Search Results (3,684)

Background/Objectives: Oxidative stress is a major contributor to the pathogenesis of cardiovascular diseases, including hypertension, ischemic cardiomyopathy, and heart failure. MicroRNAs (miRNAs) have been extensively investigated in various contexts, and some of them have been identified to play a role in cardiovascular disease. This narrative review focuses on miR-103 and miR-155, two miRNAs implicated in the modulation of oxidative stress and cardiovascular remodeling. Methods: The following queries were used in PubMed since inception until May 2026: ((“miR-155” OR “microRNA-155” OR miR155) AND (“oxidative stress” OR ROS OR “reactive oxygen species”) AND (“cardiovascular disease” OR cardiovascular OR cardiac OR heart OR vascular)); ((“miR-103” OR “microRNA-103” OR miR103) AND (“oxidative stress” OR ROS OR “reactive oxygen species”) AND (“cardiovascular disease” OR cardiovascular OR cardiac OR heart OR vascular)). Results: A total of seven citations for miR-103 and 79 citations for miR-155 were identified. Reviews and papers about diseases other than those on cardiac/vascular involvement were excluded. miR-155 emerges as a potential regulator of inflammatory-redox signaling, whereas miR-103 appears more closely linked to cell fate and metabolic pathways. In both cases, available evidence supports a context-dependent role that challenges simplistic classification as pro- or antioxidant miRNAs. Conclusions: Available evidence suggests that both miR-103 and miR-155 are important regulators of oxidative stress-related pathways in cardiovascular disease. Nevertheless, the context-dependent effects observed across different cardiovascular disorders raise concerns regarding the safety of systemic miRNA modulation-based therapeutic strategies. Future studies should clarify the determinants of this context-dependent behavior and identify the specific conditions under which these miRNAs exert protective or harmful effects, which might pave the way for the development of miRNA-based therapeutic strategies targeting oxidative stress and cardiovascular remodeling. Full article

Bone remodeling is rhythmically regulated, yet the contribution of the circadian–melatonin axis to osteoporosis remains incompletely defined, in part because mechanistic findings obtained at high experimental concentrations are frequently extrapolated to physiological signaling. This narrative review examines that inference. PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched from inception to July 2026 for English-language studies of melatonin, circadian clock genes, and bone; molecular, preclinical, epidemiological, and clinical evidence was appraised with attention to receptor dependence, exposure concentration, and study architecture. In osteoblast-lineage cells, melatonin promotes osteogenic differentiation through MT2-linked Wnt/β-catenin and MEK1/2–MEK5 signaling, post-translational stabilization of SP7, and modulation of the OPG/RANKL axis. By contrast, direct antiosteoclastic and antioxidant effects are usually reported at micromolar concentrations, four to six orders of magnitude above nocturnal plasma levels, and are increasingly attributable to receptor-independent chemistry converging on the ROS–KEAP1–NRF2 node shared with structurally unrelated antioxidant compounds. This exposure mismatch suggests that conventional oral doses engage receptor-mediated osteoblast pathways rather than reproduce high-dose antiresorptive effects; sustained exposure at or above 1 µM is not attainable by conventional oral administration, and the chronic safety of the doses that would be required has not been characterized. In humans, bone resorption has an intrinsic circadian rhythm, and night-shift work is associated with adverse skeletal outcomes, although causality remains unresolved. The five available randomized trials are small and heterogeneous; none was powered for fracture prevention, and none compared administration times for a skeletal endpoint. Melatonin therefore cannot currently be recommended for the treatment of osteoporosis. Human bone and marrow pharmacokinetics, receptor-specific in vivo dose–response experiments, and adequately powered monotherapy trials in established primary osteoporosis are the studies that would change this assessment. Full article

A 56-day feeding trial was designed to investigate the effects of alginate oligosaccharide (AOS) on the growth, immune response, antioxidant activity and apoptosis pathways of largemouth bass (Micropterus salmoides). We formulated six isonitrogenous and isoenergetic diets with different concentrations of AOS (0% (control), 0.05%, 0.1%, 0.15%, 0.2% and 0.25%). The results showed that the WGR of the AOS0.15–0.2 groups were markedly increased, and the FBW and SGR of the AOS0.1–0.2 groups were also markedly boosted. In addition, no significant differences were observed in FCR, SR and FI in the treatment groups. According to SGR and WG second-degree polynomial regression analysis, the optimum AOS addition level for juvenile largemouth bass was 0.14–0.15%. On the other hand, no notable differences were observed in crude protein, moisture, crude lipid or crude ash content between groups, and no notable differences were also observed in the levels of AST and ALT in the plasma between all groups. Additionally, ALP activities were considerably higher in the AOS0.15–0.25 groups. In terms of intestinal digestion and absorption function, AOS0.1 group and AOS0.15 group significantly increased the intestinal amylase and lipase activities, and A0S0.1–0.2 groups significantly increased the intestinal trypsin activities, while proper dietary supplementation with AOS significantly improved villus muscular thickness, villus height, and villus width. Furthermore, proper dietary supplementation with AOS significantly up-regulated the mRNA levels of occ, clau, C6A6, C7A5, C7A8B, C6A14 and pept1 in the intestine. No significant differences were observed in the mRNA levels of C7A6, C7A1A and C7A10A between all groups. With respect to the antioxidant and immune functions of the intestine, the analysis revealed no remarkable differences between the groups concerning SOD, GPX activity or T-AOC content in the intestine. However, a significant increase in CAT activity of the intestine was observed in the AOS0.05–0.15 groups, and MDA levels were lower in all AOS-added groups. Apart from the above, AOS0.15–0.25 groups significantly reduced intestinal TNF-α concentration. No notable differences were observed in the intestinal contents of TGF-β, IL-10 and IL-6 between all groups. Additionally, proper dietary supplementation with AOS could improve antioxidant effects and inhibit inflammation by regulating the gene expressions of the related-Nrf2 and NF-κB signaling pathway, including nrf2, keap1, Mn-sod, gpx, nf-κb, il-10 and tgf-β. There was no significant difference in the mRNA levels of cat, fox, il-8 and tnf-α. With respect to cell apoptosis in the intestine, TUNEL assay results showed that green positive cells were significantly lower in the AOS0.05–0.2 groups than the AOS0 group. Additionally, proper dietary supplementation with AOS could inhibit cell apoptosis by regulating the mRNA levels of bxl-xl, caspase 3, caspase 8, caspase 9 and bcl-2. However, there was no significant effect on the level of bax mRNA in any of the treatment groups. In summary, proper dietary supplementation with AOS exerted positive effects on growth, intestinal digestion and absorption function, immune antioxidant responses, and apoptosis pathways to a certain extent. Full article

Brassinosteroids (BRs) are essential steroidal phytohormones that regulate plant growth, development, and responses to environmental stresses. Recent studies have demonstrated the important roles of BRs in enhancing plant tolerance to abiotic stresses, including drought, salinity, temperature extremes, heavy metal toxicity, and oxidative stress, as well as biotic stresses caused by pathogens and herbivores. This review summarizes current advances in BR biosynthesis, metabolism, transport, and signaling pathways, focusing on key components that mediate stress adaptation. We discuss the physiological and molecular mechanisms through which BRs improve stress tolerance, including regulation of antioxidant defense, ion homeostasis, osmotic adjustment, and stress-responsive gene expression. Particular attention is given to the extensive cross talk between BRs and other phytohormones, such as abscisic acid, jasmonic acid, salicylic acid, ethylene, auxin, and gibberellins, which enables plants to balance growth and defense under adverse conditions. Furthermore, we highlighted the potential applications of BRs in crop improvement through exogenous treatments, genetic engineering, and genome-editing approaches. However, the effectiveness of BR-based strategies is highly dependent on crop species, developmental stage, stress type, BR concentration, application method, and environmental conditions. In addition, excessive BR accumulation or application may result in undesirable growth responses, and further multi-location field validation is required before widespread agricultural implementation. Finally, we discuss emerging research trends, current knowledge gaps, and future perspectives for exploring BR signaling to develop climate-resilient crops. Overall, BRs represent promising targets for improving crop stress resilience; however, optimizing BR-mediated strategies and validating their long-term performance under diverse field conditions will be essential for their successful application in sustainable agriculture. Full article

The aryl hydrocarbon receptor (AhR) is highly expressed in keratinocytes and functions as an environmental sensor regulating xenobiotic metabolism, epidermal differentiation, and inflammatory responses. Particulate matter (PM), a major environmental pollutant containing reactive oxygen species (ROS), transition metals, and polycyclic aromatic hydrocarbons (PAHs), induces oxidative stress and inflammation, leading to skin barrier dysfunction. Transition metals generate ROS via Fenton-type reactions, whereas PAHs undergo AhR-mediated metabolism that further amplifies oxidative stress. Excessive ROS promotes inflammatory cytokine expression and disrupts barrier-related protein expression. In response, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway induces antioxidant enzymes, including heme oxygenase-1 (HO-1), to counteract oxidative damage. However, sustained PM exposure may overwhelm these defense mechanisms, resulting in impaired cellular homeostasis. Although the roles of AhR and Nrf2 have been extensively investigated individually, their coordinated regulation in PM-induced skin injury remains underexplored. This review summarizes current evidence on the functional interplay between AhR and Nrf2 and discusses how coordinated activation of these pathways integrates xenobiotic metabolism, antioxidant defense, and barrier-associated functions. Overall, the available evidence supports a dual-pathway framework for maintaining epidermal homeostasis under PM-induced environmental stress. Full article

Myocardial infarction (MI) is characterized by sudden cardiomyocyte death due to impaired blood supply and remains a leading cause of mortality despite advances in management. Aloe vera, a plant rich in over 75 bioactive compounds, including vitamins, minerals, polysaccharides, and anthraquinones, has been widely used in traditional medicine and modern healthcare. Increasing evidence supports its cardioprotective potential through multiple mechanisms. Aloe vera and its derivatives have demonstrated antioxidative, anti-apoptotic, anti-inflammatory, antimicrobial, immunomodulatory, and vasodilatory effects relevant to MI pathophysiology. Compounds such as aloe-emodin, emodin, aloin, barbaloin, and selenium-enriched polysaccharides have been shown to modulate pathways including Nrf2/HO-1, TGF-β/SMAD, ERK, ferroptosis inhibition, ionic pump activity, and microRNA regulation. These molecular effects translate into reductions in oxidative damage, apoptotic signaling, inflammatory cytokine release, calcium imbalance, and creatine kinase/LDH leakage, while preserving myocardial structure and function in preclinical models. Collectively, preclinical studies suggest the potential cardioprotective effects of Aloe vera-derived preparations and compounds; however, robust clinical evidence in myocardial infarction is lacking, and their therapeutic relevance remains uncertain. Full article

Background/Objectives: Alzheimer’s disease (AD), one of the most prevalent neurodegenerative disorders in the elderly, is characterized by progressive cognitive loss, amyloid-β (Aβ) plaque deposition, and neurofibrillary tangle formation. Cerebral hypoxia has been reported as a complex modulator of AD pathology, with hypoxia-inducible factor-1 (HIF-1) emerging as a central molecular marker associated with neurodegeneration. This review aims to comprehensively report the roles of HIF-1 signaling in AD pathogenesis, emphasizing its neuroprotective and neurotoxic mechanisms along with demonstrating the therapeutic potential and challenges of translating this pathway for AD therapeutics. Methods: A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, Embase, and Google Scholar databases for articles published between January 2000 and December 2025 on the context. Results: Under mild hypoxic conditions, HIF-1 activation enhances neuronal survival through upregulation of glucose transporters, glycolytic enzymes, angiogenic factors, erythropoietin, and antioxidant defense mechanisms. In contrast, chronic hypoxia modulates HIF-1 into a pathogenic marker through transcriptional activation of β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) and γ-secretase, facilitating amyloidogenic APP processing, along with tau hyperphosphorylation. Moreover, HIF-1 exacerbates neuroinflammation through microglial activation and pro-inflammatory cytokine release. The cell-type-specific expression patterns of HIF-1α and the temporal dynamics of its activation regulate whether the pathway exerts neuroprotective or neurodegenerative effects. Conclusions: This review discusses the current understanding of HIF-1-mediated mechanistic insights in AD pathology and impacts of existing HIF-1 modulators on AD pathology, along with the therapeutic implications of targeting this pathway for translational application in AD therapeutics. Full article

Bone remodeling is a dynamic and tightly regulated process that maintains skeletal homeostasis through a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Disruption of this balance contributes to the development of bone-related disorders, particularly osteopenia, osteoporosis and osteogenesis imperfecta, which weaken, deform, or cause fractures. Increasing evidence indicates that oxidative stress and chronic inflammation impair osteoblast functions while promoting osteoclast differentiation and activity. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with cytoprotective, antioxidant, and anti-inflammatory properties. Besides its primary role in cellular defense against oxidative stress and inflammatory damage, HO-1 has been shown to be involved in both osteoblast differentiation and osteoclastogenesis. Through its interaction with key regulatory systems, including the receptor activator of nuclear factor κB (RANK)–receptor activator of nuclear factor κB ligand (RANKL)–osteoprotegerin axis and redox-sensitive signaling pathways, HO-1 contributes to maintenance of optimal bone remodeling. The enzyme also plays a role in modulating metabolic processes in the bone. This review highlights the role of HO-1 in bone formation, bone resorption, and related pathophysiologic conditions. Furthermore, the therapeutic potential of HO-1 as a target for bone disorders is discussed. Full article

Background: Drought tolerance in wheat is a complex trait controlled by multiple regulatory networks, among which calcium-dependent protein kinases (CDPKs) act as important components linking stress perception with downstream cellular responses. However, the functional contribution of individual CDPK members to drought adaptation in wheat remains largely unclear. This study aimed to identify and functionally characterize drought-responsive CDPK genes associated with differential drought responses in wheat. Methods: Two wheat lines derived from the same breeding background exhibiting contrasting drought adaption, 23B1 and 23B39, were subjected to PEG6000-induced osmotic stress. Growth traits, osmotic adjustment-related metabolites, membrane damage indicators, and antioxidant enzyme activity were evaluated. Transcriptomic analysis was performed at early drought-response stages, followed by differential expression analysis, functional enrichment, CDPK family screening, and qRT-PCR validation. The role of TaCDPK22-5A was further investigated using barley stripe mosaic virus (BSMV)-mediated virus-induced gene silencing (VIGS). Results: The drought-responsive line 23B1 maintained stronger growth, accumulated higher levels of proline and soluble sugars, exhibited enhanced peroxidase activity, and showed reduced membrane lipid peroxidation compared with 23B39. Transcriptome analysis revealed extensive transcriptional reprogramming under drought stress, with differentially expressed genes mainly associated with metabolic adjustment, transport regulation, secondary metabolism, and stress-responsive pathways. Among the identified CDPK members, TaCDPK22-5A showed a strong drought-responsive expression pattern in the line exhibiting stronger drought tolerance (23B1). Virus-induced gene silencing of TaCDPK22-5A significantly impaired drought tolerance, resulting in reduced growth, biomass accumulation, and chlorophyll retention under drought conditions. Conclusions: These findings demonstrate that TaCDPK22-5A contributes positively to drought adaptation in wheat and highlight CDPK-mediated calcium signaling as an important regulatory component of drought responses. The identified gene provides a potential target for improving drought resilience in wheat breeding. Full article

Glutathione is an abundant intracellular low-molecular-weight thiol that contributes importantly to cellular redox homeostasis. Besides its well-established role in the antioxidant defense of the cell, glutathione regulates mitochondrial function, metabolism of toxicants, protein thiol oxidation/reduction, redox signaling, and immunity. Disturbances in glutathione metabolism have been shown to play a role in various diseases; however, it has become clear that changes in glutathione metabolism are a part of a complex, multifactorial process. In this review, we summarize current knowledge of the molecular mechanisms governing glutathione synthesis, recycling, compartmentalization, and biological functions, with particular emphasis on redox signaling, the nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) pathway, and reversible protein S-glutathionylation. We further examine how disturbances in glutathione homeostasis interact with mitochondrial dysfunction, chronic inflammation, metabolic stress, and impaired cellular signaling in Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, multiple sclerosis, Wilson’s disease, type 2 diabetes, and nonalcoholic fatty liver disease. We also evaluate current translational interventions targeting restoration of glutathione balance through glutathione supplementation, precursor supplementation, pharmacological modulation of endogenous antioxidant mechanisms, dietary interventions, and changes in lifestyle. Despite the fact that many interventions have been promising at the mechanistic and experimental level, there are still insufficient clinical data because of the problems associated with glutathione availability, tissue specificity, disease variability, and a lack of sufficiently powered clinical trials. The conclusion of this review is that glutathione should not be viewed as a universal therapeutic target; instead, glutathione should be perceived as an important factor contributing to cellular resilience and able to help other disease-specific interventions. Future progress in glutathione-based interventions will likely depend on integrating redox biomarkers, patient stratification, and precision medicine strategies to identify individuals most likely to benefit from targeted modulation of glutathione homeostasis. Full article

Cadmium (Cd) is a highly toxic non-essential heavy metal that severely impairs plant growth, compromises crop yield and quality, and threatens food safety and human health. Jasmonic acid (JA) and salicylic acid (SA) are well-characterized endogenous phytohormones that serve as central regulators in modulating plant adaptive responses to Cd stress. This review comprehensively synthesizes current knowledge on the involvement of JA and SA in regulating Cd accumulation and tolerance in plants, including their Cd-induced biosynthetic dynamics and signaling transduction pathways, as well as their functions in restricting Cd uptake and translocation, modulating chelation and sequestration, reinforcing antioxidant defense systems and protecting photosynthetic apparatus. Moreover, we analyze the antagonistic and synergistic crosstalk between JA and SA, and discuss how this interplay shapes Cd resilience in plants. Finally, the application potential of JA and SA in developing Cd-safe crops and phytoremediation in Cd-contaminated farmland is explored. This review provides a systematic analysis of the regulatory roles of JA and SA in plant responses to Cd stress, along with an in-depth discussion of their crosstalk. These insights contribute to the rational development of hormone-based breeding strategies for Cd-safe crops and the optimization of agronomic management practices. Full article

Metabolic syndrome (MetS) is a clinical condition defined by the coexistence of interconnected cardiometabolic risk factors, including central obesity, dyslipidemia, elevated blood pressure, and impaired glucose regulation, which collectively increase the risk of type 2 diabetes mellitus and cardiovascular disease. Beyond these clinical diagnostic features, MetS is characterized by complex pathophysiological alterations involving systemic dysregulation of metabolic signaling across adipose tissue, skeletal muscle, liver, vascular endothelium, and the immune system. Key molecular alterations include impaired insulin receptor substrate (IRS)–Akt signaling, chronic nuclear factor kappa B (NF-κB) activation, mitochondrial dysfunction, and oxidative stress. Physical exercise is recognized as a pleiotropic biomedical intervention capable of restoring metabolic homeostasis through coordinated modulation of intracellular signaling pathways and inter-organ communication. Exercise activates AMP-activated protein kinase (AMPK), enhances peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis, and stimulates nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent antioxidant responses. These adaptations improve glucose uptake, enhance fatty acid oxidation, and reduce ectopic lipid accumulation across metabolically active tissues. At the systemic level, skeletal muscle functions as an endocrine organ by releasing myokines such as irisin, interleukin-6 (IL-6), and fibroblast growth factor 21 (FGF21), which contribute to metabolic regulation across the liver, adipose tissue, and vasculature. These exercise-induced signals promote immune modulation, reduce pro-inflammatory cytokine production, and improve endothelial function. Different exercise modalities including aerobic, resistance, and high-intensity interval training (HIIT) activate both common and modality-specific molecular pathways, supporting individualized exercise strategies. Collectively, exercise targets the multi-organ pathophysiology of MetS and provides a mechanistic foundation for precision exercise medicine in cardiometabolic disease management. Full article

Lutein is a dietary xanthophyll carotenoid valued for its antioxidant properties that has been shown to benefit liver health and reduce hepatic lipid accumulation; however, this lipid-lowering effect cannot be fully attributed to its antioxidant activity, and the underlying mechanism remains poorly understood. Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive hepatic lipid accumulation, oxidative stress, and limited therapeutic options. Transcription factor EB (TFEB) coordinates the autophagy–lysosomal pathways involved in cellular lipid clearance, including lipophagy and lysosomal exocytosis, and is sensitive to the cellular redox state; however, whether the antioxidant lutein modulates TFEB-regulated lipid homeostasis remains unclear. HepG2 cells were exposed to free fatty acids (FFAs) to induce intracellular lipid accumulation and co-treated with lutein. TFEB localization and the expression of TFEB-related genes were assessed by immunofluorescence and qPCR, respectively. Immunofluorescence was also used to evaluate lipid droplet accumulation, LC3 content, and LAMP1 localization. Lipid droplet ultrastructure was analyzed by transmission electron microscopy, and extracellular triglyceride levels were measured as a functional readout of lipid extrusion. Lutein attenuated lipid droplet accumulation in FFA-treated cells, increased nuclear TFEB immunoreactivity, upregulated LC3 mRNA expression, and enhanced LC3 colocalization with lipid droplets. Chloroquine abolished the lipid-lowering effect of lutein, supporting an autophagy-dependent mechanism. In addition, lutein increased the abundance of LAMP1-positive compartments, while ultrastructural analysis and elevated extracellular triglyceride levels suggested enhanced lipid extrusion. These findings position the antioxidant lutein as a candidate natural compound whose lipid-lowering action is associated with TFEB nuclear translocation/activation and with the autophagy–lysosomal pathway, warranting further investigation in MASLD. Full article

This study aimed to explore the protective mechanism of silybin against heat stress-induced liver injury in Peking ducks as a result of oxidative stress, inflammation, and lipid metabolism. One hundred and ninety-five 1-day-old healthy male Peking ducks with similar body weights were randomly divided into a control group, a heat-stress group, and three intervention groups treated with 400, 800, and 1600 mg/kg silybin under heat-stress from 21 d to 35 d for two weeks. The function indices, oxidative stress, inflammatory factor levels, histopathological changes and non-targeted lipidomic profiling in liver as well as growth performance were evaluated. Results showed that silybin supplementation partially alleviated the heat-stress-induced decreases in average daily feed intake and body weight gain (p > 0.05). Silybin supplementation at 400 and 800 mg/kg significantly reduced the heat-stress-induced increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (γ-GGT) (p < 0.05), whereas the effect of 1600 mg/kg silybin was not significant. Albumin (ALB) and globulin (GLB) levels were mainly improved in the 800 mg/kg group, and GLB was also increased in the 400 mg/kg group (p < 0.05). Silybin supplementation significantly improved hepatic antioxidant capacity, especially in the 400 and 800 mg/kg groups, as indicated by increased superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC), and decreased malondialdehyde (MDA) and reactive oxygen species (ROS) levels (p < 0.05). In addition, the 400 and 800 mg/kg groups showed more significant reductions in the pro-inflammatory factors IL-6 and TNF-α, while IL-10 was increased in silybin-supplemented groups (p < 0.05). Lipid metabolism disorders were improved through regulation of the sphingolipid and glycerophospholipid metabolism pathways, while it alleviated heat stress damage by reducing the expression of heat shock proteins. In conclusion, silybin holds promise as an effective feed additive to alleviate heat stress in poultry. This study provides a theoretical basis and practical approach for improving the health and productive performance of Peking ducks under heat-stress conditions. Full article

Fruit ripening is accompanied by extensive reprogramming of secondary metabolism, which determines the antioxidant value of medicine-food homologous fruits. Ziziphus jujuba Mill. cv. ‘Junzao’ (Junzao) is a high-quality cultivar rich in bioactive compounds, yet its stage-dependent metabolite accumulation and the corresponding antioxidant capacity remain poorly resolved. In this study, widely targeted metabolomics was combined with the quantification of total phenolic (TPC), total flavonoid (TFC), and total triterpenoid (TTC) contents and with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) radical-scavenging assays to profile Junzao fruits at five developmental stages. A total of 2388 secondary metabolites were identified, with flavonoids and terpenoids representing the major classes. TPC and TFC were highest at the immature YG (young-fruit) stage, whereas TTC peaked at the BS (white-ripe) stage; all three decreased during subsequent ripening, consistent with the stronger DPPH and ABTS radical-scavenging activities observed in early-stage fruits. Multivariate analyses revealed distinct metabolic profiles among developmental stages, and 2111 differentially accumulated metabolites (DAMs) were identified. K-means clustering resolved nine temporal accumulation patterns, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated dynamic regulation of flavonoid biosynthesis, phenylpropanoid metabolism, and triterpenoid-related pathways. Spearman correlation analyses further identified ten metabolites, comprising six flavonoids, three triterpenes, and one phenolic acid, that were strongly associated with antioxidant capacity (|r| ≥ 0.5, p < 0.05), highlighting their potential as biomarkers for quality evaluation. Overall, immature Junzao fruits exhibited superior antioxidant capacity, supporting their promise as functional-food ingredients and providing a basis for stage-specific harvesting and utilization. Full article