Search Results (81,155)

DNA conformational transitions in aqueous environments are strongly influenced by electrostatic interactions with surrounding cations. This review/perspective article summarizes the experimental findings reported during the last decade on the competitive/cooperative effects of cations with different valencies on DNA conformational behavior. Recent experimental studies based on single DNA observations have shown that divalent cations, such as Mg(2+) and Ca(2+), can inhibit DNA compaction induced by the trivalent cation spermidine (SPD(3+)), revealing that the effects of coexisting cations are not simply additive. Such competitive behavior cannot be adequately explained within the conventional Debye–Hückel framework, which predicts always additive electrostatic screening contributions from cations of different valencies. To elucidate the underlying mechanism of competitive effects, a theoretical framework has been proposed by extending the framework of current counterion condensation theory, which incorporates changes in translational entropy arising from the ion-exchange process between monovalent counterions and divalent or trivalent cations interacting with DNA as a highly negatively charged polyelectrolyte. In the theoretical framework, the increase in translational entropy arises from the ion exchange process between monovalent counterions and trivalent cations in the absence of divalent cations, whereas the presence of divalent cations diminishes the entropic gain associated with this exchange. By interpreting the recent experimental findings through the aid of the development of theoretical modeling, this review/perspective article provides a coherent insight on how coexisting multiple cations regulate DNA conformation. Full article

Brewer’s spent grain (BSG), the main by-product of the brewing industry, is an abundant lignocellulosic residue that remains underused. In this study, antioxidant-rich extracts were obtained from BSG using pressurized liquid extraction (PLE) and subsequently incorporated into thermoplastic starch (TPS) films for sustainable food packaging applications. The phenolic profile analysis revealed 13 compounds, with caffeic acid and its hexoside as the most abundant. Extraction conditions were optimized using response surface methodology (RSM) to maximize yield and total phenolic content, showing that temperature had a significant positive effect. The selected extract had a total phenolic content of 3.19 mg/g dw and exhibited notable antioxidant activity. It was then incorporated into the polymer matrix, and the resulting films were analyzed for their structural, thermal, and antioxidant properties. The incorporation of BSG extracts improved the film antioxidant activity. Additionally, the release of phenolic compounds was evaluated and successfully described using a diffusion model based on Fick’s law, which allowed the calculation of a diffusion coefficient D = 2.63 × 10⁻⁸ cm²/s. Overall, the findings indicate that BSG-based extracts may represent promising functional additives for biodegradable polymer films, and the developed TPS films serve as proof-of-concept active packaging materials from renewable agro-industrial residues. Full article

The cell envelope of Gram-positive bacteria is a primary target of host immune defenses and antibiotics, and its stability is influenced by environmental factors, including the availability of the divalent cations Mg²⁺ and Ca²⁺. Alanine also plays a critical role in cell envelope integrity, contributing to peptidoglycan cross-linking, D-alanine modification of teichoic acids, and protein synthesis. However, how these factors functionally interact to maintain envelope stability in S. aureus remains unclear. Here, we demonstrate that growth of S. aureus under Mg²⁺-limited and Ca²⁺-limited conditions requires increased alanine uptake mediated by the transporter AapA. Loss of AapA results in increased cell lysis and impaired growth under cation-limited conditions, and removing alanine from the growth medium phenocopies these aapA mutant defects. Alanine limitation increases susceptibility to the detergent Triton X-100 and the membrane-targeting antibiotic daptomycin, consistent with defects in envelope stability. Furthermore, aapA function contributes to bacterial fitness in insect and murine infection models. Together, these findings indicate that Mg²⁺, Ca²⁺, and alanine play overlapping roles in stabilizing the S. aureus cell envelope, pointing to AapA as a target that may leveraged to enhance antimicrobial efficacy. Full article

Background/Objectives: In case of EDTA-induced pseudothrombocytopenia (PTCP), MgSO₄-anticoagulated tubes are recommended for platelet counting, requiring the collection of an additional tube. The aim of this study was to analyze whether complete blood count (CBC) and differential performed on MgSO₄-anticoagulated tubes were comparable to the results obtained on K₃-EDTA samples, and to characterize the stability of the CBC over a 24 h period. Methods: In 355 patients (70 with a confirmed PTCP and 285 without PTCP), we compared CBC results obtained on K₃-EDTA- and MgSO₄-anticoagulated tubes, using DxH800 analyzers. In 33 cases, a differential was available for both anticoagulants, and for 10 patients, samples were re-analyzed 6, 12, and 24 h after the first determination. Results: In the presence or absence of clumps, white blood cell (WBC) count, hematocrit, and mean corpuscular volume (MCV) were slightly lower in MgSO₄ than in K₃-EDTA tubes, whereas mean corpuscular hemoglobin concentration (MCHC) was slightly higher. Mean platelet volume (MPV) was significantly lower on MgSO₄- than on K₃-EDTA-anticoagulated tubes. Values were highly correlated between both anticoagulants, and mean relative biases (MRBs) were below Ricos’s recommendations, except for MCHC and MPV. For differential, neutrophils were significantly lower on MgSO₄- in comparison to K₃-EDTA-anticoagulated tubes (MRB = −2.9%, below Ricos’s optimal bias). The morphology of white blood cells (WBCs) was similar on both anticoagulants. During storage at room temperature, MCV and red cell distribution width increased slightly, but the increase was more pronounced in K₃-EDTA than in MgSO₄ tubes. Conclusions: CBC and differentials obtained with the DxH 800 analyzer on MgSO₄-anticoagulated samples are similar to those obtained with K₃-EDTA, except for MPV. Full article

This study was conducted to investigate a novel quaternary hybrid nanocomposite (QHNC) that can successfully remove Mn(VII) ions from contaminated water. The nanocomposite was analyzed using FTIR, XRD, BET, TGA/DTG and FESEM/EDX techniques to investigate whether the synthesis led to an outcome with optimal properties that will enable it to effectively remove Mn ions from aqueous solutions. Optimal results have been achieved by conducting the analysis at a pH level of 2, using 25 mg of the adsorbent material, an interaction time of 60 min and a concentration of 500 mg/L. The Freundlich isotherm best described the adsorption equilibrium. Further analysis through advanced computational simulations indicated that a sorption process underpins the phenomenon based upon a complex geometry mechanism with a preferential horizontal to inclined orientation of the adsorbate upon the surface. The techno-economic assessment reveals the biosorbent’s viability—with a production cost that is highly competitive at USD 9.95/kg, yet with a stable removal efficiency of nearly 60% over five cycles. Such factors lead to a treatment cost of around USD 7.3 for 1 m³ of 500 mg/L Mn(VII)—confirming both the economic viability and scalability for advanced tertiary wastewater remediation applications. 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

Clarithromycin is a widely prescribed macrolide antibiotic that can enter soils using sewage treatment plant effluents, where it is frequently detected. Because it could exert selective pressure on soil microbes, this study examined whether bacterial communities in 12 agricultural soils developed tolerance to clarithromycin after 42 days of exposure to different clarithromycin concentrations (7.8 mg kg⁻¹–2000 mg kg⁻¹). Results showed that tolerance increased in a clear dose-dependent manner and was significantly higher than in control soils at concentrations of 31.3 mg kg⁻¹ and above. Soil characteristics also shaped the response. At lower clarithromycin doses, tolerance was restricted in those soils with higher values of _eCEC, clay content, organic carbon, and C/N ratio. At higher doses, tolerance increased with pH, likely due to increased clarithromycin bioavailability. This study provides evidence of the impact of clarithromycin on soil microbiota and suggests that contamination by this antibiotic may promote the development of bacterial tolerance. Future studies should be carried out to further clarify the factors that influence the development of tolerance and also to determine the possible spread of this resistance in the environment. Full article

Botrytis cinerea is a major phytopathogenic fungus responsible for substantial economic losses in horticultural crops, underscoring the need for sustainable alternatives to synthetic fungicides. This study investigated the influence of physical, chemical and biological culture parameters on the antifungal activity of culture filtrates produced by Trichoderma harzianum BOL-12QD. Culture conditions were sequentially optimised by evaluating light-filter exposure, carbon and nitrogen source composition, potato ecotype selection, co-cultivation with Botrytis cinerea, and volatile-mediated interactions. Antifungal activity was assessed using mycelial growth inhibition assays against Botrytis cinerea. Among the individual factors, violet-filter illumination, a medium containing 5 g L⁻¹ glucose and 250 g L⁻¹ potato extract, the Leke Pek’e potato ecotype, ammonium nitrate as nitrogen source, and co-cultivation with Botrytis cinerea at 10⁴ conidia mL⁻¹ produced the highest inhibitory effects. Sequential integration of these optimised conditions resulted in enhanced antifungal activity, reaching up to 62% inhibition. Volatile organic compounds produced by Trichoderma harzianum BOL-12QD exhibited only minimal antifungal activity under the conditions tested, suggesting that volatile-mediated antagonism plays a limited role in this system. In contrast, culture-dependent modulation of extracellular metabolite profiles was evidenced by comparative ¹H NMR fingerprinting, which revealed condition-specific spectral differences, with the optimised treatment displaying a distinct metabolic signature relative to all other conditions. Cytotoxicity assays in murine peritoneal macrophages showed no significant reduction in cell viability at concentrations up to 200 μg mL⁻¹. In vivo exposure to the optimised culture filtrate (250 mg kg⁻¹ d⁻¹ for 10 days) induced transient treatment-related clinical observations without mortality, indicating a need for further detailed toxicological characterisation. Overall, these findings demonstrate that the antifungal activity of Trichoderma harzianum BOL-12QD is strongly modulated by interacting environmental, nutritional and biological culture parameters. The results support the potential of optimised culture filtrates as a source of bioactive metabolites for biocontrol applications, while highlighting the importance of integrated biochemical and toxicological evaluation. Full article

Background/Objectives: Ursodeoxycholic acid (UDCA) is a bile acid widely used for the treatment of cholestatic liver diseases; however, its poor aqueous solubility represents a major limitation for the development of oral liquid formulations, particularly in pediatric patients requiring accurate and flexible dosing. This study aimed to develop and characterize a fully solubilized extemporaneous UDCA oral formulation using the ready-to-use vehicle Wagner, with particular emphasis on the role of hydroxypropyl-β-cyclodextrin (HP-β-CD) as a solubilizing excipient. Methods: Phase-solubility studies, Job’s plot analysis, and ¹H NMR spectroscopy were performed to investigate the host–guest interaction between UDCA and HP-β-CD, confirming the formation of a stable 1:1 inclusion complex responsible for a marked increase in drug solubility. The aqueous solubility of UDCA increased from approximately 0.02 mg/mL in water to 31 ± 1 mg/mL in the Wagner base containing HP-β-CD, compared to ~10 mg/mL in the corresponding cyclodextrin-free vehicle. Chemical stability was evaluated using an HPLC method adapted from the European Pharmacopoeia, employing dual detection (refractive index and photodiode array detector) to ensure specificity and stability-indicating capability. Results: The UDCA solution (20 mg/mL) remained chemically stable for at least 4 months under refrigerated (4–8 °C) and room temperature (25 °C) conditions, with only moderate degradation observed at 40 °C. Physical stability studies confirmed the absence of precipitation, phase separation, or significant pH variations under all storage conditions. Conclusions: Wagner-based formulation enabled the development of a stable and homogeneous UDCA oral solution, providing a complementary formulation strategy to conventional suspension-based preparations. This approach represents a robust and patient-oriented strategy for extemporaneous compounding, particularly suitable for pediatric use. Full article

The development of bio-based active packaging materials has gained increasing attention as a sustainable alternative to synthetic plastics. In this study, chitosan-based films incorporating yerba mate kombucha infusion (YMK-I) were developed and fully characterized. Films were prepared using different YMK-I concentrations (25–100% v/v) as solvent, with acetic acid-based chitosan films as controls. The infusion showed pH 2.5, titratable acidity of 3.5%, total solids of 6%, high phenolic content (1085 mg GAE/L), and reducing sugars (18.3 g/L). Acetic and lactic acids were identified by high-performance liquid chromatography (HPLC). Minimum Inhibitory Concentration (MIC) values ranged from 0.03 µg/mL for Staphylococcus aureus to 0.3 µg/mL for Escherichia coli and Pseudomonas aeruginosa. Rheological results indicated that YMK-I performed similarly to acetic acid as a solvent. Fourier Transformed Infrared with Attenuated Total Reflectance (FTIR-ATR) suggested interactions between chitosan and bioactive compounds. Thermal analyses showed that YMK-I acted as a plasticizer and introduced thermolabile components, altering glass transition and degradation behavior. Increasing YMK-I content reduced tensile strength and increased elongation, indicating greater flexibility, while water vapor permeability increased due to hydrophilic compounds. Films enriched with YMK-I exhibited high antioxidant activity (Radical Scavenging Activity > 85%) and strong antimicrobial effects (>98% inhibition) against E. coli and S. aureus. These results highlight the potential of chitosan–kombucha films as multifunctional materials for specialized applications. Full article

Plants of the genus Astragalus are recognized as rich sources of bioactive compounds with antioxidant and therapeutic potential; however, European species remain less explored than the well-known Astragalus membranaceus (Fisch.) Bunge. The aim of this study was to compare the phytochemical composition and in vitro biological activity of selected Astragalus species occurring in Poland (A. cicer L., A. glycyphyllos L., A. membranaceus). Phenolic compounds in methanolic extracts obtained from the roots and aerial parts were analyzed using spectrophotometric methods and UHPLC–DAD–ESI/TOF–MS. Antioxidant activity was evaluated using DPPH, ABTS, FRAP, CUPRAC, metal chelation, superoxide radical scavenging, and lipid peroxidation (TBARS) assays. Additionally, enzyme inhibition toward α-amylase, lipase, hyaluronidase, tyrosinase, and butyrylcholinesterase was assessed. The root of A. membranaceus exhibited the highest total phenolic content (199.84 ± 3.64 mg GAE/g extract) and the strongest antioxidant activity (DPPH IC₅₀ = 36.53 ± 1.22 µg/mL; ABTS IC₅₀ = 26.31 ± 0.03 µg/mL), as well as the most pronounced α-amylase inhibition (IC₅₀ = 17.78 ± 1.16 µg/mL). It also demonstrated moderate protective effects against AAPH-induced lipid peroxidation. The herb of A. cicer showed moderate radical scavenging capacity and the most effective inhibition of lipid peroxidation at higher concentrations. Extracts of A. glycyphyllos displayed weaker radical scavenging but notable metal-chelating properties. Selected extracts also exhibited moderate inhibitory activity against tyrosinase and butyrylcholinesterase. A. membranaceus remains the most potent source of phenolic compounds and antioxidant activity; European species such as A. cicer and A. glycyphyllos represent promising, locally available alternatives and may be used in phytotherapy and functional products. Full article

Background: Neovascular age-related macular degeneration (nAMD) remains a leading cause of irreversible central vision loss. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed management, pivotal trials enrolled exclusively treatment-naïve patients, leaving clinicians without pooled evidence to guide switching decisions in previously treated eyes. This systematic review and meta-analysis assessed real-world visual, anatomical, durability, and safety outcomes following switching to aflibercept 8 mg in previously treated nAMD. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, CENTRAL, Scopus, and Google Scholar through April 2026. Studies reporting switching to aflibercept 8 mg with change in best-corrected visual acuity (BCVA), central subfield thickness (CST), or treatment interval were included. Continuous outcomes were pooled using random-effects models with Hartung–Knapp–Sidik–Jonkman adjustment; proportions were estimated using generalized linear mixed models. Methodological quality was evaluated using the JBI Critical Appraisal Checklist for Case Series. Certainty of evidence was assessed using GRADE. The protocol was registered with PROSPERO (CRD420261371334). Results: Twenty-one studies met inclusion criteria. BCVA remained stable (WMD: −0.017 logMAR; 95% CI: −0.027 to −0.007; +0.83 ETDRS letters; I² = 0%). CST decreased significantly (WMD: −21.5 µm; 95% CI: −29.3 to −13.7; I² = 56.0%), and treatment intervals extended by +1.79 weeks (95% CI: +1.32 to +2.27; I² = 74.3%). Intraretinal and subretinal fluid each resolved in 37.5% of eyes. Intraocular inflammation was rare across 9959 treated eyes, though this pool was not restricted to switched eyes, with no confirmed retinal vasculitis. Sensitivity analyses confirmed robustness across all co-primary estimates. GRADE certainty was low for BCVA and very low for CST and treatment interval. Conclusions: Low-certainty evidence suggests that switching to aflibercept 8 mg preserves visual acuity, while very-low-certainty evidence suggests reductions in central subfield thickness and modest extension of treatment intervals. Intraocular inflammation was rare, though safety denominators included non-switch eyes. These findings provide preliminary pooled estimates to inform switch decisions in previously treated eyes. Full article

Green synthesis of KGM-capped CeO₂ nanoparticles was successfully achieved through a simple coprecipitation method using Konjac Glucomannan (KGM) as a biopolymeric capping and stabilizing agent. The reaction conditions were optimized by varying pH (9–11) and temperature (30–70 °C) to evaluate their influence on nanoparticle formation and photocatalytic performance. The synthesized KGM–CeO₂ nanoparticles were comprehensively characterized using FTIR, UV–Vis spectroscopy, XRD, SEM–EDS, TEM, DLS, and ZP analysis to investigate their structural, optical, morphological, and surface properties. The characterization results confirmed the successful formation of porous sponge-like branched CeO₂ nanostructures with irregular morphology. XRD analysis revealed the crystalline nature of the nanoparticles with an average crystallite size of approximately 7.7 nm, while DLS analysis showed an average hydrodynamic particle size of 29.7 nm with a biomodal particle size distribution. The positive zeta potential value (+16.75 mV) confirmed good colloidal stability and reduced agglomeration due to effective capping by KGM. The synthesized nanoparticles also exhibited favorable optical properties with band gap values suitable for photocatalytic applications. The adsorption and photocatalytic degradation performance of the KGM–CeO₂ nanoparticles was investigated against synthetic textile dyes, including Naphthol Blue Black (NBB), Methyl Orange (MO), and a mixed NBB–MO dye system under acidic conditions. Using an adsorbent dosage of 50 mg and dye concentrations of 100 mg/L, the material achieved degradation efficiencies of approximately 99% for NBB, 91% for MO, and 52% for the mixed dye system under UV irradiation for 120 min. Adsorption kinetic studies indicated that the pseudo-second-order model provided the best fit, suggesting that chemisorption is the dominant adsorption mechanism involving multifunctional surface interactions. These findings are particularly relevant for industrial wastewater treatment, since actual textile effluents typically contain complex mixtures of dyes and organic contaminants rather than single dye pollutants. The mixed dye experiments, therefore, provide a more realistic simulation of industrial wastewater conditions. Overall, the synthesized KGM–CeO₂ nanoparticles demonstrate excellent potential as an eco-friendly, cost-effective, and sustainable multifunctional material for adsorption-assisted photocatalytic treatment of dye-contaminated wastewater. Further optimization of operational conditions and catalyst surface properties may enhance its efficiency in multicomponent wastewater systems. Full article

Objectives: This randomized, single-blind study aimed to compare the effects of ultrasound-guided erector spinae plane block (ESPB), thoracic paravertebral block (TPVB) and intravenous (IV) analgesia on postoperative pain, opioid consumption and quality of recovery in patients undergoing laparoscopic cholecystectomy (LC). Methods: A total of 120 adult patients (ASA I-III) scheduled for elective LC were randomized into three groups: ESPB (GI), TPVB (GII) and IV analgesia (GIII). Bilateral ESPB or TPVB was performed preoperatively; then all patients received standardized general anesthesia and postoperative analgesia including paracetamol, tenoxicam and IV tramadol via patient-controlled analgesia. The primary outcome was 24 h tramadol consumption. Secondary outcomes included pain scores, rescue analgesia requirement, patient satisfaction, postoperative nausea and vomiting, time to first ambulation, length of hospital stay and Quality of Recovery-15 (QoR-15) scores. Results: Twenty-four-hour tramadol consumption was significantly higher in GIII (135.78 ± 22.73 mg) compared with GI (101.05 ± 26.99 mg) and GII (95.67 ± 31.49 mg) (p < 0.001), with no difference between GI and GII. Both static and dynamic pain scores were lower in GI and GII compared with GIII at most time points. Rescue analgesia requirement and patient dissatisfaction were significantly higher in GIII. QoR-15 scores were significantly improved in GI and GII compared with GIII (p < 0.001), while no difference was observed between the regional techniques. Block performance time was shorter with ESPB than TPVB (p < 0.001). No complications were reported. Conclusions: ESPB and TPVB provided effective analgesia and improved recovery after LC compared with IV analgesia alone. Both regional techniques may be considered as components of multimodal analgesia after LC. Full article

Background: Oxidative stress contributes significantly to premature skin aging and inflammatory dermatological conditions. While plant-derived antioxidants have demonstrated considerable promise in topical applications, Bougainvillea glabra Choisy remains underexplored in standardized pharmaceutical dosage form development despite its documented phytochemical richness. Objective: This study aimed to develop, standardize, and characterize topical cold cream formulations incorporating B. glabra ethanolic leaf extract, with HPTLC-based quantification of marker compounds, validated antioxidant assessment, and preliminary dermal safety evaluation. Methods: The ethanolic leaf extract was prepared by maceration and characterized by preliminary phytochemical screening and HPTLC fingerprinting with quantitative densitometric analysis of quercetin and pinitol. Three cold cream formulations were developed at 10% (F1), 20% (F2), and 30% (w/w) (F3) extract loading. Formulations were evaluated for organoleptic properties, pH, homogeneity, spreadability, and viscosity. Antioxidant activity was assessed using a validated methanol extraction procedure followed by DPPH radical scavenging and potassium permanganate reduction assays. Ex vivo skin permeation was evaluated using Franz diffusion cells with freshly excised goat skin. Accelerated stability was conducted at 40 ± 2 °C/75 ± 5% RH for 90 days with HPTLC-based marker retention monitoring. Primary dermal safety was assessed in Wistar albino rats (n = 6) following OECD Test Guideline 404. Results: Quantitative HPTLC confirmed quercetin (4.82 ± 0.14 mg/g dry extract) and pinitol (2.31 ± 0.09 mg/g) as marker compounds, with linearly increasing content across F1–F3. All formulations demonstrated acceptable physicochemical properties (pH 5.7–5.9, viscosity 440,000–460,000 cP, spreadability 11.8 ± 0.3 cm·g/s). F3 exhibited the highest DPPH scavenging activity (56.68 ± 1.05%) with IC₅₀ of 1.3 ± 0.1% w/v, demonstrating a 3.2-fold improvement over F1. Extraction recovery from the cream matrix was 96.4–97.1%, validating the antioxidant data. Ex vivo quercetin permeation through goat skin reached 51.3 ± 2.8 μg/cm² at 24 h for F3, following Higuchi diffusion kinetics (R² > 0.99). No dermal irritation was observed (Primary Irritation Index = 0). Accelerated stability confirmed ≥98.3% retention of both marker compounds and antioxidant activity after 90 days. Conclusions: B. glabra leaf extract was successfully incorporated into a physicochemically stable, non-irritating cold cream with demonstrated dose-dependent antioxidant efficacy and cutaneous delivery capability. The study establishes preliminary dermal safety and in vitro antioxidant efficacy warranting further controlled clinical evaluation. Full article