Search Results (1,414)

Chronic inflammation accelerates the aging process, and targeted clearance of senescent cells shows potential in alleviating age-related decline. PCC1, a potent senescent cell clearance agent in grape seed extract (GSE), has limited applications due to its low oral bioavailability. This study introduced a novel GSE formulation, Natural Senolytics PCC1 (NSPCC1), which significantly enhanced PCC1 absorption and metabolic characteristics. Validation in two mouse aging models demonstrated that oral administration of NSPCC1 markedly extended lifespan and promoted healthy aging. The formulation improved the capacity for hematopoietic stem/progenitor cell differentiation and reduced age-related myeloid cell bias. Comprehensive histological analysis revealed attenuated aging phenotypes in bone marrow and skin, improved peripheral blood erythroid parameters, and a partial increase in blood antioxidant capacity, alongside reduced M1 macrophage infiltration and fibrosis in liver, kidney, and lung tissues. These effects were validated through histological assessments, including H&E, Masson, F4/80, and iNOS staining. This study highlighted the pivotal role of hematopoietic stem cells in aging and established NSPCC1 as a promising natural intervention for age-related pathologies. Its enhanced efficacy lays the groundwork for deeper exploration of natural products in aging biology and provides crucial support for the development of safe and effective anti-aging therapies. Full article

Background/Objectives: Excessive alcohol consumption induces hepatic injury primarily through cytochrome P450 2E1 (CYP2E1)-mediated reactive oxygen species (ROS) generation and disruption of redox homeostasis. This study investigated the hepatoprotective effects of the ethyl acetate fraction from Dendropanax morbifera leaves (DMLEAF) against ethanol-induced oxidative damage in vitro and in vivo. Methods: The protective mechanisms of DMLEAF were evaluated in HepG2 cells exposed to ethanol (400 mM, 24 h) and in an acute ethanol-induced liver injury mouse model. Cellular ROS levels, apoptosis, antioxidant enzyme activities, and nuclear factor erythroid 2-related factor 2 (Nrf2) translocation were assessed in vitro. Serum biochemical markers, histopathological changes, and hepatic CYP2E1 mRNA expression were analyzed in vivo. Results: In HepG2 cells, DMLEAF significantly reduced intracellular ROS levels and apoptosis, improving cell viability by up to 27.2% and reducing apoptosis by approximately 32%. DMLEAF also attenuated the ethanol-induced decrease in antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and promoted nuclear translocation of Nrf2. In mice, oral administration of DMLEAF significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels, improved histopathological alterations, and suppressed hepatic CYP2E1 mRNA expression by 2.6-fold compared with ethanol-treated controls, while preventing the reduction in hepatic antioxidant enzyme activities. Conclusions: These findings suggest that DMLEAF mitigates alcohol-induced liver injury through suppression of CYP2E1-associated ROS production and activation of Nrf2-mediated antioxidant defense mechanisms. Full article

Sickle Cell Disease (SCD) is a pervasive monogenic disorder characterized by chronic hemolytic anemia, unpredictable vaso-occlusive crises, and progressive multi-organ damage, representing a significant global health burden. Driven by a point mutation in the β-globin gene, the resulting abnormal Hemoglobin S (HbS) polymerizes under deoxygenated conditions, leading to erythrocyte sickling and systemic endothelial dysfunction. While supportive therapies such as hydroxyurea and transfusions manage symptoms, the mandate for definitive curative therapies is urgent. Historically, allogeneic hematopoietic stem cell transplantation (HSCT) utilizing matched sibling donors (MSD) has been the sole curative option, offering high survival rates but constrained by limited donor availability and the risk of graft-versus-host disease (GVHD). Consequently, alternative donor sources, including matched unrelated donors, umbilical cord blood, and haploidentical donors, have expanded patient access, particularly with the integration of post-transplant cyclophosphamide (PTCy) to mitigate alloreactivity. Concurrently, the advent of autologous gene therapy, encompassing lentiviral gene addition (Lyfgenia) and CRISPR-Cas9 gene editing (Casgevy) offers a revolutionary donor-independent approach that eliminates GVHD risk. Lyfgenia employs a lentiviral vector to introduce an anti-sickling βT87Q hemoglobin variant into autologous hematopoietic stem cells, while Casgevy employs CRISPR-Cas9 to disrupt the erythroid-specific enhancer of the BCL11A transcription factor, derepressing γ-globin expression and elevating fetal hemoglobin. This review synthesizes the pathophysiological mechanisms of SCD, evaluates the clinical outcomes and limitations of both allogeneic HSCT and autologous gene therapies, and outlines the clinical decision-making paradigms and future innovations required to achieve equitable global access to these transformative treatments. Full article

Background: Parvovirus B19 (B19V) has a well-established tropism for erythroid progenitor cells and is a recognized cause of anemia in immunocompromised individuals. Patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis are predisposed to anemia due to multiple mechanisms and are frequently exposed to healthcare settings, raising concern that prior B19V infection may contribute to anemia severity or resistance to erythropoiesis-stimulating agents (ESAs). However, data regarding the clinical relevance of B19V seroprevalence in hemodialysis patients remain limited. Methods: We conducted a single-center, observational cross-sectional study including 131 adult patients on maintenance hemodialysis and 50 healthy controls. Parvovirus B19 IgG serostatus was assessed by enzyme-linked immunosorbent assay (ELISA) and used exclusively as a marker of prior (past) exposure rather than active infection; our aim was to determine whether IgG-defined prior exposure leaves a measurable long-term imprint on erythropoiesis. None of the participants had clinical features suggestive of acute parvovirus infection or an unexplained aplastic episode at enrollment. Demographic data, comorbidities, dialysis characteristics, ESA use, and laboratory parameters (hemoglobin, hematocrit, mean corpuscular volume, inflammatory markers, and albumin) were collected. Between-group and within-cohort comparisons used non-parametric tests, and multivariable logistic and linear regression models were used to adjust for age, sex, and other relevant covariates. Results: Parvovirus B19 IgG seropositivity was common in both groups (64.9% of hemodialysis patients vs. 48% of controls; crude odds ratio [OR] 2.00, 95% confidence interval [CI] 1.03–3.88, p = 0.043). However, hemodialysis patients were substantially older and more often male; after adjustment for age and sex, dialysis status was no longer independently associated with seropositivity (adjusted OR 1.4, 95% CI 0.8–2.3, p = 0.20), and within the hemodialysis cohort seropositivity was not associated with age or sex. Hemodialysis patients exhibited significantly lower hemoglobin and hematocrit and higher inflammatory markers than controls, consistent with ESRD-related anemia. Within the hemodialysis cohort, B19 IgG-positive and IgG-negative patients did not differ in hemoglobin, hematocrit, mean corpuscular volume, C-reactive protein, albumin, or ESA use, and IgG serostatus remained unrelated to hemoglobin in a multivariable model adjusting for age, sex, inflammation, nutrition, dialysis vintage, and ESA use (adjusted β = −0.20 g/dL, 95% CI −0.68 to 0.28, p = 0.42). Past Parvovirus B19 exposure was therefore not associated with anemia severity or treatment requirements. Conclusions: In this cohort of stable maintenance hemodialysis patients, prior Parvovirus B19 exposure, as indicated by IgG seropositivity, was not associated with increased anemia severity, inflammation, or ESA use, and the higher crude seroprevalence in dialysis patients was attributable to their older age rather than to dialysis itself. Because IgG reflects past exposure only and IgM and viral DNA were not assessed, these findings apply strictly to past (IgG-defined) exposure and cannot address active or persistent B19V infection. They suggest that routine Parvovirus B19 IgG screening in asymptomatic hemodialysis patients is unlikely to be useful for anemia management, whereas active or persistent infection—detectable only by molecular testing—remains the more plausible contributor to unexplained or refractory anemia and merits study in selected patients. Full article

Ferroptosis and cuproptosis are promising anti-tumor treatment strategies. Elesclomol (ES) is a kind of common cuproptosis inducer, and cisplatin (DDP) is a commonly used drug in liver cancer chemotherapy, which can induce cells to undergo ferroptosis. Both of these cell death processes require inducing cells to generate oxidative stress. Therefore, elesclomol and cisplatin may have a synergistic effect in anti-tumor treatment. Here, we designed an active oxygen-responsive nano-delivery system and conducted in vitro and in vivo to study the synergistic anti-liver cancer effect of elesclomol and cisplatin. Our data showed that the elesclomol nanoparticles can effectively inhibit the growth of liver cancer cells and showed extremely low organ toxicity. Elesclomol exhibited a synergistic effect with cisplatin in vitro, but the combined treatment of the two did not outperform single drug treatment in vivo. The reason might be that the nuclear factor erythroid 2-related factor 2 (Nrf2) protein in liver cancer cells is feedback-expressed, inhibiting the oxidative stress effects induced by elesclomol and cisplatin. Therefore, this study provides reference data for exploring the mechanism of elesclomol’s synergistic anti-liver cancer treatment with cisplatin and offers a feasible strategy for future precise liver cancer treatment and improving chemotherapy efficacy. Full article

Background: Allergic rhinitis (AR) is a common inflammatory disorder with an unclear role of lytic cell death (LCD). This study aimed to identify LCD-associated genes associated with AR and investigate their underlying regulatory pathways. Methods: Transcriptomic data from AR patients (GSE19187, GSE206149) were retrieved from public repositories, and LCD-associated genes were collected from the literature. A combination of differential expression analysis, machine learning techniques, validation of expression levels, and ROC curve analysis was employed to screen for biomarkers. These biomarkers were then subjected to comprehensive functional characterization via GSEA, subcellular localization prediction, immune infiltration profiling, construction of molecular regulatory networks, and drug prediction. Finally, clinical relevance was confirmed through expression levels in patient specimens. Results: Two key indicators, ALOX15 and TIMP1, were successfully pinpointed. GSEA revealed significant enrichment of ALOX15 and TIMP1 in several biological processes, specifically chromatin organization, immune system response, and extracellular substance transport. Subcellular distribution studies showed that ALOX15 predominantly localized in the cytosol and plasma membrane, while TIMP1 was mainly detected extracellularly. Immune infiltration studies demonstrated notable modifications in seven immune cell populations, with significant associations with megakaryocyte–erythroid progenitors and conventional dendritic cells. Based on these findings, a regulatory network composed of transcription factors and microRNAs was established, and several potential therapeutic candidates (e.g., quercetin) were identified through prediction. Consistent with predictions, mRNA expression levels of both genes were significantly upregulated in the AR group compared to controls (p < 0.01), confirming reliability. Conclusions: In summary, ALOX15 and TIMP1 were identified as exploratory biomarkers associated with AR, providing preliminary insights into its molecular mechanisms and potential therapeutic implications. Full article

Kelch-like ECH-associated protein 1 (Keap1) acts as a repressor of nuclear factor-erythroid 2-related factor 2 (Nrf2), a major transcription factor regulating cellular antioxidant response. Keap1 is the substrate adaptor subunit of the cullin 3-RING E3 ubiquitin ligase complex that specifically facilitates Nrf2 ubiquitination and its proteasomal degradation. Keap1 is rich in cysteine residues, and several of them undergo various modifications, such as sulphydration, nitrosylation and glutathionylation under cellular stress conditions. Some of these modifications alter the conformation of Keap1, preventing Nrf2 from ubiquitination and subsequent proteasome-mediated degradation. As a result, newly synthesised Nrf2 translocates to the nucleus to induce the expression of diverse genes involved in protecting cells against oxidative stress. Protein CoAlation is a reversible redox-dependent post-translational modification (PTM) in which coenzyme A (CoA) forms disulphide bonds with oxidised cysteine residues under oxidative or metabolic stress. In this study, we demonstrate for the first time that disulphide Keap1 dimer undergoes CoAlation in cellular response to oxidative stress induced by various oxidising compounds. Furthermore, glucose deprivation also induces CoAlation of the disulphide Keap1 dimer in HEK293/Pank1β cells. We also demonstrate that the Keap1^{11 Cys-less} mutant is not CoAlated in response to diamide treatment or glucose deprivation. In summary, this study uncovers a novel PTM of Keap1 by the key metabolic integrator CoA, which provides new insights into the regulation of the Keap1-Nrf2 antioxidant pathway under oxidative and metabolic stress. Full article

Head and neck cancers (HNCs) represent a major global health burden and remain associated with substantial morbidity and limited therapeutic options, particularly in advanced or recurrent disease. Increasing interest has focused on naturally derived bioactive compounds with potential chemopreventive and therapeutic properties. Sulforaphane, a dietary xenobiotic isothiocyanate derived from glucoraphanin in cruciferous vegetables, has attracted attention due to its ability to modulate redox balance, epigenetic regulation, and multiple oncogenic signaling pathways. This manuscript reviews current evidence regarding the biological effects of sulforaphane in HNCs. Particular attention is given to the molecular mechanisms underlying its modulation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a key regulator of cellular antioxidant and detoxification responses that can be activated by sulforaphane. Several studies indicate that sulforaphane can inhibit tumor growth through several mechanisms beyond Nrf2 activation, including induction of apoptosis, cell cycle arrest, epigenetic modulation, and suppression of oncogenic signaling pathways. In addition, sulforaphane has been shown to enhance the efficacy of conventional treatments, including chemotherapy, radiotherapy, and photodynamic therapy. Overall, the literature suggests that sulforaphane may represent a promising chemopreventive or therapeutic adjunct in HNC, although further clinical investigation is required to clarify its translational potential. Full article

Ultraviolet A (UVA) radiation disrupts the redox balance of melanocytes and may lead to the development of melanoma, highlighting the need for new skin protection strategies. This study assessed the effect of phytocannabinoids [cannabigerol (CBG), cannabidiol (CBD), and CBG + CBD] on redox homeostasis in control and UVA-exposed melanocytes and in melanoma cells (SK-Mel-5). UVA radiation increased the activity of prooxidant enzymes in both melanocytes and SK-Mel-5 cells and, consequently, the level of reactive oxygen species (ROS) (approx. 2-fold). It also activated nuclear factor erythroid 2 (Nrf2), as reflected by increased expression of heme oxygenase 1 (HO-1) (melanocytes approx. 2-fold; SK-Mel-5 approx. 7-fold). Concomitantly, antioxidant mechanisms were impaired, as demonstrated by reduced superoxide dismutase (SOD1/SOD2) activity and impaired glutathione and thioredoxin function. These changes were accompanied by increased levels of oxidative damage markers (isoprostanes, 4-hydroxynonenal-4-HNE, and 4-HNE-protein adducts) (43–100%) and increased inflammatory signaling, including increased expression of nuclear factor kappa B (NF-κB) subunits (melanocytes: p52 ~2-fold, p65 ~75%; SK-Mel-5: ~4–4.5-fold) and tumor necrosis factor alpha (TNF-α; ~30%). Phytocannabinoid treatment modulated these UVA-induced changes. In SK-Mel-5 cells, phytocannabinoids normalized the activity of prooxidant enzymes and consequently reduced ROS levels (~30%). They also reduced Nrf2 activation and HO-1 expression; however, CBG increased HO-1 level in melanocytes (~25–40%). Furthermore, phytocannabinoids enhanced antioxidant defense by increasing SOD activity, particularly in melanocytes (~10–40%), and restoring the glutathione and thioredoxin systems. Markers of oxidative damage were reduced by approximately 23–37% after treatment. Furthermore, phytocannabinoids attenuated NF-κB activation (p52 ~18–28%, p65 ~25–29% in melanocytes; ~20% in SK-Mel-5), while TNF-α levels remained unchanged. The effects in non-irradiated cells were modest (<15%). These results suggest that phytocannabinoid-mediated modulation of redox balance may stabilize melanocytes exposed to UVA radiation and potentially reduce the risk of neoplastic transformation. However, the observed protective effects in SK-Mel-5 cells require further investigation and detailed molecular analysis. Full article

To elucidate hematopoietic ontogeny in Monopterus albus, systematic cytological analysis was performed using Wright–Giemsa-stained peripheral blood smears and hematopoietic organ imprints. Peripheral blood smears revealed five major cell types: erythrocytes (60.05 ± 8.08%), lymphocytes (13.50 ± 4.27%), thrombocytes (8.95 ± 3.47%), neutrophils (6.40 ± 2.17%), and monocytes (5.32 ± 1.63%), with occasional basophils and no eosinophils. Microscopic analysis revealed that M. albus hematopoiesis progresses through three distinct developmental phases—primitive, juvenile (with granulocytic series exhibiting promyelocyte/myelocyte/metamyelocyte substages), and mature stages—across erythroid, monocytic, lymphoid, and granulocytic lineages. The head kidney served as the primary hematopoietic organ, containing pan-stage cells and supporting all lineages, whereas the spleen lacked myeloblasts but participated in non-granulocytic hematopoiesis, and the liver was restricted to juvenile-stage erythrocyte, lymphocyte, and neutrophil development. Notably, erythrocytes in the peripheral blood with elongated nucleus were observed in the peripheral blood. Full article

Background/Objectives: Lactobacillus rhamnosus GG (LGG) is one of the most widely utilized probiotic strains with a variety of biological functions including prevention and treatment of gastro-intestinal infections and regulation of immune responses. Methods: Here, we explored the role of LGG in regulating the differentiation of naïve CD4⁺ T cells and its effect on alleviating the dextran sulfate sodium (DSS)-induced colitis in mice. Results: In vitro, we showed that LGG-derived metabolites not only promoted the differentiation of naive CD4⁺ T cells into T-helper 17 cells (Th17 cells), but also selectively upregulated the expression of lactate-specific transporter solute carrier family 5 member 12 (SLC5A12). Interestingly, we manipulated a CD4⁺ T cell-monocytes co-culture and found that heated LGG-loaded monocytes modulate naive CD4⁺ T cells to differentiate preferentially into Treg cells rather than Th17 cells. To explain the above-mentioned contradiction, we used an experimental colitis model and found that LGG administration alleviated the DSS-induced colitis in mice, as indicated by decreases in weight loss and disease activity index. Moreover, SLC5A12 blockade (using a specific antibody) further reduced the colonic histological inflammatory score and decreased secretion of proinflammatory cytokines such as IFN-γ, IL-6, IL-17F, and IL-21. Notably, SLC5A12 blockade abolished the LGG-induced differentiation of the IL-17⁺CD4⁺ T (Th17) cells but significantly increased the frequency of Foxp3⁺CD4⁺ T (Treg) cells in the colonic lamina propria. Furthermore, a higher intracellular lactate concentration was observed in the colonic CD4⁺ T cells isolated from the LGG-treated colitic mice compared with other groups. Additionally, we also found elevated levels of oxidative stress indicators such as MDA and H₂O₂, as well as excessive reactive oxygen species (ROS) in colonic tissue of DSS-treated only mice, while LGG can scavenge ROS by inducing nuclear factor-erythroid 2-related factor 2 (Nrf2) expression in enterocytes. Conclusions: Altogether, these results indicate that LGG might alleviate preclinical colitis by modulating the Th17/Treg balance, and SLC5A12 blockade appears to enhance the anti-inflammatory properties of LGG. Full article

Premature ovarian insufficiency (POI) poses a serious risk to the reproductive health and psychological well-being of women. Here, the protective effects of hydroxytyrosol (HT), the primary phenolic component of olive oil, on POI were investigated. In vitro, human ovarian granulosa-like tumour cell lines (KGN cells) were challenged by D-galactose (D-gal) with or without HT. HT administration effectively alleviated KGN cell damage, decreased the number of senescence-associated β-galactosidase (SA-β-gal)-positive cells, increased superoxide dismutase (SOD) activity, reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, enhanced the expression level of Bcl-2, inhibited the expression level of Bax, and inhibited cell apoptosis in D-gal-treated KGN cells. In vivo, HT administration reversed the decreased ovarian index, oestrous cycle disruption, and abnormal sex hormone levels observed in D-gal-induced POI mice. HT administration increased glutathione (GSH) levels, reduced the MDA levels, and attenuated apoptosis in ovarian tissues, as evidenced by a decreased number of TUNEL-positive cells, upregulated Bcl-2 expression, and downregulated Bax expression. Mechanistically, HT downregulated the expression level of Kelch-like ECH-associated protein 1 (Keap1) and enhanced the expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in vitro and in vivo. In conclusion, HT ameliorates D-gal-induced POI in vitro and in vivo by activating the Nrf2/HO-1 signalling pathway. Full article

Zearalenone (ZEA) is a common contaminant in crops and animal feed. However, research on the effects of ZEA on animal mammary tissue is relatively limited. Sulforaphane (SFN) is a naturally active compound mainly derived from cruciferous vegetables (such as broccoli), with significant antioxidant and cytoprotective effects. The purpose of this study is the effect of SFN on ZEA-induced toxicity in bovine mammary epithelial cells (MAC-T). By treating MAC-T cells with different concentrations of ZEA and SFN for 24 h, the results showed that different concentrations of ZEA (10, 20, 40, 60, 80, or 100 μM) could inhibit MAC-T cell viability. Treatment with SFN at concentrations of 1, 2.5, and 5 μM had no significant effect on cell viability. The results of combined treatment with 10 μM ZEA and 1, 2.5, or 5 μM SFN showed that SFN could significantly reverse the decrease in cell viability caused by ZEA; reduce the increase in lactate dehydrogenase (LDH) release, reactive oxygen species (ROS), and malondialdehyde (MDA) content induced by ZEA; and increase the levels of glutathione (GSH), superoxide dismutase (SOD), and mitochondrial membrane potential that were decreased by ZEA. SFN can significantly inhibit the upregulation of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) induced by ZEA exposure and markedly reverse the increase in cell apoptosis rate caused by ZEA. Compared with the control group, the expression of genes nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase 1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier subunit (GCLM), and glutathione peroxidase 1 (GPX1) was significantly reduced in the ZEA group, while the addition of SFN effectively increased the expression levels of these genes. Corresponding protein detection results were consistent with the trends in gene expression. This study demonstrated that SFN alleviates ZEA-induced damage to MAC-T cells by activating the Nrf2 pathway, providing a theoretical basis for the subsequent application of SFN in dairy farming to prevent and control breast health risks related to mycotoxins. Full article

Vitis coignetiae Pulliat ex Planch, commonly referred to as “meoru” in Korea (crimson glory vine), is a grape species belonging to the Vitaceae family, native to East Asia. This study investigated the protective effects of a hot water extract prepared from the vine stems of V. coignetiae (CG) in a model of CCl₄-induced acute liver injury. Mice received oral administration of CG (100, 200, and 400 mg/kg) or silymarin (200 mg/kg) once daily for 7 consecutive days, followed by intraperitoneal injection of CCl₄ (0.5 mL/kg). CG attenuated CCl₄-induced oxidative stress, as indicated by reduced hepatic malondialdehyde production and decreased 4-hydroxynonenal-positive cells. These effects were accompanied by restoration of antioxidant defense systems, including increased glutathione levels and superoxide dismutase and catalase activities, along with increased nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression. Hepatic inflammatory responses were also attenuated by CG treatment, with reductions in TNF-α, interleukin (IL)-1β, and IL-6 levels, inflammatory cell infiltration, and nuclear factor-κB (NF-κB) mRNA expression. Furthermore, CG attenuated apoptotic cell death, as evidenced by decreased cleaved caspase-3-positive and cleaved poly(ADP-ribose) polymerase (PARP)-positive cells. CG also lowered serum aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase levels, and alleviated hepatocellular degeneration in histopathological analysis. Collectively, these findings suggest that CG may exert protective effects against CCl₄-induced liver injury by regulating oxidative stress, inflammation, and apoptosis. Full article

Excessive accumulation of reactive oxygen species from exogenous and endogenous stressors can cause cellular damage. Chlorella contains diverse bioactive compounds, and violaxanthin, a major carotenoid pigment found in Chlorella sp. HS-V, has been reported to possess anti-inflammatory, anticancer, and antioxidant properties. We investigated the effect of violaxanthin on hydrogen peroxide (H₂O₂)-induced oxidative stress in human keratinocytes. Chlorella sp. HS-V extract significantly restored the H₂O₂-induced decrease in cell viability. Similarly, violaxanthin reduced H₂O₂-induced cytotoxicity and intracellular reactive oxygen species levels, which was associated with the upregulation of antioxidant enzyme expression. Under H₂O₂-induced oxidative stress conditions, violaxanthin may enhance cellular antioxidant defense by promoting nuclear factor erythroid 2-related factor 2 (NRF2) translocation through the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3β (PI3K/AKT/GSK3β) signaling pathway. Additionally, violaxanthin improved H₂O₂-impaired wound healing in HaCaT human keratinocyte cells and reduced senescence-associated beta-galactosidase-positive normal human epidermal keratinocytes. Overall, these findings suggest that violaxanthin may serve as a potential therapeutic agent for mitigating oxidative stress-induced cellular dysfunction. Full article