Search Results (1,183)

Oxidative stress is a major factor in skin aging and various skin pathologies. Environmental pollutants exacerbate this stress by generating reactive oxygen species (ROS), disrupting the skin’s redox balance. Pycnogenol^®, a French maritime pine bark, extract is standardized to contain 70 ± 5% procyanidins and known to mitigate oxidative damage and inflammation. This study aims to evaluate the potential antipollution and antioxidant effects of Pycnogenol^® on skin. Ex vivo human skin explants were treated with varying concentrations of Pycnogenol^® (0.5%, 1%, and 2%) and then exposed to a mixture of pollutants. The expression of stress markers Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) and AHR (Aryl Hydrocarbon Receptor) were evaluated using immunostaining. Lipid peroxidation levels were measured by quantifying malondialdehyde (MDA) concentrations. The extract significantly decreased Nrf2 expression by 40% (p = 0.003) and 23% (p = 0.048) with a dose of 2% and 1%, respectively. After pollutant exposure, Pycnogenol^® (0.5%, 1%, and 2%) reduced Nrf2 over-expression in a dose–response manner by 29% (p = 0.03), 58% (p = 0.004) and 64% (p = 0.002) respectively. Pycnogenol^® at 0.5%, 1%, and 2% significantly reduced AHR over-expression by 61% (p < 0.0001), 76% (p < 0.0001) and 85% (p < 0.0001), respectively. Pycnogenol^® (1%, and 2%) decreased MDA levels following pollutant exposure by 17% (p = 0.06) and 25% (p = 0.01) respectively. In a dose-dependent manner, Pycnogenol^® exhibited a strong protective effect against pollution, significantly reducing pollutant-induced basal oxidative stress (MDA) and over-expression of Nrf2 and AHR, key factors in oxidative stress and detoxification. Pycnogenol^® also increased AHR expression in the absence of pollutants, which may reflect an adaptive cellular response. Full article

This review summarizes the role of nuclear factor erythroid 2–related factor 2 (Nrf2) as a common link between aging, neurodegeneration, and neuropathic pain. Aging is characterized by oxidative stress and constant inflammation, which coincides with reduced Nrf2 activity and weaker antioxidant responses, increasing vulnerability to diseases. In neurodegenerative disorders—including Alzheimer’s, Parkinson’s, Huntington’s disease, and amyotrophic lateral sclerosis—evidence indicates that impaired Nrf2 signaling contributes to oxidative damage, neuroinflammation, and mitochondrial dysfunction. Furthermore, in neuropathic pain, similar mechanisms are involved, and Nrf2 could play a role as a potential analgesic target because of its role in regulating cellular defense pathways. We also review natural Nrf2 modulators (e.g., flavonoids, other polyphenols, terpenoids, alkaloids), discussing their benefits alongside common translational limitations such as poor solubility, low oral bioavailability, rapid metabolism, and potential safety issues, including possible pro-oxidant effects and chemoresistance. We also outline future directions that should prioritize improving delivery systems, addressing NRF2/KEAP1 gene variations, evaluating combinations with standard therapies, exploring preventive applications, and defining dosing, treatment duration, and long-term safety. Overall, current evidence indicates that Nrf2 modulation is a practical, cross-cutting approach relevant to healthy aging and disease management. Full article

This study aimed to evaluate the effects of an ethanolic extract from Punica granatum L. (EE-PG) on bovine ovarian tissue vitrification, focusing on follicular morphology, ultrastructure, stromal cell density, collagen distribution, redox status, and mRNA expression of antioxidant-related genes. Bovine ovarian cortex fragments were divided into a fresh control group for in vivo tissue evaluation or vitrified either with the base vitrification solution (αMEM) alone or supplemented with different concentrations of EE-PG (10, 50, and 100 µg/mL), and subsequently stored in liquid nitrogen for 5 days. After warming, fragments were allocated for morphological and oxidative stress analyses or incubated for 24 h to resumption of cellular metabolism. The concentrations of 10 and 100 µg/mL preserved follicular morphology immediately after warming, and were therefore selected for ultrastructural evaluation. Both concentrations mitigated vitrification-induced damage. Gene expression analysis showed decreased levels of catalase (cat), Glutathione Peroxidase 1 (gpx1), and Nuclear Factor Erythroid 2-Related Factor 2 (nrf2) compared with the fresh control, whereas Superoxide Dismutase (SOD) enzymatic activity increased after incubation with 10 µg/mL EE-PG compared with all experimental groups. Moreover, Malondialdehyde (MDA) levels in tissues treated with 10 or 100 µg/mL were comparable to fresh controls after incubation. Overall, EE-PG at 10 or 100 µg/mL in the vitrification solution supported the maintenance of tissue morphology, redox balance—despite the downregulation of essential antioxidant genes, which may be associated with a reduced demand for enzymatic antioxidant defense—and cellular metabolism, indicating potential for improving bovine ovarian tissue vitrification outcomes. Full article

Background: Acacetin, a naturally occurring flavone present in various plants, is known as a promising drug candidate for cardiovascular disorders. Our previous study demonstrated that acacetin ameliorates atherosclerosis through endothelial cell protection; however, its pharmacological effects on vascular smooth muscle cells (VSMCs) remain unexplored. This study investigates the therapeutic potential of acacetin against lysophosphatidylcholine (LysoPC)-induced VSMC injury and elucidates the underlying molecular mechanisms. Methods and Results: Multiple biochemical techniques were employed in the present study. The results showed that acacetin significantly attenuated LysoPC-induced apoptosis and reactive oxygen species (ROS) generation in cultured VSMCs. Western blot analysis revealed that the cytoprotection of acacetin was associated with upregulated expression of antioxidant defense proteins, including nuclear factor erythroid 2-related factor 2 (Nrf2), catalase (CAT), NADPH quinone oxidoreductase 1 (NQO-1), and superoxide dismutase 1 (SOD1). Nrf2 silencing completely abolished these protective effects. Mechanistically, siRNA-silencing of Sirtuin 1 (Sirt1) abrogated acacetin-induced modulation of the Nrf2/Keap1/p62 signaling. In vivo validation using aortic tissues from high-fat-diet-fed ApoE^−/− mice confirmed that acacetin effectively suppressed VSMC apoptosis and ROS overproduction associated with restoring the downregulated Sirt1 expression levels. Conclusions: These findings establish a novel mechanistic paradigm wherein acacetin confers protection against LysoPC-induced VSMC apoptosis and oxidative stress through Sirt1-dependent activation of the Nrf2/p62 signaling pathway, suggesting that acacetin is a promising therapeutic drug candidate for atherosclerotic plaque stabilization. Full article

This study intends to assess oxidative stress markers and endogenous enzymes in plasma and peritumoral adipose tissues (PATs) obtained from normal subjects and patients with stages I-IV colorectal cancer (CRC). 63 participants were recruited, including 23 patients with colorectal cancer and 40 healthy subjects. CRC patients had increased circulating malondialdehyde (MDA) and protein carbonyl concentrations, as well as reduced superoxide dismutase (SOD) and catalase activities, compared to normal volunteers. (p < 0.05). The findings aligned with the oxidative parameters assessed in peritumoral adipose tissue. Superoxide production in PAT was dramatically higher in the CRC group compared to the control group (p < 0.05). Moreover, oxidative stress markers were progressively altered in relation to CRC stages. Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) protein expression was reduced in PAT isolated from CRC compared to normal subjects and associated with CRC stages. CRC patients showed a systemic and peritumoral oxidative imbalance, along with elevated superoxide production in the PAT. The oxidative modifications worsened with the progression of CRC stage and were associated with the downregulation of the Nrf2/HO-1 antioxidant cascade in peritumoral adipose tissue. Full article

Chronic sleep deprivation (CSD) disrupts redox homeostasis and enhances neuroinflammatory activation, contributing to progressive cognitive impairment. Propyl gallate (PG), a lipophilic ester of gallic acid with established antioxidant activity, has not been investigated in the context of prolonged sleep deprivation. The current study examined whether PG alleviates CSD-induced oxidative imbalance, inflammatory activation, and associated behavioral deficits. Male ICR mice were subjected to 14 days of CSD using a rolling-drum apparatus and received oral PG (50, 100, or 200 mg/kg) or Ginkgo biloba extract (GBE, 40 mg/kg). Behavioral outcomes were assessed through a battery of tests, including the open-field, novel-object recognition, step-through, and Morris water maze paradigms. Oxidative and inflammatory biomarkers were assessed in serum and hippocampus, and Western blotting quantified the expression of nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2). PG improved CSD-induced impairments in exploration, recognition memory, and spatial learning; restored antioxidant capacity; reduced lipid peroxidation; enhanced Nrf2-associated antioxidant signaling; and suppressed NF-κB-mediated inflammatory activation. These findings indicate that PG alleviates cognitive deficits induced by CSD through the modulation of redox homeostasis and neuroinflammatory responses, supporting its potential as an antioxidant derivative under chronic sleep-deprivation conditions. Full article

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the cellular antioxidant response, modulating redox homeostasis, detoxification, and cytoprotective pathways. Impaired Nrf2 signaling has been associated with a wide range of cutaneous pathologies, including photoaging, autoimmune disorders, and inflammation. In this review, we highlight roles of Nrf2 in the physiological and pathological mechanisms underlying oxidative stress, autoimmunity-associated skin damage, and fibrotic diseases, with a particular emphasis on photoaging, psoriasis, vitiligo, and autoimmune-associated skin fibrosis. Furthermore, we elucidate several natural bioactive compounds, their therapeutic applications, and delivery platforms for mitigating oxidative stress-mediated skin damage through the modulation of Nrf2 signaling, aiming to translate basic insights into clinical interventions for oxidative stress-driven skin disorders. Full article

Beneficial effects of the microbiota-derived metabolite butyrate at the colonic level are well established, particularly through its relevance in colorectal cancer (CRC) and inflammatory bowel disease (IBD), two major intestinal pathologies. Therefore, the mechanisms involved in butyrate transport across colonic epithelial cell membranes (uptake transporters: monocarboxylate transporter 1 (MCT1) and sodium-coupled monocarboxylate transporter 1 (SMCT1); efflux transporters: breast cancer resistance protein (BCRP) and MCT1/monocarboxylate transporter 4 (MCT4)), which are determinant for its intracellular levels, are of primary importance for its beneficial effects at the colonic level. The available data suggest that all these butyrate transporters can be modulated by redox and inflammatory status, but the evidence is scarce and rather inconsistent. Nevertheless, a role of nuclear factor erythroid 2-related factor 2 (Nrf2) and of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mediating the effect of oxidative stress and inflammation, respectively, on MCT1 and SMCT1 is suggested. So, more investigation on this subject is needed, given the fact that increased oxidative stress levels and inflammatory status are present in a series of intestinal conditions and pathologies, including CRC and IBD, which could help to establish these transporters as potential cellular targets in these diseases. Full article

Background: Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and are strongly influenced by dietary habits. Beyond caloric intake, nutrients act as molecular signals that regulate cardiac metabolism, mitochondrial function, inflammation, and epigenetic remodeling. Objectives: This review aims to synthesize current evidence on how dietary patterns and specific nutritional interventions regulate cardiac metabolism and function through interconnected molecular and epigenetic mechanisms, highlighting their relevance for cardiovascular disease prevention. Methods: A narrative review of the literature was conducted using PubMed, Scopus, and Web of Science, focusing on studies published between 2006 and 2025. Experimental, translational, and clinical studies addressing diet-induced modulation of cardiac metabolic pathways, oxidative and inflammatory signaling, epigenetic regulation, and gut microbiota-derived metabolites were included. Results: The analyzed literature consistently shows that unbalanced diets rich in saturated fats and refined carbohydrates impair cardiac metabolic flexibility by disrupting key nutrient-sensing pathways, including AMP-activated protein kinase (AMPK), proliferator-activated receptor alpha (PPARα), mammalian target of rapamycin (mTOR), and sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (SIRT1/PGC-1α), leading to mitochondrial dysfunction, oxidative stress, chronic inflammation, and maladaptive remodeling. In contrast, cardioprotective dietary patterns, such as caloric restriction (CR), intermittent fasting (IF), and Mediterranean and plant-based diets, enhance mitochondrial efficiency, redox balance, and metabolic adaptability. These effects are mediated by coordinated activation of AMPK-SIRT1 signaling, suppression of mTOR over-activation, modulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, and favorable epigenetic remodeling involving DNA methylation, histone modifications, and non-coding RNAs. Emerging evidence also highlights the central role of gut microbiota-derived metabolites, particularly short-chain fatty acids, in linking diet to epigenetic and metabolic regulation of cardiac function. Conclusions: Diet quality emerges as a key determinant of cardiac metabolic health, acting through integrated molecular, epigenetic, and microbiota-mediated mechanisms. Targeted nutritional strategies can induce long-lasting cardioprotective metabolic and epigenetic adaptations, supporting the concept of diet as a modifiable molecular intervention. These findings provide a mechanistic rationale for integrating personalized nutrition into cardiovascular prevention and precision cardiology, complementing standard pharmacological therapies. Full article

Diabetes mellitus (DM) leads to renal damage through oxidative stress. Carvacrol (CAR), a monoterpenoid phenol, possesses anti-inflammatory and antioxidant properties. We investigated the potential effects of CAR on histological, gene expression, and biochemical parameters in a rat model of DM. Four groups were created: group 1, control; group 2 (n = 9), DM; group 3 (n = 9), DM + dimethyl sulfoxide (DMSO); and group 4 (n = 9), DM + CAR. DM was created by injecting streptozotocin (STZ). CAR (20 mg/kg) was prepared through dissolution in 0.1% DMSO. CAR and 0.1% DMSO were administered daily for 4 weeks to groups 4 and 3, respectively. At the end of this study, urea, creatinine, paraoxonase-1 (PON-1), and arylesterase (ARES) were measured in serum samples. Histopathological changes and expression of Nuclear factor erythroid 2–related factor 2 (Nrf-2) in renal tissues were assessed. Immunohistochemical(ihc) staining and RT-qPCR analysis were performed to evaluate apoptosis, focusing on Bax and Bcl-2gene expression. Masson’s trichrome(MT) staining and RT-qPCR analysis of COL1A1 and COL3A1 mRNA levels were used to assess fibrosis. Increased urea and creatinine levels in DM were significantly decreased after CAR administration. CAR application also improved reduced levels of PON 1 and ARES, which are associated with diabetes. Both immunohistochemistry and RT-qPCR analyses revealed that CAR therapy mitigated the diabetes-induced elevation in Bax and reduction in Bcl-2 expression. CAR treatment improved histopathological findings and renal Nrf-2 immunofluorescence(if) intensity. Furthermore, gene expression analysis demonstrated that COL1A1 and COL3A1 were upregulated in DM, while CAR administration downregulated them. In conclusion, CAR has a protective role in decreasing renal impairment linked to DM by regulating Bax and Bcl-2 levels and rectifying histological damage. Full article

This review synthesizes research on nuclear factor erythroid 2-related factor 2 (Nrf2) in intestinal health across human, livestock, and mouse models. The Nrf2 signaling pathway serves as a master regulator of cellular antioxidant defenses and a key therapeutic target for intestinal inflammatory disorders, including ulcerative colitis and Crohn’s disease. The interplay between oxidative stress, Nrf2 signaling, and NF-κB inflammatory cascades represents a critical axis in the pathogenesis and resolution of intestinal inflammation. Under normal physiological conditions, Nrf2 remains sequestered in the cytoplasm by Kelch-like ECH-associated protein 1 (Keap1), which facilitates its ubiquitination and proteasomal degradation. However, during oxidative stress, reactive oxygen species (ROS) and electrophilic compounds modify critical cysteine residues on Keap1, disrupting the Keap1-Nrf2 interaction and enabling Nrf2 nuclear translocation. Once in the nucleus, Nrf2 binds to antioxidant response elements (ARE) in the promoter regions of genes encoding phase II detoxifying enzymes and antioxidant proteins, including heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase. This comprehensive review synthesizes current evidence demonstrating that activation of Nrf2 signaling confers protection against intestinal inflammation through multiple interconnected mechanisms: suppression of NF-κB-mediated pro-inflammatory cascades, enhancement of cellular antioxidant capacity, restoration of intestinal barrier integrity, modulation of immune cell function, and favorable alteration of gut microbiota composition. We systematically examine a diverse array of therapeutic agents targeting Nrf2 signaling, including bioactive peptides, natural polyphenols, flavonoids, terpenoids, alkaloids, polysaccharides, probiotics, and synthetic compounds. The mechanistic insights and therapeutic evidence presented underscore the translational potential of Nrf2 pathway modulation as a multi-targeted strategy for managing intestinal inflammatory conditions and restoring mucosal homeostasis. Full article

The therapeutic potential of functional nutrients has garnered considerable attention for enhancing resilience signaling and counteracting the damage to human health caused by microplastic pollutants. The intricate interactions between microplastics (MPs) and nanoplastics (NPs) and functional nutrients, including polyphenols, flavonoids, phenylpropanoids, phenolic acids, diterpenoids, and triterpenoids, have been shown to improve blood–brain barrier (BBB) homeostasis and brain function by inhibiting oxidative stress, ferroptosis, and inflammation linked to the pathogenesis of metabolic and brain disorders. Interestingly, nutrients exhibit biphasic dose–response effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and stress-resilience proteins at minimum doses, thereby preventing or blocking MP and NP-induced damage. Notably, chronic exposure to environmental pollutants causes aberrant regulation of NFE2L2 gene and related antioxidant signaling, which can exacerbate selective susceptibility to brain insulin resistance under inflammatory conditions. This, in turn, impairs glucose metabolism and facilitates β-amyloid (Aβ) plaque synthesis leading to the onset and progression of Alzheimer’s disease (AD), also known as “Type 3 diabetes”. This pathological process triggered by oxidative stress, inflammation, and ferroptosis creates a vicious cycle that ultimately contributes to neuronal damage and loss. The review aims to investigate the therapeutic potential of functional nutrients targeting the Nrf2 pathway and stress resilience proteins to regulate epigenetic alterations, and to explore the underlying molecular mechanisms using innovative in vitro platforms for the development of promising preventive strategies and personalized nutritional interventions to attenuate oxidative stress, ferroptosis, and inflammation, with the goal of ultimately improving clinical outcomes. Full article

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in regulating cellular defense against oxidative stress and maintaining redox homeostasis. In the context of viral infections, Nrf2 signaling emerges as a double-edged sword. On one hand, it activates a broad spectrum of antioxidant and cytoprotective genes, contributing to host defense and antiviral immunity. On the other hand, certain viruses exploit the Nrf2 pathway to create a favorable environment for replication, persistence, or immune evasion. This review summarizes the current understanding of Nrf2’s antiviral and proviral roles in both RNA and DNA virus infections, delineates the underlying mechanisms, and discusses the therapeutic implications of targeting Nrf2. We emphasize the need for context-dependent modulation of Nrf2 activity and highlight future directions in precision antiviral strategies. Full article

Nuclear factor erythroid 2-related factor 2 (NRF2) orchestrates redox balance, metabolism, and cellular stress responses, acting as both a tumor suppressor and promoter depending on the disease stage. In advanced cancers, persistent NRF2 activation—through KEAP1/NFE2L2 mutations or oxidative adaptation—drives epithelial-to-mesenchymal transition, metabolic reprogramming, and immune evasion, promoting tumor invasion (T) and metastasis (M). Recent pharmacologic efforts seek to exploit this duality. NRF2 inhibitors such as brusatol, halofuginone, and ML385 suppress NRF2 transcriptional activity or disrupt DNA binding, reducing motility, invasion, and metastatic dissemination in preclinical models. In contrast, NRF2 activators, such as bardoxolone methyl (CDDO-Me), sulforaphane, and dimethyl fumarate, exhibit chemopreventive effects by enhancing detoxification and mitigating oxidative DNA damage during early tumorigenesis. Furthermore, metabolic interventions, such as glutaminase or G6PD inhibitors, target NRF2-driven anabolic and antioxidant pathways essential for metastatic fitness. Therefore, understanding the temporal and contextual effects of NRF2 signaling is crucial for therapeutic design. The aim of this review is to examine how pharmacological modulation of NRF2 influences the invasive and metastatic dimensions of tumor progression, in addition to discussing its potential integration into TNM-based prognostic and treatment frameworks. Full article

Background: Acute pancreatitis is a significant global disease. This study investigated the phytochemical composition and potential protective effects of Equisetum arvense L. (horsetail) ethanol extract and Olea europaea L. (olive leaves) aqueous extract against metronidazole (MTZ)-induced pancreatic damage in rats. Materials and Methods: Rats were randomly divided into six groups: Group I (control) received saline; Group II (Metronidazole) received only MTZ (400 mg/kg). Group III (Equisetum arvense group) received E. arvense 100 mg/kg. Group IV (Olea europaea) received 400 mg/kg of O. europaea. Group V (MTZ + E. arvense) received both MTZ (400 mg/kg) and E. arvense (100 mg/kg). Group VI (MTZ + O. europaea) received MTZ (400 mg/kg) and O. europaea (400 mg/kg). All treatments were delivered daily via the oral route. After 60 days, serum amylase, lipase, protease, and glucose levels, oxidative parameters “malondialdehyde (MDA), catalase (CAT), mRNA relative expression of pancreatic Pik3ca (phosphatidylinosi-tol-4,5-bisphosphate 3-kinase, catalytic subunit alpha), AKT (AKT Serine/Threonine Kinase 1), Nrf-2 (Nuclear factor, erythroid 2-like 2), TNFα (tumor necrosis factor alpha), and IL-1β (interleukin-1 beta genes, an apoptotic marker “caspase-3,” and histopathological changes were estimated. Results: HPLC analysis revealed that horsetail extract contained caffeic acid, catechin, rutin, and kaempferol, while olive leaf extract was dominated by oleuropein. MTZ administration significantly elevated serum levels of pancreatic enzymes (lipase, amylase, and protease) and glucose and increased oxidative stress markers, such as MDA, while reducing catalase (CAT) activity. Co-treatment with MTZ and horsetail, or MTZ and olive extracts, mitigated these effects, especially horsetail, which restored CAT levels and reduced MDA concentrations. qPCR analysis showed MTZ upregulated inflammatory genes (TNFα, IL-1β) and downregulated antioxidant and survival-related genes (Pik3ca, AKT, Nrf-2). Horsetail co-treatment significantly reversed these gene expression patterns. Histopathological and immunohistochemical analyses confirmed MTZ-induced pancreatic tissue degeneration and increased cleaved caspase-3 expression, both of which were notably alleviated by horsetail extract. Conclusions: These findings highlight the superior protective efficacy of Equisetum arvense over Olea europaea in ameliorating MTZ-induced pancreatic toxicity, potentially through anti-inflammatory, antioxidant, and anti-apoptotic mechanisms. Full article