Search Results (1,369)

Oxidative stress, arising from an imbalance between reactive oxygen species (ROS) and antioxidant defenses, is a shared pathogenic mechanism underlying numerous chronic diseases in humans and, increasingly, in companion animals that consume structurally similar processed diets. This narrative review synthesizes current evidence on dietary and feed-derived sources of ROS, spanning intrinsic pro-oxidant systems in unprocessed foods (lipid hydroperoxides, heme iron, and polyphenol autoxidation) and heat processing-generated toxicants (advanced glycation end products, acrylamide, heterocyclic aromatic amines, and lipid oxidation products), and examines the molecular mechanisms that link these compounds to organ-specific and systemic disease, including receptor-mediated signaling, cytochrome P450 activation, mitochondrial dysfunction, and antioxidant depletion. Comparative analysis across humans, dogs, and cats reveals parallel disease burdens in metabolic syndrome, chronic kidney disease, inflammatory bowel disease, and cancer, alongside instructive species-specific divergences in atherosclerosis and neurodegenerative disease driven by differences in lipoprotein metabolism and toxicokinetics. The review further reassesses canonical dietary antioxidants, including polyphenols and omega-3 polyunsaturated fatty acids, as context-dependent redox modulators capable of both cytoprotective and pro-oxidant activity. Collectively, these findings position dietary and feed processing as an under-recognized, modifiable contributor to chronic disease across species. In this context, companion animals emerge as valuable naturalistic translational models for studying diet-induced oxidative pathology. Priority research needs include standardized dose–response and biomarker frameworks, characterization of gut microbiome-mediated effects, and assessment of combinatorial pro-oxidant exposures. Full article

The “unexplained failure” of rotator cuff repair is multifactorial, but its structural endpoint is anatomically consistent, i.e., the failure of the tendon-to-bone interface (enthesis) to heal. The native enthesis is a four-zone fibrocartilaginous gradient that does not regenerate but heals as a mechanically inferior fibrovascular scar, so the outcome of repair hinges on the interface’s healing capacity—which chronological age predicts poorly. This review organizes the aging biology governing bone-to-tendon healing capacity into eight domains: progenitor competence, cellular senescence and the SASP, immune aging, extracellular-matrix and collagen aging via advanced glycation end-product cross-linking, footprint angiogenesis, morphogen signaling, mechanotransduction, and bone quality. We then precisely define the DNA-methylation epigenetic clock—a continuous value produced by weighted CpG methylation, with defined units, reproducibility, and effect sizes—and propose it as a candidate quantitative readout of these domains; whether or not it truly integrates them into a single biologically meaningful measure at the enthesis is a hypothesis of this review, not an established mechanism. In 1087 twins, epigenetic age acceleration predicted fracture and osteoporosis risk, with hazard ratios of 1.29–3.17 per standard deviation; moreover, aging is tissue-specific, so the enthesis may run ahead of blood. Critically, the clock provides a single axis on which current regenerative-medicine strategies—stem cells, exosomes, immunomodulation, biomimetic gradient scaffolds, growth factors, senolytics, and epigenetic reprogramming—can be systematically categorized by how far each shifts biological age toward a healing-competent state; partial reprogramming, which rewinds the clock directly, shows that the clock is simultaneously the readout and the therapeutic target. We integrate this into a “hidden biological age of bone-to-tendon healing”, explicitly stating that this remains an unvalidated hypothesis requiring prospective validation. Full article

Introduction: Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus (DM). Among the established risk factors for DR, “metabolic memory” plays a key role. Its development is mainly driven by advanced glycation end-products (AGEs), some of which possess characteristic fluorescent properties. Aims: To examine the relationship between skin AGEs, noninvasively assessed through skin autofluorescence (SAF), and the presence and severity of DR in subjects with long-standing type 1 DM (T1DM) and no history of atherosclerotic cardiovascular disease. Methods: 81 subjects with T1DM and 45 healthy controls were included. All individuals underwent SAF measurements and fundus photographs were taken in subjects with T1DM. Associations between SAF, its change over time and the presence and severity of DR were analyzed. Results: A significant positive correlation was found between SAF and the severity of DR. Only SAF and renal parameters showed a significant positive association with the presence of sight-threatening DR (STDR). There was a statistically significant increase in SAF levels over 3 years in STDR. Conclusions: SAF, but not HbA1c or diabetes duration, was associated with the severity of DR. SAF may therefore represent a promising, rapid, and non-invasive biomarker for identifying individuals at increased risk of STDR. Full article

Diabetes mellitus and periodontitis are bidirectionally associated chronic disorders linked through metabolic dysregulation, host inflammation, microbial dysbiosis, and impaired tissue remodeling. This review summarizes clinical, molecular, cellular, genomic, epigenomic, transcriptomic, and microbial evidence concerning the mechanisms underlying this relationship and their potential translational relevance. Chronic hyperglycemia is associated with advanced glycation end product signaling through the receptor for advanced glycation end products, mitogen-activated protein kinase/nuclear factor-κB activation, reactive oxygen species production, oxidative stress, and NLR family pyrin domain-containing 3 inflammasome activation, which may contribute to enhanced cytokine responses and periodontal tissue injury. Diabetes is also associated with altered neutrophil and macrophage function, increased T helper 17/interleukin-17 signaling, and an elevated receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio, thereby favoring osteoclastogenesis and alveolar bone loss. Conversely, periodontal inflammation and microbial products may contribute to systemic low-grade inflammation, insulin resistance, and metabolic dysregulation. Multi-omics studies have identified shared susceptibility loci, regulatory networks, and disease-associated cell states, although their causal and clinical significance remains incompletely defined. These findings suggest potential roles for integrated medical–dental care, glycemic screening in dental settings, periodontal inflammation control, host-modulatory therapies, and regenerative biomaterials. Further longitudinal and experimental studies are needed to determine their clinical applicability. Full article

Advanced glycation end products arise during thermal processing and endogenous metabolism, contributing to oxidative stress, inflammation, and the progression of chronic diseases. Dietary polyphenols have emerged as promising advanced glycation end product (AGE) inhibitors through antioxidant activity, carbonyl trapping, metal chelation, and modulation of inflammatory pathways. This review summarizes current evidence on the effects of polyphenols in food systems and highlights how different polyphenol subclasses vary in their antiglycation potential depending on chemical structure, food matrix, and cooking conditions. Although experimental studies consistently demonstrate inhibitory effects, the translation to humans remains limited by low bioavailability, metabolic transformation, and heterogeneous analytical methods. Standardized AGE measurements are needed to improve mechanistic insight, and evaluations of dose–response relationships are needed to clarify their relevance in real-world diets. Future research should prioritize long-term human studies and practical culinary strategies to determine whether polyphenol-rich foods can meaningfully reduce dietary AGE exposure and support chronic disease prevention. Full article

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, pancreatic β-cell dysfunction, and dysregulated glucose and lipid metabolism. Sustained hyperglycemia and hyperlipidemia promote excessive reactive oxygen species (ROS) production, antioxidant defense depletion, and chronic low-grade inflammation, thereby aggravating insulin signaling impairment, β-cell injury, and diabetes-related complications. Although current glucose-lowering therapies have improved glycemic control, weight management, and cardiorenal outcomes, oxidative stress and inflammation remain incompletely addressed in many individuals with T2DM. Curcumin, a natural polyphenol derived from Curcuma longa L., exhibits antioxidant, anti-inflammatory, lipid-regulating, insulin-sensitizing, and tissue-protective activities. Evidence suggests that curcumin may alleviate T2DM-associated oxidative stress by suppressing ROS generation, reducing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, modulating the advanced glycation end-product/receptor for advanced glycation end-product (AGE/RAGE) axis, activating nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling, preserving mitochondrial homeostasis, and protecting β-cells. It may also inhibit nuclear factor-κB (NF-κB) and mitogen-activated protein kinase/c-Jun N-terminal kinase (MAPK/JNK) signaling, decrease pro-inflammatory cytokines and C-reactive protein (CRP), improve metabolic tissue inflammation, and attenuate gut-derived inflammation by regulating gut microbiota and intestinal barrier function. However, current clinical evidence mainly supports modest improvements in metabolic, inflammatory, oxidative stress-related, and selected complication-related biomarkers rather than definitive disease-modifying outcomes. Moreover, formulation heterogeneity, low bioavailability, limited pharmacokinetic reporting, and insufficient long-term endpoint data remain major translational barriers. This review summarizes the molecular mechanisms, clinical evidence, formulation-dependent interpretation, safety considerations, and translational limitations of curcumin as a candidate adjunctive intervention for T2DM, rather than as a replacement for evidence-based antidiabetic therapy. Full article

Background/Objectives: Methylglyoxal-derived hydroimidazolone-1 (MG-H1), an advanced glycation end product, has implications in the pathogenesis of diabetic kidney disease (DKD). Although liquid chromatography–mass spectrometry is the current gold standard for quantifying MG-H1, its overall complexity limits its utility. We developed an ELISA to measure MG-H1 using a specific monoclonal antibody. Methods: Competitive ELISA was used to quantify total, high-molecular-weight (HMW), and low-molecular-weight (LMW) MG-H1 in serum. The assay’s specificity was validated against structurally related compounds. Spike-and-recovery experiments were conducted to assess accuracy and precision. Serum samples from healthy controls, diabetic patients without kidney disease, and patients with DKD were analyzed (n = 10, 23, and 19, respectively). MG-H1’s correlation with renal biomarkers and diagnostic performance was assessed using receiver operating characteristic analyses. Results: The ELISA exhibited preferential reactivity toward MG-H1 compared with structurally related compounds. Spike-and-recovery experiments resulted in recovery rates ranging 108–119%. MG-H1 levels were increased in patients with DKD, although the magnitude of the changes varied among the MG-H1 forms. All MG-H1 forms correlated positively with serum creatinine and blood urea nitrogen, and negatively with estimated glomerular filtration rate. No significant correlations were observed with glycoalbumin, and only a modest association was observed between LMW MG-H1 and HbA1c. Exploratory ROC analyses suggested that all MG-H1 forms could discriminate DKD from DM, with total and HMW MG-H1 showing performance comparable to that of conventional renal function markers. Conclusions: This competitive ELISA enables high-throughput quantification of MG-H1 in serum and demonstrates analytical feasibility; further multicenter validation is required before clinical implementation. Full article

In modern societies, the renewed concept of food as medicine coexists with unprecedented consumption of highly processed foods, food additives, environmental xenobiotics, and pharmacological agents, contributing to the increasing prevalence of metabolic and degenerative diseases and accelerated aging. Although modern pharmacotherapies have transformed disease management, long-term drug exposure introduces additional metabolic burdens, off-target effects, and cumulative toxicities that are profoundly influenced by nutritional status. Collectively, dietary constituents, environmental chemicals, endogenous metabolic by-products, and therapeutic agents constitute a complex exposome that requires continuous recognition, utilization, detoxification, and clearance. Within this context, the liver sinusoidal clearance system (LSCS) emerges as a central regulator of systemic homeostasis. We propose a conceptual framework in which circulating molecules are classified as self (S), modified self (M), and foreign (F) molecules according to their physiological handling by the LSCS. Through coordinated hepatic utilization of S molecules and selective clearance of M and F molecules, fenestrated liver sinusoidal endothelial cells (LSECs) maintain metabolic homeostasis, immune tolerance, and physiological pharmacokinetics. Conversely, chronic dietary overload, poor dietary quality, food processing, and sustained exposure to pro-inflammatory and oxidative dietary and environmental molecules initiate chronic low-grade inflammation, which promotes LSEC capillarization, impairs hepatic clearance, increases the modification of S molecules into M molecules and establishes a feed-forward cycle that further amplifies chronic inflammation and metabolic dysfunction. Finally, we discuss recent advances in the programmable modulation of the LSCS, including its transient suppression to prolong therapeutic exposure and its activation to enhance the clearance of metabolically harmful M and F molecules through coordinated upregulation of the endoglin–stabilin-2–FcγRIIb axis and the LSEC markers Oit3 and Dnase1L3. We highlight dual-function supramolecular nanofiber platforms that enable bidirectional regulation of the LSCS through nanofiber complexes with therapeutic proteins, thereby expanding their therapeutic potential and enhancing efficacy in the treatment of metabolic, inflammatory, and age-related diseases. Full article

Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article

While Alzheimer’s disease (AD) is primarily considered a disorder of protein aggregation, converging evidence from clinical, neuropathological, and mechanistic studies strongly supports the notion that brain endothelial dysfunction is a primary and early event in AD pathogenesis. Brain endothelial pathways are among the most differentially expressed in human AD brains. Brain endothelial alterations precede amyloid deposition and cognitive deficits in experimental AD models and closely parallel the degree of neuronal loss in human AD brains. Despite growing evidence to support brain endothelial contributions to neurodegeneration, studies examining the potential of the brain endothelium as a druggable target in AD have been scarce. Further, there has been a relative paucity of validated fluid biomarkers that can reliably measure brain endothelial injury in AD, independently of overt vascular disease or disruption to other cerebrovascular constituents. In this perspective, we propose a brain endothelial glycocalyx-centric model of AD in which brain endothelial dysfunction, driven predominantly by non-enzymatic glycation and carbonyl stress, acts as a key upstream regulator of aberrant protein trafficking, blood–brain barrier instability, and dysregulated neuro-immune cascades. Further, recent evidence suggests the presence of direct interactions of the brain endothelium with key pathways involved in neuronal survival and synaptic signaling, highlighting potential direct contributions of brain endothelial disturbances to cognitive impairment. Within this framework, we identify several brain endothelial axes, including reduction in carbonyl stress, improved glycation-dependent signaling, attenuation of advanced glycation end-product (AGE)-mediated toxicity, and enhanced endothelial glycocalyx stability and resilience as potential therapeutic approaches in AD. Modulating brain endothelial glycation has potential as a novel therapeutic strategy in AD which may complement other disease-modifying treatments, particularly in the earliest preclinical stages. In conclusion, this framework positions the brain endothelium as a mechanistic hub linking metabolic stress to aberrant protein aggregation and neurodegeneration in AD with potential therapeutic implications in AD and other neurodegenerative disorders. Full article

The geropsychosis hypothesis proposes that anxiety, mood, psychotic, and neurocognitive disorders may share a common biophysical origin with aging itself, rather than arising from wholly disparate pathological routes in many instances. Specifically, we postulate that these conditions may emerge from the bioaccumulation of metals, advanced glycation end products (AGEs), advanced lipoxidation end products (ALEs), and their hybrid complexes in post-pubescent individuals. Such inputs may drive self-reinforcing molecular feedback loops underlying clinically meaningful insults against the nervous system, extending emerging conceptualizations of aging to mental health. Through comprehensive analysis of upstream molecular damage and neural function, this framework offers a mechanistic foundation for conceptualizing several mental disorders as emerging from a unified source. In doing so, the geropsychosis hypothesis may help identify new therapeutic targets and intervention strategies to address underlying contributors to psychiatric pathology. Full article

High fructose intake rapidly induces protein glycation, oxidative stress, inflammation, and disturbances in the cultivable fraction of gut bacteria, contributing to early metabolic impairment. This study examined whether selected plant-derived bioactives and a prebiotic–probiotic formulation could mitigate fructose-induced biochemical and microbial alterations. Male Wistar rats were fed fructose for 45 days, and advanced glycation end product (AGE)-associated fluorescence, oxidative stress markers, and lipid peroxidation were measured to assess metabolic changes. Culture-dependent enumeration of intestinal and fecal bacteria was performed to evaluate shifts in cultivable aerobic and facultative bacterial counts, while limonene, eugenol, and emodin were tested for antibacterial activity against aerobic and facultative bacterial isolates obtained from fructose-fed rats during our previous study. The prebiotic–probiotic formulation was assessed alone and in combination with these bioactives. Fructose feeding increased protein glycation, oxidative stress, lipid peroxidation, and reduced counts of cultivable gut bacteria. Treatment with the bioactives and the formulation lowered glycation-related fluorescence, reduced oxidative stress, and decreased lipid peroxidation. The bioactives exhibited antioxidant and antiglycation activity and inhibited growth of selected cultivable bacterial isolates, including Corynebacterium stationis. While emodin contributed primarily through its known α-glucosidase inhibitory and antiglycation properties rather than antibacterial activity. Combined treatment partially restored cultivable bacterial counts and improved metabolic parameters. Overall, the interventions attenuated fructose-induced biochemical disturbances and modulated the cultivable gut bacterial counts, suggesting a complementary approach to managing early metabolic changes in rats associated with high fructose intake. Full article

Individuals with Laron syndrome, a rare condition characterized by congenital insulin-like growth factor 1 (IGF-1) deficiency, display a remarkably low incidence of cancer, suggesting the existence of protective mechanisms linking reduced IGF-1 signaling to decreased cancer susceptibility. Consistent with this observation, IGF-1 is a recognized promoter of prostate cancer (PCa) progression, although the underlying mechanisms remain incompletely understood. Methylglyoxal (MG)-derived glycative stress, reflected by the accumulation of MG-derived hydroimidazolone 1 (MG-H1), has been implicated in PCa progression but has never been investigated in Laron syndrome. We found that liver tissues from Laron mice exhibited lower MG-H1 levels, suggesting reduced MG-derived glycative stress associated with low IGF-1 signaling. These findings prompted us to investigate whether MG-derived glycative stress contributes to IGF-1-driven PCa progression. Compared with the less aggressive LNCaP cells, PC3 cells displayed higher basal IGF-1 and MG-H1 levels, consistent with a potential association between IGF-1 and MG-derived glycative stress in PCa progression. Moreover, IGF-1 stimulation of LNCaP cells increased MG-H1 accumulation, proliferation, colony formation, invasiveness, and gene expression of matrix metalloproteinase (MMP)-1, MMP-7, MMP-9, receptor for advanced glycation end-products (RAGE), and Osteopontin (OPN), all of which were markedly attenuated by the MG scavenger aminoguanidine (AG). Collectively, these findings support a potential contribution of MG-derived glycative stress to IGF-1-driven PCa progression. Full article

Increased S100 calcium-binding protein A9 (S100A9)-related signals have been reported in selected hepatic and ocular inflammatory settings. This structured narrative review evaluates S100A9-related species as candidate participants in hepato–ocular crosstalk. Across human, ocular fluid, animal, and cellular studies, the available findings provide context-specific support for disease-associated hepatic expression and ocular responsiveness, with stronger evidence for selected local S100A9–Toll-like receptor 4 (TLR4)-associated effects than for S100A9-specific receptor for advanced glycation end products (RAGE) signaling. Clinical associations involving metabolic dysfunction-associated steatotic liver disease, diabetic retinopathy, chronic liver disease, dry eye disease, and uveitis are heterogeneous and confounded. Interpretation is further limited by the non-equivalence of S100A9, S100A8/A9, calprotectin, and higher-order complexes. Current evidence, therefore, suggests that S100A9-related species may serve as exploratory indicators of inflammatory activity or contribute to local inflammatory amplification in selected settings, rather than acting as established liver-derived causal signals. Future studies should prioritize analyte-specific measurement, source tracing, and selective perturbation. S100A9 is best regarded as a testable candidate node within a broader metabolic–inflammatory network. Full article

Background/Objectives: Chronic complications of diabetes mellitus are closely associated with increased oxidative stress and the formation of advanced glycation end products (AGEs). This study aimed to investigate the antioxidant and antiglycation potential of hesperetin-7-O-glucoside (HCD) and diosmetin-7-O-glucoside (DCD) formulations complexed with cyclodextrins, using in vitro and in silico experimental models to evaluate their efficacy in mitigating hyperglycemia-induced molecular damage. Methods: Antioxidant activity was assessed using chemical and erythrocyte-based oxidative stress models, whereas antiglycation activity was evaluated in BSA–fructose, BSA–methylglyoxal, and arginine–methylglyoxal models. Results: Both formulations showed measurable antioxidant effects, with concentration-dependent behavior observed in some of the evaluated assays. In the DPPH assay, HCD and DCD achieved maximum inhibition values of 30.71% and 26.61%, respectively. Furthermore, DCD exhibited higher total antioxidant capacity (102.80 µg vitamin C equivalents/mL) and nitric oxide scavenging activity (37.89%) than HCD. In a cellular model, both formulations (200 µg/mL) significantly reduced AAPH-induced hemolysis, with DCD providing superior protection (7.05% vs. 16.63% for HCD). Under oxidative stress induced by high glucose concentration in erythrocytes, HCD and DCD reduced non-protein thiol levels, and HCD significantly increased catalase enzyme activity. Regarding antiglycation activity, DCD demonstrated superior efficacy relative to HCD in the BSA-fructose system, achieving 43.23% inhibition. DCD also displayed concentration-dependent inhibition of fructosamine formation (up to 47.99%) and BSA glycation by methylglyoxal (up to 45.20%). Both formulations significantly reduced carbonylated protein levels and preserved free thiol groups. In the arginine–methylglyoxal model, DCD and HCD reached 44.03% and 48.82% inhibition, respectively. Molecular docking revealed high binding affinity of both flavonoids to the protein active site (−9.00 kcal/mol for hesperetin-7-O-glucoside and −9.04 kcal/mol for diosmetin-7-O-glucoside), suggesting a structural protective role. Conclusions: The HCD and DCD formulations demonstrated antioxidant and antiglycation activities that may contribute to attenuating molecular alterations associated with chronic hyperglycemia through complementary mechanisms, including antioxidant effects, protection against protein carbonylation, and inhibition of glycation. While these findings highlight the potential of the evaluated formulations, additional mechanistic and in vivo studies are required to establish their pharmacological applicability. Full article