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Keywords = cytotoxic natural products

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24 pages, 1244 KiB  
Article
HPLC-ESI-HRMS/MS-Based Metabolite Profiling and Bioactivity Assessment of Catharanthus roseus
by Soniya Joshi, Chen Huo, Rabin Budhathoki, Anita Gurung, Salyan Bhattarai, Khaga Raj Sharma, Ki Hyun Kim and Niranjan Parajuli
Plants 2025, 14(15), 2395; https://doi.org/10.3390/plants14152395 - 2 Aug 2025
Viewed by 976
Abstract
A comprehensive metabolic profiling of Catharanthus roseus (L.) G. Don was performed using tandem mass spectrometry, along with an evaluation of the biological activities of its various solvent extracts. Among these, the methanolic leaf extract exhibited mild radical scavenging activity, low to moderate [...] Read more.
A comprehensive metabolic profiling of Catharanthus roseus (L.) G. Don was performed using tandem mass spectrometry, along with an evaluation of the biological activities of its various solvent extracts. Among these, the methanolic leaf extract exhibited mild radical scavenging activity, low to moderate antimicrobial activity, and limited cytotoxicity in both the brine shrimp lethality assay and MTT assay against HeLa and A549 cell lines. High-performance liquid chromatography–electrospray ionization–high-resolution tandem mass spectrometry (HPLC-ESI-HRMS/MS) analysis led to the annotation of 34 metabolites, primarily alkaloids. These included 23 indole alkaloids, two fatty acids, two pentacyclic triterpenoids, one amino acid, four porphyrin derivatives, one glyceride, and one chlorin derivative. Notably, two metabolites—2,3-dihydroxypropyl 9,12,15-octadecatrienoate and (10S)-hydroxypheophorbide A—were identified for the first time in C. roseus. Furthermore, Global Natural Products Social Molecular Networking (GNPS) analysis revealed 18 additional metabolites, including epoxypheophorbide A, 11,12-dehydroursolic acid lactone, and 20-isocatharanthine. These findings highlight the diverse secondary metabolite profile of C. roseus and support its potential as a source of bioactive compounds for therapeutic development. Full article
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21 pages, 1458 KiB  
Article
Production of a Biosurfactant for Application in the Cosmetics Industry
by Ana Paula Barbosa Cavalcanti, Gleice Paula de Araújo, Káren Gercyane de Oliveira Bezerra, Fabíola Carolina Gomes de Almeida, Maria da Glória Conceição da Silva, Alessandra Sarubbo, Cláudio José Galdino da Silva Júnior, Rita de Cássia Freire Soares da Silva and Leonie Asfora Sarubbo
Fermentation 2025, 11(8), 451; https://doi.org/10.3390/fermentation11080451 - 2 Aug 2025
Viewed by 329
Abstract
The cosmetics industry has been seeking to develop products with renewable natural ingredients to reduce the use of or even replace synthetic substances. Biosurfactants can help meet this demand. These natural compounds are renewable, biodegradable, and non-toxic or have low toxicity, offering minimal [...] Read more.
The cosmetics industry has been seeking to develop products with renewable natural ingredients to reduce the use of or even replace synthetic substances. Biosurfactants can help meet this demand. These natural compounds are renewable, biodegradable, and non-toxic or have low toxicity, offering minimal risk to humans and the environment, which has attracted the interest of an emerging consumer market and, consequently, the cosmetics industry. The aim of the present study was to produce a biosurfactant from the yeast Starmerella bombicola ATCC 22214 cultivated in a mineral medium containing 10% soybean oil and 5% glucose. The biosurfactant reduced the surface tension of water from 72.0 ± 0.1 mN/m to 33.0 ± 0.3 mN/m after eight days of fermentation. The yield was 53.35 ± 0.39 g/L and the critical micelle concentration was 1000 mg/L. The biosurfactant proved to be a good emulsifier of oils used in cosmetic formulations, with emulsification indices ranging from 45.90 ± 1.69% to 68.50 ± 1.10%. The hydrophilic–lipophilic balance index demonstrated the wetting capacity of the biosurfactant and its tendency to form oil-in-water (O/W) emulsions, with 50.0 ± 0.20% foaming capacity. The biosurfactant did not exhibit cytotoxicity in the MTT assay or irritant potential. Additionally, an antioxidant activity of 58.25 ± 0.32% was observed at a concentration of 40 mg/mL. The compound also exhibited antimicrobial activity against various pathogenic microorganisms. The characterisation of the biosurfactant using magnetic nuclear resonance and Fourier transform infrared spectroscopy revealed that the biomolecule is a glycolipid with an anionic nature. The results demonstrate that biosurfactant produced in this work has potential as an active biotechnological ingredient for innovative, eco-friendly cosmetic formulations. Full article
(This article belongs to the Special Issue The Industrial Feasibility of Biosurfactants)
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22 pages, 1916 KiB  
Article
Freeze-Dried Probiotic Fermented Camel Milk Enriched with Ajwa Date Pulp: Evaluation of Functional Properties, Probiotic Viability, and In Vitro Antidiabetic and Anticancer Activities
by Sally S. Sakr and Hassan Barakat
Foods 2025, 14(15), 2698; https://doi.org/10.3390/foods14152698 - 31 Jul 2025
Viewed by 338
Abstract
Noncommunicable diseases (NCDs) like diabetes and cancer drive demand for therapeutic functional foods. This study developed freeze-dried fermented camel milk (FCM) with Ajwa date pulp (ADP), evaluating its physical and functional properties, probiotic survival, and potential benefits for diabetes and cancer. To achieve [...] Read more.
Noncommunicable diseases (NCDs) like diabetes and cancer drive demand for therapeutic functional foods. This study developed freeze-dried fermented camel milk (FCM) with Ajwa date pulp (ADP), evaluating its physical and functional properties, probiotic survival, and potential benefits for diabetes and cancer. To achieve this target, six FCM formulations were prepared using ABT-5 starter culture (containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Streptococcus thermophilus) with or without Lacticaseibacillus rhamnosus B-1937 and ADP (12% or 15%). The samples were freeze-dried, and their functional properties, such as water activity, dispersibility, water absorption capacity, water absorption index, water solubility index, insolubility index, and sedimentation, were assessed. Reconstitution properties such as density, flowability, air content, porosity, loose bulk density, packed bulk density, particle density, carrier index, Hausner ratio, porosity, and density were examined. In addition, color and probiotic survivability under simulated gastrointestinal conditions were analyzed. Also, antidiabetic potential was assessed via α-amylase and α-glucosidase inhibition assays, while cytotoxicity was evaluated using the MTT assay on Caco-2 cells. The results show that ADP supplementation significantly improved dispersibility (up to 72.73% in FCM15D+L). These improvements are attributed to changes in particle size distribution and increased carbohydrate and mineral content, which facilitate powder rehydration and reduce clumping. All FCM variants demonstrated low water activity (0.196–0.226), indicating good potential for shelf stability. The reconstitution properties revealed that FCM powders with ADP had higher bulk and packed densities but lower particle density and porosity than controls. Including ADP reduced interstitial air and increased occluded air within the powders, which may minimize oxidation risks and improve packaging efficiency. ADP incorporation resulted in a significant decrease in lightness (L*) and increases in redness (a*) and yellowness (b*), with greater pigment and phenolic content at higher ADP levels. These changes reflect the natural colorants and browning reactions associated with ADP, leading to a more intense and visually distinct product. Probiotic survivability was higher in ADP-fortified samples, with L. acidophilus and B. bifidum showing resilience in intestinal conditions. The FCM15D+L formulation exhibited potent antidiabetic effects, with IC50 values of 111.43 μg mL−1 for α-amylase and 77.21 μg mL−1 for α-glucosidase activities, though lower than control FCM (8.37 and 10.74 μg mL−1, respectively). Cytotoxicity against Caco-2 cells was most potent in non-ADP samples (IC50: 82.22 μg mL−1 for FCM), suggesting ADP and L. rhamnosus may reduce antiproliferative effects due to proteolytic activity. In conclusion, the study demonstrates that ADP-enriched FCM is a promising functional food with enhanced probiotic viability, antidiabetic potential, and desirable physical properties. This work highlights the potential of camel milk and date synergies in combating some NCDs in vitro, suggesting potential for functional food application. Full article
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19 pages, 2509 KiB  
Article
Semi-Synthesis, Anti-Leukemia Activity, and Docking Study of Derivatives from 3α,24-Dihydroxylup-20(29)-en-28-Oic Acid
by Mario J. Noh-Burgos, Sergio García-Sánchez, Fernando J. Tun-Rosado, Antonieta Chávez-González, Sergio R. Peraza-Sánchez and Rosa E. Moo-Puc
Molecules 2025, 30(15), 3193; https://doi.org/10.3390/molecules30153193 - 30 Jul 2025
Viewed by 407
Abstract
Current treatments against leukemia present several limitations, prompting the search for new therapeutic agents, particularly those derived from natural products. In this context, structural modifications were performed on the triterpene 3α,24-dihydroxylup-20(29)-en-28-oic acid (T1), isolated from Phoradendron wattii. Among [...] Read more.
Current treatments against leukemia present several limitations, prompting the search for new therapeutic agents, particularly those derived from natural products. In this context, structural modifications were performed on the triterpene 3α,24-dihydroxylup-20(29)-en-28-oic acid (T1), isolated from Phoradendron wattii. Among the five derivatives obtained, 3α,24-dihydroxy-30-oxolup-20(29)-en-28-oic acid (T1c) exhibited the highest activity, with an IC50 value of 12.90 ± 0.1 µM against THP-1 cells. T1c significantly reduced cell viability in both acute lymphoblastic leukemia (CCRF-CEM, REH, JURKAT, and MOLT-4) and acute myeloid leukemia (THP-1) cell lines, inducing apoptosis after 48 h of treatment, while showing minimal cytotoxicity toward normal mononuclear cells (MNCs). In silico molecular docking studies were conducted against three key protein targets: BCL-2 (B-cell lymphoma 2), EGFR (epidermal growth factor receptor, tyrosine kinase domain), and FLT3 (FMS-like tyrosine kinase 3). The lowest binding energies (kcal/mol) observed were as follows: T1–BCL-2: −10.12, EGFR: −12.75, FLT3: −14.05; T1c–BCL-2: −10.23, EGFR: −14.50, FLT3: −14.07; T2–BCL-2: −11.59, EGFR: −15.00, FLT3: −14.03. These findings highlight T1c as a promising candidate in the search for anti-leukemic drugs which deserves further study. Full article
(This article belongs to the Special Issue Synthesis and Derivatization of Heterocyclic Compounds)
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19 pages, 4477 KiB  
Article
Agapanthussaponin A from the Underground Parts of Agapanthus africanus Induces Apoptosis and Ferroptosis in Human Small-Cell Lung Cancer Cells
by Tomoki Iguchi, Tamami Shimazaki and Yoshihiro Mimaki
Molecules 2025, 30(15), 3189; https://doi.org/10.3390/molecules30153189 - 30 Jul 2025
Viewed by 222
Abstract
To explore the potential seed compounds from natural products as anticancer agents against small-cell lung cancer (SCLC), the underground parts of Agapanthus africanus, a plant commonly used for ornamental purposes, were investigated. Three spirostan-type steroidal glycosides (13) were [...] Read more.
To explore the potential seed compounds from natural products as anticancer agents against small-cell lung cancer (SCLC), the underground parts of Agapanthus africanus, a plant commonly used for ornamental purposes, were investigated. Three spirostan-type steroidal glycosides (13) were isolated and identified by nuclear magnetic resonance spectral analysis. Compounds 13 exhibited cytotoxicity against SBC-3 human SCLC cells, with IC50 values of 0.56, 1.4, and 7.4 µM, respectively. Compound 1, also known an agapanthussaponin A, demonstrated the most potent cytotoxicity among the isolated compounds and was evaluated for its apoptosis- and ferroptosis-inducing activities. Compound 1 arrested the cell cycle of SBC-3 cells in the G2/M phase and induced apoptosis primarily via the mitochondrial pathway, characterized by caspases-3 and -9 activation, loss of mitochondrial membrane potential, and overproduction of reactive oxygen species. Additionally, 1 triggered ferroptosis via a dual mechanism consisting of enhanced cellular iron uptake through upregulation of transferrin and transferrin receptor 1 expression and impaired glutathione synthesis via downregulation of both xCT and glutathione peroxidase 4 expression. Compound 1 induces cell death via the apoptosis and ferroptosis pathways, suggesting its promise as a seed compound for the development of anticancer therapeutics against SCLC. Full article
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15 pages, 1375 KiB  
Article
Photodegradation of Turmeric Oleoresin Under Fluorescent Light and White LED: Impacts on the Chemical Stability, Bioactivity, and Photosensitizing Property of Curcuminoids
by Heejeong Kim, Juyeon Oh and Jungil Hong
Molecules 2025, 30(15), 3187; https://doi.org/10.3390/molecules30153187 - 30 Jul 2025
Viewed by 241
Abstract
Turmeric oleoresin (TO), a natural pigment derived from Curcuma longa rhizomes, is valued for its health benefits, which are primarily attributed to its rich curcuminoid content (curcumin, demethoxycurcumin, and bisdemethoxycurcumin). Despite these benefits, curcuminoids are known to be light-sensitive and possess photosensitizing properties. [...] Read more.
Turmeric oleoresin (TO), a natural pigment derived from Curcuma longa rhizomes, is valued for its health benefits, which are primarily attributed to its rich curcuminoid content (curcumin, demethoxycurcumin, and bisdemethoxycurcumin). Despite these benefits, curcuminoids are known to be light-sensitive and possess photosensitizing properties. This study investigated the impact of common light sources, fluorescent light and white LED (both at 10 W/m2), on the chemical stability, antioxidant activity, cytotoxicity, and photosensitizing properties of TO. Exposure to both light sources significantly reduced TO’s color and fluorescence intensity, with white LED causing greater instability. HPLC analysis confirmed a decrease in individual curcuminoid levels, with curcumin degrading most rapidly under both conditions. The DPPH radical scavenging activity of irradiated TO decreased compared to fresh or dark-stored turmeric, whereas its ABTS radical scavenging activity increased upon light exposure. Photosensitizing potency, measured by formazan decolorization and lipid peroxide formation, declined as TO decomposed under light. Conversely, the cytotoxicity of TO against B16F10 melanoma cells was significantly enhanced under light exposure, though this effect was diminished significantly after 24 h of pre-irradiation. These findings underscore the instability of turmeric pigment under common lighting conditions, which should be a crucial consideration when processing, storing, and distributing turmeric-containing products. Full article
(This article belongs to the Special Issue Photochemistry in Asia)
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17 pages, 1500 KiB  
Article
Comprehensive Receptor Repertoire and Functional Analysis of Peripheral NK Cells in Soft Tissue Sarcoma Patients
by Luana Madalena Sousa, Jani-Sofia Almeida, Tânia Fortes-Andrade, Patrícia Couceiro, Joana Rodrigues, Rúben Fonseca, Manuel Santos-Rosa, Paulo Freitas-Tavares, José Manuel Casanova and Paulo Rodrigues-Santos
Cancers 2025, 17(15), 2508; https://doi.org/10.3390/cancers17152508 - 30 Jul 2025
Viewed by 312
Abstract
Background: Soft tissue sarcomas (STSs) are a rare and heterogeneous group of mesenchymal tumors with limited response to current therapies, particularly in advanced stages. STS tumors were traditionally considered “cold” tumors, characterized by limited immune infiltration and low immunogenicity. However, emerging evidence is [...] Read more.
Background: Soft tissue sarcomas (STSs) are a rare and heterogeneous group of mesenchymal tumors with limited response to current therapies, particularly in advanced stages. STS tumors were traditionally considered “cold” tumors, characterized by limited immune infiltration and low immunogenicity. However, emerging evidence is challenging this perception, highlighting a potentially critical role for the immune system in STS biology. Objective: Building on our previous findings suggesting impaired natural killer (NK) cell activity in STS patients, we aimed to perform an in-depth characterization of peripheral NK cells in STS. Methods: Peripheral blood samples from STS patients and sex- and age-matched healthy donors were analyzed to assess NK cell degranulation, IFNγ production, and receptor repertoire. Results: Functional assays revealed a notable reduction in both degranulation and IFNγ production in NK cells from STS patients. STS patients also exhibited dysregulated expression of activating and inhibitory NK cell receptors. Principal component analysis (PCA) identified CD27 and NKp44 as critical markers for distinguishing STS patients from healthy donors. Increased CD27 expression represents a shift towards a more regulatory NK cell phenotype, and we found that CD27 expression was negatively correlated with NK cell degranulation and IFNγ production. ROC curve analysis demonstrated strong potential to distinguish between the groups for both CD27 (AUC = 0.85) and NKp44 (AUC = 0.94). Conclusion: In conclusion, STS patients exhibited impaired NK cell function, altered receptor repertoire, and a shift towards a less cytotoxic and more regulatory phenotype. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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14 pages, 842 KiB  
Article
Immunoenhancing Effects of Jeju Agastache rugosa Extracts on NK Cell Activity and Lymphocyte Proliferation in Cyclophosphamide-Induced Immunosuppression
by Sung Jin Kim, Seong-Il Kang, Nari Lee, Jung Min Oh, Hiyoung Kim, Mi-Gi Lee, Ji Hoon Song and Myoung-Sook Shin
Pharmaceuticals 2025, 18(8), 1129; https://doi.org/10.3390/ph18081129 - 28 Jul 2025
Viewed by 286
Abstract
Background/objectives: This study evaluated the immunoenhancing effects of Agastache rugosa extract in a cyclophosphamide-induced immunosuppressed mouse model. Methods: Jeju A. rugosa was processed via hot water extraction and 20% ethanol extraction. For immunosuppression induction, 7-week-old male BALB/c mice received intraperitoneal CPA injections (150 [...] Read more.
Background/objectives: This study evaluated the immunoenhancing effects of Agastache rugosa extract in a cyclophosphamide-induced immunosuppressed mouse model. Methods: Jeju A. rugosa was processed via hot water extraction and 20% ethanol extraction. For immunosuppression induction, 7-week-old male BALB/c mice received intraperitoneal CPA injections (150 mg/kg, day −3; 110 mg/kg, day −1), followed by oral administration of hot water extract (ARE-W) and ethanol extract (ARE-E) at 100 and 300 mg/kg for 14 days. Oral administration of ARE-W and ARE-E was started on day 0, immediately following the final CPA injection on day −1. Immune function was assessed through body weight changes, spleen weight, NK cell activity, IFN-γ production, and splenic lymphocyte proliferation. Results: Results demonstrated that CPA treatment induced comprehensive immune dysfunction, while A. rugosa extracts significantly ameliorated these immunosuppressive conditions. Notably, ARE-W (300 mg/kg) significantly enhanced NK cell cytotoxicity against tumor cells and IFN-γ production compared to the CPA group, and effectively restored spleen weight and lymphocyte proliferation. ARE-E also exhibited dose-dependent immune function recovery; however, ARE-W showed superior efficacy across most immune parameters. Conclusions: These findings suggest that A. rugosa extract, particularly ARE-W, effectively restores immune function in immunosuppressed conditions, indicating potential application as a natural functional material for ameliorating immunosuppression caused by cancer treatment or immune diseases. Full article
(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention 2025)
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33 pages, 1777 KiB  
Review
Immunomodulatory Natural Products in Cancer Organoid-Immune Co-Cultures: Bridging the Research Gap for Precision Immunotherapy
by Chang-Eui Hong and Su-Yun Lyu
Int. J. Mol. Sci. 2025, 26(15), 7247; https://doi.org/10.3390/ijms26157247 - 26 Jul 2025
Viewed by 619
Abstract
Natural products demonstrate potent immunomodulatory properties through checkpoint modulation, macrophage polarization, and T cell/natural killer (NK) cell activation. While cancer organoid-immune co-culture platforms enable physiologically relevant modeling of tumor–immune interactions, systematic investigation of natural product immunomodulation in these systems remains entirely unexplored. We [...] Read more.
Natural products demonstrate potent immunomodulatory properties through checkpoint modulation, macrophage polarization, and T cell/natural killer (NK) cell activation. While cancer organoid-immune co-culture platforms enable physiologically relevant modeling of tumor–immune interactions, systematic investigation of natural product immunomodulation in these systems remains entirely unexplored. We conducted a comprehensive literature analysis examining natural products tested in cancer organoids, immunomodulatory mechanisms from traditional models, technical advances in organoid-immune co-cultures, and standardization requirements for clinical translation. Our analysis reveals a critical research gap: no published studies have investigated natural product-mediated immunomodulation using organoid-immune co-culture systems. Even though compounds like curcumin, resveratrol, and medicinal mushroom polysaccharides show extensive immunomodulatory effects in two-dimensional (2D) cultures, and organoid technology achieves high clinical correlation for drug response prediction, all existing organoid studies focus exclusively on direct cytotoxicity. Technical challenges include compound stability, limited matrix penetration requiring substantially higher concentrations than 2D cultures, and maintaining functional immune populations in three-dimensional (3D) systems. The convergence of validated organoid-immune co-culture platforms, Food and Drug Administration (FDA) regulatory support through the Modernization Act 2.0, and extensive natural product knowledge creates unprecedented opportunities. Priority research directions include systematic screening of immunomodulatory natural products in organoid-immune co-cultures, development of 3D-optimized delivery systems, and clinical validation trials. Success requires moving beyond cytotoxicity-focused studies to investigate immunomodulatory mechanisms in physiologically relevant 3D systems, potentially unlocking new precision cancer immunotherapy approaches. Full article
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18 pages, 2943 KiB  
Article
Cadmium Inhibits Proliferation of Human Bronchial Epithelial BEAS-2B Cells Through Inducing Ferroptosis via Targeted Regulation of the Nrf2/SLC7A11/GPX4 Pathway
by Huan Li, Zixin Qiu, Long Chen, Tianbao Zhang, Diandian Wei, Xue Chen and Yun Wang
Int. J. Mol. Sci. 2025, 26(15), 7204; https://doi.org/10.3390/ijms26157204 - 25 Jul 2025
Viewed by 251
Abstract
Cadmium (Cd)-induced pulmonary toxicity is closely associated with ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation (LPO). Luteolin (Lut) is a natural flavonoid compound that exists in many plants. In this study, we used human bronchial epithelial BEAS-2B cells [...] Read more.
Cadmium (Cd)-induced pulmonary toxicity is closely associated with ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation (LPO). Luteolin (Lut) is a natural flavonoid compound that exists in many plants. In this study, we used human bronchial epithelial BEAS-2B cells to explore the impact of ferroptosis in the inhibition of Cd-induced BEAS-2B cells proliferation. BEAS-2B cells were exposed to Cd (5 μM) with/without Lut (10 μM), ferroptosis modulators (Ferrostatin-1 (Fer-1)/Erastin), or nuclear factor erythroid 2-related factor 2 (Nrf2) regulators (tert-butylhydroquinone (TBHQ)/ML385). Viability, iron content, reactive oxygen species (ROS), LPO, mitochondrial membrane potential (MMP), and glutathione peroxidase (GSH-PX) activity were assessed. Exposure to Cd significantly decreased cell viability, increased intracellular iron levels, ROS production, and LPO activity, while simultaneously reducing MMP and GSH-PX activity. Fer-1 mitigated Cd-induced cytotoxicity, but Erastin intensified these effects. Mechanistically, Cd exposure suppressed the Nrf2/Solute Carrier Family 7 Member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway, which plays a crucial role in maintaining redox homeostasis. Activation of Nrf2 using TBHQ mitigated oxidative stress and upregulated the expression of key proteins within this pathway, while inhibition of Nrf2 with ML385 exacerbated cellular damage. Notably, Lut treatment could significantly alleviate Cd-induced cytotoxicity, oxidative stress, and downregulation of Nrf2/SLC7A11/GPX4 proteins. These findings demonstrate that ferroptosis is a critical mechanism underlying Cd-mediated lung epithelial injury and identify Lut as a promising therapeutic candidate via its activation of Nrf2-driven antioxidant defense mechanisms. This study provides novel insights into molecular targets for the prevention and treatment of Cd-associated pulmonary disorders. Full article
(This article belongs to the Section Biochemistry)
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21 pages, 3048 KiB  
Article
Transfersome-Based Delivery of Optimized Black Tea Extract for the Prevention of UVB-Induced Skin Damage
by Nadia Benedetto, Maria Ponticelli, Ludovica Lela, Emanuele Rosa, Flavia Carriero, Immacolata Faraone, Carla Caddeo, Luigi Milella and Antonio Vassallo
Pharmaceutics 2025, 17(8), 952; https://doi.org/10.3390/pharmaceutics17080952 - 23 Jul 2025
Viewed by 321
Abstract
Background/Objectives: Ultraviolet B (UVB) radiation contributes significantly to skin aging and skin disorders by promoting oxidative stress, inflammation, and collagen degradation. Natural antioxidants such as theaflavins and thearubigins from Camellia sinensis L. (black tea) have shown photoprotective effects. This study aimed to optimize [...] Read more.
Background/Objectives: Ultraviolet B (UVB) radiation contributes significantly to skin aging and skin disorders by promoting oxidative stress, inflammation, and collagen degradation. Natural antioxidants such as theaflavins and thearubigins from Camellia sinensis L. (black tea) have shown photoprotective effects. This study aimed to optimize the extraction of theaflavins and thearubigins from black tea leaves and evaluate the efficacy of the extract against UVB-induced damage using a transfersome-based topical formulation. Methods: Extraction of theaflavins and thearubigins was optimized via response surface methodology (Box-Behnken Design), yielding an extract rich in active polyphenols. This extract was incorporated into transfersomes that were characterized for size, polydispersity, zeta potential, storage stability, and entrapment efficiency. Human dermal fibroblasts (NHDF) were used to assess cytotoxicity, protection against UVB-induced viability loss, collagen degradation, and expression of inflammatory (IL6, COX2, iNOS) and matrix-degrading (MMP1) markers. Cellular uptake of the extract’s bioactive marker compounds was measured via LC-MS/MS. Results: The transfersomes (~60 nm) showed a good stability and a high entrapment efficiency (>85%). The transfersomes significantly protected NHDF cells from UVB-induced cytotoxicity, restored collagen production, and reduced gene expression of MMP1, IL6, COX2, and iNOS. Cellular uptake of key extract’s polyphenols was markedly enhanced by the nanoformulation compared to the free extract. Conclusions: Black tea extract transfersomes effectively prevented UVB-induced oxidative and inflammatory damage in skin fibroblasts. This delivery system enhanced bioavailability of the extract and cellular protection, supporting the use of the optimized extract in cosmeceutical formulations targeting photoaging and UV-induced skin disorders. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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26 pages, 6375 KiB  
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 528
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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18 pages, 2563 KiB  
Article
The Potential Anti-Cancer Effects of Polish Ethanolic Extract of Propolis and Quercetin on Glioma Cells Under Hypoxic Conditions
by Małgorzata Kłósek, Anna Kurek-Górecka, Radosław Balwierz, Grażyna Pietsz and Zenon P. Czuba
Molecules 2025, 30(14), 3008; https://doi.org/10.3390/molecules30143008 - 17 Jul 2025
Viewed by 658
Abstract
Tissue hypoxia is commonly observed in head cancers and contributes to both molecular and functional changes in tumour cells. It is known to stimulate erythropoiesis, angiogenesis, and metabolic alterations within tumour cells. Glioblastoma, a type of brain tumour, is characterized by rapid proliferation [...] Read more.
Tissue hypoxia is commonly observed in head cancers and contributes to both molecular and functional changes in tumour cells. It is known to stimulate erythropoiesis, angiogenesis, and metabolic alterations within tumour cells. Glioblastoma, a type of brain tumour, is characterized by rapid proliferation and aggressive growth. Recent studies have indicated that natural products may hold potential as components of cancer therapy. Among these, Polish propolis and its active compound, quercetin, have demonstrated promising anti-cancer properties. The aim of this study was to evaluate the concentrations of selected cytokines—specifically IL-6, IL-9, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1)—produced by astrocytes of the CCF-STTG1 cell line. The cytotoxic effects of ethanolic extract of propolis (EEP) and quercetin were assessed using the MTT assay. Astrocytes were stimulated with lipopolysaccharide (LPS, 200 ng/mL) and/or IFN-α (100 U/mL), followed by treatment with EEP or quercetin (25–50 µg/mL) under hypoxic conditions for two hours. Cytokine concentrations were measured using the xMAP Luminex Multiplex Immunoassay and the Multiplex Bead-Based Cytokine Kit. Our study demonstrated that Polish propolis and its component quercetin modulate the tumour microenvironment in vitro, primarily by altering the levels of specific cytokines. The HCA analysis revealed that IL-6 and MCP-1 formed a distinct cluster at the highest linkage distance (approximately 100% of Dmax), suggesting that their expression patterns are significantly different from those of the other cytokines and that they are more similar to each other than to the rest. PCA analysis showed that EEP-PL (50 μg/mL) with IFN-α and EEP-PL (50 μg/mL) with LPS exert similar activities on cytokine secretion by astrocytes. Similar effects were demonstrated for EEP-PL 50 μg/mL + LPS + IFN-α, EEP-PL 25 μg/mL + IFN-α and EEP-PL 25 μg/mL + LPS + IFN-α. Our findings suggest that Polish propolis and quercetin may serve as promising natural agents to support the treatment of stage IV malignant astrocytoma. Nonetheless, further research is needed to confirm these results. Full article
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21 pages, 385 KiB  
Review
Emerging Mycotoxins in Aquaculture: Current Insights on Toxicity, Biocontrol Strategies, and Occurrence in Aquafeed and Fish
by Patrizio Lorusso, Giusy Rusco, Alessio Manfredi, Nicolaia Iaffaldano, Angela Di Pinto and Elisabetta Bonerba
Toxins 2025, 17(7), 356; https://doi.org/10.3390/toxins17070356 - 17 Jul 2025
Viewed by 383
Abstract
Mycotoxins are secondary metabolites produced by various fungal species that can contaminate food and feed, posing significant risks to human and animal health. In aquaculture, the replacement of fishmeal with alternative protein sources has increased the risk of mycotoxin contamination, becoming a major [...] Read more.
Mycotoxins are secondary metabolites produced by various fungal species that can contaminate food and feed, posing significant risks to human and animal health. In aquaculture, the replacement of fishmeal with alternative protein sources has increased the risk of mycotoxin contamination, becoming a major challenge in fish feed production. Current data highlights that fish are exposed not only to common mycotoxins but also to emerging ones, raising concerns about human exposure through fish consumption. In this review, we draw attention to the toxicity data of key emerging mycotoxins from Fusarium (enniatins, ENNs; beauvericin, BEA) and Alternaria (alternariol monomethyl ether, AME; alternariol, AOH), their occurrence in aquafeeds and in commercially relevant fish species in Europe, and potential biocontrol approaches to prevent/mitigate contaminations. From the present review, it emerged that these mycotoxins exhibit in vitro cytotoxic properties. Their prevalence and concentrations vary widely both among aquafeeds, depending on the sample’s origin, and among fish species. Biocontrol approaches using microorganisms or natural compounds show promise as sustainable solutions to limit contamination. However, further research is essential to address data gaps and to allow for a proper risk assessment and, if necessary, the implementation of effective management measures. Full article
(This article belongs to the Special Issue Risk Assessment of Mycotoxins: Challenges and Emerging Threats)
23 pages, 12860 KiB  
Article
Antimicrobial Composite Films Based on Alginate–Chitosan with Honey, Propolis, Royal Jelly and Green-Synthesized Silver Nanoparticles
by Corina Dana Dumitru, Cornelia-Ioana Ilie, Ionela Andreea Neacsu, Ludmila Motelica, Ovidiu Cristian Oprea, Alexandra Ripszky, Silviu Mirel Pițuru, Bianca Voicu Bălașea, Florica Marinescu and Ecaterina Andronescu
Int. J. Mol. Sci. 2025, 26(14), 6809; https://doi.org/10.3390/ijms26146809 - 16 Jul 2025
Viewed by 370
Abstract
Honey, propolis or royal jelly are considered natural remedies with therapeutic properties since antiquity. Many papers explore the development of antimicrobial biomaterials based on individual bee products, but there is a lack of studies on their synergistic effects. Combining honey, propolis and royal [...] Read more.
Honey, propolis or royal jelly are considered natural remedies with therapeutic properties since antiquity. Many papers explore the development of antimicrobial biomaterials based on individual bee products, but there is a lack of studies on their synergistic effects. Combining honey, propolis and royal jelly with silver nanoparticles in a biopolymer matrix offers a synergistic strategy to combat antibiotic-resistant bacterial infections. This approach supports progress in wound healing, soft tissue engineering and other domains where elimination of the microorganisms is needed like food packaging. In this study we have obtained antimicrobial films based on bee products and silver nanoparticles (AgNPs) incorporated in an alginate–chitosan blend. The novel biomaterials were analyzed by UV-Vis, fluorescence and FTIR spectroscopy or microscopy, SEM and thermal analysis. Antibacterial tests were conducted against both Gram-positive and Gram-negative bacteria, while the antifungal properties were tested against Candida albicans. The diameters for growth inhibition zones were up to 10 mm for bacterial strains and 8 mm for the fungal strain. Additionally, cytotoxicity assays were performed to evaluate the biocompatibility of the materials, the results indicating that the combination of honey, propolis, royal jelly and AgNPs does not produce synergistic toxicity. Full article
(This article belongs to the Section Materials Science)
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