Search Results (790)

Introduction: Sarcopenia, the progressive age-related decline in skeletal muscle mass, strength, and function, represents a major contributor to morbidity, frailty, and reduced quality of life in older adults. Oxidative stress and chronic low-grade inflammation are increasingly recognized as central mechanisms driving its onset and progression, through pathways involving mitochondrial dysfunction, impaired satellite cell activity, and dysregulated protein turnover. Objective: The purpose of the following manuscript is to summarize current research on the molecular and cellular interactions between oxidative stress and inflammation in sarcopenia, as well as to assess Aronia melanocarpa’s potential as a nutritional intervention. Methods: A narrative review was conducted by searching PubMed, Scopus, and Web of Science for peer-reviewed literature published between 2000 and 2024. Keywords included “sarcopenia”, “oxidative stress”, “inflammation”, “Aronia melanocarpa”, “polyphenols”, and even “functional foods”. Eligible publications provided mechanistic, preclinical, or clinical findings on skeletal muscle biology and A. melanocarpa bioactivity. Results: This narrative review examines the relationship between oxidative stress and inflammation in sarcopenia, focusing on NF-κB-mediated inflammatory signaling, Nrf-2-dependent antioxidant defenses, myokines like myostatin and irisin, and macrophage polarization in muscle homeostasis. Aronia melanocarpa (black chokeberry) is highlighted as a polyphenol-rich fruit with a distinct profile of anthocyanins and proanthocyanidins that have strong antioxidant and anti-inflammatory properties. According to preclinical, clinical, and nutritional studies, A. melanocarpa bioactives modulate redox balance, suppress pro-inflammatory cytokine production, increase antioxidant enzyme activity, and regulate metabolic and regenerative signaling pathways important for skeletal muscle health. Conclusions: Overall, the data suggest A. melanocarpa’s potential as a functional food and nutraceutical candidate for the prevention and treatment of sarcopenia. However, further translational and clinical research is needed to determine the appropriate intake, bioavailability, and long-term efficacy in human populations. Full article

Background: Chronic inflammatory skin disorders, including atopic dermatitis, psoriasis, acne, and chronic wounds, affect nearly two billion people worldwide, impose substantial morbidity and economic burden, and remain only partially controlled by existing therapies. The cutaneous endocannabinoid system (ECS), comprising cannabinoid receptors, endocannabinoids, and their metabolic enzymes, regulates inflammation, pruritus, barrier integrity, and tissue repair; cannabinoid receptor type 2 (CB₂) has emerged as a particularly relevant target. β-Caryophyllene (BCP), a dietary sesquiterpene and highly selective CB₂ agonist with favorable safety and pharmacokinetic attributes, has attracted attention as a promising topical candidate. Methods: We systematically searched PubMed, Embase, and Web of Science (inception–30 July 2025) for studies on “β-caryophyllene” and dermatological outcomes, prioritizing purified BCP and analytically characterized BCP-rich fractions. Quantitative parameters, including tested concentration ranges (0.5 µM–10%) and principal mechanistic outcomes, were extracted to provide a translational context. Results: BCP penetrates the stratum corneum, suppresses NF-κB/MAPK and IL-4/TSLP pathways, enhances Nrf2-driven antioxidant defenses, and accelerates re-epithelialization and collagen remodeling. Across in vitro, in vivo, and formulation studies, BCP produced consistent anti-inflammatory and barrier-restorative effects within this concentration range. CB₂ antagonism attenuated these responses, confirming receptor specificity. BCP’s volatility and autoxidation to β-caryophyllene oxide (BCPO) necessitate stability-by-design strategies using antioxidants, low-oxygen processing, and protective packaging. Human evidence, limited to BCP-rich botanicals such as Copaifera oleoresins, suggests benefits for scars, wounds, and acne but lacks compound-specific validation. Conclusions: BCP exhibits coherent CB₂-mediated anti-inflammatory, antipruritic, antioxidant, and reparative actions with a favorable safety profile. Dose-defined, oxidation-controlled clinical trials of purified BCP are warranted to establish its potential as a steroid-sparing topical therapy. Full article

A large body of evidence suggests that flaxseed oil (FSO), one of the richest sources of essential omega-3 fatty acids, has neuroprotective properties. Purinergic signaling plays a crucial role in pathophysiological processes in the nervous system. There is a lack of evidence regarding the effects of FSO on the purinergic system under both physiological and neurotoxic conditions. Here we report the effects of dietary FSO consumption in a rat model of trimethyltin (TMT) intoxication. Exposure to TMT selectively induces hippocampal neuronal damage and glial reactivation associated with oxidative stress and neuroinflammation, causing severe behavioral impairments. When administered orally (1 mL/kg) before and during TMT intoxication (single dose 8 mg/kg, i.p.) to female Wistar rats, FSO effectively prevented the behavioral disturbances induced by TMT. FSO selectively increased CAT-mRNA level in both healthy and TMT-intoxicated animals, while preventing TMT-induced upregulation of Nrf2, NF-κB, and GPx1 without affecting SOD2 or Gsr-mRNA levels. FSO prevented microgliosis, microglial NTPDase1-eN upregulation, and the increase in purinergic receptors involved in microglial reactivity. Pretreatment with FSO in TMT-intoxicated rats maintained the activity and expression of NTPDase1 at control level, while the activity and expression of eN and ADA were increased. FSO upregulated eN, A₁R, A_2BR, A₃R, ADA, and NGF, while downregulating NTPDase1, A_2AR, and ENT1 in TMT-intoxicated rats. This suggests complex modulation of purinergic signaling, particularly the adenosine system. These findings may contribute to a better understanding of the effects of FSO, highlighting the impact of the dietary intake of this oil on the brain. Full article

Background/Objectives: Endometrial cancer (EC), a malignancy arising from the uterine lining, is a leading gynecological cancer in developed countries. Syringic acid (SA), a naturally occurring phenolic compound, possesses various bioactivities including antioxidant, anti-inflammatory, chemoprotective, and anti-angiogenic properties. This study aimed to investigate the effects of SA on the proliferation and migration of RL95-2 EC cells, its protective role in normal endometrial stromal cells (HESCs), and the underlying molecular mechanisms. Furthermore, the potential synergistic anticancer effects of SA in combination with chemotherapeutic agents against EC were evaluated. Methods: Cell viability was assessed using nuclear fluorescence staining, the MTT assay, and clonogenic survival assay. Cell migration was evaluated through wound closure and Transwell migration assays. Gene expression levels were analyzed by the RT-PCR method. Results: SA significantly inhibited the proliferation of RL95-2 EC cells, with an IC₅₀ value of 27.22 μM. Co-treatment with SA and the chemotherapeutic agent doxorubicin (Dox) demonstrated an additive inhibitory effect. Mechanistically, both SA and the SA-Dox combination induced apoptosis by upregulating the expression of caspases-3, -8, and -9, increasing the expression of pro-apoptotic genes (Bax and Bad), and downregulating anti-apoptotic genes (Bcl-XL and Bcl-2). Cell cycle analysis revealed the downregulation of cyclin D and the upregulation of tumor suppressors p21 and p27, contributing to growth arrest. In addition, both SA and the combination treatment effectively suppressed cell migration by downregulating matrix metalloproteinases (MMPs) and β-catenin. SA treatment also induced the expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and activated NF-κB signaling, leading to an elevated expression of inflammatory mediators such as COX-2 and iNOS. Furthermore, SA promoted oxidative stress in RL95-2 cells by inhibiting the Nrf2 pathway and reducing the expression and activities of antioxidant enzymes including catalase, glutathione peroxidase, and superoxide dismutase, thereby enhancing reactive oxygen species (ROS) accumulation. In contrast, in lipopolysaccharide-stimulated HESC cells, SA attenuated inflammation and ROS generation, indicating its selective cytoprotective role in normal endometrial cells. Conclusions: SA may serve as a promising adjuvant candidate to enhance chemotherapeutic efficacy while protecting normal cells by mitigating inflammation and oxidative stress. Full article

The global demand for processed foods has increased reliance on synthetic phenolic antioxidants (SPAs), including tert-butylhydroquinone (TBHQ), a widely used additive to prevent lipid oxidation and extend shelf life. TBHQ is considered safe at present regulated levels; however, studies suggest potential adverse effects, including oxidative stress, genotoxicity, and impacts on immune function, raising concerns about human health and ecological risks. Herein, we investigated the immunomodulatory effects of TBHQ on RAW 264.7 murine macrophages pre-exposed to 0.1, 1, and 5 µM TBHQ and then stimulated with lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly I:C, PIC) to model bacterial and viral immune challenges. We then used functional assays and transcriptomic profiling to assess inflammatory responses and oxidative stress signaling. TBHQ reduced nitric oxide production and IL-10 secretion at the highest non-cytotoxic dose, and enhanced phagocytosis and IL-6 secretion at the lowest concentrations. Overall, transcriptomics revealed significant downregulation of proinflammatory pathways and induction of glutathione and xenobiotic metabolism. Pre-treatment with TBHQ increased gene transcript counts of key metabolic genes/transporters such as Cbr3, Adh7, Gstp1/3, Gsta3, Hmox1 and Gclm. Following treatment with LPS or PIC several genes for classical proinflammatory chemokines and cytokines such as Cxcl2, Ccl2, Ccl12, Acod1, Ptgs2, Nos2, and Il6 were downregulated. Genes involved in NF-κB signaling, such as Nfkbia, Nfkb1, and Ikbke were also downregulated. Our study suggests that the induction of Nrf2-related antioxidant pathways by TBHQ is the main driver for reduced inflammatory signaling in macrophages. Full article

Cardiovascular aging is a multifactorial and systemic process that contributes significantly to the global burden of cardiovascular disease, particularly in older populations. This review explores the molecular and cellular mechanisms underlying cardiovascular remodeling in age-related conditions such as hypertension, atrial fibrillation, atherosclerosis, and heart failure. Central to this process are chronic low-grade inflammation (inflammaging), oxidative stress, cellular senescence, and maladaptive extracellular matrix remodeling. These hallmarks of aging interact to impair endothelial function, promote fibrosis, and compromise cardiac and vascular integrity. Key molecular pathways—including the renin–angiotensin–aldosterone system, NF-κB, NLRP3 inflammasome, IL-6, and TGF-β signaling—contribute to the transdifferentiation of vascular cells, immune dysregulation, and progressive tissue stiffening. We also highlight the role of the senescence-associated secretory phenotype and mitochondrial dysfunction in perpetuating inflammatory and fibrotic cascades. Emerging molecular therapies offer promising strategies to reverse or halt maladaptive remodeling. These include senescence-targeting agents (senolytics), Nrf2 activators, RNA-based drugs, and ECM-modulating compounds such as MMP inhibitors. Additionally, statins and anti-inflammatory biologics (e.g., IL-1β inhibitors) exhibit pleiotropic effects that extend beyond traditional risk factor control. Understanding the molecular basis of remodeling is essential for guiding future research and improving outcomes in older adults at risk of CVD. Full article

Background: Gallic acid (GA) is a dietary polyphenol widely found in walnuts, tea leaves, and grapes, and it is recognized for its potent antioxidant and anti-inflammatory properties. Chronic sleep deprivation (CSD) is known to disrupt redox balance, promote neuroinflammation, and impair cognition, while effective nutritional strategies to mitigate these effects remain scarce. This study was designed to evaluate the protective potential of GA against CSD-induced cognitive deficits in mice and to elucidate the underlying mechanisms. Methods: Seventy-two male ICR mice were randomly allocated to six groups, including control, CSD model, Ginkgo biloba extract, and GA at three doses (50, 100, and 200 mg/kg). After 28 days of treatment, cognitive performance was assessed using the open field test (OFT), novel object recognition (NOR), step-through passive avoidance (ST), and Morris water maze (MWM). Redox status and inflammatory mediators were determined by ELISA, while the hippocampal expression of proteins related to antioxidant defense and NF-κB signaling was analyzed by Western blotting. Results: GA supplementation improved exploratory activity, recognition memory, and spatial learning in the CSD mice. Biochemical evaluation revealed that total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were restored, while malondialdehyde (MDA) levels, an indicator of lipid peroxidation, were reduced. These changes were accompanied by decreased circulating concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). At the molecular level, GA enhanced the expression of Nrf2, HO-1, and NQO1, while inhibiting p-p65, iNOS, and COX2 in the hippocampus. Conclusions: These findings demonstrate that GA alleviates CSD-induced cognitive deficits through the activation of the Nrf2/HO-1 antioxidant pathway and inhibition of NF-κB–mediated inflammatory responses. Thus, GA may represent a promising nutraceutical candidate for maintaining cognitive health under chronic sleep loss. Full article

This study investigated the role of miR-144 in mitigating oxidized fish oil (OFO)-induced muscle oxidative stress and quality deterioration in Megalobrama amblycephala. The feeding trial was conducted for 5 weeks, and four experimental diets were formulated, namely NC (fresh fish oil), OF (OFO), OF + ago (OFO and miR-144 agomir), and OF + anta (OFO and miR-144 antagomir). Histological results showed that OFO significantly reduced myofiber density (from 758.00 ± 13.69 to 636.57 ± 13.44 N/mm²) and decreased the percentage of myofibers with diameters > 50 μm (from 53.45% to 38.52%). OFO intake significantly increased the content of malondialdehyde (MDA), protein carbonyl (PC), advanced oxidation protein product (AOPP), and 3-nitrotyrosine (3-NT), and significantly decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity in muscle. OFO treatment significantly up-regulated the expression of inflammatory factors (NF-κB, TNF-α, HO-1, and IL-6), significantly down-regulated NQO1. Moreover, OFO reduced muscle differentiation and maturation by down-regulating the expression of MyoG, MYHC1, and protein synthesis genes (AKT3, TOR, and S6K1), and up-regulating the expression of protein hydrolysis genes (FoxO3a, MuRF1, HSP70, Beclin-1, P62, and ATG8). Moreover, miR-144 agomir exacerbated OFO-induced muscle damage by suppressing Nrf2, whereas miR-144 antagomir mitigated these effects. Silencing miR-144 re-activates Nrf2, alleviating oxidative damage, enhancing protein deposition, and improving muscle quality. These findings suggest that targeting the miR-144/Nrf2 axis could counteract OFO-induced muscle deterioration. Full article

This review provides a comprehensive overview of the therapeutic potential of omaveloxone (OMA) for the treatment of Friedreich’s ataxia (FA), along with an analysis of the historical development and current status of the synthetic strategies for OMA production. OMA activates the nuclear factor-2-(erythroid-2)-related (Nrf2) pathway in vitro and in vivo, in both animal models and humans. The Nrf2 pathway plays a crucial role in the cellular response to oxidative stress. Furthermore, OMA has been shown to mitigate mitochondrial dysfunction, restore redox homeostasis and downregulate nuclear factor-κB (NF-κB), a key mediator of inflammatory responses. Through these mechanisms, OMA contributes to tissue protection and inflammation reduction in patients with FA. The review also highlights future perspective, focusing on the challenges associated with OMA reprofiling through innovative drug delivery approaches and its potential repurposing for diseases beyond FA. Full article

Oxidative stress and inflammation are deeply interconnected processes implicated in the onset and progression of numerous chronic diseases. Despite promising mechanistic insights, conventional antioxidant and anti-inflammatory therapies such as NSAIDs, corticosteroids, and dietary antioxidants have shown limited and inconsistent success in long-term clinical applications due to challenges with efficacy, safety, and bioavailability. This review explores the molecular interplay between redox imbalance and inflammatory signaling and highlights why conventional therapeutic translation has often been inconsistent. It further examines emerging strategies that aim to overcome these limitations, including mitochondrial-targeted antioxidants, Nrf2 activators, immunometabolic modulators, redox enzyme mimetics, and advanced delivery platforms such as nanoparticle-enabled delivery. Natural polyphenols, nutraceuticals, and regenerative approaches, including stem cell-derived exosomes, are also considered for their dual anti-inflammatory and antioxidant potential. By integrating recent preclinical and clinical evidence, this review underscores the need for multimodal, personalized interventions that target the redox-inflammatory axis more precisely. These advances offer renewed promise for addressing complex diseases rooted in chronic inflammation and oxidative stress. Full article

Aging results from the combined effects of oxidative stress, chronic low-grade inflammation, mitochondrial decline, and cellular senescence, which together drive age-related disorders. Natural products ranging from polyphenols and terpenoids to alkaloids, polysaccharides, peptides, and marine metabolites can influence central pathways such as Nrf2/ARE, NF-κB, MAPK, JAK/STAT, AMPK/PGC1-α, mTOR, and SIRT1/FOXO. By doing so, they strengthen antioxidant defenses, temper inflammation, preserve mitochondrial balance, and regulate autophagy. There is increasing attention to synergy, where combinations of bioactives can achieve stronger and more balanced effects than single agents alone. Advances in artificial intelligence are accelerating this discovery process, while greener extraction and smarter delivery systems such as deep eutectic solvents and nanostructured carriers are improving bioavailability and consistency. Together, these developments underscore the promise of natural product-based strategies for healthy aging. Grounded in rigor and reproducibility, this Special Issue aims to inspire translational advances toward healthier and more graceful aging. Full article

Cancer cells possess endogenous antioxidant systems such as nuclear factor erythroid 2-related factor 2 (NRF2). The electroneutral sodium bicarbonate cotransporter NBCn1, known as a migratory module, is closely associated with cancer metastasis; however, its regulatory signaling in cancer remains unclear. In particular, the regulation of NBCn1 in response to oxidative stress and its relationship with NRF2 need to be elucidated. In the present study, we found that hydrogen peroxide–induced oxidative stress dysregulated NBCn1 via inhibition of NF-κB, thereby suppressing cellular migration in non-small cell lung cancer A549 cells. Phosphorylation of NF-κB was required for maintaining NBCn1 function in A549 cells. Oxidative stress also induced NRF2 nuclear translocation, reduced NBC activity, and activated oxidative stress–responsive gene expression. Treatment with the NBC inhibitor S0859 impaired ERK activation, NRF2 nuclear translocation, and oxidative stress defense gene expression in A549 cells. Furthermore, oxidative stimulation in the presence of S0859 disrupted the NRF2-mediated oxidative stress defense system and cellular migration in A549 lung cancer cells. Collectively, these findings suggest that S0859, as a potential NRF2 inhibitor, may exert anti-cancer properties. Full article

Age-related macular degeneration (AMD) progresses to vision-threatening dry and wet forms, with no effective dry AMD treatments available. The sulfated polysaccharide (GNP, 25.8 kDa) derived from Gelidium crinale exhibits diverse biological activities and represents a potential source of novel therapeutic agents. This study employed a hydrogen peroxide (H₂O₂)-induced oxidative stress and epithelial–mesenchymal transition (EMT) model in retinal pigment epithelial (RPE) cells to investigate GNP’s protective mechanisms against both oxidative damage and EMT. The results demonstrated that GNP effectively suppressed oxidative stress, with the 600 μg/mL dose significantly inhibiting excessive reactive oxygen species (ROS) generation to levels comparable to untreated controls. Concurrently, at concentrations of 200–600 μg/mL, GNP inhibited NF-κB signaling and increased the Bax/Bcl-2 ratio, effectively counteracting H₂O₂-induced oxidative damage and cell apoptosis. Furthermore, in H₂O₂-treated ARPE-19 cells, 600 μg/mL GNP significantly reduced the secretion of N-cadherin (N-cad), Vimentin (Vim), and α-smooth muscle actin (α-SMA), while increasing E-cadherin (E-cad) expression, consequently inhibiting cell migration. Mechanistically, GNP activated the Nrf2/HO-1 pathway, thereby mitigating oxidative stress. These findings suggest that GNP may serve as a potential therapeutic agent for dry AMD. Full article

Brazilian red propolis (BRP) has emerged as a promising source of multifunctional phytochemicals with potent anti-inflammatory activity. This review provides a comprehensive analysis of the anti-inflammatory effects of BRP’s bioactive compounds, their molecular targets, and their mechanisms of action. Isolated compounds from BRP (such as formononetin, biochanin A, daidzein, calycosin, medicarpin, vestitol, and neovestitol) have demonstrated the ability to modulate critical pro-inflammatory signaling pathways, including NF-κB, TLR4, JAK/STAT, and PI3K/AKT, while concurrently activating antioxidant and cytoprotective responses via the Nrf2/HO-1 axis. These effects are further supported by the suppression of pro-inflammatory cytokines, regulation of immune cell infiltration and activation, inhibition of inflammasome components such as NLRP3, induction of autophagy, and polarization of macrophages and microglia from a pro-inflammatory (M1) to an anti-inflammatory (M2) phenotype. Collectively, these findings reinforce the potential of BRP as a rich source of multifunctional phytochemicals with broad therapeutic relevance for chronic inflammation and related pathologies. Future research should address the identified knowledge gaps by employing rigorous in vitro and in vivo toxicity assessments, exploring structure–activity relationships, and leveraging advanced delivery systems to optimize bioavailability. Such methodological approaches will be essential for translating the promising biological activities of BRP compounds into clinically viable therapeutic agents. Full article

Diabetic nephropathy (DN) is a consequence of diabetes mellitus (DM), in which hyperglycemia triggers osmotic and oxidative stress and activates inflammatory pathways. These processes damage kidney cells, with mesangial cells (MCs) undergoing mesangial expansion. Antihyperglycemic drugs prevent the progression of renal disease. Although tamsulosin is not conventionally used for the treatment of DN, its previously reported anti-fibrotic and anti-inflammatory effects in liver and lung injury models suggest that it may exert renoprotective actions like those of pioglitazone, which has also been shown to improve cellular carbohydrate and lipid metabolism. MCs were exposed to 20 mM glucose medium and treated with either 50 nM tamsulosin or 100 nM pioglitazone. Subsequently, cell proliferation, inflammatory markers (NF-κB, IL-1β, IL-17), fibrogenic markers (TGF-β, collagen I), oxidative stress parameters (NRF2, superoxide), and indicators of mesangial activation (α-SMA, rhodamine–phalloidin) were assessed in vitro. Both treatments reduced cellular proliferation and hypertrophy, attenuated the release of reactive oxygen species (ROS), decreased IL-17 and α-SMA expression, and reduced mesangial activation and hypertrophy. In an in vivo model of DN in Wistar rats, both treatments decreased mesangial cell activation and expansion. In conclusion, tamsulosin and pioglitazone exert anti-fibrogenic and anti-inflammatory effects in MCs exposed to HG, thereby limiting mesangial activation and expansion. Full article