Common beans contain insoluble-bound phenolic compounds with potential bioactive properties; however, their recovery generally depends on harsh hydrolytic conditions and organic solvents. This study evaluated alternative extraction strategies for the recovery of insoluble-bound phenolic compounds from raw and cooked common bean flours of two Andean varieties (Peumo and Magnum), using Viscozyme L®, ultrasound, and pretreatment with ultrasound followed by Viscozyme L®. The resulting extracts were characterized in terms of phenolic profile by UPLC-ESI-MS/MS, total phenolic content (TPC), and antioxidant activity. Enzymatic treatment improved the recovery of insoluble-bound phenolic compounds and antioxidant activity compared with the control, while ultrasound alone showed limited effectiveness under the evaluated conditions. The combination of ultrasound pretreatment and Viscozyme L® generally improved recovery of some phenolic compounds and antioxidant-related endpoints relative to control conditions. Cooking generally reduced TPC and antioxidant activity, although the effect on individual phenolic compounds depended on the extraction treatment. Overall, enzyme-assisted extraction, especially when combined with ultrasonic pretreatment, represents a promising strategy for improving the recovery of insoluble phenolic compounds from common bean flour. Further optimization is still needed to improve the sustainability of the process and its industrial applicability.
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.
Flavonoids play critical roles in plant adaptation to abiotic stress by acting as potent antioxidants that regulate reactive oxygen species (ROS) homeostasis. In Atriplex canescens (Pursh) Nutt., a halophytic shrub well-adapted to saline and arid environments, transcriptomic analyses revealed that salt stress induces strong upregulation of flavanone 3-hydroxylase (F3H), a key enzyme in the flavonoid biosynthetic pathway. However, the functional role of AcF3H in stress adaptation remains poorly understood. Here, we cloned the AcF3H gene from A. canescens and generated transgenic Arabidopsis thaliana (L.) Heynh. lines constitutively overexpressing this gene. Overexpression of AcF3H significantly enhanced flavonoid accumulation, as confirmed by DPBA staining and total flavonoid quantification, and selectively upregulated the expression of downstream biosynthetic genes AcDFR and AcANS, which encode the dihydroflavonol 4-reductase (DFR) and anthocyanidin synthase (ANS), respectively. Under salt and drought stress, transgenic lines exhibited improved root elongation, increased shoot and root biomass, and higher relative water content compared to wild-type plants. Mechanistic investigations revealed that AcF3H overexpression led to reduced H2O2 accumulation and lower plasma membrane permeability under stress conditions, indicating enhanced antioxidative capacity and cellular membrane stability. These results suggest that AcF3H confers enhanced tolerance to abiotic stresses by promoting flavonoid-mediated ROS homeostasis. Our findings highlight AcF3H as a promising genetic target for engineering salt- and drought-tolerant crops.
Bio-based and biodegradable polymer composites based on polylactic acid (PLA) and polybutylene succinate-co-adipate (PBSA) were developed for rigid food packaging applications. Agro-industrial residues consisting of ground leaves and branches derived from tangerine tree cultivation (pruning) were used as fillers at high loading (30 wt%) before (PRE) or after (POST) extraction of bioactive compounds. The influence of blend composition (PLA/PBSA 60/40 and 30/70), filler extraction, and the addition of antioxidants (0.5 wt%) on material properties was systematically investigated. Composites were processed via extrusion and injection molding and characterized through FTIR, SEM, tensile testing and thermal analysis. The results show that polymer blend morphology affects mechanical behavior, with co-continuous structures (60/40) exhibiting improved ductility compared to dispersed systems (30/70). The incorporation of lignocellulosic residues increased stiffness but reduced elongation at break. Extraction treatment significantly modified filler morphology and interfacial interactions, slightly improving dispersion and processability. The effect of the extracted bioactive compounds on the thermal stabilization of biocomposites was also investigated. Overall, the findings demonstrate the potential of combining biodegradable polymer blends with treated agricultural residues to produce sustainable rigid packaging materials while supporting a bio-circular approach. In fact, preliminary extraction of valuable compounds from tangerine pruning waste appears to be a convenient strategy for its efficient cascade valorization.
Cirsium arvense (L.) Scop is a perennial plant of the family Asteraceae that is mainly distributed in the temperate regions of the Northern Hemisphere. Despite being widely recognized as an invasive weed in agriculture, most of the scientific evidence shows its significant phytochemical and pharmacological importance. In the present review article, a comprehensive summary of the available literature on C. arvense's botanical properties, phytochemical composition, biological activities, standardization potential, and future therapeutic prospects has been carefully provided. This plant has been used traditionally for the treatment of inflammation, infections, bleeding disorders, and liver-related disorders. Phytochemical investigations showed the presence of many bioactive compounds such as flavonoids, phenolic acids, triterpenes, sterols, tannins, glycosides, and volatile compounds. Among the reported biological activities, antioxidants and antimicrobial properties are the most studied activities. In addition, anticancer, antidiabetic, neuroprotective, anti-inflammatory, and antiproliferative activities have also been investigated. The environmental adaptability, rapid growth, and extensive root system of C. arvense highlight its potential for development as a sustainable medicinal and industrial crop. However, there are critical research gaps present in phytochemical standardization, toxicity assessment, pharmacokinetics, and clinical validation, warranting further comprehensive studies.
Agri-food by-products such as sweet potato peel (SP) represent a sustainable and valuable source of bioactive compounds for improving gluten-free (GF) foods. This study evaluated the nutritional and functional impact of incorporating SP at 8% and 16%, either untreated or ultrasound-assisted extraction (UAE)-treated, into GF brownies. An untargeted metabolomics approach combined with chemometrics was applied to characterize phytochemical modulation after in vitro digestion of the brownies, while antioxidant and anti-inflammatory effects were assessed using RAW264.7 macrophages. SP incorporation increased the dietary fiber (reaching a content of 7.86%) and glycosylated flavonoid content in reformulated brownies, leading to a reduction of inflammatory markers in the cellular model. Sensory evaluation showed that SP addition did not significantly affect texture-related attributes or extract-related perception. In contrast, UAE acted as an efficient extraction strategy, enhancing terpenoid-like compounds and total phenolic content (TPC), reaching values of 401.97 mg GAE 100 g-1 after 16% incorporation. Overall, combining SP valorization with UAE represents a promising strategy to develop nutritionally enhanced GF products, providing a foodomics-based framework for next-generation functional bakery products.
Many rhizobia use quorum sensing (QS) systems to detect their population density and modify their symbiotic behavior with the legume host. There are three LuxRI-type QS systems in Rhizobium etli CFN42, and CinR plays a key role in symbiotic performance. However, the details of how CinR regulates the symbiotic process remain unknown. In this study, we employed the RNA-Seq method to screen differentially expressed genes between the wild-type strain and the ΔcinR mutant of R. etli CFN42. We found that most of the genes related to reactive oxygen species (ROS) were expressed at lower levels in the ΔcinR mutant than in CFN42. We also found that the ΔcinR mutant was more sensitive to H2O2 than to CFN42. We then showed that CinR positively regulated katG expression and possessed an affinity to bind the katG promoter in the absence of the AHL ligand. The addition of AHLs promoted CinR binding to the katG promoter and enhanced katG expression. Accumulation of H2O2 and O2•- was observed in root nodules formed by the ΔcinR mutant. Crucially, katG overexpression rescued the H2O2-sensitive phenotype in vitro and partially restored defective symbiotic performance in nodules formed by the ΔcinR mutant on the common bean. These results suggest that CinR globally regulates ROS scavenging gene expression in order to balance oxidative stress within root nodules, promoting nitrogenase activity of R. etli CFN42.
Glaucoma is the leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) loss and optic nerve degeneration. While elevated intraocular pressure (IOP) remains the primary modifiable risk factor, a certain proportion of patients continue to deteriorate despite adequate IOP control, pointing to IOP-independent mechanisms of neurodegeneration. Oxidative stress-defined as an imbalance between the production of reactive oxygen species and the capacity of endogenous antioxidant defenses-has emerged as a central, multi-tiered contributor to glaucoma pathogenesis. In the anterior segment, chronic oxidative damage to the trabecular meshwork impairs aqueous humor outflow and drives IOP elevation. In addition, oxidative stress may impair ocular biomechanical integrity, including corneal hysteresis and lamina cribrosa, resulting in heightened susceptibility to IOP fluctuations. In the posterior segment, oxidative stress directly contributes to mitochondrial damage and vascular endothelial injury, leading to RGC apoptosis. The nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) pathway coordinates the principal endogenous antioxidant response, while nicotinamide adenine dinucleotide (NAD+) depletion links redox imbalance to metabolic vulnerability of RGCs. This narrative review synthesizes evidence published up to March 2026 on the molecular mechanisms of oxidative stress in glaucoma, the role of biomarkers in aqueous humor and systemic circulation, and the translational landscape of antioxidant-based neuroprotection-including nicotinamide, coenzyme Q10, alpha-lipoic acid, and Nrf2-activating compounds. We highlight gaps between preclinical promise and clinical evidence, and outline priorities for future randomized controlled trials.
Anemia in aging is multifaceted and may be in part caused by increased inflammation and oxidative stress. Almonds contain nutrients that may improve inflammation or antioxidant activity, which can improve red blood cell (RBC) integrity and mitigate anemia. The aim of this study is to investigate the effects of almond consumption on hematologic markers in a mouse model of aging. Forty-eight 18-month-old male and female C57BL/6 mice were randomized to receive a control diet or an almond-supplemented diet (15% calories from almond meal) for 12 or 21 weeks (four groups, n = 12/group). Blood and tissues were collected after respective intervention periods for analyses of hematologic markers (complete blood count analysis) and antioxidant status (RBC alpha-tocopherol concentration and superoxide dismutase activity). Mice consuming the almond-supplemented diet had significantly lower red cell distribution width at 12 weeks (p = 0.05) and significantly higher RBC count at 21 weeks (p = 0.04). Regression analyses indicated that almond intake resulted in higher RBC count (β = 0.82, p = 0.026) and lower odds of anemia (OR = 0.20, p = 0.046) after adjusting for sex of mice and length of intervention. These findings suggest that almond intake in aging mice improved selected hematologic markers and reduced anemia risk.
SQSTM1/p62 is a multifunctional scaffold protein that plays important roles in selective autophagy and cellular redox homeostasis. While phosphorylation-dependent regulation of p62 has been extensively studied, the functional significance of oxidative modification remains incompletely understood. Our previous studies showed that the natural small compound Alternol induces cancer cell-specific killing via a xanthine oxidase-mediated strong oxidative stress. In this study, we investigated p62-associated oxidative responses under Alternol-induced oxidative stress conditions in prostate cancer cells. Using biochemical assays and cell-based models, we found that Alternol treatment was associated with the accumulation of oxidized and high-molecular-weight p62 species, accompanied by altered KEAP1 association and increased Nrf2-associated signaling. Furthermore, Alternol-induced p62 oxidative modification was associated with autophagy-related responses and adaptive cellular survival under oxidative stress conditions. Disruption of the Cys105/113-dependent oxidative modification response attenuated Nrf2-associated transcriptional activity and increased cellular sensitivity to Alternol treatment. Collectively, our findings support an association between p62 oxidative modification and redox-responsive autophagy- and antioxidant-associated signaling pathways under Alternol-induced oxidative stress conditions, providing new insight into adaptive stress responses in prostate cancer cells.
Cerebral ischemia/reperfusion (I/R) injury triggers oxidative stress, neuroinflammation, neuronal degeneration, and white matter damage not only in directly affected cerebral regions but also in remote brain areas such as the cerebellum. Skimmianine, a naturally occurring furoquinoline alkaloid, has been reported to possess antioxidant and anti-inflammatory properties. This study investigated the protective effects of skimmianine pretreatment against secondary cerebellar injury following experimental cerebral I/R. Thirty-two female Wistar rats were randomly assigned to sham, Skimmianine, I/R, and I/R + Skimmianine groups (n = 8/group). Cerebral I/R was induced by transient middle cerebral artery occlusion for 60 min followed by 23 h reperfusion. Skimmianine (40 mg/kg/day, intraperitoneally) was administered for 14 days before ischemia induction. Oxidative stress markers, neuroinflammatory mediators, histopathological alterations, behavioral outcomes, and ultrastructural changes were evaluated. In addition, network pharmacology and molecular docking analyses were performed to explore potential molecular mechanisms. Cerebral I/R significantly decreased TAS levels compared with sham (0.89 ± 0.15 vs. 1.52 ± 0.18 mmol Trolox Eq/L) and increased TOS (15.60 ± 3.03 vs. 6.80 ± 1.41 µmol H2O2 Eq/L), OSI (17.48 ± 0.50 vs. 4.43 ± 0.47), TNF-α (68.4 ± 10.2 vs. 18.6 ± 4.4 pg/mL), Iba1 (41.3 ± 9.7 vs. 11.7 ± 1.6 pg/mL), and GFAP levels (334.5 ± 12.5 vs. 87.7 ± 9.5 ng/mL; all p < 0.001). I/R also impaired motor performance, as shown by increased beam crossing time (11.7 ± 2.2 vs. 4.8 ± 0.7 s) and grid foot fault rate (18.6 ± 4.0% vs. 3.4 ± 1.1%). Skimmianine pretreatment significantly improved these alterations, increasing TAS to 1.29 ± 0.20 mmol Trolox Eq/L and reducing TOS, OSI, TNF-α, Iba1, and GFAP levels to 9.20 ± 2.04, 7.07 ± 0.47, 34.9 ± 7.4, 24.2 ± 6.9, and 237.0 ± 7.9, respectively, compared with the untreated I/R group. Histopathological scores for Purkinje cell loss, edema, vascular congestion, and TNF-α expression were also significantly reduced by skimmianine. Quantitative TEM analysis showed that I/R reduced myelin thickness (0.29 ± 0.05 vs. 0.53 ± 0.07 µm), increased G-ratio values (0.75 ± 0.05 vs. 0.63 ± 0.04), and increased vacuolized fibers (24.70 ± 4.20% vs. 3.20 ± 1.10%), whereas skimmianine partially restored myelin thickness (0.42 ± 0.07 µm), reduced the G-ratio (0.68 ± 0.05), and decreased vacuolized fibers (11.20 ± 2.80%; p < 0.05 vs. I/R). Molecular docking demonstrated favorable binding between skimmianine and TNF-α, with a predicted binding energy of -6.953 kcal/mol. These findings indicate that skimmianine exerts neuroprotective effects against secondary cerebellar injury following cerebral I/R through coordinated modulation of oxidative stress, systemic neuroinflammatory responses, astroglial injury-associated pathways, and inflammation-related mechanisms.
Scorpion venom peptides, with their stable disulfide backbone, compact structural framework, and highly selective regulation of ion channels, have long been regarded as important molecular probes in neuropharmacology. However, recent studies have revealed their potential for regulating oxidative stress, inflammation, and neuroprotection, making them a new research frontier. In this article, we focus on scorpion venom peptides as drugs, constructing an integrated knowledge framework from structural classification to clinical translation. First, scorpion venom peptides are systematically classified based on cysteine arrangement patterns and three-dimensional folding topology, and their structure-activity relationships are summarized. Based on this, the molecular mechanisms by which scorpion venom peptides regulate ion channels are systematically analyzed. We review the emerging pharmacological activities of scorpion venom peptides. Of particular note, the representative molecule SVHRSP has shown multi-target synergistic antioxidant and neuroprotective activity in models of Parkinson's disease. We also systematically evaluate the application of engineering strategies, including cyclisation modification, nanodelivery, recombinant expression, and AI-assisted optimization, to overcome the translational bottlenecks in the development of scorpion venom peptides. However, it should be noted that most SVHRSP-related findings have been reported by a single research group; independent replication, pharmacokinetic characterization, and human efficacy data are still lacking. Its IND approval permits clinical investigation but does not yet constitute proven therapeutic benefit in patients. By integrating molecular structure, redox regulation mechanisms, and translational medicine perspectives, this review aims at providing a theoretical basis and practical pathways for scorpion venom peptides as precision therapeutic molecules for oxidative stress-related diseases.
Propolis is a widely studied natural raw material, the composition of which varies depending on the plant origin, harvest season, geographical area, climate and bee species. This large variety of chemical composition limits the use of propolis extracts in the pharmaceutical industry, which makes it difficult to ensure standardization of the raw material. One of the challenges that limit the modeling of oral pharmaceutical forms with propolis extract is the limited solubility and bioavailability of active compounds. Solid dispersion technology is commonly used in the production of oral capsules. The aim of this study is to evaluate the influence of different materials (HPMC, poloxamer and β-cyclodextrin) on the dissolution kinetics of phenolic compounds of propolis dry extract contained in capsules and their antioxidant activity in vitro. Analysis of the selected formulations showed that the major phenolic compounds detected in the propolis extract were also present in the dissolution medium samples. The auxiliary polymeric materials selected for the capsules formed a prerequisite for the dissolution kinetics profile. The addition of poloxamer and cyclodextrin increased the solubility and dissolution kinetics of hydrophobic propolis compounds in the test media. The addition of HPMC prolonged the dissolution kinetics of propolis active compounds. The antioxidant activity of the tested samples depends on the concentration of active compounds in the receptor medium by both the ABTS and DPPH methods.
Background/Objectives: Dioscorea batatas Decne (yam), which contains various bioactive compounds, has been utilized in the cosmetics industry, while most of the peel of D. batatas (DBP) is discarded without further use. Recent studies have shown that DBP contains higher levels of bioactive substances than the rhizome flesh. The aim of this study was to evaluate the skin biological activities of DBP extracts obtained using 70% ethanol (70% EtOH DBP), 95% ethanol (95% EtOH DBP), and ethyl acetate (EA DBP), with particular attention to their antioxidant-associated protective effects. Methods: Skin-related bioactivities of DBP extracts prepared using ultrasonic extraction were evaluated using in vitro tyrosinase and matrix metalloproteinase-1 (MMP-1) assays, alpha-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis in B16F10 cells, ultraviolet B (UVB)-irradiated HaCaT viability assays, and Western blot analysis of pro-collagen type I alpha 1(Pro-COL1A1) and MMP-1 in HDF cells. In addition, the ABTS and DPPH radical scavenging activities of DBP extracts and representative DBP derivatives were assessed. Results: DBP extracts inhibited tyrosinase activity in vitro and reduced melanogenesis in B16F10 cells. DBP extracts also protected skin cells from UVB by increasing the viability of UVB-irradiated HaCaT cells. In UVB-irradiated HDF cells, DBP extracts restored Pro-COL1A1 expression and suppressed MMP-1 levels. Additionally, DBP extracts inhibited MMP-1 activity in a concentration-dependent manner. The DBP extracts themselves exhibited ABTS and DPPH radical scavenging activities, with EA DBP showing the highest vitamin C equivalent antioxidant capacity among the tested extracts. Representative DBP-derived phenanthrene compounds also showed radical scavenging activities, supporting the antioxidant potential of peel-derived phytochemicals. Conclusions: These findings indicate that DBP extracts possess skin-whitening and anti-photoaging effects and suggest that these protective activities may be associated with the antioxidant potential of both DBP extracts and DBP derivatives.
Mitochondrial dysfunction has been increasingly implicated in the pathobiology of neurodevelopmental conditions, particularly autism and attention-deficit/hyperactivity disorder (ADHD). Because the developing brain is critically dependent on sustained ATP production, impairments in oxidative phosphorylation, mitochondrial dynamics, and redox balance may disrupt neuronal maturation, synaptic development, and neural circuit refinement during sensitive developmental periods. This review examines evidence from postmortem neurochemistry, genomics, magnetic resonance spectroscopy, and biomarker research to characterize mitochondrial impairment across autism and ADHD. Studies in autism report an elevated burden of heteroplasmic mitochondrial DNA (mtDNA) variants, along with alterations in mtDNA copy number, respiratory chain capacity, fission-fusion dynamics, and antioxidant defenses. Postmortem data demonstrate reduced activity of electron transport chain Complexes I, III, and V in the frontal cortex, temporal lobe, and cerebellum. These bioenergetic abnormalities are accompanied by elevated oxidative stress markers alongside mitochondria-mediated immune activation. In vivo neuroimaging corroborates these findings through elevated cerebral lactate and reduced phosphocreatine-to-ATP ratios. Evidence in ADHD is limited, but similarly implicates mitochondrial dysfunction, consistent with the frequent co-occurrence of these conditions and their partially shared architecture. The available literature supports mitochondrial dysfunction as a transdiagnostic biological feature of neurodevelopmental conditions, with relevance to mechanistic biomarker identification and targeted therapeutic development.
Ungernia victoris and U. sewerzowii (Amaryllidaceae J.St.-Hil.) are rare medicinal species of Central Asia known as sources of biologically active alkaloids, including galantamine. In this study, antioxidant activity was comparatively evaluated across different types of plant material, including natural populations, botanical garden specimens, in vitro regenerants, callus cultures, in vitro obtained bulbs, and seeds. Micropropagation systems based on direct and indirect organogenesis were developed using Murasige and Skoog and Vollosovich et al. media with various plant growth regulator combinations. Antioxidant activity was determined with the use of DPPH and ABTS assays and expressed as IC50 values. Significant variability was observed depending on population origin, type of biological material, and in vitro cultivation conditions. U. sewerzowii demonstrated higher antioxidant activity than U. victoris in natural populations. The highest activity was recorded in callus cultures, whereas in vitro-derived bulbs showed relatively low activity. A strong positive correlation between DPPH and ABTS assays confirmed the reliability of the results and indicated the contribution of multiple types of secondary metabolites. These findings highlight the potential of Ungernia callus cultures as a promising biotechnological platform for the production of antioxidant-active compounds and support sustainable utilization strategies.
The cone berries of Juniperus communis L. are rich in bioactive compounds, but biological properties of extracts are strongly influenced by the solvents used to obtain them. Therefore, this study aimed to evaluate the effect of solvent fractionation on the targeted polyphenolic profile and associated antioxidant, antimicrobial, and anticancer activities of pseudo-fruit extracts. The crude ethanolic extract was subjected to liquid-liquid partitioning to obtain ethyl acetate and n-butanol-soluble fractions, which were characterized by HPLC-MS and FTIR, while total polyphenol content was determined using the Folin-Ciocâlteu method and biological activities were assessed through DPPH, antimicrobial assays, and in vitro cytotoxicity on A375 melanoma and HaCaT keratinocyte cell lines. The ethyl acetate-soluble fraction showed the highest polyphenol content (361.08 ± 17.72 mg chlorogenic acid equivalents/g extract) and was enriched in hyperoside, whereas the n-butanol-soluble fraction contained lower phenolic levels and higher rutoside content; both fractions exhibited antioxidant activity correlated with phenolic content and weak-to-moderate antimicrobial activity, particularly against Streptococcus pyogenes. Cytotoxicity assays revealed a dose-dependent antiproliferative effect, with the ethyl acetate fraction displaying higher activity and greater selectivity toward melanoma cells, confirmed by apoptosis-related morphological changes. These findings demonstrate that solvent polarity plays a critical role in enriching bioactive phytochemicals and support the potential of J. communis fractions as sources of antioxidant and selective anticancer compounds.
Diabetic wounds remain a major clinical challenge due to impaired healing associated with persistent inflammation, oxidative stress, and microvascular dysfunction. Plasma-based therapies have emerged as promising approaches for promoting tissue repair; however, comparative evidence regarding different plasma modalities remains limited. In this study, we evaluated and compared the effects of atmospheric pressure cold plasma (APCP) and plasma-activated water (PAW) on wound healing in a streptozotocin-induced diabetic rat model. Forty Wistar albino rats were randomly assigned to five groups: isotonic wet dressing, hydrocolloid dressing, APCP treatment, PAW application, and a non-diabetic control group. Wound healing was assessed using macroscopic evaluation, histopathological analysis, and biochemical measurements of systemic oxidative status. PAW treatment significantly accelerated wound closure during the early healing phase compared with conventional dressing methods (p < 0.05). Histological findings demonstrated enhanced re-epithelialization, increased collagen deposition, and improved follicular regeneration in the PAW group. Although total oxidant status (TOS) did not differ significantly among groups (p = 0.996), total antioxidant status (TAS) was significantly increased following PAW treatment (p < 0.05), indicating a more favorable systemic antioxidant profile. These findings suggest an association between improved wound healing and a more favorable systemic antioxidant profile following PAW treatment. However, because local wound-level redox parameters and molecular markers were not assessed, the contribution of redox-related mechanisms remains to be clarified. Moreover, PAW demonstrated superior therapeutic efficacy compared with direct plasma application, highlighting its potential as a non-invasive approach for diabetic wound management.
Chronic kidney disease (CKD) affects approximately 700 million people worldwide and is a major contributor to end-stage renal disease (ESRD), cardiovascular morbidity, and premature mortality. Although oxidative stress has long been considered central to CKD progression, conventional antioxidant strategies have not consistently improved clinical outcomes, suggesting that excess reactive oxygen species (ROS) alone cannot fully account for the underlying disease pathophysiology. Emerging evidence supports a broader paradigm of redox network failure, characterized by the disruption of coordinated signaling among ROS, nitric oxide (NO), and reactive sulfur species (RSS). Within this framework, hydrogen sulfide (H2S), a major endogenous RSS, functions as a key regulator of renal redox homeostasis. CKD is consistently associated with systemic and renal H2S deficiency, accompanied by downregulation of cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), as well as impaired transsulfuration and disrupted mitochondrial sulfide oxidation. Importantly, this deficiency cannot be explained solely by reduced renal function but instead reflects active suppression of H2S biosynthesis. Uremic toxins, particularly indoxyl sulfate (IS), contribute to this process through activation of the aryl hydrocarbon receptor (AhR), which inhibits specificity protein 1 (Sp1)-dependent transcription of H2S-producing enzymes. This IS-AhR-Sp1 axis provides a mechanistic link between toxin accumulation and disruption of the sulfur arm of the redox network, amplifying oxidative stress, endothelial dysfunction, mitochondrial impairment, ferroptotic vulnerability, and fibrotic remodeling. Beyond H2S itself, downstream RSS, including persulfides, polysulfides, and thiosulfate, may represent the principal bioactive mediators of sulfur-dependent redox signaling, and their coordinated depletion in CKD may impair redox buffering capacity beyond what H2S measurement alone reflects. This review integrates current evidence to propose a conceptual model in which CKD progression involves failure of coordinated redox signaling-characterized by feed-forward network collapse and threshold-dependent transition to a self-sustaining high-ROS state-with H2S deficiency representing one mechanistically supported component of this broader network disruption. This framework highlights the therapeutic potential of targeting redox network restoration rather than isolated oxidative pathways in CKD.
Nepeta govaniana and Nepeta subsessilis display metabolomes typical for the genus Nepeta L. (Lamiaceae), predominated by monoterpenoid iridoids and phenolic acids. Underexplored phytochemical composition and largely undefined biological potential are the main reasons for the underutilized status of these two intriguing species. This study fills some of the existing knowledge gaps by comprehensively analyzing the composition of methanol-soluble nonpolar, semi-polar, and polar metabolites in leaves, and providing the information about antimicrobial and antioxidant potential. Integration of comprehensive HPLC/MS and GC/MS metabolomics with plastid loci-derived (trnL-F, rbcL, and matK) phylogenetic data, revealed the phylogenetic relatedness of N. govaniana and N. subsessilis with congeneric species, and placed them within the Nepeta's chemotype A whose members produce both iridoid aglycones and glycosylated iridoids. Methanol extracts of these two phylogenetically related species displayed a notable antioxidant potential, but were less efficient as antimicrobial agents. Such results draw from the predominance of methanol-soluble polar compounds (polyphenolics and iridoid glycosides), exhibiting respectable antioxidant potential, and lower abundance of nepetalactone-type iridoids, known as potent antimicrobials. N. govaniana is here highlighted as a slightly more efficient antimicrobial and antioxidant agent than N. subsessilis, which can be ascribed to a higher content of methanol-soluble metabolites in leaves.