distilling fermented plant raw materials. Unlike vodka, which is produced from highly purified ethyl alcohol of agricultural origin, ‘okowita’ is characterised by the preservation of [...] Read more.

Spirit drink, known in Central and Eastern Europe as ‘okowita’ (its official designation is ‘spirit’), is obtained by distilling fermented plant raw materials. Unlike vodka, which is produced from highly purified ethyl alcohol of agricultural origin, ‘okowita’ is characterised by the preservation of the natural aromatic and flavour compounds originating from the raw material and produced during the process of alcoholic fermentation. The study aimed to assess the impact of production technology on the quality of potato spirits. The effects of the methods used for the pretreatment of raw material, starch hydrolysis and fermentation, and yeast strains were examined in relation to the fermentation efficiency and the chemical composition of the distillates. The yeast strains were the key factor determining fermentation efficiency. The SafSpirit and Pinnacle yeast strains provided the highest fermentation yields (85.0–97.7% of the theoretical), while the Ethanol Red strain provided the lowest yield (<83%). No advantage of separate hydrolysis and fermentation (SHF) over simultaneous saccharification and fermentation (SSF) was observed. A characteristic feature of potato distillates was their high isobutyl alcohol content, ranging from 557 to 1437 mg/L of 100% v/v alcohol, i.e., more than twice that of 3-methyl-1-butanol. Methanol concentrations remained below the limit specified in EU Regulation 2024/1143 (≤1000 g/hL of 100% v/v alcohol). The results are promising in terms of the potential for the production of craft potato spirit drinks. Full article

(This article belongs to the Special Issue New Development in Fermented Products—Third Edition)

19 pages, 2130 KB

Open AccessArticle

Exploring the Scope of Functionalized N-Acylneuraminic Acid β-Methyl Glycosides as Inhibitors of Neisseria meningitidis CMP-Sialic Acid Synthetase

by Pradeep Chopra, Jana Führing, Preston Ng, Thomas Haselhorst, Jeffrey C. Dyason, Faith J. Rose, Robin J. Thomson, Rita Gerardy-Schahn, I. Darren Grice, Michael P. Jennings, Anja K. Münster-Kühnel and Mark von Itzstein

Molecules 2025, 30(22), 4329; https://doi.org/10.3390/molecules30224329 - 7 Nov 2025

Abstract

Cell surface sialylation is utilized by a number of pathogenic bacteria to evade the host immune system through molecular mimicry of host sialoglycoconjugates. Human pathogen Neisseria meningitidis serotype B (NmB) expresses both sialylated capsule and surface lipooligosaccharides as pivotal virulence factors. [...] Read more.

Cell surface sialylation is utilized by a number of pathogenic bacteria to evade the host immune system through molecular mimicry of host sialoglycoconjugates. Human pathogen Neisseria meningitidis serotype B (NmB) expresses both sialylated capsule and surface lipooligosaccharides as pivotal virulence factors. An essential enzyme in the sialylation pathway of NmB is CMP-sialic acid synthetase (CSS), which produces the activated nucleotide sugar necessary for sialic acid transfer. In this work, novel C-4, -5, -7, and -9 functionalized derivatives of neuraminic acid β-methyl glycoside (Neuβ2Me) were synthesized as candidate CSS inhibitors. A number of these were found to reduce the activity of NmB CSS in vitro. The highest inhibition of NmB CSS, in a mixed mode manner, was observed with a Neu5Acβ2Me C-9 serine carboxamide. Direct interaction with the enzyme was confirmed by Saturation Transfer Difference (STD) NMR. Supplementation of growth media with this compound reduced lipooligosaccharide (LOS) sialylation of living N. meningitidis, thus providing an interesting starting point for the development of specific NmB CSS inhibitors as an alternative treatment strategy to fight bacterial infections. Full article

(This article belongs to the Special Issue Contemporary Synthetic Glycoscience: A Theme Issue Dedicated to the Memory of Hans Paulsen)

► Show Figures

Graphical abstract

41 pages, 7586 KB

Open AccessReview

Unlocking the Therapeutic Potential of Ellagitannins: A Comprehensive Review of Key Representatives

by Rositsa Mihaylova, Viktoria Elincheva, Georgi Momekov and Rumyana Simeonova

Molecules 2025, 30(22), 4328; https://doi.org/10.3390/molecules30224328 - 7 Nov 2025

Abstract

The present review offers a comprehensive synthesis of the structural diversity, natural occurrence, and therapeutic promise of key ellagitannins (punicalagin, sanguiin H-6, corilagin, geraniin, oenothein B, chebulagic, and chebulinic acids) within the hydrolyzable ellagitannin pool. Distributed in medicinal and dietary plants long used [...] Read more.

The present review offers a comprehensive synthesis of the structural diversity, natural occurrence, and therapeutic promise of key ellagitannins (punicalagin, sanguiin H-6, corilagin, geraniin, oenothein B, chebulagic, and chebulinic acids) within the hydrolyzable ellagitannin pool. Distributed in medicinal and dietary plants long used in traditional medicine, ellagitannin-rich species serve as sources of both complex polyphenolic scaffolds and their bioactive metabolites, urolithins, which mediate many of their health-promoting effects. Special emphasis is placed on the multifaceted mechanisms that contribute to their potent antioxidant, anti-inflammatory, antimicrobial, and anticancer effects, extending to both non-communicable and communicable diseases. Despite their broad therapeutic spectrum, clinical translation is limited by challenges such as poor bioavailability, host-gut microbiota variability, and a lack of robust in vivo evidence. The review highlights future directions aimed at unlocking ellagitannins’ potential, including microbiota-targeted strategies for urolithin production, the design of stable prodrugs and analogs, and innovative delivery platforms. By integrating phytochemical, mechanistic and translational insights, this article positions ellagitannins as promising candidates for the development of novel polyphenol-based interventions. Full article

(This article belongs to the Special Issue New Insights into Bioactive Compounds from Natural Sources—Second Edition)

► Show Figures

Graphical abstract

15 pages, 1985 KB

Open AccessArticle

Purification and Characterization of Punein, a Pomegranate PR-4 Protein Showing Structural Similarities with the Hevein Precursor

by Lisa Tuppo, Claudia Alessandri, Laura Zaccaro, Ivana Giangrieco, Maurizio Tamburrini, Adriano Mari and Maria Antonietta Ciardiello

Molecules 2025, 30(22), 4327; https://doi.org/10.3390/molecules30224327 - 7 Nov 2025

Abstract

The detection of molecules belonging to the pathogenesis-related protein-4 (PR-4) family as a cause of allergic reactions towards the pomegranate fruit has already been suggested, although information regarding their isolation and characterization is not available in the literature. The objective of this study [...] Read more.

The detection of molecules belonging to the pathogenesis-related protein-4 (PR-4) family as a cause of allergic reactions towards the pomegranate fruit has already been suggested, although information regarding their isolation and characterization is not available in the literature. The objective of this study was the purification and description of some features of a pomegranate PR-4 protein. This protein, named punein, was purified by classical biochemical methods, identified by direct protein sequencing and mass spectrometry and analyzed by bioinformatic tools. Biochemical characterization shows that punein has a molecular mass of 13.29 kDa by mass spectrometry and about 14 kDa on SDS-PAGE, and it displays a blocked N-terminus. Bioinformatic analysis highlights that its primary structure shows similarity with the allergens prohevein (containing the strong allergen Hev b 6) and Bra r 2, from latex and turnip, respectively. In particular, punein could be aligned with the C-terminal region of prohevein, which shows IgE epitope regions, the amino acid sequences of which are partially conserved in the two molecules. However, further investigations are needed to understand the clinical relevance of this PR-4 food protein and the factors affecting the concentration of specific proteins, including punein, that are recognized by the immune systems of patients sensitized to pomegranate. Full article

► Show Figures

Figure 1

2 pages, 594 KB

Open AccessCorrection

Correction: Sun et al. Angelica Sinensis Polysaccharide-Based Nanoparticles for Liver-Targeted Delivery of Oridonin. Molecules 2024, 29, 731

by Henglai Sun, Jijuan Nai, Biqi Deng, Zhen Zheng, Xuemei Chen, Chao Zhang, Huagang Sheng and Liqiao Zhu

Molecules 2025, 30(22), 4326; https://doi.org/10.3390/molecules30224326 - 7 Nov 2025

Abstract

Figure 11B,C Legend [...] Full article

► Show Figures

Figure 12

16 pages, 2577 KB

Open AccessArticle

Zinc β-Diketonates with Donor-Acceptor Ligands: Synthesis and Comprehensive Structural, Thermal, and Photophysical Characterization

by Ahmad Daher, Manjiri Choudhari, Thomas Roland, Vincent De Waele and Stéphane Daniele

Molecules 2025, 30(22), 4325; https://doi.org/10.3390/molecules30224325 - 7 Nov 2025

Abstract

We report the synthesis, spectroscopic, structural, and ultrafast photophysical investigation of a series of homoleptic and heteroleptic Zn(II) complexes based on the donor-acceptor β-diketonate ligand 4,4,4-trifluoro-1-phenylbutane-1,3-dione. Mass spectrometry, infrared, and NMR analyses confirm complexation and indicate possible fragmentation pathways involving the sequential loss [...] Read more.

We report the synthesis, spectroscopic, structural, and ultrafast photophysical investigation of a series of homoleptic and heteroleptic Zn(II) complexes based on the donor-acceptor β-diketonate ligand 4,4,4-trifluoro-1-phenylbutane-1,3-dione. Mass spectrometry, infrared, and NMR analyses confirm complexation and indicate possible fragmentation pathways involving the sequential loss of β-diketonate ligands. Single-crystal X-ray diffraction revealed that all complexes adopt monomeric octahedral geometries, with the ancillary nitrogen-based ligands introducing variable distortions. Thermal analyses confirmed that the complexes are non-volatile and have an onset >250 °C, with thermal decomposition primarily to ZnO and ZnF₂. Complexes with aromatic Lewis base led to higher residue percentages, likely due to the final graphitic carbon content. UV-Vis absorption and femtosecond transient absorption spectroscopy demonstrate that the chelated β-diketonate ring serves as the main optically active chromophore, a property unaffected by the nitrogen ligands. The free ligand undergoes rapid internal conversion, whereas coordination to Zn stabilizes the triplet state via LMCT, producing long-lived and chemically reactive species relevant to dissociation processes. This study demonstrates how tailored ligand environments can be exploited to tune excited-state properties, offering a rational framework for the design of functional precursors suitable for nonlinear photolysis and advanced nanomaterial synthesis. Full article

(This article belongs to the Special Issue 30th Anniversary of Molecules—Recent Advances in Inorganic Chemistry)

► Show Figures

Figure 1

27 pages, 14168 KB

Open AccessArticle

Cardamonin Inhibits the Nuclear Translocation and DNA Binding of RelA in the Tumor Necrosis Factor-α-Induced NF-κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells

by Nhat Thi Vu, Quy Van Vu, Nghia Trong Vo, Riho Tanigaki, Hue Tu Quach, Yasunobu Miyake, Tomoo Shiba and Takao Kataoka

Molecules 2025, 30(22), 4324; https://doi.org/10.3390/molecules30224324 - 7 Nov 2025

Abstract

Tumor necrosis factor α (TNF-α) activates the nuclear factor κB (NF-κB) signaling pathway, which promotes the expression of NF-κB-responsive genes, including intercellular adhesion molecule 1 (ICAM-1). We previously reported that cardamonin, a chalcone-type flavonoid, inhibited TNF-α-induced ICAM-1 expression in human lung adenocarcinoma A549 [...] Read more.

Tumor necrosis factor α (TNF-α) activates the nuclear factor κB (NF-κB) signaling pathway, which promotes the expression of NF-κB-responsive genes, including intercellular adhesion molecule 1 (ICAM-1). We previously reported that cardamonin, a chalcone-type flavonoid, inhibited TNF-α-induced ICAM-1 expression in human lung adenocarcinoma A549 cells. However, the mechanisms by which cardamonin inhibits the TNF-α-induced NF-κB signaling pathway have yet to be elucidated. Therefore, we herein investigated the effects of cardamonin on TNF-α-induced gene expression and the NF-κB-dependent signaling pathway. Cardamonin reduced TNF-α-induced ICAM-1 mRNA expression and NF-κB reporter activity. It did not affect the inhibitor of NF-κB α (IκBα) degradation, but prevented RelA nuclear translocation and binding to the ICAM-1 promoter. Consistent with this result, three other chalcone derivatives (4′-hydroxychalcone, isoliquiritigenin, and xanthohumol) did not affect the degradation of IκBα, but inhibited nuclear RelA translocation. Cardamonin exhibited the same inhibitory profiles in human breast cancer MCF-7 cells and human fibrosarcoma HT-1080 cells. Cysteine 38 (C38) of RelA was not a primary target site of cardamonin because cardamonin inhibited the nuclear translocation of the RelA C38S mutant. An in silico molecular docking analysis confirmed that cardamonin was not positioned close enough to RelA C38 to mediate covalent binding, and also that cardamonin interacted with RelA at different sites. Mutations in these interaction sites abrogated the nuclear translocation of RelA in response to a TNF-α stimulation. The present results demonstrate that cardamonin inhibited the nuclear translocation of RelA and its DNA binding in the NF-κB signaling pathway in response to a TNF-α stimulation. Full article

(This article belongs to the Special Issue Natural Products with Pharmaceutical Activities, 2nd Edition)

► Show Figures

Graphical abstract

11 pages, 1827 KB

Open AccessArticle

Synergistic Enhancement of Photocatalytic H₂O₂ Production over Carbon Nitride Oxide/Biochar Composites

by Ruolin Cheng, Yue Wang and Shijian Lu

Molecules 2025, 30(22), 4323; https://doi.org/10.3390/molecules30224323 - 7 Nov 2025

Abstract

The green synthesis of hydrogen peroxide (H₂O₂) is crucial for sustainable chemical production, but pristine graphitic carbon nitride (g-C₃N₄) suffers from low H₂O₂ yield owing to limited visible light absorption and swift [...] Read more.

The green synthesis of hydrogen peroxide (H₂O₂) is crucial for sustainable chemical production, but pristine graphitic carbon nitride (g-C₃N₄) suffers from low H₂O₂ yield owing to limited visible light absorption and swift charge recombination. Herein, a novel metal-free carbon nitride oxide/biochar photocatalytic system (CNO-B) was developed via a simple low-temperature calcination without post-treatment. The synergistic effect of carbonyl functionalization and biochar integration significantly enhanced light harvesting capabilities and charge carrier separation efficiency, achieving an exceptional H₂O₂ production rate of 2483 μmol g⁻¹ h⁻¹ upon irradiation (five times higher compared with pure g-C₃N₄). This work provides valuable insights into minimalist synthesis strategies for designing functional materials and demonstrates a practical approach for valorizing biomass waste in sustainable photocatalytic applications. Full article

(This article belongs to the Special Issue Recent Research on Photocatalysis for Energy Storage and Conversion)

► Show Figures

Graphical abstract

26 pages, 6195 KB

Open AccessArticle

From Chains to Chromophores: Tailored Thermal and Linear/Nonlinear Optical Features of Asymmetric Pyrimidine—Coumarin Systems

by Prescillia Nicolas, Stephania Abdallah, Dong Chen, Giorgia Rizzi, Olivier Jeannin, Koen Clays, Nathalie Bellec, Belkis Bilgin-Eran, Huriye Akdas-Kiliç, Jean-Pierre Malval, Stijn Van Cleuvenbergen and Franck Camerel

Molecules 2025, 30(21), 4322; https://doi.org/10.3390/molecules30214322 - 6 Nov 2025

Abstract

Eleven novel asymmetric pyrimidine derivatives were synthesized. The pyrimidine core was functionalized with a coumarin chromophore and a pro-mesogenic fragment bearing either chiral or linear alkyl chains of variable length and substitution patterns. The thermal properties were investigated using polarized optical microscopy, differential [...] Read more.

Eleven novel asymmetric pyrimidine derivatives were synthesized. The pyrimidine core was functionalized with a coumarin chromophore and a pro-mesogenic fragment bearing either chiral or linear alkyl chains of variable length and substitution patterns. The thermal properties were investigated using polarized optical microscopy, differential scanning calorimetry, and small-angle X-ray scattering, revealing that only selected derivatives exhibited liquid crystalline phases with ordered columnar or smectic organizations. Linear and nonlinear optical properties were characterized by UV–Vis absorption, fluorescence spectroscopy, two-photon absorption, and second-harmonic generation. Optical responses were found to be highly sensitive to the substitution pattern: derivatives functionalized at the 4 and 3,4,5 positions exhibited enhanced 2PA cross-sections and pronounced SHG signals, whereas variations in alkyl chain length exerted only a minor influence. Notably, compounds forming highly ordered non-centrosymmetric mesophases produced robust SHG-active thin films. Importantly, strong SHG responses were obtained without the need for a chiral center, as the inherent asymmetry of the linear alkyl chain derivatives was sufficient to drive self-organization into non-centrosymmetric materials. These results demonstrate that asymmetric pyrimidine-based architectures combining π-conjugation and controlled supramolecular organization are promising candidates for nonlinear optical applications such as photonic devices, multiphoton imaging, and optical data storage. Full article

(This article belongs to the Section Materials Chemistry)

► Show Figures

Figure 1

19 pages, 2212 KB

Open AccessArticle

Advances in Lycopene Production: From Natural Sources to Microbial Synthesis Using Yarrowia lipolytica

by Paweł Moroz, Aleksandra Bartusiak, Julia Niewiadomska, Kacper Szymański, Tomasz Janek, Anna Kancelista, Anna Gliszczyńska and Zbigniew Lazar

Molecules 2025, 30(21), 4321; https://doi.org/10.3390/molecules30214321 - 6 Nov 2025

Abstract

Lycopene, a natural carotenoid with antioxidant and health-promoting properties, has attracted attention as a valuable compound for the food, pharmaceutical, and cosmetic industries. Conventional production methods based on plant extraction or chemical synthesis are limited by low yields, high costs, and environmental concerns. [...] Read more.

Lycopene, a natural carotenoid with antioxidant and health-promoting properties, has attracted attention as a valuable compound for the food, pharmaceutical, and cosmetic industries. Conventional production methods based on plant extraction or chemical synthesis are limited by low yields, high costs, and environmental concerns. In this study, the oleaginous yeast Yarrowia lipolytica was engineered as an alternative microbial cell factory for sustainable lycopene biosynthesis using short-chain fatty acids (SCFAs)—such as acetate, butyrate, and propionate—as inexpensive, renewable carbon sources. Four heterologous genes from Pantoea agglomerans (crtI, crtB, crtE, and idi) were codon-optimized and integrated into the Y. lipolytica genome using different expression systems, including the Golden Gate Assembly strategy. Among the tested strains, PS05/4lyc/GGA, characterized by enhanced phospholipid biosynthesis, demonstrated the highest lycopene yield of 462.9 mg/g dry cell weight and a titer of 3.41 g/L on butyrate medium—values comparable to or exceeding those reported for bioreactor-scale fermentations. The results indicate that co-activation of phospholipid and carotenoid biosynthesis pathways creates favorable intracellular conditions for hydrophobic pigment accumulation. Moreover, the use of SCFAs improved acetyl-CoA availability and redirected carbon flux through the mevalonate pathway, enhancing productivity. Strains with elevated membrane lipid biosynthesis also exhibited higher metabolic stability and stress tolerance. Full article

(This article belongs to the Section Chemical Biology)

► Show Figures

Figure 1

19 pages, 2384 KB

Open AccessArticle

Non-Invasive Regional Neurochemical Profiling of Zebrafish Brain Using Localized Magnetic Resonance Spectroscopy at 28.2 T

by Rico Singer, Wanbin Hu, Li Liu, Huub J. M. de Groot, Herman P. Spaink and A. Alia

Molecules 2025, 30(21), 4320; https://doi.org/10.3390/molecules30214320 - 6 Nov 2025

Abstract

Localized ¹H magnetic resonance spectroscopy (MRS) is a powerful tool in pre-clinical and clinical neurological research, offering non-invasive insight into neurochemical composition in localized brain regions. Zebrafish (Danio rerio) are increasingly being utilized as models in neurological disorder research, providing [...] Read more.

Localized ¹H magnetic resonance spectroscopy (MRS) is a powerful tool in pre-clinical and clinical neurological research, offering non-invasive insight into neurochemical composition in localized brain regions. Zebrafish (Danio rerio) are increasingly being utilized as models in neurological disorder research, providing valuable insights into disease mechanisms. However, the small size of the zebrafish brain and limited MRS sensitivity at low magnetic fields hinder comprehensive neurochemical analysis of localized brain regions. Here, we investigate the potential of ultra-high-field (UHF) MR systems, particularly 28.2 T, for this purpose. This present study pioneers the application of localized ¹H spectroscopy in zebrafish brain at 28.2 T. Point resolved spectroscopy (PRESS) sequence parameters were optimized to reduce the impact of chemical shift displacement error and to enable molecular level information from distinct brain regions. Optimized parameters included gradient strength, excitation frequency, echo time, and voxel volume specifically targeting the 0–4.5 ppm chemical shift regions. Exceptionally high-resolution cerebral metabolite spectra were successfully acquired from localized regions of the zebrafish brain in voxels as small as 125 nL, allowing for the identification and quantification of major brain metabolites with remarkable spectral clarity, including lactate, myo-inositol, creatine, alanine, glutamate, glutamine, choline (phosphocholine + glycerol-phospho-choline), taurine, aspartate, N-acetylaspartyl-glutamate (NAAG), N-acetylaspartate (NAA), and γ-aminobutyric acid (GABA). The unprecedented spatial resolution achieved in a small model organism enabled detailed comparisons of the neurochemical composition across distinct zebrafish brain regions, including the forebrain, midbrain, and hindbrain. This level of precision opens exciting new opportunities to investigate how specific diseases in zebrafish models influence the neurochemical composition of specific brain areas. Full article

(This article belongs to the Section Analytical Chemistry)

► Show Figures

Figure 1

Journal Description

Molecules

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI