Antioxidants最新文献

Mitochondria are highly dynamic organelles that integrate metabolic regulation, signal transduction, and programmed cell death with their canonical role in adenosine triphosphate (ATP) production. Their ability to undergo continuous remodeling through the opposing processes of fusion and fission is essential for maintaining cellular homeostasis, preserving organelle quality control, and enabling adaptive responses to metabolic and oxidative stress. Among the core regulators of mitochondrial dynamics, the dynamin-related guanosine triphosphatase (GTPase) OPA1 plays a central role in inner membrane fusion, cristae architecture maintenance, bioenergetic efficiency, and the modulation of redox balance and apoptotic signaling. Accumulating evidence indicates that dysregulation of OPA1 expression or activity contributes to the initiation and progression of multiple malignancies, underscoring its importance in tumor cell survival, proliferation, metabolic adaptation, and resistance to stress. Here, we summarize current knowledge on OPA1 dysregulation in cancer and, based on preliminary, unpublished in silico analyses, we highlight the growing relevance of OPA1 as a therapeutic target, particularly through its GTPase domain and the still understudied Interface 7. Overall, these findings outline how integrated computational approaches could potentially guide the identification of novel OPA1 modulators, offering a conceptual framework that highlights OPA1 as a promising, yet still largely underexplored, target in oncology.

The main objective of this study was to preliminarily analyze the major flavonoid and phenolic acid components of the ethanolic extract of Gerbera delavayi Franch (E-GDF), and to evaluate its anti-inflammatory and antioxidant properties in lipopolysaccharide (LPS)-stimulated murine macrophage RAW264.7 cells and systemic inflammation mouse models. Results indicated that E-GDF was rich in flavonoids (16.35 ± 0.19 mg RT/g d.w. Plant Material) and polyphenolic compounds (36.15 ± 0.20 mg GAE/g d.w. Plant Material). LC-MS analysis of E-GDF revealed that its major flavonoid components included kaempferol glycosides, luteolin, and their glycosylated derivatives, while its phenolic acids were predominantly chlorogenic acid, caffeic acid, ferulic acid, and their corresponding glycosides. E-GDF exhibited good antioxidant activities, including the scavenging of DPPH, ABTS, ^•OH, and O₂^•- radicals. E-GDF treatment significantly inhibited the production of ROS and inflammatory mediators (NO, IL-6, TNF-α) in LPS-stimulated macrophages (RAW 264.7), while concurrently down-regulating the mRNA expression of COX-2, IL-1β, Casp1, and GSDMD-1. In addition, in vivo experiments revealed that E-GDF treatment effectively reduced the serum LPS, AST levels, as well as hepatic TNF-α, IL-6 levels in mice with LPS-induced acute liver injury. Furthermore, E-GDF significantly ameliorated LPS-induced liver pathological damage. These results provide a basis for G. delavayi as a potential antioxidant, anti-inflammatory, and hepatoprotective herbal medicine.

Osmotic stress affects ion transport and cell hydration, potentially disrupting redox homeostasis through altered proteostasis and mitochondrial metabolism. However, how immune hemocytes coordinate volume regulation with these stress-linked processes, particularly oxidative stress and antioxidant responses, remains unclear in crustaceans. This study integrated quantitative cytology, RNA sequencing, and network analysis to profile hemocyte volume plasticity in the euryhaline shrimp Penaeus monodon across a salinity gradient. Hemocytes were incubated for 24 h in hypoosmotic, isosmotic, and hyperosmotic media, with significant volume shifts observed while maintaining membrane integrity and morphology. The permeability of solutes (urea and sorbitol) suggested that volume adjustment is coupled with solute transport. Transcriptomic analyses identified key salinity-responsive pathways, including oxidative phosphorylation, MAPK signaling, ribosome biogenesis, and antioxidant defense mechanisms, underscoring the activation of redox-regulatory systems under osmotic stress. Weighted gene co-expression network analysis highlighted ribosomal proteins as central hubs in a salinity-responsive module, with qRT-PCR confirming the co-regulation of these hubs alongside representative osmoregulatory and antioxidant genes (AQP4, Na⁺/K⁺-ATPase, HSP70, CHOP, and antioxidant enzymes). These findings reveal how hemocyte volume dynamics are coupled to redox regulation, providing a mechanistic framework for understanding osmotic stress-redox coupling in crustacean immune cells.

Pulmonary fibrosis (PF) is a group of chronic progressive lung diseases characterized by irreversible remodeling of lung tissue structure, abnormal proliferation of fibroblasts, and excessive deposition of extracellular matrix (ECM), among which idiopathic pulmonary fibrosis (IPF) is the most typical subtype. Currently, the only two clinically approved therapeutic drugs (nintedanib and pirfenidone) can only partially slow disease progression without reversing fibrotic lesions, and are associated with varying degrees of adverse effects. Oxidative stress, defined as a pathological imbalance between systemic oxidant and antioxidant systems, has been substantiated by extensive research as a pivotal mechanism driving the pathogenesis and progression of pulmonary fibrosis. This review summarizes the regulatory mechanisms of oxidative stress in pulmonary fibrosis, with a focus on its critical role in inducing and promoting fibrosis through relevant target cells and signaling pathways. We also specifically highlight the latest progress and challenges in therapeutic strategies targeting oxidative stress, and discuss next-generation therapies, including the modulation of endogenous antioxidant pathways, supplementation of exogenous antioxidants, as well as nanomaterials, exosomes, and combination therapies. We hope this review will deepen the understanding of oxidative stress and pulmonary fibrosis, and provide new directions for improving the clinical efficacy of oxidative stress-targeted therapies.

Plant-based extracts are rich sources of phenolic compounds, which may act as skin antiaging mediators. Herein, Cistus albidus L. (Ca), Cistus ladanifer L. subsp. ladanifer (Cl) and Cistus salviifolius L. (Cs) were selected to test whether their phytochemical profile and bioactive potential align to target human skin aging. Hydroethanolic extracts (HEs) were prepared and characterized using infrared vibrational spectroscopy (FTIR-ATR) and liquid chromatography-mass spectrometry (LC-MS). Non-toxic concentrations were screened, and cytoprotective and antioxidant effects were studied in tert-butyl hydroperoxide-stimulated normal human dermal fibroblasts (NHDFs). Lipopolysaccharide-stimulated RAW 264.7 macrophages were used to assess anti-inflammatory activity, the Organization for Economic Co-operation and Development (OECD) Test Guideline No. 439 was used to assess irritant effects, and the anti-senescence potential was assessed in etoposide-stimulated NHDFs. A series of enzymatic inhibition assays was performed. All extracts comprised ellagic acid derivatives, as well as myricetin and quercetin derivatives in Cs and Ca. The HE of Cs was also markedly composed of ligstroside. At non-toxic concentrations, cytoprotective effects were observed in NHDFs. However, only Cs and Cl exhibited significant antioxidant activity in these cells (p < 0.001 and p < 0.0001, respectively). In addition to that, Cl demonstrated highly significant anti-inflammatory (p < 0.0001) and anti-senescence (p < 0.0001) effects. Cs and Cl showed a remarkable potential to inhibit elastase; in addition, Cs also showed anti-hyaluronidase and anti-tyrosinase activities. Meaningfully, Cs and Cl extracts did not exhibit skin irritant effects. The unveiled potential of Cl in skin aging offset highlights the need to elucidate the detailed mechanisms of action, paving the way for the development of skin anti-aging formulations.

Short-term hypothermic storage at 4 °C represents a promising non-freezing alternative for transporting bovine embryos and synchronizing assisted reproductive procedures. However, chilling induces oxidative stress, mitochondrial dysfunction, and apoptosis, which markedly impair post-preservation embryonic viability. Glutathione (GSH), a key intracellular antioxidant, may mitigate these damaging effects, yet its protective mechanisms during bovine blastocyst hypothermic preservation remain unclear. Here, we investigated the impact of exogenous GSH supplementation on the survival, hatching ability, cellular integrity, mitochondrial function, and developmental potential of bovine blastocysts preserved at 4 °C for seven days. Optimization experiments revealed that 4 mM GSH provided the highest post-chilling survival and hatching rates. Using DCFH-DA, TUNEL, and γ-H2AX staining, we demonstrated that 4 °C preservation significantly increased intracellular reactive oxygen species (ROS), DNA fragmentation, and apoptosis. GSH supplementation markedly alleviated oxidative injury, reduced apoptotic cell ratio, and decreased DNA double-strand breaks. MitoTracker and JC-1 staining indicated severe chilling-induced mitochondrial suppression, including decreased mitochondrial activity and membrane potential (ΔΨm), which were largely restored by GSH. Gene expression analyses further revealed that chilling downregulated antioxidant genes (SOD2, GPX1, TFAM, NRF2), pluripotency markers (POU5F1, NANOG), and IFNT, while upregulating apoptotic genes (BAX, CASP3). GSH effectively reversed these alterations and normalized the BAX/BCL2 ratio. Moreover, SOX2/CDX2 immunostaining, total cell number, and ICM/TE ratio confirmed improved embryonic structural integrity and developmental competence. Collectively, our findings demonstrate that exogenous GSH protects bovine blastocysts from chilling injury by suppressing ROS accumulation, stabilizing mitochondrial function, reducing apoptosis, and restoring developmental potential. This study provides a mechanistic foundation for improving 4 °C embryo storage strategies in bovine reproductive biotechnology.

Docosahexaenoic acid (DHA), an omega-3 fatty acid essential for human health, is highly prone to oxidation in nanoemulsions due to their large interfacial area and presence of transition metal ions. This study investigated macroalgal chelators for stabilizing DHA-rich nanoemulsions. Sequential enzymatic-alkaline extraction using Alcalase^® produced an extract with the strongest Fe²⁺-chelating activity (IC₅₀ = 1.22 mg/mL), protein content of 10.11 ± 0.15%, and total phenolics ≈ 17 µg GAE/mL. This extract was incorporated into nanoemulsions (5 wt% DHA oil, 1 wt% Tween^® 20) at 0.61, 1.22, and 2.44 mg/mL and compared with controls containing EDTA (0.025 mg/mL) or no antioxidant. Droplet size remained stable (D_3,2 ≈ 77-80 nm; D_4,3 ≈ 199-215 nm) and zeta potential averaged -17 to -19 mV, confirming physical stability. Confocal microscopy revealed concentration-dependent interfacial adsorption of extract components. During iron-accelerated storage, extract-treated nanoemulsions slowed hydroperoxide formation and delayed tocopherol depletion compared to the control, while reducing volatile oxidation markers such as 1-penten-3-ol by up to 40%. However, EDTA consistently provided superior protection against oxidation. These findings highlight the potential of macroalgal extracts as clean-label, natural chelators for mitigating metal-driven oxidation in DHA nanoemulsions, though synthetic chelators remain more effective under severe prooxidant conditions.

Tea production in Europe represents an emerging segment of the specialty tea market, but a structured comparative analysis remains unexplored. This study employs a standardized approach to systematically characterize hot brews from black and green teas across five European gardens. Antioxidant capacity, total polyphenolic content (TPC), total flavonoid content (TFC), and metabolomic profiling by ultra-high performance liquid chromatography-mass spectrometry were evaluated, and for the first time, sensory profiling of these teas was conducted. Green teas consistently exhibited higher TPC, TFC, and antioxidant capacity compared to black teas, confirming the influence of processing methods. Metabolomic analysis revealed variability in caffeine linked to geographical origin and propagation method (cuttings vs. seeds). Importantly, sensory evaluation suggested a negative correlation between high TPC and overall consumer appreciation. The two most highly appreciated teas often showed lower TPC. These reliable findings advance knowledge in European tea research, providing valuable data for growers to enhance cultivar selection and marketing strategies in alignment with consumer preferences.

The downregulation of Klotho in renal injury predicts the progression of chronic kidney disease (CKD). Klotho acts as an antagonist of the Wnt/β-catenin pathway, which is involved in the pathogenesis of proteinuria, glomerulosclerosis and tubulointerstitial fibrosis. We investigated whether losartan (L, angiotensin II type-1 receptor blocker) alone or combined with synthetic (tempol, T) or natural antioxidants (olive leaf extract, O) could alter Klotho/Wnt4/β-catenin signaling, thus reducing fibrosis and slowing the progression of focal segmental glomerulosclerosis (FSGS) in spontaneously hypertensive rats (SHR). The rats were divided into five groups. The control rats received a vehicle. The other groups received adriamycin (2 mg/kg, i.v., twice in a 3-week interval) for FSGS induction. Treatments with L, L+T and L+O (10, 10 + 100 and 10 + 80 mg/kg/day, respectively) were administered by gavage during six weeks. In the kidneys of model rats, Klotho and Wnt4 were downregulated, whereas β-catenin and fibronectin levels were increased compared with the control group. L+T did not alter Klotho, Wnt4 or fibronectin levels, while it further increased β-catenin. In contrast, L+O improved Klotho, and reduced β-catenin and fibronectin levels, although it increased PAI-1. The L+O combination reduced proteinuria more efficiently than L and decreased renal injury close to control levels. Although these findings indicate that combined treatment of losartan and olive leaf extract is promising in slowing the progression of the experimental FSGS, further clinical studies are needed to confirm its favorable outcomes and safety in CKD patients.

Major depressive disorder (MDD) is a leading cause of global morbidity and mortality. Although pharmacological treatments are widely used, their effects are often limited, and nearly half of patients show resistance to current antidepressants, including those unresponsive to all available therapies. These challenges highlight the need to better understand the neurobiological mechanisms driving MDD and to develop novel therapeutic strategies, especially those involving natural compounds with multitarget actions. Baicalin, a bioactive flavonoid from Scutellaria baicalensis, exhibits antioxidant, anti-inflammatory, and neuroprotective properties and has recently gained attention for its potential to improve cognitive deficits and mood disorders. In this study, we investigated baicalin's antidepressant potential and its underlying mechanisms across multiple experimental levels. We found that oral administration of baicalin produced antidepressant-like effects in both naïve mice and those subjected to chronic restraint stress (CRS). CRS impaired hippocampal long-term potentiation (LTP), whereas baicalin restored these synaptic deficits. Importantly, intra-dorsal hippocampal microinjection of the TrkB receptor antagonist ANA-12 abolished baicalin's antidepressant effects, indicating the involvement of BDNF-TrkB signaling. Baicalin also reduced reactive oxygen species (ROS)/H₂O₂ production in a BDNF-associated manner, demonstrating clear antioxidant activity. Molecular docking further suggested that baicalin binds more effectively to the TrkB receptor than ANA-12, supporting its capacity to activate TrkB-mediated signaling. By integrating in vivo, ex vivo, in vitro, and in silico approaches, our study shows that baicalin exerts robust antioxidant in vitro and antidepressant effects in vivo. These benefits are primarily mediated through activation of BDNF-TrkB signaling, leading to reduced ROS/H₂O₂ accumulation and alleviation of CRS-induced depression-like behaviors.