Search Results (9,222)

Introduction: Extrinsic skin damage is often a result of oxidative stress caused by exposure to environmental factors such as ultraviolet (UV) radiation, ozone (O₃), and various pollutants. As a result, topical antioxidants have been evaluated for their effectiveness in mitigating or reversing skin damage caused by environmental factors. Topical antioxidants containing a combination of l-ascorbic acid, tocopherol, and ferulic acid have significantly improved markers of skin health after exposure to environment-induced skin damage. However, research suggests that l-ascorbic acid and tocopherol tend to be relatively unstable, possibly affecting their efficacy against outdoor stressor damage. It has been shown that ferulic acid significantly improves the stability of both l-ascorbic acid and tocopherol, but its long-term stabilization effects on these antioxidants are relatively unknown. Material and Methods: This study evaluated the time-dependent effectiveness of a topical antioxidant mix containing 15% l-ascorbic acid, 1% tocopherol, and 0.5% ferulic acid (AOX) on UV-induced skin damage. Skin biopsies (12 mm, n = 60) were placed in a 6-well plate with medium and incubated at 37 °C and 5% CO₂ overnight. The day after, skin samples were pretreated with 10 µL of differently aged AOX (0-, 6-, 12-, and 36-month-old) and then exposed to different doses of UV light (100, 200, 400 mJ/cm²) daily over four days. AOX formulations were stored in a cool, dry, and dark place at approximately 20–22 °C during the whole study. This study evaluated 4-hydroxynonenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) as oxidative damage and skin DNA damage markers, Collagen1 and Filaggrin as skin structure, and IL-8 and Nrf2 as inflammatory and defensive response. Results: UV exposure significantly increased oxidative and inflammatory markers in human skin explants affecting also filaggrin and collagen levels. However, pre-treatment with the antioxidant formulation, particularly in its younger formulations (0-, 6-, and 12-month-old), significantly reduced the damaging effect of UV. Additionally, all antioxidant formulations effectively mitigated UV-induced damage across all doses. Conclusions: Our results indicate that pre-treatment with this formulation consistently reduces UV-induced oxidative damage and DNA damage in human skin explants, regardless of the formulation age and the discoloration state. Although effective, the protective capacity of aged formulations may be reduced only when extreme UV exposure is tested, a condition that is unlikely to occur under typical environmental conditions. These results support ferulic acid as a stabilization agent for topical antioxidant mixtures. Full article

With increasing interest in natural therapeutic strategies for skin aging, plant-derived compounds have gained attention for their potential to protect against oxidative stress and inflammation. In this study, we investigated the anti-aging and anti-inflammatory effects of flavonoids isolated from Cercidiphyllum japonicum using a tumor necrosis factor-alpha (TNF-α)-stimulated normal human dermal fibroblast (NHDF) model. The aerial parts of C. japonicum were extracted and analyzed by high-performance liquid chromatography (HPLC), leading to the identification of four major compounds: maltol, chlorogenic acid, ellagic acid, and quercitrin. Each compound was evaluated for its antioxidant and anti-aging activities in TNF-α-stimulated NHDFs. Among them, ellagic acid exhibited the most potent biological activity and was selected for further mechanistic analysis. Ellagic acid significantly suppressed intracellular reactive oxygen species (ROS) generation and matrix metalloproteinase-1 (MMP-1) secretion (both p < 0.001), while markedly increasing type I procollagen production (p < 0.01). Mechanistic studies demonstrated that ellagic acid inhibited TNF-α-induced phosphorylation of mitogen-activated protein kinases (MAPKs), downregulated cyclooxygenase-2 (COX-2), and upregulated heme oxygenase-1 (HO-1), a key antioxidant enzyme. Additionally, ellagic acid attenuated the mRNA expression of inflammatory cytokines, including interleukin-6 (IL-6) and interleukin-8 (IL-8), indicating its broad modulatory effects on oxidative and inflammatory pathways. Collectively, these findings suggest that ellagic acid is a promising plant-derived bioactive compound with strong antioxidant and anti-inflammatory properties, offering potential as a therapeutic agent for the prevention and treatment of skin aging. Full article

Background: In this study, the preparation of pea glycopeptides based on the Maillard glycosylation pathway (PPH-M) and its antagonistic mechanism against alcoholic liver injury in zebrafish were studied. Results: The results showed that the conjugation of D-xylose significantly improved the antioxidant activity of pea protein hydrolysates (PPHs). The structural characterization indicated that PPH was successfully covalent binding to D-xylose, which was mainly manifested as a stretching vibration change in Fourier transform infrared spectroscopy (FTIR) and molecular size increase. Scanning electron microscopy (SEM) and zeta potential also confirmed the covalently bound of the two. In addition, a model of alcohol-induced liver injury in zebrafish was established. Through the intervention of different doses of PPH-M, it was found that the intervention of PPH-M could significantly increase superoxide dismutase (SOD) activity, reduce malondialdehyde (MDA) content, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activity, and significantly improve alcohol-induced liver injury in zebrafish. The protective effect of PPH-M was also confirmed by liver pathology and fluorescence microscopy. Finally, reverse transcription-polymerase chain reaction (qRT-PCR) results indicated that PPH-M could significantly regulate the expression level of antioxidant-related mRNA. PPH-M could also regulate the expression of the Keap1/Nrf2 signaling pathway and up-regulated glutathione synthesis signaling pathway to antagonize alcohol-induced liver injury in zebrafish. Conclusion: This study revealed the mechanism of PPH-M antagonized alcoholic liver injury and laid a theoretical foundation for its development as functional foods. Full article

Background: Androgenetic alopecia (AGA) and alopecia areata (AA) impose significant psychosocial burdens. While pharmacological and surgical treatments exist, the role of dietary factors remains underexplored due to methodological limitations in observational studies. This Mendelian randomization (MR) study investigates causal relationships between 187 dietary exposures and hair loss, leveraging genetic variants to address confounding biases. Methods: Genome-wide association study (GWAS) data from 161,625 UK Biobank participants were analyzed, focusing on food preferences and intake patterns. Genetic instruments for each of the 187 dietary exposures were selected at a genome-wide significance threshold (p < 5 × 10⁻⁸), with rigorous sensitivity analyses (MR-Egger, MR-PRESSO) to validate causality. Outcomes included AA and AGA datasets from the FinnGen consortium. Results: MR analysis identified 18 specific dietary exposures significantly associated with non-scarring hair loss (FDR < 0.05). Protective effects emerged for antioxidant-rich dietary exposures, represented by higher preferences for melon, onions, and tea. Elevated risks were observed for certain exposures, including croissants, goat cheese, and whole milk. Alcohol consumption exhibited the strongest risk associations. Our extensive analysis of alcohol intake, combining data from multiple studies, consistently identified it as a significant risk factor for both alopecia areata and androgenetic alopecia. Conclusions: These findings imply modifiable dietary patterns in hair loss pathophysiology. A dual strategy is proposed: prioritizing polyphenol-rich plant foods while minimizing pro-inflammatory triggers like processed carbohydrates and alcohol. Clinically, tailored dietary adjustments—reducing ultra-processed foods and alcohol—may complement existing therapies for hair loss management. Full article

Background/Objectives: The breast cancer susceptibility gene 1 (BRCA1) is a tumor suppressor gene whose mutations are associated with increased susceptibility to develop breast or ovarian cancer. BRCA1 mainly exerts its protective effects through DNA double-strand break repair. Although not itself a transcriptional factor, BRCA1, through its multiple protein interaction domains, exerts transcriptional coregulation. In addition, BRCA1 expression alters cellular metabolism including inhibition of de novo fatty acid synthesis, changes in cellular bioenergetics, and activation of antioxidant defenses. Some of these actions may contribute to its global oncosuppressive effects. However, the breadth of metabolic pathways reprogrammed by BRCA1 is not fully elucidated. Methods: Breast cancer cells expressing BRCA1 were investigated by multiplatform metabolomics, metabolism-related transcriptomics, and joint metabolomics/transcriptomics data processing techniques, namely two-way orthogonal partial least squares and pathway analysis. Results: Joint analyses revealed the most important metabolites, genes, and pathways of metabolic reprogramming in BRCA1-expressing breast cancer cells. The breadth of metabolic reprogramming included fatty acid synthesis, bioenergetics, HIF-1 signaling pathway, antioxidation, nucleic acid synthesis, and other pathways. Among them, rewiring of glycerophospholipid (including phosphatidylcholine, -serine and -inositol) metabolism and increased arginine metabolism have not been reported yet. Conclusions: Rewired glycerophospholipid and arginine metabolism were identified as components of BRCA1-induced metabolic reprogramming in breast cancer cells. The study helps to identify metabolites that are candidate biomarkers of the BRCA1 genotype and metabolic pathways that can be exploited in targeted therapies. Full article

Quercetin, a natural polyphenolic flavonoid with antioxidant and anti-allergic properties, is extensively found in foods and holds significant importance for human health. In this study, a simple switch-off fluorescent sensor based on copper nanoclusters (Cu NCs) was proposed for the sensitive determination of quercetin. Glutathione acted as the reducing and protective agent in the synthesized process of Cu NCs via a facile, green one-pot method. As anticipated, the glutathione-capped Cu NCs (GSH-Cu NCs) exhibited favorable water solubility and ultrasmall size. The fluorescence property of GSH-Cu NCs was further enhanced with Al³⁺ ion through the aggregation-induced emission effect. When quercetin was present in the sample solution, the system exhibited effective fluorescence quenching, which was attributed to the internal filter effect. The GSH-Cu NCs/Al³⁺-based fluorescent sensor showed a good linear relationship to quercetin in the concentration range from 0.1 to 60 μM. A detection limit of 24 nM was obtained. Moreover, the constructed sensor was employed for the successful determination of quercetin in tea samples. Full article

Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. Full article

Brown algae such as Ascophyllum nodosum (AN) and Fucus vesiculosus (FV) are gaining considerable attention as functional feed additives due to their health-beneficial properties. This study evaluated the antioxidant potential of AN and FV extracts in intestinal epithelial cells and the in vivo model Caenorhabditis elegans (C. elegans). Aqueous AN and FV extracts were characterized for total phenolic content (TPC), antioxidant capacity (TEAC, FRAP), and phlorotannin composition using LC-HRMS/MS. Antioxidant effects were assessed in vitro, measuring AAPH-induced ROS production in Caco-2 and IPEC-J2 cells via H₂DCF-DA, and in vivo, evaluating the effects of paraquat-induced oxidative stress and AN or FV treatment on worm motility, GST-4::GFP reporter expression, and gene expression in C. elegans. FV exhibited higher total phenolic content, antioxidant capacity (TEAC, FRAP), and a broader phlorotannin profile (degree of polymerization [DP] 2–9) than AN (DP 2–7), as determined by LC-HRMS/MS. Both extracts attenuated AAPH-induced oxidative stress in epithelial cells, with FV showing greater efficacy. In C. elegans, pre-treatment with AN and FV significantly mitigated a paraquat-induced motility decline by 22% and 11%, respectively, compared to PQ-stressed controls. Under unstressed conditions, both extracts enhanced nematode healthspan, with significant effects observed at 400 µg/g for AN and starting at 100 µg/g for FV. Gene expression analysis indicated that both extracts modulated antioxidant pathways in unstressed worms. Under oxidative stress, pre-treatment with AN and FV significantly reduced GST-4::GFP expression. In the nematode, AN was more protective under acute stress, whereas FV better supported physiological function in the absence of stressors. These findings demonstrate that AN and FV counteract oxidative stress in intestinal epithelial cells and in C. elegans, highlighting their potential as stress-reducing agents in animal feed. Full article

Essential oils (EOs) constitute intricate mixtures of volatile phytochemicals that have garnered significant attention due to their multifaceted biological effects. Notably, the presence of bioactive constituents capable of inhibiting tyrosinase enzyme activity and scavenging reactive oxygen species (ROS) underpins their potential utility in skin-related applications, particularly through the modulation of melanin biosynthesis and protection of skin-relevant cells from oxidative damage—a primary contributor to hyperpigmentation disorders. Zingiber officinale Rosc. (ginger) and Humulus lupulus L. (hop) are medicinal plants widely recognized for their diverse pharmacological properties. To the best of our knowledge, this study provides the first report on the synergistic interactions between essential oils derived from these species (referred to as EOZ and EOH) offering novel insights into their combined bioactivity. The purpose of this study was to evaluate essential oils extracted from ginger rhizomes and hop strobiles with respect to the following: (1) chemical composition, determined by gas chromatography–mass spectrometry (GC-MS); (2) tyrosinase inhibitory activity; (3) capacity to inhibit linoleic acid peroxidation; (4) ABTS^•+ radical scavenging potential. Furthermore, the study utilizes both the combination index (CI) and dose reduction index (DRI) as quantitative parameters to evaluate the nature of interactions and the dose-sparing efficacy of essential oil (EO) combinations. GC–MS analysis identified EOZ as a zingiberene-rich chemotype, containing abundant sesquiterpene hydrocarbons such as α-zingiberene, β-bisabolene, and α-curcumene, while EOH exhibited a caryophyllene diol/cubenol-type profile, dominated by oxygenated sesquiterpenes including β-caryophyllene-9,10-diol and 1-epi-cubenol. In vitro tests demonstrated that both oils, individually and in combination, showed notable anti-tyrosinase, radical scavenging, and lipid peroxidation inhibitory effects. These results support their multifunctional bioactivity profiles with possible relevance to skin care formulations, warranting further investigation. Full article

Ultraviolet B (UVB) radiation is a key factor in the overproduction of melanin in the skin. Melanocytes produce melanin through melanogenesis to protect the skin from UVB radiation-induced damage. However, excessive melanogenesis can lead to hyperpigmentation and increase the risk of malignant melanoma. Tyrosinase is the rate-limiting enzyme in melanogenesis; it catalyzes the oxidation of tyrosine to 3,4-dihydroxy-L-phenylalanine and subsequently to dopaquinone. Thus, inhibiting tyrosinase is a promising strategy for preventing melanogenesis and skin hyperpigmentation. White mulberry (Morus alba L.) is rich in antioxidants, and mulberry fruit extracts have been used as cosmetic skin-lightening agents. However, data on the capacity of mulberry fruit extracts to inhibit tyrosinase under UVB radiation-induced melanogenic conditions remain scarce, especially in an in vivo model. In this study, we evaluated the effects of a mulberry crude extract (MCE) on UVB radiation-induced melanogenesis in B16F10 melanoma cells and zebrafish embryos. The MCE significantly reduced tyrosinase activity and melanogenesis in a dose-dependent manner without inducing cytotoxicity. These effects are likely attributable to the antioxidant constituents of the extract. Our findings highlight the potential of this MCE as an effective tyrosinase inhibitor for the prevention of UVB radiation-induced skin hyperpigmentation. Full article

Morus alba L. (MA) is a member of the Moraceae family, known as “white mulberry”. Due to the high levels of bioactive compounds, mulberry plants can be considered a good source of nutrients and antioxidant compounds. Our study aims to analyze the effect of MA extract leaves on erythrocytes, focusing on its action on metabolism and membrane integrity. The choice of erythrocytes as a study model is based on their metabolic simplicity and their easy availability. Cell viability, following exposure of the cells to the extract, was evaluated by hemolysis, methemoglobin, caspase 3 activity and flow cytofluorimetric analysis; in addition, the effect of the pretreatment with the MA was detected after incubation of erythrocytes with different stressors. The impact on cell metabolism was evaluated by measuring anion flux kinetics, ATP levels and phosphatase activity. The results obtained show a peculiar (double) effect of the extract, which, on the one hand, probably by exploiting its component with antioxidant properties, protects the cell membrane by accumulating on the bilayer. On the other hand, the alteration of anion exchange could lead to the triggering of apoptosis and consequent cell death. The hypotheses, although excluded by our data, all point toward a beneficial and protective action of the extract on the health and vitality of RBCs. Full article

Ferroptosis is a distinct form of regulated cell death driven by iron-dependent lipid peroxidation participating in various diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a central regulator of cellular redox homeostasis and a key determinant of ferroptosis resistance. Nrf2 activates the expression of downstream antioxidant genes to protect cells from oxidative stress and ferroptosis. Consequently, precise regulation of Nrf2 expression is crucial. Recent studies have revealed that complex epigenetic mechanisms involving DNA methylation, histone modifications, and non-coding RNA networks regulate Nrf2 expression. DNA methylation usually suppresses while histone acetylation promotes Nrf2 expression. The influences of histone methylation on NFE2L2 are site- and methylation degree-dependent. m6A modification stabilizes NFE2L2 mRNA to promote Nrf2 expression and thereby inhibit ferroptosis. This article summarizes current understanding of the epigenetic mechanisms controlling Nrf2 expression and Nrf2-mediated ferroptosis pathways and their implications in disease models. The challenges associated with the epigenetic regulation of Nrf2 and future research directions are also discussed. A comprehensive understanding of this regulatory interplay could open new avenues for intervention in ferroptosis-related diseases by fine-tuning cellular redox balance through the epigenetic modulation of Nrf2. Full article

Although acetaminophen (APAP) overdose represents the predominant cause of drug-induced acute liver failure (ALF) worldwide and has been extensively studied, the modes of cell death remain debatable and the treatment approach for APAP-induced acute liver failure is still limited. This study investigated the mechanisms of APAP hepatotoxicity in primary mouse hepatocytes (PMHs) by using integrated methods (MTT assay, HPLC analysis for glutathione (GSH), Calcein-AM for labile iron pool detection, confocal microscopy for lipid peroxidation and mitochondrial superoxide measurements, electron microscopy observation, and Western blot analysis for ferritin), focusing on the role of iron dysregulation under oxidative stress. Our results showed that 20 mM APAP treatment induced characteristic features of ferroptosis, including GSH depletion, mitochondrial dysfunction, and iron-dependent lipid peroxidation. Further results showed significant ferritin degradation and subsequent iron releasing. Iron chelator deferoxamine (DFO) and N-acetylcysteine (NAC) could alleviate APAP-induced hepatotoxicity, while autophagy inhibitors did not provide a protective effect. In vitro experiments confirmed that hydrogen peroxide directly damaged ferritin structure, leading to iron releasing, which may aggravate iron-dependent lipid peroxidation. These findings provide evidence that APAP hepatotoxicity involves a self-amplifying cycle of oxidative stress and iron-mediated oxidative damaging, with ferritin destruction playing a key role as a free iron source. This study offers new insights into APAP-induced liver injury beyond conventional cell death classifications, and highlights iron chelation as a potential therapeutic strategy alongside traditional antioxidative treatment with NAC. Full article

An imbalance between the generation of reactive oxygen species (ROS) and antioxidant defenses is known as oxidative stress, and it is implicated in a number of diseases. The superoxide radical O^2– is produced by numerous biochemically relevant redox processes and is thought to play role in diseases and pathological processes, such as aging, cancer, membrane or DNA damage, etc.; SOD, or superoxide dismutase, is essential for reducing oxidative stress. As a result, the elimination of ROS by SOD may be a useful disease prevention tactic. There have been reports of protective effects against neurodegeneration, apoptosis, carcinogenesis, and radiation. Exogenous SODs’ low bioavailability has drawn criticism. However, this restriction might be removed, and interest in SOD’s medicinal qualities increased with advancements in its formulation. This review discusses the findings of human and animal studies that support the benefits of SOD enzyme regulation in reducing oxidative stress in various ways. Additionally, this review summarizes contemporary understandings of the biology of Cu/Zn superoxide dismutase 1 (SOD1) from SOD1 genetics and its therapeutic potential. Full article

Nano- and microplastic pollution, together with the ongoing rise in global temperatures driven by climate change, represent increasingly critical environmental challenges. Although these stressors often co-occur in the environment, their combined effects on plant systems remain largely unexplored. To test the hypothesis that their interaction may exacerbate the effects observed under each stressor individually, we investigated the response of seedlings of Triticum turgidum to treatments with fluorescent polystyrene nanoplastics under optimal (25 °C) and elevated (35 °C) temperature conditions. We evaluated seedling growth, photosynthetic pigment content, and oxidative stress markers using both biochemical and histochemical techniques. In addition, we assessed enzymatic and non-enzymatic antioxidant responses. The use of fluorescently labeled nanoplastics enabled the visualization of their uptake and translocation within plant tissues. Elevated temperatures negatively affect plant growth, increasing the production of proline, a key protective molecule, and weakly activating secondary defense mechanisms. Nanoplastics disturbed wheat seedling physiology, with these effects being amplified under high temperature conditions. Combined stress enhances nanoplastic uptake in roots, increases oxidative damage, and alters antioxidant responses, reducing defense capacity in leaves while triggering compensatory mechanisms in roots. These findings underscore a concerning interaction between plastic pollution and climate warming in crop plants. Full article