Search Results (4,569)

Blueberries are widely consumed due to their richness in nutrients, yet they are also prone to quality deterioration after being harvested, even at cold temperatures. Non-thermal physical technology is an important auxiliary method worth considering for maintaining the quality of this fruit while refrigerated. In this study, a static magnetic field (SMF) was applied as a complementary pretreatment strategy prior to cold storage of blueberries. The optimal SMF parameters were identified as 5 mT exposure for 12 h, as this significantly retarded decay and softening. The contents of ascorbic acid, total polyphenols, flavonoids and proanthocyanidins were elevated by 20.0%, 17.7%, 23.9%, and 9.1%, respectively. Concurrently, DPPH (1,1-diphenyl-2-picrylhydrazyl) radical-scavenging capacity, catalase (CAT), and superoxide dismutase (SOD) activity markedly improved. Targeted metabolomic analysis revealed that SMF pretreatment significantly regulated polyphenol metabolic pathways and redirected polyphenol biosynthesis toward more stable and functional compounds, including three hydroxycinnamic acids, quercetin, dihydromyricetin, glycosylated hesperetin, and acylated delphinidin derivates. The synergistic effect of these SMF-elevated phenolics and the reinforced antioxidant system preserved the overall cold-storage quality of blueberries. These findings underscore the potential of SMF pretreatment as an effective physical technique for reducing postharvest blueberry losses. Full article

Background: Intervertebral disc degeneration (IVDD) is driven by the interplay between inflammatory signaling, extracellular matrix (ECM) degradation, and impaired cellular adaptation. Although several nutraceutical compounds have been reported to exert protective effects in IVDD-related models, their multitarget mechanisms within integrated molecular networks remain incompletely characterized. Methods: An in silico framework integrating molecular docking with network-based analyses was employed to evaluate resveratrol, quercetin, melatonin, curcumin, and baicalein against a predefined panel of IVDD-associated targets, within an exploratory in silico framework. Binding affinities and interaction profiles were assessed using molecular docking, followed by protein–protein interaction (PPI) network construction, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and hub gene identification. Results: Docking analyses revealed binding energies ranging from −4.59 to −13.25 kcal/mol, with curcumin and quercetin showing plausible docking poses across a subset of selected targets under the applied protocol. Network analysis showed a highly interconnected structure centered on key inflammatory regulators, including NFKB1, IL6, TNF, IL1B, STAT3, and NLRP3, together with ECM-associated components such as ACAN, COL2A1, SOX9, MMP13, and ADAMTS5. Enrichment analyses further suggested significant associations with inflammatory signaling pathways, cytokine regulation, and ECM organization. Conclusions: These findings are compatible with a distributed, multitarget interaction pattern of nutraceutical compounds within IVDD-associated molecular networks. By integrating molecular docking with network-based analyses, this study offers a system-level framework for interpreting previously reported effects within a disease-specific context. Docking-derived interaction patterns should be interpreted as qualitative and exploratory observations, as docking scores represent model-dependent estimates and do not establish comparable pharmacological effects across heterogeneous targets. The results should be considered hypothesis-generating and require experimental validation. Full article

Antioxidant supplementation during in vitro maturation (IVM) has been proposed as a strategy to influence transcriptional responses in oocytes and cumulus–oocyte complexes. In this study, we investigated whether vitamin C, rosmarinic acid, or quercetin influence the expression of key fertilisation-associated genes (CD9, ITGA6, MFGE8, ZP2, and ZP3) in porcine cumulus–oocyte complexes (COCs). COCs were classified into three intrinsic quality groups (I–III) and matured in the presence or absence of antioxidants. Gene expression was quantified by RT-qPCR and analysed using a two-way ANOVA model to assess the effects of COC quality and treatment. ZP2 and ZP3 transcript levels were consistently lower in class II and III COCs than in class I controls (p < 0.001). Antioxidant supplementation was associated with treatment- and quality-dependent differences in gene expression. Quercetin was associated with the most pronounced upregulation, with Q I increasing ZP2 expression to 2.95-fold and ZP3 to 2.43-fold relative to class I controls (p < 0.001). Vitamin C was also associated with increased transcript abundance across several treatment groups, including class II and class III COCs, whereas rosmarinic acid exhibited more moderate and gene-specific effects. In contrast, MFGE8 expression, which was elevated in lower-quality COCs, was reduced in antioxidant-treated class II and III complexes. These findings provide transcript-level evidence that antioxidant exposure during IVM is associated with treatment- and quality-dependent changes in fertilisation-related gene expression in porcine COCs. Full article

Plant extracts are widely used as natural pesticides, cosmetic ingredients, and in pharmaceutical applications. However, their poor water solubility and stability limit their usability. Lipid nanoparticles (LNPs) offer an effective encapsulation strategy to overcome these challenges. This study demonstrates the encapsulation of three representative substances from these industries: quercetin as a pesticide, irones as a cosmetic ingredient, and nucleic acids for pharmaceutical use. Ultrasonic treatment was used for the encapsulation of quercetin and irones, and a concept for continuous encapsulation in a plug flow reactor was proposed for process intensification. Inline multi-angle light scattering and dynamic light scattering measurements proved effective for real-time monitoring and enabled the replacement of traditional batch measurements. In the pharmaceutical area, mRNA-based therapies require LNP encapsulation to prevent nucleic acid degradation. Plant-based β-sitosterol was used as an alternative helper lipid to cholesterol, resulting in an average particle diameter of 72 nm and an encapsulation efficiency of 91%, comparable to commercial formulations such as the Comirnaty vaccine. Furthermore, a novel process model based on population balances was developed to simulate the entire manufacturing process, from rapid mixing in a T-mixer to particle stabilization via buffer exchange during diafiltration. By applying a quantitative and distinctive model validation workflow, the model was shown to be as accurate and precise as the experimental data, enabling its use as a digital twin for autonomous continuous operation. In summary, this study contributes to reducing the facility footprint and cost of goods through the implementation of continuous processing and model-based control. This approach improves productivity by 20% and reduces process time by a factor of two. Full article

Neuroblastoma is characterized by noticeable resistance to chemotherapy, largely driven by the ability of tumour cells to reorganize stress-adaptive signalling networks rather than relying on single oncogenic drivers. We conducted a study to investigate the pharmacological mode of action of doxorubicin in modifying adaptive signalling pathways in SH-SY5Y neuroblastoma cells, and whether the capacity of plant metabolites can exploit emergent biochemical vulnerabilities. Transcriptomic profiling through RNA sequencing conducted 48 h post-doxorubicin exposure unveiled the organized disruption of pathways linked with amyloidogenic processes, oncogenic signalling pathways, oxidative stress, and DNA repair. The protein–protein interactions, coupled with Kyoto Encyclopedia of Genes and Genomes pathway evaluations, revealed five network-central-hubs: BRAF, GSK3β, PARP1, BACE1, and MAOB. Structural docking integrated with 200 ns molecular dynamics simulations illustrated binding stability across multiple targets driven by three metabolites, Lactol binding to BRAF (−54.13 kcal/mol) and MAOB (−39.08 kcal/mol), Amino(1H-indol-2-yl)acetic acid to BACE1 (−41.07 kcal/mol) and GSK3β (−47.38 kcal/mol), and Quercetin-3-(6″-malonyl-glucoside) binding to PARP1 (−46.03 kcal/mol). In vitro Cell Counting Kit-8 proliferation assays validated the significant anti-neuroblastoma efficacy, with the lowest IC₅₀ (0.2397 µM) being exhibited by Amino(1H-indol-2-yl)acetic acid, followed by Lactol (1.226 µM) and Quercetin-3-(6″-malonyl-glucoside) (1.301 µM), which mirrored the cytotoxic action of doxorubicin (1.306 µM). These results suggest that plant-derived metabolites may interact with stress-adaptive signalling pathways connected with neuroblastoma. However, direct experimental validation of target engagement and pathway modulation will be required to confirm these predicted interactions. Full article

Background/Objectives: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and chronic neuroinflammation. Increasing evidence suggests that the imbalance between pro-inflammatory Th17 cells and anti-inflammatory regulatory T (Treg) cells plays a critical role in AD pathogenesis. However, a comprehensive synthesis of how natural compounds modulate Th17/Treg balance in AD remains lacking. This review aims to summarize current preclinical evidence on Th17/Treg dysregulation and evaluate the immunomodulatory potential of natural compounds in AD. Methods: This review focuses on preclinical evidence derived from experimental AD models and related inflammatory models to evaluate how natural compounds modulate Th17/Treg balance, neuroinflammation, and cognitive function, with an emphasis on underlying molecular and immunometabolic mechanisms. Results: Th17/Treg imbalance contributes significantly to AD-associated neuroinflammation and disease progression. Representative natural compounds, including paeoniflorin, quercetin, and ganoderic acid A, have demonstrated the ability to rebalance Th17/Treg responses, suppress neuroinflammation, and improve neuronal survival in experimental models. These compounds are highlighted due to their relatively stronger evidence in AD-related models and more clearly defined immunomodulatory mechanisms. These effects are partially mediated through modulation of key signaling pathways and immunometabolic reprogramming. Conclusions: Targeting Th17/Treg balance with natural compounds represents a promising multi-target immunomodulatory strategy for AD. However, most current evidence is derived from preclinical or non-AD models, and clinical validation remains limited. Future studies should prioritize AD-specific models and translational research to evaluate therapeutic potential in humans. Full article

Background/Objectives: The most abundant flavonoid, quercetin, which is mostly found as glycosides, is widely distributed in plants. Quercetin is rapidly metabolized, having a short half-life in the blood circulation, and forms its conjugates by undergoing ring cleavage of the benzopyranone ring system. Despite its fast clearance in the body, quercetin was demonstrated to have clinically anti-inflammatory, cardioprotective, antidiabetic, and anti-obesity activities. This study aimed to determine whether quercetin itself or its metabolites are responsible for these activities. Methods: We performed molecular docking of 27 metabolites, including quercetin itself, against ten inflammation-related proteins in silico. We then conducted microscale thermophoresis (MST) of selected metabolites towards the NLRP3 inflammasome. Results: Overall, Phase II metabolites yielded better binding energies compared to the metabolites formed by degradation. MST results revealed that isorhamnetin, the 4-O-methylated metabolite of quercetin, gave the best results, with a binding affinity (K_D value) of 16.12 ± 5.16 µM, even better than quercetin itself, which has a binding affinity of 44.84 ± 4.21 µM. Glucuronide metabolites of quercetin (isorhamnetin 3-O-glucuronide, quercetin 7-O-glucuronide, and quercetin 3-O-glucuronide) were found to bind to the inflammasome protein with low binding affinities, whereas small degradation products (hippuric acid and 3,4-dihydroxytoluene) did not bind at all. Conclusions: These results suggest that Phase II metabolites, specifically isorhamnetin, may contribute more significantly to the biological activity of quercetin than the parent compound, however, degradation products appear inactive. Full article

The phytochemical variability in Cannabis sativa L. chemovars represents an underexplored factor in environmentally sustainable nanomaterial production. In this study, three distinct chemovars, (i) High-Δ⁹-Tetrahydrocannabinol (THC) (89% THC), (ii) Balanced (60% Cannabidiol (CBD)), and (iii) High-CBD (89% CBD), were comparatively evaluated to determine their suitability for the green synthesis of silver nanoparticles (AgNPs). Ethanolic inflorescence extracts were used to recover bioactive secondary metabolites; among them, the High-CBD extract exhibited the highest total phenolic (3.34 mg gallic acid equivalent/g) and flavonoid (29.49 mg quercetine equivalent/g) contents, together with superior antioxidant capacity (53.16% 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) inhibition), indicating enhanced redox potential for nanoparticle formation. The terpene profile of High-CBD showed a dominance of myrcene (21.4%), contributing to the stabilization of the system. Using the High-CBD extract, predominantly spherical nanoparticles of 5 ± 0.9 nm were synthesized and confirmed by UV–vis, EDS, and TEM. The biogenic AgNPs demonstrated significant dose-dependent antibacterial activity, with minimum bactericidal concentration (MBC) of 1.0 mg/mL against Staphylococcus aureus and 4.5 mg/mL against Escherichia coli. These findings highlight the critical role of chemovar-dependent phytochemical composition and support a phytochemistry-guided approach for developing silver nanoparticles with potential biomedical applications. Full article

Sweet peppers (Capsicum annuum L.) are an important dietary source of antioxidants. Optimizing fruit antioxidant quality under reduced inputs is essential to valorize sustainable pepper production. Here, we evaluated seven Spanish genotypes (traditional/local, derived experimental hybrids and commercial hybrids) across six treatments combining two fertilization (100% and 50%) and irrigation (100% and 75%) regimes, with plant growth-promoting rhizobacteria (PGPR) applied under reduced fertilization treatments. Vitamin C and flavonoids were quantified by HPLC at the green-ripe and fully ripe stages, and carotenoids were determined spectrophotometrically at the fully ripe stage. Several genotypes largely maintained antioxidant content under stress treatments, whereas specific genotype × ripening stage combinations showed maximum increases in vitamin C (+102%), flavonoids (+86% for kaempferol) and carotenoids (+67% for yellow-orange carotenoids) under certain low-input treatments compared to the control. The PGPR effects on vitamin C and carotenoids were generally small, with occasional reductions. However, the PGPR increased total and some individual flavonoids by up to 96% (luteolin) in green-ripe Piquillo and 128% (quercetin) in fully ripe Isabel F1 fruits compared to the corresponding non-inoculated treatments. This multi-genotype, two ripening-stage evaluation identifies Spanish traditional germplasm and derived hybrids with stable or improved antioxidant profiles under low-input conditions and provides insight into PGPR effects. These results support the use of traditional genotypes in breeding for sustainable production. Full article

Pulmonary arterial hypertension (PAH) is a severe and progressive cardiopulmonary disorder with limited treatment options. Camellia petelotii (Merr.) Sealy (CP) contains multiple flavonoids and other phytochemicals, but its active compounds and molecular mechanisms in PAH remain unclear. Active compounds of CP were screened by comprehensive literature mining and absorption, distribution, metabolism, and excretion (ADME) evaluation. PAH-related hub targets were identified from transcriptomic data using weighted gene co-expression network analysis (WGCNA), machine learning, and external validation. Functional enrichment, immune infiltration, and single-cell RNA-sequencing analyses were performed to characterize their biological roles and cellular localization. Molecular docking and molecular dynamics simulations assessed compound–target interactions. The effects of CP were further evaluated in hypoxia-induced rat pulmonary artery smooth muscle cells (RPASMCs). Five core bioactive compounds were identified, among which luteolin and quercetin were prioritized for further analysis. HSP90AA1 and ROCK2 were screened as hub targets. Bioinformatic analyses suggested that these targets were mainly associated with the “Lipid and atherosclerosis” pathway, metabolic reprogramming, and modulation of the immune microenvironment. Single-cell analysis showed broad expression of HSP90AA1 and enrichment of ROCK2 in fibroblasts and endothelial cells. Molecular docking and molecular dynamics simulations supported stable binding of luteolin to HSP90AA1. In vitro, CP extract inhibited hypoxia-induced hyperproliferation of RPASMCs and reduced HSP90AA1 protein expression. HSP90AA1 may represent a candidate molecular mediator of CP in PAH, and CP inhibited hypoxia-induced RPASMC proliferation in association with downregulation of HSP90AA1. Full article

Background: Liver inflammation and fibrosis are directly associated with non-alcoholic fatty liver disease (NAFLD). Dysregulation of the potent pro-inflammatory cytokine interleukin-1 beta (IL-1β), inducible nitric oxide synthase (iNOS), and tissue leukocyte infiltration (CD45 +ve) are connected with multiorgan injury and fibrosis. We investigated whether the induction of NAFLD can cause dysregulation in the hepatic IL-1β/iNOS and IL-1β/CD45 axes of inflammation and fibrosis, as well as in endogenous metabolites (lipids, glucose, and insulin) and apoptosis, in the presence and absence of the flavonoid quercetin. Methods: The model group of rats was fed with a high-fat and high-carbohydrate diet (HFCD) for 4 weeks. The protective group of rats was given both quercetin (50 mg/kg) and HFCD for 4 weeks. All rats were sacrificed on day 29. Results: NAFLD was induced in rats as demonstrated by dyslipidemia, hyperglycemia, insulin resistance, liver inflammation, and elevation of liver injury enzymes. NAFLD was also associated with the upregulation of hepatic IL-1β, iNOS, CD45, and apoptosis (p53). Biomarkers of fibrosis (TIMP-1 and α-SMA) were also elevated, and fibrosis was confirmed in the model group by increased collagen deposition and elevated stages of fibrosis score (Stage 1 to 2 of Brunt’s NASH classification). All these parameters were significantly (p < 0.01) modulated by quercetin treatment. Additionally, a significant (p < 0.001) correlation between IL-1β and hepatic injury parameters was observed. Conclusions: These findings suggest a potential association between NAFLD and the IL-1β/iNOS and IL-1β/CD45 axes of liver injury and fibrosis, as well as dyslipidemia, glycemia, and apoptosis, with quercetin exhibiting beneficial hepatic pleiotropic effects. Full article

Background/Objectives: Natural compounds occupy a pharmacologically rich chemical space, characterized by abundant scaffolds, extensive functional group elaboration, and defined stereochemistry. In this context, Helichrysum italicum, a Mediterranean medicinal plant, represents a valuable source of polyphenols with multiple biological and pharmacological activities. Methods: Here, we introduce an inverse molecular docking fingerprint approach to systematically investigate eight major Helichrysum italicum polyphenols, including $\alpha$-pyrones (arzanol, ethylpyrone), flavonols (gnaphaliin, kaempferol, quercetin), and flavanones (naringenin, pinocembrin, hesperetin). More than 40,000 human protein structures from the Protein Data Bank were screened to generate target-based inverse docking score fingerprints for each compound. Results: Hierarchical clustering of these fingerprints revealed shared binding patterns among structurally related polyphenols and enabled hypothesis generation regarding potential synergistic effects. Notably, favorable interactions were identified with PPARG and CARM1, supporting therapeutic relevance in inflammation and cancer, alongside additional targets associated with neurodegeneration and bone metabolism. Conclusions: This study establishes inverse docking fingerprints as a robust, mechanism-oriented method for natural product research and highlights Helichrysum italicum polyphenols as starting points for medicinal chemistry and drug discovery. Full article

Onion peel represents a valuable food by-product rich in bioactive phenolic compounds. Building on previous phytochemical investigations, an onion peel extract from the Rossadi Tropea variety was developed as a standardized bioactive ingredient (OPI-T), defined by flavonol (quercetin and its glycosylated and oxidized derivatives) and anthocyanin (cyanidin derivatives) markers, ensuring batch-to-batch consistency, and evaluated for its potential against hepatic steatosis. The present study aimed to assess the protective effects of OPI-T against palmitate-induced steatosis and oxidative stress in HepG2 cells, a widely used in vitro model of hepatic lipid accumulation. An onion peel extract derived from the Ramata di Montoro variety was included as a natural negative reference to account for varietal variability. HepG2 cells were co-treated with palmitate (500 µM) and OPI-T (25 or 50 µg/mL). Lipid accumulation was evaluated by Oil Red O and BODIPY staining, while oxidative stress was assessed by the DCF assay. Mitochondrial dynamics and autophagy were investigated through the analysis of key protein markers, including MFN2, DRP1, SQSTM1/p62 and LC3 II/I. OPI-T significantly attenuated palmitate-induced lipid accumulation (−18%) and reduced intracellular ROS production (−75%), while modulating mitochondrial dynamics toward a reduced fission phenotype with a marked increase in the MFN2/DRP1 ratio (1.66) and improving autophagy flux. In contrast, the Ramata di Montoro variety showed weaker or inconsistent effects under the same experimental conditions. Overall, these findings support the functional validation of a standardized onion peel-derived ingredient, highlighting its potential application as a bioactive component for functional food or nutraceutical development targeting hepatic steatosis and oxidative stress. Full article

Background/Objectives: Phthalates are a group of organic compounds widely used for enhancement in flexibility and transparency of polyvinyl chloride (PVC) products. Exposure to phthalate-containing substances has been shown to affect brain function, particularly in learning and memory processes. Quercetin is a plant-derived flavonoid with remarkable anti-oxidant and anti-inflammatory potential. This study investigated the possible protective effects of quercetin on spatial learning and memory, histomorphometric changes, and hippocampal expression of inflammatory cytokines (TNF-α and IL-6) in male mice exposed to di(2-ethylhexyl) phthalate (DEHP). Methods: A total of 42 male mice were divided into seven groups. Quercetin was administered orally at doses of 25 and 50 mg/kg/day, either alone or in combination with DEHP (200 mg/kg/day). Following the final day of the treatment, spatial learning and memory were assessed by the Morris Water Maze test. Hippocampal tissues were sampled for Nissl, H&E, and immunofluorescence staining. Quantitative real-time PCR was used to measure the expression of TNF-α and IL-6. Results: The DEHP group exhibited significant impairments in learning and memory, neuronal damage, and cellular disorganization in the hippocampus, along with increased astrocyte activation and elevated expression of TNF-α and IL-6. On the other hand, quercetin supplementation significantly reduced these inflammatory markers and histological damages and also improved spatial learning and memory. Conclusions: Overall, quercetin improves cognitive function that is associated with attenuating astrocyte activation and inflammation. Full article

Aging is associated with an increased risk of developing many age-related diseases (ARDs), which are of major global health concern. In recent years, cellular senescence, characterized by cell cycle arrest and development of a senescence-associated secretory phenotype (SASP), has emerged as a key mechanism of aging and ARDs and has been increasingly explored as a promising therapeutic target. Among dietary bioactive ingredients, fisetin and quercetin have gained attention because of their potential to act as senolytics and senomorphics. This narrative literature review summarizes existing evidence exploring the potential of fisetin and quercetin to modulate senescence and SASP biomarkers in animal models of aging and progeria, as well as in interventional studies involving human subjects with geriatric syndromes and/or various ARDs. It also provides a brief overview of the molecular mechanisms of senescence and attempts to identify potential drivers and barriers for the clinical translation of those nutrients. Full article