Search Results (8,778)

Anti-vascular endothelial growth factor agents (anti-VEGFs) are the cornerstone of treatment for neovascular age-related macular degeneration (AMD). Resveratrol is a natural polyphenol with well-established antioxidant and anti-apoptotic properties. This study investigated whether resveratrol exerts cytoprotective effects when combined with anti-VEGFs on ARPE-19 cells in vitro. Cells were treated with ranibizumab (RNZ), aflibercept (AFL), or ziv-aflibercept (ZFL), either alone or in combination with resveratrol. Mitochondrial and cytosolic reactive oxygen species (MitROS and CytROS), mitochondrial membrane depolarization (MitDep), caspase-3, -8 and -9 activities, cell viability, apoptosis, and VEGF-A levels were evaluated using confocal microscopy, plate reader-based assays, and ELISA techniques. Anti-VEGFs induced tolerable oxidative or apoptotic stress in ARPE-19 cells but did not exhibit intrinsic antioxidant and cytoprotective effects. The addition of resveratrol significantly enhanced beneficial effects by reducing oxidative stress, preserving mitochondrial integrity, and suppressing intrinsic apoptotic signalling, while increasing cell viability. VEGF-A levels were effectively reduced by anti-VEGF treatment, and this suppression was further augmented by resveratrol without compromising cellular survival. These findings indicate that resveratrol acts as an additive modulator that strengthens the cellular effects of anti-VEGFs on ARPE-19 cells. The combination strategy may represent a supportive approach to optimize long-term anti-VEGF therapy in AMD. Full article

The immune response is essential in the protection of our body against pathogens; however, the inflammatory response caused by the immune system can become a disease itself. In fact, anti-inflammatory and immune-suppressive drugs are applied to limit the immune response to treat inflammatory diseases. Flavonoids are plant-derived polyphenols extensively investigated for their anti-inflammatory and antioxidant properties in inflammatory diseases. Studies applying isolated compounds as well as using supplements as nutraceuticals based on flavonoids have been conducted. Our review systematically analyzed the top five studied flavonoids between 2020 and 2025: quercetin (1742 articles), kaempferol (642), luteolin (589), apigenin (419), and epicatechin (354), highlighting their major therapeutic applications in diseases affecting the liver (12%), nervous system (11%), and lungs (10%). Mechanistically, these compounds act as multi-target agents mainly by inhibiting NF-κB and inducing Nrf2-dependent antioxidant programs. Application of advanced delivery systems, which increase oral bioavailability by up to 20-fold, overcomes pharmacokinetic bottlenecks. Clinical highlights demonstrated promising therapeutic effects, including reduced intrahepatic lipid accumulation in non-alcoholic fatty liver disease patients following quercetin supplementation (11.5% to 9.6%) and accelerated SARS-CoV-2 clearance after quercetin phytosome administration. The translation of flavonoids into standardized clinical therapies remains limited by the lack of large-scale, well-controlled clinical trials. Full article

Circaea lutetiana (Onagraceae) is a perennial medicinal species widely distributed across temperate forest ecosystems of Europe, Asia, and North America. This mini-review integrates current knowledge on the botanical characteristics, ecological distribution, phytochemical composition, and biological properties of Circaea lutetiana, with particular emphasis on its dominant polyphenolic constituents. Available studies demonstrate that the species is rich in flavonoids, phenolic acids, ellagic acid derivatives, and ellagitannins, among which oenothein B represents a characteristic and major constituent. Beyond polyphenols, structurally characterized glycosides, lipophilic metabolites, phytosterols, triterpenoids, fatty acids, tocopherols, and mineral elements contribute to the chemical complexity of the species. The reported biological activities of Circaea lutetiana, including antioxidant, anti-inflammatory, antihypertensive, and antimicrobial effects, are discussed in relation to the phytochemical profile of the plant and the biological significance of its major constituents. Recent research in green nanotechnology has additionally highlighted the potential of Circaea lutetiana extracts, particularly in the biosynthesis of silver nanoparticles, where plant metabolites act as reducing and stabilizing agents and may contribute to improved antimicrobial performance. Full article

Background/Objectives: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia, dyslipidemia, and oxidative stress, leading to severe systemic complications. Medicinal plants rich in polyphenolic compounds have gained increasing attention as complementary therapeutic agents. This study aimed to comparatively evaluate the chemical composition, as well as the antidiabetic, hypolipidemic, and antioxidant effects of Polygonum persicaria and Vaccinium myrtillus in a streptozotocin-induced diabetic model. Although Vaccinium myrtillus has been more extensively investigated for its antidiabetic potential, the pharmacological relevance of Polygonum persicaria in diabetes remains insufficiently characterized, particularly in direct comparison with a recognized phytotherapeutic comparator. Methods: Hydroalcoholic tinctures prepared from Polygonum persicaria L. herb and Vaccinium myrtillus L. leaves were subjected to phytochemical analysis using High-Performance Thin-Layer Chromatography (HPTLC) for the identification of flavonoids and phenolcarboxylic acids, alongside spectrophotometric determination of total polyphenol and flavonoid content. Experimental diabetes was induced in CD1 mice by streptozotocin administration. Animals were treated orally for 35 days, and glycemic parameters, lipid profile, body weight, food and water intake, and oxidative stress markers (MDA, SOD, TAC, and GPx) were evaluated. Results: HPTLC/CSS screening indicated the presence of rutin, chlorogenic acid, and caffeic acid in Polygonum persicaria, while Vaccinium myrtillus showed stronger densitometric signals for phenolcarboxylic acid-type compounds, particularly chlorogenic and caffeic acids. Total polyphenol and flavonoid content were also higher in Vaccinium myrtillus (433.89 ± 8.67 mg/L GAE; 154.38 ± 3.08 mg/L QE) compared to Polygonum persicaria (269.28 ± 5.25 mg/L GAE; 132.75 ± 2.65 mg/L QE). Functionally, Vaccinium myrtillus demonstrated a significant antihyperglycemic effect from day 14 (p = 0.009) and improved lipid parameters, while Polygonum persicaria showed a delayed glycemic effect, significant only at day 35 (p = 0.014), without significant hypolipidemic activity. In contrast, Polygonum persicaria exerted a marked antioxidant effect, significantly increasing GPx activity (p = 0.025) and reducing MDA levels (p = 0.053). Conclusions: Vaccinium myrtillus showed stronger antihyperglycemic and hypolipidemic effects, while Polygonum persicaria was mainly associated with antioxidant-related biochemical changes. These differences may be influenced by phytochemical composition, but they cannot be attributed solely to total polyphenol or flavonoid content. Full article

Breast cancer remains one of the most frequently diagnosed malignancies and a leading cause of cancer-related mortality among women worldwide. The growing interest in natural bioactive compounds has highlighted plant-derived phytochemicals as promising agents for cancer prevention and adjunctive therapy due to their pleiotropic biological activities and relatively low toxicity. In parallel, increasing attention has been directed toward agro-industrial by-products generated during food processing, which represent abundant and sustainable sources of valuable phytochemicals. This review provides a comprehensive overview of recent advances in the identification, extraction, and biological evaluation of phytochemicals derived from plants and agro-industrial residues, using pomegranate (Punica granatum) peels, onion (Allium cepa) skins, and citrus by-products as representative examples of phytochemical-rich agro-industrial residues. These by-products are rich in polyphenols, flavonoids, and other secondary metabolites—including punicalagins, ellagic acid, quercetin, hesperidin, and naringin—that have demonstrated significant antioxidant, anti-inflammatory, and anticancer properties. Recent in vitro and in vivo studies indicate that these compounds can modulate key molecular pathways involved in breast cancer initiation and progression, such as oxidative stress regulation, apoptosis induction, inhibition of cell proliferation, and suppression of signaling cascades including PI3K/Akt, NF-κB, and MAPK pathways. Furthermore, the valorization of agro-industrial waste offers a sustainable strategy to recover high-value bioactive compounds while reducing environmental impact. Overall, phytochemicals obtained from plant materials and food processing by-products represent promising functional agents for breast cancer prevention and therapy, although further studies are required to improve bioavailability, elucidate mechanisms of action, and validate their clinical potential. Full article

The aim of this study was to evaluate the effect of matrix type and dose of polyphenolic core from rose petals on the physicochemical and functional properties of microcapsules. Microcapsules were obtained by ionotropic gelation using four carrier systems: sodium alginate (SA), sodium alginate with added starch (SA + S), protein isolate (SA + P), and vegetable gum (SA + G). Polyphenolic compounds isolated from rose petals (E) were used as the core at six concentrations (0.25, 0.5, 1.0, 1.5, 2.0, and 2.5%). Differences between microcapsules were assessed based on physicochemical properties, polyphenol and anthocyanin content, antioxidant activity, swelling index, and biocompatibility. The results showed that both the extract dose and the matrix system significantly affected the analyzed parameters. The highest encapsulation efficiency was demonstrated for the lowest dose (0.25%), regardless of the matrix used. Total polyphenol and anthocyanin content significantly increased for all microcapsule versions with increasing extract dose, with the highest concentrations obtained for the SA + G system. These results strongly correlated with antioxidant activity and biocompatibility with human colonocyte membranes. In turn, the swelling index decreased with extract dose, showing the highest values in small intestinal fluid and the lowest in gastric fluid. These findings may have significant implications for the design of functional carriers for use in food and dietary supplement production. Full article

Crackers and cookies have become the most widely consumed snacks due to their low production costs, long shelf life, and ability to deliver essential nutrients. Increasing consumer health consciousness has shifted preferences toward foods perceived as natural and beneficial. This shift elevates demand for cracker formulations with novel, health-promoting natural ingredients. This study examined the effects of incorporating freeze-dried olive leaf powder (FDOLP) into crackers on their physicochemical properties, phenolic and volatile compound profiles, antioxidant capacity, and sensory acceptability. Total polyphenol content of crackers was determined using the Folin–Ciocalteu method, while antioxidant capacity was evaluated by FRAP and DPPH assays. The UHPLC-ESI-HRMS analysis evaluated olive-derived compounds, including tyrosol, oleuropein derivatives, and pinoresinol 4-O-glucoside, present in olive leaf-enriched crackers. The characterisation of volatile compounds in crackers was performed using headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME/GC-MS). A darker colour was observed in the enriched crackers compared to the control samples. Results demonstrated that increasing the proportion of FDOLP led to enhanced phenolic composition and antioxidant activity, as well as changes in the volatile profile of the crackers. Sensory analyses indicated that crackers enriched with moderate levels of FDOLP maintained acceptable overall sensory scores, suggesting a potential for the development of functional snacks. These findings demonstrate that olive leaves can be effectively utilised as a natural functional ingredient in cracker formulations to enhance their nutritional value and bioactive properties. Full article

Fruit and vegetable processing by-products, such as peels and pomace, are rich in antioxidant polyphenols and represent promising sources of functional ingredients, but how their galloyl-based polyphenols interact with starch remains insufficiently understood. In this study, corilagin with three non-free galloyl moieties and 1,2,3,4,6-O-pentagalloyl glucose with five free galloyl moieties were used as model polyphenols to clarify how galloyl moiety number and accessibility modulate their complexation with high-amylose maize starch (HAMS). Size-exclusion chromatography showed that both polyphenols preferentially complexed with amylose, while FTIR confirmed that complex formation occurred mainly through non-covalent interactions. The two polyphenols induced distinct changes in HAMS structure. Corilagin disrupted short-range order and produced no detectable crystalline structure, whereas 1,2,3,4,6-O-pentagalloyl glucose enhanced molecular order and induced V-type crystallization. Isothermal titration calorimetry revealed more binding sites but weaker affinity for corilagin, with thermodynamic signatures indicating hydrogen bonding and van der Waals interactions. By contrast, 1,2,3,4,6-O-pentagalloyl glucose showed stronger affinity and hydrophobic interaction-dominated binding. Molecular dynamics simulations further confirmed that 1,2,3,4,6-O-pentagalloyl glucose formed a more stable association with the amylose helix than corilagin. These results indicate that galloyl moiety characteristics markedly influence starch–polyphenol interaction mechanisms, providing guidance for the utilization of polyphenol-rich agro-processing by-products in functional starch-based foods. Full article

Mitochondrial reactive oxygen species (mtROS) are central regulators of cellular function, yet their biological roles are often reduced to an oxidative-stress/antioxidant dichotomy. This review reframes mtROS through the concept of mitohormesis, in which outcomes are neither inherently harmful nor beneficial but are determined by a defined set of contextual variables. We present a mechanistic framework in which mtROS effects depend on chemical species identity, sub-mitochondrial site of production, temporal dynamics, redox-buffering capacity, and metabolic state; together, these variables determine whether mtROS promote adaptive eustress or pathological distress. We then show that, across polyphenols, isothiocyanates, terpenoids, alkaloids, and quinones, the biologically relevant effects of natural redox-modulating compounds are mediated less by direct radical scavenging than by pro-hormetic mechanisms, including mild electron transport chain perturbation, nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (NRF2/KEAP1) activation, modulation of mitochondrial membrane potential, mitochondrial quality control, and NAD⁺/NADPH regulation. Applying this framework to disease reveals strong tissue and state dependence: neurodegeneration favors buffering expansion and mitophagy; metabolic disease may benefit from exercise-mimetic and NRF2-activating strategies; cardiovascular disease illustrates mitohormesis through ischemic preconditioning and CoQ10 supplementation; and cancer requires distinction between prevention and therapy because redox buffering can either protect normal tissue or support tumor survival. Finally, we argue that the failure of non-specific antioxidant supplementation is mechanistically predictable and propose context-aware, biomarker-guided, temporally optimized, and compartment-targeted redox interventions as a more rational translational path. Full article

Antioxidant activity of plant extracts is commonly interpreted as a directly comparable property despite substantial methodological differences among analytical assays and extraction systems. This study investigated how extraction selectivity and assay chemistry influence antioxidant-associated responses in hop (Humulus lupulus L.) extracts by integrating experimental and literature-derived datasets. Extracts obtained using different solvents and extraction techniques were evaluated using ABTS, DPPH, and Folin–Ciocalteu (TPC) systems. Multivariate statistical analyses, including principal component analysis (PCA), correlation analysis, and non-parametric comparisons, were applied to normalized datasets to assess assay-dependent variability and cross-study comparability. The results suggested substantial divergence between ABTS- and DPPH-associated responses, including a statistically significant negative correlation between both assay systems. PCA indicated assay-selective separation patterns, while TPC values did not consistently correlate with antioxidant-associated responses. Different extraction conditions were associated with distinct antioxidant response profiles, suggesting selective redistribution of analytically detectable antioxidant fractions rather than uniform changes in antioxidant capacity. Based on these observations, this study proposes the Assay–Extraction Interaction Framework (AEIF), an interpretative framework that views antioxidant activity as a context-dependent analytical response rather than a universal intrinsic property of the extract. Full article

Morus alba L. fruit extract (MFE), which is rich in cyanidin 3-glucoside (C3G), demonstrates antioxidant properties and pharmacological effects, but its reproductive safety remains poorly understood. Polyphenols modulate steroidogenesis, spermatogenesis, and sperm acrosome integrity; therefore, toxicity assessment is needed for use. This study aimed to evaluate the antioxidant profiles and subchronic reproductive effects of MFE. MFE was standardized using high-performance liquid chromatography (HPLC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays. Male rats were administered MFE (250 or 500 mg/kg BW) for 56 days. Assessments included computer-assisted sperm analysis (CASA), testosterone, seminal fructosamine, and testicular CYP11A1 and androgen receptor (AR) expression. Acrosomal status was determined using PNA lectin staining. The results showed that MFE contained C3G (119.42 mg/g), antioxidant capacity (DPPH IC₅₀: 0.101 mg/mL; FRAP: 465.01 µmol Fe (II)/g), and total contents (phenolics: 41.15 mg GAE/g; flavonoids: 3.15 mg CE/g; anthocyanidins: 11.04 mg C3G/g). MFE did not alter testicular histology and seminiferous stages VII-IX. High doses significantly increased sperm concentration, while both doses reduced sperm beat cross frequency. Testosterone, fructosamine, and CYP11A1/AR expressions showed increasing trends. Significantly, high doses induced a precocious acrosome reaction. In conclusion, MFE has no reproductive toxicity and pro-fertility effects on sperm quantity or androgenic markers, supporting safe subchronic use. Full article

Heat stress leads to excessive hepatic lipid deposition and oxidative imbalance in laying hens, especially during peak laying period. Chlorogenic acid (CGA), a dietary polyphenol with antioxidant and lipid-modulating properties, may improve hepatic lipid homeostasis, yet its effects under heat-stress conditions remain unclear. In this study, 240 Hy-Line Brown laying hens at 36 weeks of age were randomly assigned to one of two treatments (120 hens per treatment, with six replicates of 20 hens each): a basal diet or a basal diet supplemented with 300 mg/kg CGA and subjected to heat-stress conditions for 8 weeks. CGA supplementation significantly reduced liver weight (25.3%), liver index (14.4%), hepatic triglyceride content (29.1%), and serum triglyceride level (61.7%) (p < 0.05). Histological assessment revealed lower steatosis and inflammation scores, alongside increased hepatic SOD activity (13.6%) and decreased MDA content (58.7%) (p < 0.05). RNA-seq analysis identified 420 differentially expressed genes that were significantly enriched in PPAR signaling and fatty acid β-oxidation pathways. CGA upregulated fatty acid oxidation-related genes (ACSL1, CPT1A, ACOX1, ACAA1) and downregulated lipogenic markers (FASN, ACACA). Serum metabolomics revealed coordinated changes in lipid and carbon metabolism. These results indicate that dietary CGA alleviates hepatic lipid accumulation and oxidative stress in heat-stressed peak-laying hens, potentially via PPARα-mediated enhancement of fatty acid oxidation and inhibition of de novo lipogenesis. Full article

Bauhinia forficata leaves were subjected to ultrasonic pretreatment and subsequently dried using a refractance window (RW) and tray drying (TD). The physical, chemical, and biological properties of the dried leaves were evaluated under both drying methods, with and without ultrasound. RW combined with ultrasound (RW-US) resulted in the shortest drying time (90 min) and the lowest values of water activity (0.21), color difference (ΔE = 0.61), and maximum shear force (14.72 N), indicating improved drying efficiency and texture preservation. In addition, the RW-US samples exhibited the highest water solubility capacity (13.75%), water absorption capacity (5.56 g water/g dry matter), and swelling power (9.95%). With respect to structural changes, thickness showed the greatest percentage reduction during drying. The RW-US treatment also preserved bioactive compounds more effectively, yielding the highest total polyphenol content (61.96 mg GAE/g extract), flavonoid content (308.44 mg QE/g extract), antioxidant activity (60.50% by DPPH• and 70.15% by ABTS•+), and chlorophyll content (2.65 mg/g), the values of which were closest to those of fresh leaves. None of the extracts showed cytotoxic effects, with respect to hypoglycemic activity, the best treatments were RW, RW-US, and TD, which resulted in glucose reductions of 51.64%, 41.95% and 39.70%, respectively. Overall, RW-US drying preserved most of the physical, chemical, and biological properties, resulting in the production of a potential functional ingredient for foods. Full article

Grape pomace is one of the most abundant byproducts of the wine industry. This by-product contains many valuable bioactive substances, including polysaccharides, amino acids, and polyphenols. To enable its effective reuse, this study developed and optimized a micelle-assisted extraction process using a 2% (w/w) decyl glucoside solution aqueous as an extraction medium. The influence of key process parameters—the pomace-to-medium ratio, extraction temperature, and extraction time—was systematically evaluated to determine their impact on extraction yield and the physicochemical properties of the recovered compounds. Extraction efficiency was assessed by determining total phenolic content (TPC) and antioxidant capacity (DPPH, ABTS) using UV-VIS spectrophotometry and by determining selected phenolic compounds, amino acids, and sugars using Ultraperformance Liquid Chromatography Coupled with Tandem Mass Spectrometry (UPLC-MS/MS) The results demonstrated that all the parameters investigated significantly influenced the recovery of bioactive substances. The developed decyl glucoside-based micellar extraction proved to be an efficient, low-temperature, and environmentally favorable method for valorizing grape pomace, offering strong potential for cosmetic and related applications. Full article

Pulses are rich in diverse phenolic compounds, which play a vital role in human health. The biological activity of pulses’ polyphenols is highly dependent on their interaction with the gastrointestinal tract and gut microbiota. Polyphenols from pulses have been proven to be effective in the regulation of gut homeostasis, exerting antioxidant and anti-inflammatory effects, and alleviating various intestinal health problems caused by chronic diseases, thus receiving extensive attention. Furthermore, in view of the prebiotic potential of pulse polyphenols in gut health, they can be enriched by fermentation, germination, and physical-assisted technologies to realize their effective applications. In this review, we systematically summarize and analyze the phenolic compound profiles, which confer extensive gut health benefits, with emphasis on their potential enrichment strategies. A better understanding of polyphenols in pulses may open up new avenues for their application in the development of functional foods. Full article