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Search Results (451)

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Keywords = antioxidant of natural origin

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31 pages, 8190 KB  
Article
Sustainable MnO2/MgO Bimetallic Nanoparticles Capped with Sword Fern Methanol Extract Attain Antioxidant/Anti-Biofilm Potential: A UPLC-ESI/LC/MS and Network Pharmacology-Supported Study
by Esraa A. Elhawary, Raya Soltane, Mohamed H. Moustafa, Amer Morsy Abdelaziz, Mohamed A. Said and Eman Maher Zahran
Pharmaceuticals 2025, 18(9), 1262; https://doi.org/10.3390/ph18091262 - 25 Aug 2025
Viewed by 384
Abstract
Background: Nephrolepis exaltata (sword fern) possesses a considerable amount of phytochemicals and different biological activities. The current study investigates the anti-biofilm potential of greenly synthesized bimetallic nanoparticles of Nephrolepis exaltata leaf methanol extract (NEME-MnO2-MgO BNPs). Methods: The NEME was [...] Read more.
Background: Nephrolepis exaltata (sword fern) possesses a considerable amount of phytochemicals and different biological activities. The current study investigates the anti-biofilm potential of greenly synthesized bimetallic nanoparticles of Nephrolepis exaltata leaf methanol extract (NEME-MnO2-MgO BNPs). Methods: The NEME was subjected to UPLC/MS analysis, followed by characterization of its NPs by size, zeta potential, FTIR, entrapment efficiency, and release. Then, antioxidant, antimicrobial and antibiofilm assays were employed, followed by in silico studies. Results: The UPLC/MS analysis of NEME led to the tentative identification of 27 metabolites, mostly phenolics. The MnO2-MgO BNPs presented a uniform size and distribution and exhibited IC50 values of 350 and 215.6 μg/mL, in the DPPH and ABTS assays, respectively. Moreover, the NPs exhibited antimicrobial and anti-biofilm efficacies against Pseudomonas aeruginosa, Klebsiella pneumonia (ATCC-9633), Staphylococcus aureus (ATCC-6538), Escherichia coli, Bacillus cereus, and C. albicans, with MIC values of 250–500 μg/mL. The MnO2-MgO BNPs inhibited Candida albicans biofilms with a % inhibition of 66.83 ± 2.45% at 1/2 MIC. The network pharmacology highlighted epigallocatechin and hyperoside to be the major compounds responsible for the anti-biofilm potential. The ASKCOS facilitated the prediction of the redox transformations that occurred in the green synthesis, while the docking analysis revealed enhanced binding affinities of the oxidized forms of both compounds towards the outer membrane porin OprD of P. aeruginosa, with binding scores of −4.6547 and −5.7701 kcal/mol., respectively. Conclusions: The greenly synthesized Nephrolepis exaltata bimetallic nanoparticles may provide a promising, eco-friendly, and sustainable source for antimicrobial agents of natural origin with potential biofilm inhibition. Full article
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22 pages, 2145 KB  
Article
α-Bisabolol, a Dietary Bioactive Terpene Attenuates Oxidative Stress and Inflammation in Colonic Mucosa of Acetic Acid-Induced Colitis in Rats
by Salim M. A. Bastaki, Naheed Amir, Shreesh Ojha and Ernest Adeghate
Int. J. Mol. Sci. 2025, 26(17), 8168; https://doi.org/10.3390/ijms26178168 - 22 Aug 2025
Viewed by 396
Abstract
Inflammatory bowel diseases (IBDs), such as ulcerative colitis, and Crohn’s disease are chronic idiopathic inflammatory diseases of the gastrointestinal system involving interaction between genetic and environmental factors mediating the occurrence of oxidative stress and inflammation. There is no permanent cure for IBD except [...] Read more.
Inflammatory bowel diseases (IBDs), such as ulcerative colitis, and Crohn’s disease are chronic idiopathic inflammatory diseases of the gastrointestinal system involving interaction between genetic and environmental factors mediating the occurrence of oxidative stress and inflammation. There is no permanent cure for IBD except long-term treatment or surgery (resection of the intestine), and the available agents in the long term appear unsatisfactory and elicit numerous adverse effects. To keep the disease in remission, prevent relapses and minimize adverse effects of currently used medicines, novel dietary compounds of natural origin convincingly appear to be one of the important therapeutic strategies for the pharmacological targeting of oxidative stress and inflammation. Therefore, it is imperative to investigate plant-derived dietary agents to overcome the debilitating conditions of IBD. In the present study, the effect of α-Bisabolol (BSB), a dietary bioactive monoterpene commonly found in many edible plants as well as important components of traditional medicines, was investigated in acetic acid (AA)-induced colitis model in rats. BSB was orally administered to Wistar male rats at a dose of 50 mg/kg/day either for 3 days before or 30 min after induction of IBD for 7 days through intrarectal administration of AA. The changes in body weight, macroscopic and microscopic analysis of the colon and calprotectin levels in the colon of rats from different experimental groups were observed on day 0, 2, 4, and 7. The levels of myeloperoxidase (MPO), a marker of neutrophil activation, reduced glutathione (GSH) and malondialdehyde (MDA), a marker of lipid peroxidation, and the levels of pro-inflammatory cytokines were measured. AA caused a significant reduction in body weight and induced macroscopic and microscopic ulcers, along with a significant decline of endogenous antioxidants (superoxide dismutase (SOD), catalase, and GSH), with a concomitant increase in MDA level and MPO activity. BSB significantly improved the AA-induced reduction in body weight, colonic mucosal histology, inhibited MDA formation, and restored antioxidant levels along with a reduction in MPO activity. AA also induced the release of pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-23 (IL-23) and tumor necrosis factor-α (TNF-α). Furthermore, AA also increased levels of calprotectin, a protein released by neutrophils under inflammatory conditions of the gastrointestinal tract. BSB treatment significantly reduced the release of calprotectin and pro-inflammatory cytokines. The findings of the present study demonstrate that BSB has the potential to improve disease activity and rescue colonic tissues from damage by inhibiting oxidative stress, lipid peroxidation and inflammation. The findings are suggestive of the benefits of BSB in IBD treatment and substantiate its usefulness in colitis management, along with its gastroprotective effects in gastric ulcer. Full article
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23 pages, 2553 KB  
Review
Anti-DNA Damage Mechanisms and the Role of Carotenoids, Vitamin A, and Its Derivatives
by Agnieszka Maria Kołodziejczyk and Bolesław Karwowski
Nutrients 2025, 17(17), 2721; https://doi.org/10.3390/nu17172721 - 22 Aug 2025
Viewed by 569
Abstract
All forms of vitamin A have a similar structure and physiological functions in the body. These compounds can be classified as retinoids, including moieties with a common structure of four isoprenoid units of natural or synthetic origin. Vitamin A is generally uptake from [...] Read more.
All forms of vitamin A have a similar structure and physiological functions in the body. These compounds can be classified as retinoids, including moieties with a common structure of four isoprenoid units of natural or synthetic origin. Vitamin A is generally uptake from products of animal origin (retinol and its derivatives) or from plants as provitamin A (carotenoids). Vitamin A is fat-soluble, so it is easily absorbed and transported in the body. The main storage sites are the liver and adipose tissue. Excessive amounts of the vitamin may lead to the development of different abnormal processes in the human body. Apart from being crucial for retina conditions and functions and the immune system, vitamin A is also deeply involved in DNA repair mechanisms. Its antioxidant nature helps to reduce the oxidative damage to DNA by neutralizing free radicals and thus decreasing the oxidative stress. On the other hand, vitamin A deficiency leads to lower antioxidant enzyme activity, which results in the weakening of the defense system against free radicals. This study aims to elucidate the mechanisms of DNA repair and determine the role of carotenoids, vitamin A, and its derivatives as contributing factors in this process. This review synthesizes the current knowledge on the dual role of vitamin A in DNA integrity by examining the conditions under which it acts as a genotoxic agent versus a facilitator of DNA repair. This article also discusses the role of vitamin A in inhibiting oxidative stress and its anti- and pro-cancer impact. Full article
(This article belongs to the Special Issue The Importance of Carotenoids in Age-Related Disease—Current Data)
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30 pages, 1430 KB  
Review
Propolis-Functionalized Biomaterials for Wound Healing: A Systematic Review with Emphasis on Polysaccharide-Based Platforms
by Lydia Paulina Loya-Hernández, Carlos Arzate-Quintana, Alva Rocío Castillo-González, Javier Camarillo-Cisneros, César Iván Romo-Sáenz, María Alejandra Favila-Pérez and Celia María Quiñonez-Flores
Polysaccharides 2025, 6(3), 74; https://doi.org/10.3390/polysaccharides6030074 - 20 Aug 2025
Viewed by 576
Abstract
Wound healing is a complex process, and propolis, a natural resin with antimicrobial, anti-inflammatory, and antioxidant properties, emerges as a promising candidate for its treatment. This systematic review analyzed 26 studies on propolis-functionalized biomaterials. Great diversity was observed in materials and incorporation techniques, [...] Read more.
Wound healing is a complex process, and propolis, a natural resin with antimicrobial, anti-inflammatory, and antioxidant properties, emerges as a promising candidate for its treatment. This systematic review analyzed 26 studies on propolis-functionalized biomaterials. Great diversity was observed in materials and incorporation techniques, including direct blending, surface coating, and nanoencapsulation. Mostly based on polysaccharides like chitosan, pectin, and bacterial cellulose, these formulations showed biocompatibility, biodegradability, and promoted inflammation reduction and tissue repair. In vitro assays confirmed high biocompatibility (>80% cell viability) and antimicrobial activity, while in vivo studies validated regenerative benefits. Despite their potential, marked heterogeneity in propolis composition (intrinsically variable due to its botanical and geographical origin, and processing methods), coupled with diverse concentrations used and the lack of standardization in assessment methods and results reporting, significantly limits cross-study comparability and reproducibility. Overcoming these challenges requires promoting greater standardization in extraction, characterization, and evaluation protocols, including chemical fingerprinting and more detailed and consistent reporting of findings. Despite these limitations, propolis–polysaccharide systems hold strong clinical potential, with further standardization and well-designed preclinical studies being essential for their effective translation, especially in chronic wound management. Full article
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19 pages, 1165 KB  
Article
Integrated (Statistical) Analysis of Honey Enriched with Aromatic Herbs: Phenolic Profile, Heavy Metal and NIR Spectroscopy
by Berat Durmishi, Vesna Knights, Tamara Jurina, Smajl Rizani, Gorica Pavlovska, Valbonë Mehmeti, Ana Jurinjak Tušek, Maja Benković, Davor Valinger and Jasenka Gajdoš Kljusurić
Processes 2025, 13(8), 2598; https://doi.org/10.3390/pr13082598 - 17 Aug 2025
Viewed by 376
Abstract
Honey is recognized as a nutritionally rich and functional option, often used as a natural sweetener due to its content of glucose, fructose, vitamins, minerals, enzymes and antioxidants. Its antioxidant, antibacterial and anti-inflammatory properties are well known. Recently, interest has grown in functional [...] Read more.
Honey is recognized as a nutritionally rich and functional option, often used as a natural sweetener due to its content of glucose, fructose, vitamins, minerals, enzymes and antioxidants. Its antioxidant, antibacterial and anti-inflammatory properties are well known. Recently, interest has grown in functional honey enriched with bioactive plant components, such as extracts of rosemary, lavender, oregano, and sage, which can enhance phenolic content and antioxidant capacity. However, such enrichment may alter honey’s sensory characteristics and introduce contaminants, including heavy metals, necessitating comprehensive quality assessment. This study aimed to evaluate the chemical and functional quality of honey enriched with aromatic plant extracts from Kosovo, Albania, and North Macedonia, using an integrated approach. The research included the quantification of total phenolic compounds (TPCs), analysis of heavy metal content, and the application of near-infrared (NIR) spectroscopy with two devices (laboratory and portable). The results showed that geographical origin and herbal additions significantly affect TPC and heavy metal concentrations. Honey from Kosovo had the highest TPC, while Albanian honey showed higher concentrations of iron and nickel. Enrichment with oregano and rosemary significantly increased TPC and, levels of heavy metals such as lead and nickel. These findings underscore both the nutritional potential and safety considerations of enriched honey products. Accurate, non-destructive techniques like NIR spectroscopy offer valuable tools for quality control; however, further work is needed to evaluate sensory acceptance and long-term safety of enriched honey. Full article
(This article belongs to the Section Chemical Processes and Systems)
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13 pages, 1100 KB  
Article
Molecular Networking-Guided Annotation of Flavonoid Glycosides from Quercus mongolica Bee Pollen
by Yerim Joo, Eunbeen Shin, Hyunwoo Kim, Mi Kyeong Lee and Seon Beom Kim
Int. J. Mol. Sci. 2025, 26(16), 7930; https://doi.org/10.3390/ijms26167930 - 17 Aug 2025
Viewed by 390
Abstract
Bee pollen is a primary and secondary metabolite-rich natural product collected by pollinators such as honeybees. Polyphenols, particularly flavonoids, are well known for their potent antioxidant activities. Numerous phytochemical and biological studies have focused on Quercus mongolica, a member of the Fagaceae [...] Read more.
Bee pollen is a primary and secondary metabolite-rich natural product collected by pollinators such as honeybees. Polyphenols, particularly flavonoids, are well known for their potent antioxidant activities. Numerous phytochemical and biological studies have focused on Quercus mongolica, a member of the Fagaceae family. However, research focusing specifically on pollen is limited. Moreover, bee pollen chemical composition varies significantly depending on its geographical origin and cultivation conditions. In this study, the flavonoid glycosides of Q. mongolica pollen were profiled using LC–MS/MS-based molecular networking, which revealed that the largest molecular cluster corresponded to flavonoid glycosides. A total of 69 flavonoid glycosides, primarily comprising 2 kaempferol derivatives, 14 quercetin derivatives, and 46 isorhamnetin derivatives, were annotated based on MS/MS fragmentation patterns, spectral library matches in GNPS (Global Natural Products Social Molecular Networking), and comparison with previously reported data. Two primary compounds, isorhamnetin 3-O-β-D-xylopyranosyl (1→6)-β-D-glucopyranoside and isorhamnetin-3-O-neohesperidoside, were identified by comparison with reference standards. This study offers foundational insights into the flavonoid diversity of Q. mongolica pollen, contributing to a broad understanding of its secondary metabolite profile. Full article
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28 pages, 3218 KB  
Systematic Review
Antioxidant Potential of Opuntia dillenii: A Systematic Review of Influencing Factors and Biological Efficacy
by Ruymán Santana-Farré, Nisa Buset-Ríos and Mussa Makran
Nutraceuticals 2025, 5(3), 22; https://doi.org/10.3390/nutraceuticals5030022 - 13 Aug 2025
Viewed by 307
Abstract
Opuntia dillenii has gained considerable scientific attention as a potential natural source of antioxidants. This systematic review compiles and evaluates current evidence regarding its antioxidant activity. A PRISMA-guided literature search was conducted using PubMed, Scopus, and Web of Science, identifying 37 eligible studies. [...] Read more.
Opuntia dillenii has gained considerable scientific attention as a potential natural source of antioxidants. This systematic review compiles and evaluates current evidence regarding its antioxidant activity. A PRISMA-guided literature search was conducted using PubMed, Scopus, and Web of Science, identifying 37 eligible studies. These studies employed two main methodological approaches: chemical-based assays and biological models. Chemical assays, including radical scavenging and reducing power assays, demonstrated a broad range of antioxidant activity influenced by factors such as the extraction method, plant part, plant maturity, and geographic origin. Polysaccharides, betalains, and polyphenols were consistently identified as primary contributors to these effects. Biological models further supported the antioxidant properties of O. dillenii extracts. In animal studies, administration of the extracts significantly improved oxidative stress biomarkers, increasing glutathione levels, reducing malondialdehyde concentrations, and enhancing the activity of antioxidant enzymes, particularly in the liver and other digestive tissues like the colon, stomach, and pancreas. Cellular studies using hepatocyte, macrophage, enterocyte, and neuronal cell lines produced comparable results, confirming the antioxidant effects. In conclusion, O. dillenii exhibits promising antioxidant potential across various experimental models. However, the absence of human clinical trials highlights the need for further research to establish its efficacy and safety as a nutraceutical product. Full article
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8 pages, 467 KB  
Proceeding Paper
Role of a Natural Antioxidant in the Secondary Shelf Life of Ready-to-Use Meat Pâté
by Beatrice Sordini, Sonia Esposto, Arianna Bonucci, Ilenia Dottori, Luigi Daidone, Stefania Urbani, Gianluca Veneziani, Roberto Selvaggini, Maurizio Servili, Davide Nucciarelli and Agnese Taticchi
Proceedings 2025, 119(1), 10; https://doi.org/10.3390/proceedings2025119010 - 11 Aug 2025
Viewed by 231
Abstract
By-products from the agro-food industry can be natural ingredients for reformulating traditional foods, enhancing quality, extending secondary shelf life (SSL), and reducing food waste. This study evaluates the impact of an olive vegetation water phenolic extract (OVWPE) at two concentrations on ready-to-use meat [...] Read more.
By-products from the agro-food industry can be natural ingredients for reformulating traditional foods, enhancing quality, extending secondary shelf life (SSL), and reducing food waste. This study evaluates the impact of an olive vegetation water phenolic extract (OVWPE) at two concentrations on ready-to-use meat pâté (MP1 and MP2) under simulated retail storage. We evaluated the phenolic composition, volatile compounds, antioxidant activity, and sensory quality of the OVWPE-added pâté and compared it to the control sample (CTRL; without antioxidant). Results indicated that OVWPE minimized oxidation products, enhancing lipid stability, and also reduced the formation of C6–C9 aldehydes linked to rancid off-flavor. Without sensory defects, the OVWPE pâtés showed higher antioxidant activity and α-tocopherol content than the CTRL. OVWPE appears to be a promising antioxidant of natural origin for food formulations, supporting SSL extension and food waste reduction. Full article
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19 pages, 1996 KB  
Review
Honey as a Neuroprotective Agent: Molecular Perspectives on Its Role in Alzheimer’s Disease
by María D. Navarro-Hortal, Jose M. Romero-Márquez, Johura Ansary, Daniel Hinojosa-Nogueira, Cristina Montalbán-Hernández, Alfonso Varela-López and José L. Quiles
Nutrients 2025, 17(16), 2577; https://doi.org/10.3390/nu17162577 - 8 Aug 2025
Viewed by 1162
Abstract
Alzheimer’s disease (AD) is the most prevalent form of dementia and a major global health challenge, characterized by progressive cognitive decline and neurodegeneration. Despite decades of research, there is currently no cure, and available treatments provide only limited symptomatic relief without halting disease [...] Read more.
Alzheimer’s disease (AD) is the most prevalent form of dementia and a major global health challenge, characterized by progressive cognitive decline and neurodegeneration. Despite decades of research, there is currently no cure, and available treatments provide only limited symptomatic relief without halting disease progression. In this context, natural compounds with multi-targeted biological activities are being explored as potential complementary therapeutic strategies. Honey, a complex natural substance rich in bioactive phytochemicals, has emerged as a promising candidate due to its antioxidant, anti-inflammatory, anti-apoptotic, and enzyme-inhibitory properties. This review summarizes the molecular mechanisms underlying the neuroprotective effects of honey in the context of AD, with a particular focus on its ability to modulate oxidative stress, mitochondrial dysfunction, inflammation, apoptosis, β-amyloid accumulation, tau hyperphosphorylation, and neurotransmission-related enzymes. Notably, the botanical origin of honey significantly influences its composition and biological activity, as evidenced by studies on avocado, manuka, acacia, kelulut, chestnut, coffee, or tualang honeys. While preclinical findings are encouraging, especially in vitro and in invertebrate and rodent models, clinical validation is still lacking. Therefore, further research, including well-designed in vivo and human studies, is needed to clarify the therapeutic relevance of honey in AD. Overall, honey may represent a promising natural adjunct in the prevention or management of AD, but current evidence remains preliminary. Full article
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22 pages, 775 KB  
Review
Bioactive Compounds, Technological Advances, and Sustainable Applications of Avocado (Persea americana Mill.): A Critical Review
by Amanda Priscila Silva Nascimento, Maria Elita Martins Duarte, Ana Paula Trindade Rocha and Ana Novo Barros
Foods 2025, 14(15), 2746; https://doi.org/10.3390/foods14152746 - 6 Aug 2025
Cited by 1 | Viewed by 711
Abstract
Avocado (Persea americana), originally from Mesoamerica, has emerged as a focus of intense scientific and industrial interest due to its unique combination of nutritional richness, bioactive potential, and technological versatility. Its pulp, widely consumed across the globe, is notably abundant in [...] Read more.
Avocado (Persea americana), originally from Mesoamerica, has emerged as a focus of intense scientific and industrial interest due to its unique combination of nutritional richness, bioactive potential, and technological versatility. Its pulp, widely consumed across the globe, is notably abundant in monounsaturated fatty acids, especially oleic acid, which can comprise over two-thirds of its lipid content. In addition, it provides significant levels of dietary fiber, fat-soluble vitamins such as A, D, E and K, carotenoids, tocopherols, and phytosterols like β-sitosterol. These constituents are consistently associated with antioxidant, anti-inflammatory, glycemic regulatory, and cardioprotective effects, supported by a growing body of experimental and clinical evidence. This review offers a comprehensive and critical synthesis of the chemical composition and functional properties of avocado, with particular emphasis on its lipid profile, phenolic compounds, and phytosterols. It also explores recent advances in environmentally sustainable extraction techniques, including ultrasound-assisted and microwave-assisted processes, as well as the application of natural deep eutectic solvents. These technologies have demonstrated improved efficiency in recovering bioactives while aligning with the principles of green chemistry. The use of avocado-derived ingredients in nanostructured delivery systems and their incorporation into functional foods, cosmetics, and health-promoting formulations is discussed in detail. Additionally, the potential of native cultivars and the application of precision nutrition strategies are identified as promising avenues for future innovation. Taken together, the findings underscore the avocado’s relevance as a high-value matrix for sustainable development. Future research should focus on optimizing extraction protocols, clarifying pharmacokinetic behavior, and ensuring long-term safety in diverse applications. Full article
(This article belongs to the Special Issue Feature Review on Nutraceuticals, Functional Foods, and Novel Foods)
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19 pages, 3697 KB  
Article
Investigating the Behavior of a Natural Emulsifier in One-Pot and Standard Cosmetic Emulsions
by Mauro Battaiotto, Paolo Sonzini, Simone Conti, Miryam Chiara Malacarne and Enrico Caruso
Cosmetics 2025, 12(4), 164; https://doi.org/10.3390/cosmetics12040164 - 5 Aug 2025
Viewed by 689
Abstract
The cosmetic industry is growing at an impressive rate worldwide. In the cosmetic field, natural-origin ingredients represent the new frontier in this industry. Among the main components of cosmetics, lipids, emulsifiers, rheological modifiers, preservatives, colorants, and antioxidants can be found. These compounds form [...] Read more.
The cosmetic industry is growing at an impressive rate worldwide. In the cosmetic field, natural-origin ingredients represent the new frontier in this industry. Among the main components of cosmetics, lipids, emulsifiers, rheological modifiers, preservatives, colorants, and antioxidants can be found. These compounds form emulsions, which are among the main cosmetic formulations. An important aspect in this regard is the evaluation of emulsions’ stability over time and emulsions’ production methodology. In this paper, a comparison is made between two emulsion production technologies, the Standard and the “One-Pot” methods, through the characterization of the raw material ABWAX® Revomul, a multifunctional wax for cosmetic use which consists of a low-melting structuring wax of vegetal origin (Rhus wax) and a natural emulsifier (Polyglyceril-3 Stearate). First, we evaluated the affinity between the wax raw materials and emollients of different chemical nature; then, we analyzed the impact of the production method on the emulsions to identify similarities and differences. ABWAX® Revomul demonstrated a high level of effectiveness in regard to stabilizing oil-in-water emulsions. This study suggests that from an industrial point of view, the application of the two procedures allows products with different characteristics to be obtained, consequently allowing a specific method to be chosen to obtain the desired product. Full article
(This article belongs to the Special Issue Advanced Cosmetic Sciences: Sustainability in Materials and Processes)
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29 pages, 2729 KB  
Article
Computational Evaluation and Multi-Criteria Optimization of Natural Compound Analogs Targeting SARS-CoV-2 Proteases
by Paul Andrei Negru, Andrei-Flavius Radu, Ada Radu, Delia Mirela Tit and Gabriela Bungau
Curr. Issues Mol. Biol. 2025, 47(7), 577; https://doi.org/10.3390/cimb47070577 - 21 Jul 2025
Viewed by 526
Abstract
The global impact of the COVID-19 crisis has underscored the need for novel therapeutic candidates capable of efficiently targeting essential viral proteins. Existing therapeutic strategies continue to encounter limitations such as reduced efficacy against emerging variants, safety concerns, and suboptimal pharmacodynamics, which emphasize [...] Read more.
The global impact of the COVID-19 crisis has underscored the need for novel therapeutic candidates capable of efficiently targeting essential viral proteins. Existing therapeutic strategies continue to encounter limitations such as reduced efficacy against emerging variants, safety concerns, and suboptimal pharmacodynamics, which emphasize the potential of natural-origin compounds as supportive agents with immunomodulatory, anti-inflammatory, and antioxidant benefits. The present study significantly advances prior molecular docking research through comprehensive virtual screening of structurally related analogs derived from antiviral phytochemicals. These compounds were evaluated specifically against the SARS-CoV-2 main protease (3CLpro) and papain-like protease (PLpro). Utilizing chemical similarity algorithms via the ChEMBL database, over 600 candidate molecules were retrieved and subjected to automated docking, interaction pattern analysis, and comprehensive ADMET profiling. Several analogs showed enhanced binding scores relative to their parent scaffolds, with CHEMBL1720210 (a shogaol-derived analog) demonstrating strong interaction with PLpro (−9.34 kcal/mol), and CHEMBL1495225 (a 6-gingerol derivative) showing high affinity for 3CLpro (−8.04 kcal/mol). Molecular interaction analysis revealed that CHEMBL1720210 forms hydrogen bonds with key PLpro residues including GLY163, LEU162, GLN269, TYR265, and TYR273, complemented by hydrophobic interactions with TYR268 and PRO248. CHEMBL1495225 establishes multiple hydrogen bonds with the 3CLpro residues ASP197, ARG131, TYR239, LEU272, and GLY195, along with hydrophobic contacts with LEU287. Gene expression predictions via DIGEP-Pred indicated that the top-ranked compounds could influence biological pathways linked to inflammation and oxidative stress, processes implicated in COVID-19’s pathology. Notably, CHEMBL4069090 emerged as a lead compound with favorable drug-likeness and predicted binding to PLpro. Overall, the applied in silico framework facilitated the rational prioritization of bioactive analogs with promising pharmacological profiles, supporting their advancement toward experimental validation and therapeutic exploration against SARS-CoV-2. Full article
(This article belongs to the Special Issue Novel Drugs and Natural Products Discovery)
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25 pages, 3050 KB  
Review
REG3A: A Multifunctional Antioxidant Lectin at the Crossroads of Microbiota Regulation, Inflammation, and Cancer
by Jamila Faivre, Hala Shalhoub, Tung Son Nguyen, Haishen Xie and Nicolas Moniaux
Cancers 2025, 17(14), 2395; https://doi.org/10.3390/cancers17142395 - 19 Jul 2025
Viewed by 799
Abstract
REG3A, a prominent member of the human regenerating islet-derived (REG) lectin family, plays a pivotal and multifaceted role in immune defense, inflammation, and cancer biology. Primarily expressed in gastrointestinal epithelial cells, REG3A reinforces barrier integrity, orchestrates mucosal immune responses, and regulates host–microbiota interactions. [...] Read more.
REG3A, a prominent member of the human regenerating islet-derived (REG) lectin family, plays a pivotal and multifaceted role in immune defense, inflammation, and cancer biology. Primarily expressed in gastrointestinal epithelial cells, REG3A reinforces barrier integrity, orchestrates mucosal immune responses, and regulates host–microbiota interactions. It also functions as a potent non-enzymatic antioxidant, protecting tissues from oxidative stress. REG3A expression is tightly regulated by inflammatory stimuli and is robustly induced during immune activation, where it limits microbial invasion, dampens tissue injury, and promotes epithelial repair. Beyond its antimicrobial and immunomodulatory properties, REG3A contributes to the resolution of inflammation and the maintenance of tissue homeostasis. However, its role in cancer is highly context-dependent. In some tumor types, REG3A fosters malignant progression by enhancing cell survival, proliferation, and invasiveness. In others, it acts as a tumor suppressor, inhibiting growth and metastatic potential. These opposing effects are likely dictated by a combination of factors, including the tissue of origin, the composition and dynamics of the tumor microenvironment, and the stage of disease progression. Additionally, the secreted nature of REG3A implies both local and systemic effects, further modulated by organ-specific physiology. Experimental variability may also reflect differences in methodologies, analytical tools, and model systems used. This review synthesizes current knowledge on the pleiotropic functions of REG3A, emphasizing its roles in epithelial defense, immune regulation, redox homeostasis, and oncogenesis. A deeper understanding of REG3A’s pleiotropic effects could open up new therapeutic avenues in both inflammatory disorders and cancer. Full article
(This article belongs to the Special Issue Lectins in Cancer)
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26 pages, 6375 KB  
Article
Photoprotective Effects of Quercetin and Hesperidin in Polymorphous Light Eruption: A Comparative Study with Alpha-Glucosylrutin
by Yoon-Seo Choi, Sang-Hoon Park, Inhee Jung, Eun-Ju Park, Wonki Hong, Jin-Hee Shin, Won-Sang Seo and Jongsung Lee
Curr. Issues Mol. Biol. 2025, 47(7), 567; https://doi.org/10.3390/cimb47070567 - 19 Jul 2025
Viewed by 1775
Abstract
Polymorphous Light Eruption (PLE) is a prevalent UV-induced photodermatosis characterized by abnormal immune responses, oxidative stress, and cutaneous inflammation. Alpha-glucosylrutin (AGR), a chemically modified flavonoid widely used for its antioxidant and photoprotective effects, has shown clinical efficacy; however, its synthetic origin and classification [...] Read more.
Polymorphous Light Eruption (PLE) is a prevalent UV-induced photodermatosis characterized by abnormal immune responses, oxidative stress, and cutaneous inflammation. Alpha-glucosylrutin (AGR), a chemically modified flavonoid widely used for its antioxidant and photoprotective effects, has shown clinical efficacy; however, its synthetic origin and classification as a potential skin sensitizer and aquatic toxin raise safety and environmental concerns. These limitations underscore the need for safer, naturally derived alternatives. In this study, we investigated the comparative efficacy of quercetin (QC) and hesperidin (HPN)—two plant-based flavonoids—against AGR in in vitro and ex vivo models of sun-induced skin damage. An optimized QC:HPN 8:1 (w/w) complex significantly restored antioxidant enzyme activities (SOD: 4.11 ± 0.32 mU/mg; CAT: 1.88 ± 0.04 mU/mg) and suppressed inflammatory cytokine production (IL-6: 155.95 ± 3.17 pg/mL; TNF-α: 62.34 ± 0.72 pg/mL) more effectively than AGR. β-hexosaminidase secretion, a marker of allergic response, was reduced to 99.02 ± 1.45% with QC:HPN 8:1, compared to 121.33 ± 1.15% with AGR. QC alone exhibited dose-dependent cytotoxicity at ≥10 μg/mL, whereas HPN maintained >94% cell viability at all tested concentrations. These findings highlight the QC:HPN 8:1 complex as a safe, natural, and effective alternative to synthetic AGR for preventing and managing PLE and UV-induced dermal inflammation. Further research should focus on clinical validation and formulation development for topical use. Full article
(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products, 3rd Edition)
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21 pages, 3526 KB  
Article
Prenatal Bisphenol A Exposure Impairs Fetal Heart Development: Molecular and Structural Alterations with Sex-Specific Differences
by Alessandro Marrone, Anna De Bartolo, Vittoria Rago, Francesco Conforti, Lidia Urlandini, Tommaso Angelone, Rosa Mazza, Maurizio Mandalà and Carmine Rocca
Antioxidants 2025, 14(7), 863; https://doi.org/10.3390/antiox14070863 - 14 Jul 2025
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Abstract
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, with increasing evidence suggesting that their origins may lie in prenatal life. Endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA), have been implicated in the alteration of fetal programming mechanisms that [...] Read more.
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, with increasing evidence suggesting that their origins may lie in prenatal life. Endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA), have been implicated in the alteration of fetal programming mechanisms that cause a predisposition to long-term cardiovascular vulnerability. However, the impact of prenatal endocrine disruption on fetal heart development and its sex-specific nature remains incompletely understood. This study investigates the molecular and structural effects of low-dose prenatal BPA exposure on fetal rat hearts. Our results reveal that BPA disrupts estrogen receptor (ER) signaling in a sex-dependent manner, with distinct alterations in ERα, ERβ, and GPER expression. BPA exposure also triggers significant inflammation, oxidative stress, and ferroptosis; this is evidenced by elevated NF-κB, IL-1β, TNF-α, and NLRP3 inflammasome activation, as well as impaired antioxidant defenses (SOD1, SOD2, CAT, and SELENOT), increased lipid peroxidation (MDA) and protein oxidation, decreased GPX4, and increased ACSL4 levels. These alterations are accompanied by increased markers of cardiac distension (ANP, BNP), extracellular matrix remodeling mediators, and pro-fibrotic regulators (Col1A1, Col3A1, TGF-β, and CTGF), with a more pronounced response in males. Histological analyses corroborated these molecular findings, revealing structural alterations as well as glycogen depletion in male fetal hearts, consistent with altered cardiac morphogenesis and metabolic stress. These effects were milder in females, reinforcing the notion of sex-specific vulnerability. Moreover, prenatal BPA exposure affected myocardial fiber architecture and vascular remodeling in a sex-dependent manner, as evidenced by reduced expression of desmin alongside increased levels of CD34 and Ki67. Overall, our findings provide novel insights into the crucial role of prenatal endocrine disruption during fetal heart development and its contribution to the early origins of CVD, underscoring the urgent need for targeted preventive strategies and further research into the functional impact of BPA-induced alterations on postnatal cardiac function and long-term disease susceptibility. Full article
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