Search Results (5,992)

Metabolic associated fatty liver disease (MAFLD), redefined from non-alcoholic fatty liver disease (NAFLD), is a global health concern driving the search for dietary interventions based on natural compounds. Phloroglucinaldehyde (PGA), a primary phenolic metabolite of the widely consumed anthocyanin cyanidin-3-glucoside (C3G) found in berries and other fruits, has emerged as a promising candidate due to its potential higher bioavailability than its parent compound. This study investigates the protective effects of PGA against high-fat diet (HFD)-induced MAFLD. Using both in vitro (LO2 cells) and in vivo (C57BL/6J mice) models, we found that PGA administration significantly attenuated body weight gain and hepatic steatosis, while reducing serum levels of TG, TC, liver transaminases (AST & ALT), and insulin resistance (p < 0.05). Further liver lipidomic profiling revealed that PGA supplementation specifically down-regulated 46 lipid species (p < 0.05), predominantly triglycerides characterized by long-chain and very-long-chain saturated fatty acids. Mechanistically, PGA enhanced the hepatic antioxidant capacity by increasing superoxide dismutase (SOD) activity (p < 0.05) and decreasing malondialdehyde (MDA) (p < 0.05) and exerted anti-inflammatory effects by reducing pro-inflammatory cytokines (IL-6, TNF, MCP-1) (p < 0.05) and endotoxin levels (p < 0.05). Correlation analyses further linked the down-regulated lipids to improvements in oxidative stress and inflammation. Our findings underscore that PGA, a key bioactive metabolite derived from dietary anthocyanins, alleviates MAFLD through its potent antioxidant and anti-inflammatory properties, highlighting its potential as a functional food ingredient or nutraceutical for metabolic health. Full article

Background/Objectives: Whole-body cryotherapy (WBC), a brief exposure to extreme cold (−90 °C), has been proposed to modulate immune, metabolic, and stress-related pathways. This exploratory one-armed pilot study investigated the effects of an 18-session WBC protocol on immune markers, body composition, and perceived stress in healthy adults. Methods: Nineteen participants (mean age 52.9 ± 9.8 years) completed 18 WBC sessions over 9 weeks (3–6 min each), followed by a 9-week follow-up. Assessments were performed at baseline (M1), post-intervention (M2), and follow-up (M3). Primary outcomes included immune parameters (lymphocytes, granulocytes, cytokines, soluble ACE2), body composition (waist circumference, water compartments, lean mass), and perceived stress (Trier Inventory for Chronic Stress, TICS). Results: Waist circumference decreased from 83.8 ± 5.7 cm (M1) to 80.2 ± 4.2 cm (M2) (p = 0.001; M1 vs. M2; p = 0.004). Total body water (p = 0.008), lean body mass (p = 0.008), intracellular water (p = 0.005), and extracellular water (p = 0.021) also showed time-dependent effects. Immune modulation included increased lymphocytes (25.6 ± 7.1% to 29.3 ± 8.3%, p = 0.012) and decreased granulocytes (63.5 ± 6.8% to 58.7 ± 7.9%, p = 0.011) at M2. Anti-inflammatory IL-10 (virus-stimulated) rose markedly (33.5 ± 29.3 to 63.5 ± 50.5 pg/mL, p < 0.001), while IFN-γ (virus-stimulated) increased over time (p = 0.031). Soluble ACE2 decreased at follow-up (0.5 ± 0.7 to 0.3 ± 0.4 ng/mL, p = 0.029). Perceived stress improved in several TICS domains, including Work Overload (p = 0.009) and Pressure to Succeed (p = 0.018). Conclusions: This pilot study demonstrates that repeated WBC at −90 °C induces measurable changes in immune regulation, body composition, and perceived stress. These findings support the feasibility and potential physiological relevance of WBC and providing effect-size estimates for future randomized controlled trials. Full article

Endometriosis is a hormone-dependent gynecological disease manifested by cyclic pelvic pain and female infertility. Although many studies have shown that neoangiogenesis plays an essential role in the development of early endometriosis, the underlying pathophysiological mechanisms remain unclear. Recent evidence suggests that macrophages play an important role in the pathogenesis of endometriosis and that the hypoxia-inducible factor-1alpha (HIF-1α) may be involved, but when and how are largely unknown. Herein, we explore the role of macrophages in the early development of endometriosis using an in vivo subcutaneous implantation murine model. Upon depletion of macrophages, the subcutaneous injection of syngeneic endometrial material resulted in significant reduction in oxidative stress, endometriotic lesion size, and neovascularization. Likewise, inactivation of the lipid peroxidative gene Alox15 induced similar reduction in oxidative stress, lesion growth, and angiogenesis. Since HIF-1α is an important trigger of neoangiogenesis, we further administered a HIF-1α-specific inhibitor (PX-478) to our endometriotic model and further confirmed the same effects on the lesions. Taken together, these data suggest that an intact Alox15 pathway and HIF-1α signaling may play important roles in the macrophage-mediated oxidative stress and neovascularization of endometriosis in the early stages, suggesting anti-inflammation and antioxidation as potential therapeutic targets for the development of endometriosis. Full article

Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation pathway that relies on the molecular chaperone heat shock cognate 70 kDa protein (HSC70) and the lysosomal receptor LAMP-2A. By recognizing substrate proteins containing KFERQ-like pentapeptide motif, CMA plays a central role in multiple infectious contexts. In host defense and cellular homeostasis, CMA contributes to organelle quality control by selectively degrading damaged or misfolded proteins, including stress- or organelle-associated substrates, thereby limiting pathogen replication while mitigating infection-induced stress and preserving cellular function. Although its detailed mechanisms remain incompletely defined, CMA is thought to involve coordinated steps in which molecular chaperones recognize specific target sequences, recruit autophagy-related components, and deliver substrates for lysosomal translocation and degradation. Recent studies have revealed substantial progress in understanding CMA during viral, bacterial, and fungal infections, identifying key regulatory nodes and signaling pathways. These advances underscore the therapeutic potential of CMA-targeted strategies, such as stabilizing LAMP-2A or enhancing HSC70-mediated substrate recognition. However, the spatiotemporal specificity of CMA’s pro- or antiviral effects remains a major challenge for clinical translation. This review summarizes current progress in this emerging field and highlights unresolved questions, particularly whether tissue- or cell-type-specific regulation of CMA occurs during infection and how precise modulation of CMA activity might achieve optimal anti-infective outcomes. Full article

Rosacea is a chronic inflammatory skin disorder characterized by oxidative stress, innate immune dysregulation, vascular instability, and microbiome-related triggers. Glycyrrhiza glabra (Gg, licorice) root contains phenolics and triterpenoids with antioxidant, anti-inflammatory, antimicrobial, and anti-angiogenic properties that may benefit rosacea-prone skin. Xanthan-gum hydrogels containing 2% methanolic Gg extract (S1, S2) were prepared and characterized. Rheology, in vitro release, and in vitro permeation were evaluated, with the aim of assessing their suitability as topical formulations for rosacea-prone skin. Antioxidant activity was assessed using DPPH, ABTS, and FRAP assays. Antimicrobial effects were tested against S. pyogenes, S. aureus, and C. acnes. Safety and bioactivity were examined through HaCaT keratinocyte assays (MTT, Neutral Red, LDH), the HET-CAM irritation test, and the CAM angiogenesis assay. Immunocytochemistry was performed on rosacea-related inflammatory markers. Both hydrogels showed suitable rheology, sustained release, and preserved strong antioxidant activity. Moderate antimicrobial effects were observed, particularly against S. pyogenes and C. acnes. HaCaT cell viability remained above 84% for the S2 formulation at the highest concentration (200 µg/mL), indicating improved cytocompatibility compared with formulation S1. The hydrogels were non-irritant in the HET-CAM model and reduced neovascularization in the CAM assay, with a more sustained effect observed for formulation S2. Immunohistochemistry supported potential modulation of inflammatory pathways relevant to rosacea, evidencing suppressed VEGF expression and preserved CD44-mediated integrity, particularly in the Labrasol-based formulation (S2), while Caspase-3 staining indicated a controlled apoptotic profile. Overall, Gg hydrogels are safe, biocompatible, non-irritant, and exhibit antioxidant, antimicrobial, and anti-angiogenic activities, supporting their potential as biocompatible topical formulations with antioxidant and pathway-modulating properties relevant to the biological features associated with rosacea, while underscoring the importance of formulation design. Full article

Inflammatory bowel disease (IBD) is characterized by excessive oxidative stress, mitochondrial dysfunction, and persistent activation of pro-inflammatory signaling pathways. Danthron, a natural anthraquinone derivative from rhubarb, has been reported to possess anti-inflammatory and antioxidant properties, yet its regulatory mechanisms in intestinal inflammation remain unclear. In this study, we combined network pharmacology, transcriptomic profiling, cell-based assays, intestinal organoids, and a dextran sulfate sodium (DSS)-induced colitis model to determine the protective effects of Danthron against oxidative injury. Integrated target prediction and RNA-seq analysis identified EGFR–PI3K–AKT and Nrf2–HO-1 as key signaling axes modulated by Danthron. In macrophages and intestinal epithelial cells, Danthron markedly suppressed LPS- or H₂O₂-induced ROS accumulation, lipid peroxidation, and mitochondrial membrane potential collapse, while restoring superoxide dismutase activity and reducing malondialdehyde levels. Danthron also inhibited M1 macrophage polarization, preserved epithelial tight-junction proteins, and maintained transepithelial electrical resistance. CETSA, DARTS, and molecular docking confirmed direct engagement of Danthron with components of both the EGFR–PI3K–AKT and Nrf2–HO-1 pathways. In vivo, Danthron significantly ameliorated DSS-induced colitis, reducing inflammatory cytokines, epithelial apoptosis, oxidative stress, and myeloid cell infiltration while improving mucosal architecture and enhancing organoid regenerative capacity. These findings demonstrate that Danthron exerts potent antioxidant and anti-inflammatory effects through coordinated inhibition of EGFR–PI3K–AKT signaling and activation of the Nrf2–HO-1 axis, suggesting its promise as a multi-target therapeutic candidate for IBD. Full article

Liver fibrosis induced by Schistosoma japonicum Katsurada, 1904 (S. japonicum) infection lacks effective diagnostic markers and specific anti-fibrotic therapies. Although dysregulated iron homeostasis and ferroptosis pathways may contribute to its pathogenesis, the core regulatory mechanisms remain elusive. To unravel the ferroptosis-related molecular features, this study integrated transcriptomic datasets (GSE25713 and GSE59276) from S. japonicum-infected mouse livers. Following batch effect correction and normalization, ferroptosis-related differentially expressed genes (FRDEGs) were identified. Subsequently, core hub genes were screened through the construction of a protein–protein interaction (PPI) network, functional enrichment analysis, immune infiltration evaluation, and receiver operating characteristic (ROC) analysis. The expression patterns of these hub genes were further validated in an S. japonicum-infected mouse model using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The study identified 7 hub genes (Lcn2, Timp1, Cth, Cp, Hmox1, Cbs, and Gclc) as key regulatory molecules. Functional enrichment analysis revealed that these hub genes are closely associated with sulfur amino acid metabolism and oxidative stress responses. Specifically, key enzymes involved in cysteine and glutathione (GSH) synthesis (Cth, Cbs, Gclc) were consistently downregulated, suggesting a severe impairment of the host antioxidant defense capacity. Conversely, pro-fibrotic and pro-inflammatory markers (Timp1, Lcn2, Hmox1) were upregulated. This molecular pattern was significantly associated with a remodeled immune microenvironment, characterized by increased infiltration of neutrophils and eosinophils. In vivo validation confirmed the expression trends of 6 hub genes, corroborating the bioinformatics predictions, while the discrepancy in Cp expression highlighted the complexity of post-transcriptional regulation in vivo. The identified hub genes demonstrated excellent diagnostic potential, with Timp1 achieving an area under the curve (AUC) of 1.000. This study elucidates the molecular link between S. japonicum infection and the ferroptosis pathway, suggesting that these hub genes may drive liver fibrosis progression by regulating sulfur metabolism and the immune microenvironment. These findings offer potential diagnostic biomarkers and novel therapeutic targets for schistosomal liver fibrosis. Full article

The aim of this study was to improve surgical caponisation and identify stress factors associated with different pain management methods and post-operative periods. A total of 72 Prelux-G cockerels were caponised at six weeks of age. Eight experimental groups were established based on caponisation status and pain management. Four groups were caponised using different pain management protocols (none, anaesthesia only, analgesia only, or both), while four non-caponised groups served as controls, including one group that received anaesthesia and analgesia without surgery. The remaining three groups served as non-caponised controls with varying levels of handling. The researchers monitored body weight, feed intake, respiratory and heart rate, vocalisations, response to pain, and depth of anaesthesia. The results confirmed that caponisation is painful, as reflected in increased physiological responses and vocalisations. The use of non-steroidal anti-inflammatory drugs alone did not provide effective pain relief. Additionally, the surgical procedure had no significant effect on weight gain or feed intake during the seven days following surgery. Stress levels, measured by blood serum corticosterone concentration, also increased during the procedure. The study concludes that anaesthesia significantly reduces pain and facilitates surgery, which is essential for improving animal welfare. Full article

Neurodegeneration is closely linked to neuroinflammation and is frequently accompanied by comorbidities with inflammatory features. Tripartite motif (TRIM) proteins are known to play an important role in innate immunity and inflammatory signaling in various tissues and organs of the body, including the central nervous system. Among the main cell types of the brain, TRIMs’ functions in microglia are largely associated with the regulation of intracellular inflammatory signaling, while in neurons they mainly relate to cell survival and oxidative stress. Data concerning TRIMs’ activity in astrocytes remain limited. Many TRIM proteins exert similar pro- or anti-inflammatory effects in neuroinflammation and in other inflammatory disorders in the body, although for some members their roles are reported to be opposite, contradictory, or insufficiently characterized, highlighting the need for further research. The aim of this review was to summarize published data on the common mechanisms of TRIMs’ actions as modulators of inflammation, and compare available reports in the context of neuroinflammation and peripheral inflammatory pathologies. We suggested that such an analysis may be valuable for guiding future research—both by identifying existing gaps in knowledge and by supporting the rational selection of specific TRIM proteins for investigation as therapeutic targets, with careful consideration of their systemic effects. Full article

Introduction: Massage therapy delivers structured mechanosensory input that can influence brain function, yet the central mechanisms and potential for neuroplastic change have not been synthesized across neuroimaging modalities. This mechanistic review integrates evidence from electroencephalography (EEG), functional MRI (fMRI), and functional near-infrared spectroscopy (fNIRS) to map how massage alters human brain activity acutely and over time and to identify signals of longitudinal adaptation. Materials and Methods: We conducted a scoping, mechanistic review informed by PRISMA/PRISMA-ScR principles. PubMed/MEDLINE, Cochrane Library, Google Scholar, and ResearchGate were queried for English-language human trials (January 1990–July 2025) that (1) delivered a practitioner-applied manual massage (e.g., Swedish, Thai, shiatsu, tuina, reflexology, myofascial techniques) and (2) measured brain activity with EEG, fMRI, or fNIRS pre/post or between groups. Non-manual stimulation, structural-only imaging, protocols, and non-English reports were excluded. Two reviewers independently screened and extracted study, intervention, and neuroimaging details; heterogeneity precluded meta-analysis, so results were narratively synthesized by modality and linked to putative mechanisms and longitudinal effects. Results: Forty-seven studies met the criteria: 30 EEG, 12 fMRI, and 5 fNIRS. Results: Regarding EEG, massage commonly increased alpha across single sessions with reductions in beta/gamma, alongside pressure-dependent autonomic shifts; moderate pressure favored a parasympathetic/relaxation profile. Connectivity effects were state- and modality-specific (e.g., reduced inter-occipital alpha coherence after facial massage, preserved or reorganized coupling with hands-on vs. mechanical delivery). Frontal alpha asymmetry frequently shifted leftward (approach/positive affect). Pain cohorts showed decreased cortical entropy and a shift toward slower rhythms, which tracked analgesia. Somatotopy emerged during unilateral treatments (contralateral central beta suppression). Adjuncts (e.g., binaural beats) enhanced anti-fatigue indices. Longitudinally, repeated programs showed attenuation of acute EEG/cortisol responses yet improvements in stress and performance; in one program, BDNF increased across weeks. In preterm infants, twice-daily massage accelerated EEG maturation (higher alpha/beta, lower delta) in a dose-responsive fashion; the EEG background was more continuous. In fMRI studies, in-scanner touch and reflexology engaged the insula, anterior cingulate, striatum, and periaqueductal gray; somatotopic specificity was observed for mapped foot areas. Resting-state studies in chronic pain reported normalization of regional homogeneity and/or connectivity within default-mode and salience/interoceptive networks after multi-session tuina or osteopathic interventions, paralleling symptom improvement; some task-based effects persisted at delayed follow-up. fNIRS studies generally showed increased prefrontal oxygenation during/after massage; in motor-impaired cohorts, acupressure/massage enhanced lateralized sensorimotor activation, consistent with use-dependent plasticity. Some reports paired hemodynamic changes with oxytocin and autonomic markers. Conclusions: Across modalities, massage reliably modulates central activity acutely and shows convergent signals of neuroplastic adaptation with repeated dosing and in developmental windows. Evidence supports (i) rapid induction of relaxed/analgesic states (alpha increases, network rebalancing) and (ii) longer-horizon changes—network normalization in chronic pain, EEG maturation in preterm infants, and neurotrophic up-shifts—consistent with trait-level recalibration of stress, interoception, and pain circuits. These findings justify integrating massage into rehabilitation, pain management, mental health, and neonatal care and motivate larger, standardized, multimodal longitudinal trials to define dose–response relationships, durability, and mechanistic mediators (e.g., connectivity targets, neuropeptides). Full article

Background/Objectives: Oats and oat bran are rich in polyphenols and soluble fiber, which are metabolized by gut microbiota into bioactive compounds. Previous studies identified ursodeoxycholic acid (UDCA), 3-(3-hydroxyphenyl)propionic acid (3-HPP), and avenanthramide C (AVC) as key microbial metabolites with protective effects against colitis. Methods: This study aimed to elucidate their antioxidant and anti-inflammatory activities and underlying mechanisms using LPS-induced RAW 264.7 macrophages and AAPH-induced oxidative stress in zebrafish embryos. All three metabolites significantly reduced intracellular reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA), and pro-inflammatory cytokines (IL-6, TNF-α). They also restored mitochondrial membrane potential and enhanced superoxide dismutase (SOD) activity. Results:In vivo, treatment improved zebrafish survival, normalized SOD activity to 76–89% of control levels, and decreased ROS and MDA by 2.4 to 3.8 fold, with UDCA showing the greatest efficacy. Molecular docking revealed strong binding affinities to Keap1, particularly UDCA, which interacted with residues Met577, Ala440, Val532, and Val486. qRT-PCR further demonstrated downregulation of Keap1 and upregulation of Nrf2 and SOD, indicating activation of the Keap1-Nrf2 pathway. Conclusions: Collectively, these findings show that oats and bran-derived microbial metabolites exert potent antioxidant and anti-inflammatory effects via modulation of the Keap1-Nrf2 axis. Among the metabolites, UDCA exhibited the strongest biological activity at equivalent concentrations. This study provides mechanistic insight into how microbiota-derived oat metabolites contribute to redox balance and immune regulation, supporting their potential as functional components in dietary strategies for managing oxidative stress-related inflammatory diseases. Full article

Sepsis-associated acute kidney injury (S-AKI) is a frequent and life-threatening condition, characterized by rapid functional decline, which is followed by intense inflammation and tissue injury. Experimental lipopolysaccharide (LPS)-induced sepsis reproduces functional and morphological features of human S-AKI and enables investigation of melatonin which has numerous beneficial properties, such as antioxidant properties. In this study, the effects of melatonin (50 mg/kg) on kidney dysfunction, oxidative damage, inflammation, apoptosis, and histopathological alterations in a rat model of S-AKI induced by LPS application (10 mg/kg) were studied. Acute LPS exposure caused statistically significant (p ≤ 0.05) marked renal dysfunction, increased lipid and protein oxidation, suppression of antioxidant enzymes, enhanced NO/iNOS signaling, elevated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), activation of apoptotic pathways, and pronounced tubular and glomerular injury. Co-administration of melatonin statistically significantly (p ≤ 0.05) attenuated oxidative stress, reduced production of inflammatory cytokines, suppressed apoptosis, and ameliorated structural kidney damage, leading to partial restoration of renal function. These findings suggest that melatonin exerts renoprotective effects in S-AKI through combined antioxidant, anti-inflammatory, and anti-apoptotic actions, likely involving modulation of different signaling pathways. Full article

The objective of this study was to determine if the use of human chorionic gonadotrophin (hCG) and ketoprofen would affect the pregnancy percentages of dairy cows following timed artificial insemination (TAI). This experiment was conducted on a commercial dairy farm in China involving 799 healthy Holstein cows (2–4 parities) between October and December 2024. Cows were randomly assigned to three groups: hCG-3 = treated with (0 d: GnRH, 100 μg; 7–8 d: PGF_2α, 0.4 mg; 52 h: GnRH, 100 μg; 14–16 h: TAI) + hCG 3 vials (300 µg)/cow on day 7 of TAI; hCG-2 group = TAI + 2 vials (200 µg) hCG/cow on day 7; and hCG+ketoprofen = TAI + 300 µg hCG/cow + ketoprofen 10 mL/cow on days 15 and 16 of TAI. Metabolomic profiling (untargeted and targeted) of 22 pregnant cows was conducted on serum collected on days 17 and 21 post-TAI. Results indicated greater pregnancy percentages in the cows of the hCG+ketoprofen-treated group compared to those in the other two groups (60.1% compared with 49.6% and 41.9%). The cows treated with hCG+ketoprofen had less oxidative stress markers, downregulation of arachidonic acid metabolism and upregulation of glycerophospholipid metabolism on day 17 after TAI, indicating that there was upregulation of tryptophan and serotonergic pathways, increased amino acid metabolism and continued anti-inflammatory effects on day 21 after TAI. These findings were confirmed by evaluation data collected by conducting the targeted metabolomic procedures, as indicated by the greater progesterone and melatonin and lesser 17-estradiol and 21-deoxycortisol concentrations. These findings indicate that combined hCG+ketoprofen administrations following the TAI treatment regimen improve pregnancy percentages in dairy cattle as a result of metabolic and endocrine milieu modulations. Full article

The neonatal heart possesses a unique capacity for reparative healing after myocardial injury, unlike the adult heart. While immune cells, particularly T cells, regulate post-infarction inflammation, their role in age-dependent cardiac repair remains unclear. This study aimed to characterize the temporal activation of T cell subsets and their contribution to immune homeostasis and myocardial repair. Myocardial infarction was induced in mice of different ages, and T cell subsets (CD4+ T cells, CD8+ T cells, and CD4+Foxp3+ T [T-reg] cells) were analyzed using flow cytometry and RNA sequencing. Neonatal hearts exhibited CD4+ T cells, CD8+ T cells, and T-reg cells that gradually increased until seven days post-injury. Transcriptome analysis identified Rcn3 as a neonatal-specific, injury-responsive gene in T-reg cells, with minimal induction in adult and aged hearts, promoting a reparative microenvironment and exerting anti-fibrotic effects via the PI3K/Akt pathway. Under endoplasmic reticulum stress, Rcn3 activated unfolded protein response genes, and Rcn3-conditioned media reduced fibrosis-associated gene expression in adult cardiac fibroblasts. In a conditional knockout mouse model (Lck-cre; Rcn3^fl/fl), Rcn3 deletion in T cells led to impaired cardiac function recovery and increased fibrosis post-injury. These findings suggest that neonatal T-reg cells play a crucial role in cardiac repair, with Rcn3 as a potential therapeutic target for enhancing immune-mediated cardiac repair and limiting pathological remodeling in the adult heart. Full article

Background: Cardiac ischemia (CI) remains a leading cause of death worldwide, prompting an ongoing search for new treatment options. This study explored and compared the preventive cardioprotective effects of polyphenols extracted from red (RGP) and white grape pomace (WGP) against isoproterenol (ISO)-induced myocardial ischemia, with a focus on their antioxidant and anti-inflammatory properties. Materials and Methods: Fifty male Wistar rats were divided into five groups: I—Saline, II—Saline+ISO, III—Ramipril+ISO, IV—WGP+ISO, and V—RGP+ISO. CI was induced in Groups II–V with ISO (45 mg/kg, on day 13), a dose widely used to reproducibly induce myocardial ischemic injury in experimental models. Electrocardiographic parameters, serum oxidative markers, cytokines, and tissue homogenates from the liver and heart were analyzed on day 14. Results: ISO significantly shortened the RR interval and increased the ventricular rate, without significant modulation by any treatment. The reduction in R-wave amplitude caused by ISO was lessened in all treated groups, with RGP showing values closer to Saline (RGP+ISO vs. Saline, p = 0.329). No differences were found among groups for PR segment, QRS duration, QT, or QTc intervals. Furthermore, all treated groups (III–V) showed significant improvements in oxidative and inflammatory markers compared to Saline+ISO (p < 0.05), with RGP demonstrating the strongest antioxidant activity by maintaining MDA and NO levels close to Saline (RGP+ISO vs. Saline, p > 0.05), while WGP exhibited superior anti-inflammatory effects in cardiac tissue by preserving IL-6 and IL-1β levels comparable to controls (WGP+ISO vs. Saline, p > 0.05). Conclusions: Grape pomace, especially RGP, may offer cardioprotection by decreasing oxidative stress, while WGP more effectively reduces inflammation. The complementary antioxidant and anti-inflammatory effects observed suggest that combining GP extracts may represent a promising hypothesis for future cardiovascular research. Full article