Antioxidants最新文献

Cannabinoids can bind to several cannabinoid receptors and modulate cellular signaling and gene expression relevant to inflammation and lipid homeostasis. Likewise, several vitamin E analogs can modulate inflammatory signaling and foam cell formation in macrophages by antioxidant and non-antioxidant mechanisms. We analyzed the regulatory effects on the expression of genes involved in cellular lipid homeostasis (e.g., CD36/FAT cluster of differentiation/fatty acid transporter and scavenger receptor SR-B1) and inflammation (e.g., inflammatory cytokines, TNFα, IL1β) by cannabinoids (cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC)) in human THP-1 macrophages with/without co-treatment with natural alpha-tocopherol (RRR-αT), natural RRR-αTA (αTAn), and synthetic racemic all-rac-αTA (αTAr). In general, αTAr inhibited both lipid accumulation and the inflammatory response (TNFα, IL6, IL1β) more efficiently compared to αTAn. Our results suggest that induction of CD36/FAT mRNA expression after treatment with THC can be prevented, albeit incompletely, by αTA (either αTAn or αTAr) or CBD. A similar response pattern was observed with genes involved in lipid efflux (ABCA1, less with SR-B1), suggesting an imbalance between uptake, metabolism, and efflux of lipids/αTA, increasing macrophage foam cell formation. THC increased reactive oxygen species (ROS), and co-treatment with αTAn or αTAr only partially prevented this. To study the mechanisms by which inflammatory and lipid-related genes are modulated, HEK293 cells overexpressing cannabinoid receptors (CB1 or TRPV-1) were transfected with luciferase reporter plasmids containing the human CD36 promoter or response elements for transcription factors involved in its regulation (e.g., LXR and NFκB). In cells overexpressing CB1, we observed activation of NFκB by THC that was inhibited by αTAr.

Ulcerative colitis (UC) is an inflammatory bowel disease associated with oxidative stress. Pogostemon oil (PO) exhibits potent antioxidant and anti-inflammatory activities but is limited by high volatility and poor gastrointestinal stability. In this study, sporopollenin exine capsules (SECs) were engineered as natural micro-carriers for PO, achieving efficient encapsulation (η > 69%) and a high adsorption capacity (27.64 g/g). A pH-sensitive calcium alginate shell was subsequently applied to construct colon-targeted microspheres (Ca-Alg@PO-SECs). The resulting system improved the thermal and photostability of PO. In vitro dissolution assays confirmed the system's pH-responsiveness, maintaining integrity under simulated gastric conditions while enabling localized release at intestinal pH. In a DSS-induced acute UC mouse model, Ca-Alg@PO-SECs effectively alleviated clinical symptoms, as evidenced by improved body weight, colon length, and disease activity index. At the inflammatory level, the formulation modulated key cytokines (IL-1β, IL-6, and IL-10). Overall, Ca-Alg@PO-SECs provides a biocompatible, colon-targeted delivery strategy that preserves the bioactivity of essential oils and offers a promising preclinical approach for localized UC therapy.

Ischemic stroke is a major cause of long-term disability and death, with oxidative stress contributing substantially to post-ischemic injury. Reperfusion restores oxygen supply but simultaneously increases reactive oxygen species (ROS), amplifying secondary neuronal damage. This study examined time-dependent changes in systemic thiol redox status following transient middle cerebral artery occlusion (tMCAO) in rats. Plasma concentrations of cysteine (CySH), cystine (CySS), glutathione (GSH), and glutathione disulfide (GSSG), along with corresponding CySS/CySH and GSSG/GSH ratios and redox potentials (Eh), were evaluated 24 and 48 h after occlusion. At 24 h, thiol concentrations and redox ratios showed no significant differences between sham and tMCAO groups. By 48 h, a marked oxidative shift emerged, characterized by reduced CySH, elevated GSSG, and significant increases in both CySS/CySH and GSSG/GSH ratios. Redox potentials also demonstrated substantial oxidation at this time point. These findings indicate that prolonged ischemia-reperfusion induces systemic oxidative stress, with plasma redox status serving as a sensitive indicator of reperfusion-related injury. The results underscore the plasma redox status as a potentially sensitive biomarker of reperfusion-induced oxidative injury and support the therapeutic value of targeting redox imbalance to mitigate oxidative damage following stroke.

Cataracts remain the leading cause of blindness worldwide, and surgery is currently the only effective clinical treatment, as no pharmacological therapy has yet been validated. Here, we explore Fullerenol, a hydroxylated fullerene derivative formulated as eye drops, as a potential nanomedicine for delaying cataract onset and progression. In UVB-induced mouse cataract models, topical Fullerenol preserved the lens transparency and histological structure. In human lens epithelial cells, Fullerenol reduced the oxidative stress, restored the mitochondrial function, alleviated the DNA damage, and suppressed the cellular senescence. RNA sequencing and pathway enrichment analyses further indicated that Fullerenol modulated the oxidative stress- and senescence-associated signaling pathways, including MAPK and TGF-β cascades, while downregulating the p53-CDKN1A (p21) axis. These findings provide new evidence that Fullerenol can mitigate photo-oxidative damage and age-related cellular dysfunction, highlighting its promise as a non-invasive and clinically translatable nanomedicine strategy for cataract management.

Natural compounds, as honey-derived flavonoids and phenolic compounds, are increasingly investigated for their potential to mitigate skin aging and prevent oxidative stress-induced cellular damages. In this context, a dynamic cell culture model was employed to assess the protective influence of honey pre-treatment on stem cell-associated genes and the Wingless-related integration site (Wnt) signaling pathway following ultraviolet (UV)-induced aging. Using a bioreactor, skin stem cells (SSCs) derived from healthy skin biopsies and human skin fibroblasts (HFF1) were pre-treated with 1% honey for 48 h and then exposed to UV. Real-time quantitative polymerase chain reaction (RT-qPCR) analyses were performed on Wnt signaling and anti-aging molecular responses. Honey pre-treatment enhanced the expression of pluripotency markers (Octamer-binding transcription factor 4 (Oct4); SRY-box transcription factor 2 (Sox2)) and reduced senescence-related cell cycle regulators (cyclin-dependent kinase inhibitor 2A (p16); cyclin-dependent kinase inhibitor 1A (p21); tumor protein 53 (p53)) in SSCs. In UV-damaged SSCs, honey also significantly increased Wnt3a expression. In fibroblasts, honey pre-treatment upregulated Heat shock protein 70 (Hsp70) and Hyaluronan synthase 2 (HAS2) expression, while downregulating caspase-8 (CASP8), indicating a protective role against UV-mediated cellular stress. We also analyzed nitric oxide release and the total antioxidant capacity of cells after treatment. Collectively, these findings suggest that honey may safeguard skin stem cells from UV-induced aging by modulating pluripotency and senescence-associated genes and regulating differentiation through alterations in Wnt signaling. Furthermore, Hsp70 upregulation in fibroblasts appears to strengthen cellular stress responses and support homeostatic stability.

Ferroptosis is a distinct form of regulated necrotic cell death driven by iron-dependent phospholipid peroxidation, characterized by flexible and context-dependent mechanisms rather than a single fixed linear pathway. This study elucidates the critical lipid peroxidation networks and antioxidant defense systems used in determining ferroptosis, specifically emphasizing how these mechanisms underpin the plasticity of this cell death mode and its correlation with therapeutic resistance. We examine the catastrophic propagation of ferroptosis, detailing the multi-layered amplification mechanisms-ranging from intracellular organelle crosstalk to intercellular trigger waves-that may facilitate massive tissue damage in degenerative diseases and ischemic injuries. Furthermore, the evolutionary conservation of ferroptosis-like phenomena across diverse species is summarized, underscoring its fundamental role in development and host-pathogen interactions. To conclude, we explore pivotal knowledge gaps that remain in our understanding of ferroptosis. By integrating these complex regulatory networks, this review provides a comprehensive framework for understanding ferroptosis as an adaptable, self-amplifying process, informing future efforts to modulate ferroptosis in disease contexts. Notably, this review focuses on the amplification, execution, and propagation phases of ferroptosis rather than on its initial triggering mechanisms, which remain an area of active investigation.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly linked to systemic metabolic disturbances and features a lipid-driven cascade that promotes hepatic inflammation and fibrosis. Choline insufficiency contributes to disease advancement by altering phospholipid turnover and redox homeostasis; however, its spatial and temporal regulatory roles throughout MASLD progression remain insufficiently defined. A 10-week high-fat, choline-deficient (HFCD) mouse model was established, and liver pathology was evaluated at weeks 6, 8, and 10. Time-resolved assessments combined untargeted metabolomics, magnetic resonance imaging-proton density fat fraction (MRI-PDFF), serum biochemistry, histological staining, immunofluorescence, and transmission electron microscopy to characterize dynamic alterations in lipid metabolism, redox status, inflammation, and fibrogenesis. The HFCD diet produced a clear temporal sequence of liver injury. Steatosis, phosphatidylcholine depletion, and early antioxidant loss appeared by week 6. By week 8, mitochondrial structural damage and pronounced cytokine elevation were evident. At week 10, collagen deposition and α-SMA activation signaled fibrotic progression. Metabolomics indicated significant disruptions in pathways related to ATP-binding cassette (ABC) transporters, one-carbon metabolism, and the tricarboxylic acid (TCA) cycle. Using integrated analytical strategies, this study suggests that choline deficiency may be associated with a time-dependent pathological cascade in MASLD, beginning with phospholipid destabilization and extending to altered mitochondria-endoplasmic reticulum crosstalk at mitochondria-associated membranes, alongside amplified oxidative-inflammatory responses, which collectively may contribute to progressive fibrogenesis as the disease advances.

Background: The development of lung cancer is strongly influenced by oxidative stress (OS), which results when the balance between oxidants and antioxidants is disturbed. Evaluation of both specific redox markers such as thiol/disulfide homeostasis (TDH) and overall indicators including total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) may provide a more comprehensive view of oxidative imbalance in lung cancer. We examined OS indices and TDH in patients with lung cancer versus healthy controls. Methods: Eighty participants were enrolled, consisting of 40 patients with newly diagnosed lung cancer and 40 age- and sex-matched healthy controls. Serum levels of native thiol (NT), total thiol (TT), and disulfide were determined using an automated spectrophotometric method. Additionally, TAS, TOS, and the OSI were evaluated to provide an overall assessment of oxidative balance. Routine hematological and biochemical parameters were compared between groups. Results: White blood cell and neutrophil counts were notably higher in lung cancer patients compared with controls (p < 0.05). NT and TT levels were remarkably decreased, whereas disulfide levels, TOS, and OSI were significantly elevated in the lung cancer group (p < 0.05). TAS levels tended to be lower in patients, although not reaching statistical significance. No significant association was observed between oxidative parameters and tumor stage or localization. Conclusions: Patients with lung cancer exhibited a marked oxidative imbalance, characterized by elevated oxidant burden and impaired TDH. Combined assessment of TAS, TOS, OSI, and thiol/disulfide parameters may provide valuable insight into the oxidative pathophysiology of lung cancer and hold potential as complementary biomarkers for disease evaluation. Further large scale studies are needed to confirm these findings.

In recent years, heavy metal emissions in Lhasa have been increasing, which has an impact on the local water environment. The negative effects of copper (Cu²⁺) on aquatic ecosystems have attracted much attention, as even low concentrations of Cu²⁺ can exert toxic effects on aquatic organisms. However, the impact of Cu²⁺ on native fish species from the Lhasa River remains poorly understood. In this study, Schizopygopsis younghusbandi (S. younghusbandi) larvae were exposed to Cu²⁺ at concentrations of 0. 5, 5, 50, and 500 μg/L for 7 or 14 days to evaluate its toxic effects on thyroid function and the antioxidant system. The results indicate that whole-body total thyroxine (T4) and triiodothyronine (T3) levels were significantly decreased following Cu²⁺ exposure. This decrease was accompanied by a marked increase in dio1 and dio2 gene expression and decreased expression of thyroid hormone synthesis genes (nis, tg, ttf1 and pax8) after exposure to Cu²⁺. Furthermore, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) and the content of lipid peroxidation were increased, while the content of glutathione (GSH) was decreased. In addition, the survival rates and body lengths of S. younghusbandi larvae were significantly reduced following 7- and 14-day Cu²⁺ exposure. The Integrated Assessment of Biomarker Response (IBR) analysis further revealed dose- and time-dependent effects of Cu²⁺ on the larvae. In conclusion, the findings demonstrate that Cu²⁺ exposure induced disruption of thyroid endocrine and antioxidant systems and caused developmental toxicity in S. younghusbandi larvae.

Carrots are exceptional sources of bioactive compounds with potential health benefits. This study investigated the relationship between the biodiversity of carrot cultivars (colour and size) and their potential chemopreventive properties. Four distinct carrot cultivars (orange, white, yellow, and purple) of normal and miniature sizes were comprehensively analysed for polyphenolic composition, bio-accessibility through in vitro simulated digestion, and in vitro antiproliferative activity against the HCT-116 colon cancer cell line. Our findings revealed that vegetable size influenced phytochemical composition more than vegetable colour, with mini purple carrots exhibiting exceptionally high polyphenolic concentrations and superior antiproliferative activity compared to orange, yellow, or white varieties. Notably, the bioaccessibility of bioactive compounds remained remarkably low across all samples, suggesting that these phytochemicals reach the colon in intact form, potentially enabling direct interaction with cancer cells. Interestingly, we found no direct correlation between total phenolic content and antiproliferative activity. In vitro cell cycle analysis revealed that mini purple carrot extracts induced S-phase arrest similar to the chemotherapeutic agent 5-FU, whereas other extracts caused G0/G1-phase arrest. The specific polyphenolic composition appears to be fundamentally important for bioactivity, with chlorogenic acid and diferulic acid-derivative isomer 2 potentially acting synergistically. These findings highlight the importance of carrot biodiversity in delivering functional foods with enhanced health-promoting properties, particularly for colorectal cancer prevention.