Search Results (543)

Ulcerative colitis (UC) and Crohn’s disease (CD), known as inflammatory bowel diseases (IBDs), result from a complex interaction of genetic, immunological, microbial and environmental factors. There is growing evidence suggesting that imbalances in the gut microbiota, or dysbiosis, play a causal role in IBD and are strongly influenced by aspects of the Western lifestyle. Diet is an important modulator of gut health, and whole cereals have attracted attention for their potential to positively shape gut microbiota and intestinal function. Germination further enhances the content of prebiotic substrates and bioactive compounds such as polyphenols, GABA and fiber, which may modulate inflammation, oxidative stress and immune responses. In vitro and clinical studies suggest that these compounds may reduce pro-inflammatory cytokines and improve symptoms in IBD, although robust evidence in patients is still lacking. Here, we provide an overview of whole and sprouted cereals and their effects on inflammation and gut microbiota, with particular focus on IBD. We also discuss the potential of sprouted grains as a complementary approach to diet alongside conventional therapy, highlighting their possible support to gut health to mitigate inflammation. Finally, we emphasize the need for further well-designed clinical studies to confirm their therapeutic potential and to better understand the mechanisms underlying their beneficial effects. Full article

Heat shock proteins (HSPs) are a family of conserved molecular chaperons present in both prokaryotic and eukaryotic species, playing a crucial role in maintaining cellular proteostasis and enhancing stress resilience. HSPs have a multitude of roles in regulating cell signaling transduction, antioxidant defenses, apoptosis, and protein folding, thereby contributing to overall cellular homeostasis. Insulin resistance is characterized by elevated oxidative stress, dysregulated pro-inflammatory signaling, and impaired cellular stress response, ultimately leading to deficient glucose uptake in skeletal muscle. Many studies have illustrated the benefits of exercise in improving insulin resistance and reducing the risk of metabolic disorders, such as type 2 diabetes. Habitual exercise and lifestyle modifications have been shown to activate heat shock response, enhancing HSP70 expression and promoting cellular adaptations that protect against metabolic dysfunction. However, the link between HSPs, particularly HSP70, and skeletal muscle insulin resistance remains complex and not fully elucidated. In this review, we discuss the mechanistic pathways by which HSP70 modulates insulin resistance, mitochondrial function, and inflammatory responses in skeletal muscle. Additionally, we discuss the protective effects of exercise-induced HSP70 expression and its potential as a therapeutic target for improving insulin sensitivity and metabolic health. Full article

Background/Objectives: Watercress (Nasturtium officinale), a cruciferous vegetable rich in phenethyl isothiocyanate (PEITC) and bioactive phytochemicals, has demonstrated anti-inflammatory and cytoprotective activities in multiple disease models; however, its effects on colitis remain insufficiently characterized. In the present study, we investigated the effects of watercress extract supplementation in dextran sulfate sodium (DSS)-induced experimental colitis. Methods: Male C57BL/6 mice were fed either a standard AIN-93G diet or a diet supplemented with 0.5% (w/w) watercress extract for 4 weeks, followed by DSS administration to induce acute colitis. Colonic histopathological injury, immune responses, barrier integrity, and gut microbiota composition were evaluated. In addition, the activity of PEITC, a major bioactive constituent of watercress, was examined in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in vitro. Results: Watercress extract attenuated DSS-induced colon shortening and reduced histopathological injury. The supplementation of watercress extract also decreased colonic immune cell accumulation, suppressed the expression of pro-inflammatory mediators, and preserved intestinal barrier integrity. The 16S rRNA gene amplicon sequencing further revealed that watercress extract reshaped gut microbial composition, including increased abundance of Monoglobus and Adlercreutzia, and reduced abundance of microbial taxa such as Enterococcus and Enterorhabdus. Moreover, PEITC suppressed LPS-induced inflammatory activation in RAW264.7 macrophages by reducing nitric oxide production, inhibiting p38 MAPK phosphorylation, and downregulating multiple inflammatory cytokines and chemokines. Conclusions: These findings demonstrate that watercress extract alleviates experimental colitis through attenuating mucosal inflammation, preserving intestinal barrier function, and modulating the gut microbiota, highlighting watercress as a promising dietary strategy for improving gut health and mitigating intestinal inflammation. Full article

Background/Objectives: Metabolic dysfunction-associated alcoholic liver disease (MetALD) is a serious worldwide health concern, exhibiting metabolic dysfunction-associated lipid accumulation, alcohol-associated oxidative damage, and endotoxin-induced inflammation. Rb1-enriched red ginseng saponin fraction (RGSF) has been known to exhibit anti-inflammatory and anti-oxidative properties, but its role in MetALD remains to be fully elucidated. This study aims to investigate the specific mechanism of RGSF in the MetALD mouse model. Methods: The MetALD mouse model was administered with or without Rb1-RGSF for 7 weeks. Histopathological and molecular analyses, along with primary cell isolation, were conducted for in vivo and ex vivo investigations. M1 macrophage polarization was assessed by analyzing pro-inflammatory cytokine expression. NF-kB/p65 and TLR4 protein expression were measured before being visualized using immunofluorescence assays and confocal microscopy. Results: Histopathological examination revealed that RGSF treatment markedly reduced hepatic steatosis and attenuated inflammatory lesions in MetALD independent of oxidative stress. Notably, RGSF administration suppressed the LPS-induced internalization of surface TLR4. During the early inflammatory phase, RGSF prevented the LPS-mediated loss of the 130 kDa TLR4 form at the cell membrane, thereby limiting the generation of its 110 kDa cytoplasmic form. LPS-binding assay confirmed the direct interactions between TLR4 and RGSF. Conclusions: Collectively, these findings demonstrate that RGSF regulates TLR4 expression and trafficking, leading to the suppression of M1 macrophage polarization by inhibiting LPS–TLR4 surface interactions, thus exhibiting hepatoprotective effects. Full article

Carrot processing for juice generates substantial pomace residues rich in bioactive compounds, which represent both an environmental challenge and an unexploited resource. This study investigated the protective effects of a polyphenolic extract derived from carrot pomace (CP) against Escherichia coli lipopolysaccharide (LPS)-induced damage. For that, we used IPEC-1 (Intestinal Porcine Epithelial Cells) as an in vitro model of the intestinal epithelium. The total phenolic content of the CP polyphenolic extract (CPE) was 1.017 mg GAE/mL, with flavan-3-ols (epicatechin, catechin, epigallocatechin) accounting for 71.3% of that value. Before being exposed to LPS (10 μg/mL) for 24 h, the cells were pre-treated with CP extract (20.34 µg and 10.17 µg polyphenols/mL of extract corresponding to 1/50 and 1/100 dilution) for 4 h. Epithelial renewal (cell viability, cell proliferation and apoptosis), monolayer/barrier integrity (TEER, FD4 permeability, LDH release), as well as epithelial functionality (synthesis of pro-inflammatory cytokines: TNF-α, IL-1β, IL-6, reactive oxygen species (ROS), nitric oxide (NO) production), MAPK signalling and mitochondrial morphology and function were assessed. The results showed that CP extract had no cytotoxic effects and successfully counteracted LPS-induced loss of cell viability and proliferation. The pre-treatment with CPE at both dilutions significantly reduced LPS-induced apoptosis and cell death. Barrier integrity was preserved with TEER values maintained near baseline: −0.43% and −0.24% for 1/50 and 1/100 dilutions of CPE vs. −53.47% at 72 h for LPS alone, and paracellular FD4 passage was restored to control levels. At the molecular level, CP extract reduced pro-inflammatory cytokine gene expression (IL-6 by 40%, TNF-α by 50–56%) and suppressed LPS-induced MAPK activation by 62.9% and 46.5%, for 1/50 and 1/100 dilutions of CPE, respectively. The pre-treatment of cells with CP extract normalised LPS-induced ROS production and protected mitochondrial morphology and function. These in vitro findings demonstrate that CP extract exerts a protective effect on intestinal epithelial cells, acting through anti-inflammatory, antioxidant and barrier-preserving mechanisms. This supports the hypothesis for valorisation of carrot agro-industrial by-products as functional feed additives for promoting intestinal health. Further in vivo studies are needed to validate this hypothesis and to establish the concentration/rate of inclusion of carrot by-products to achieve the maximal positive effects. Full article

Background: Type 2 inflammatory diseases are among the most common chronic inflammatory conditions in childhood and represent a growing global health burden. Increasing evidence suggests that early-life nutritional exposures may influence immune programming and allergic disease development. This Position Paper aims to summarize the current evidence regarding the immunomodulatory role of polyunsaturated fatty acids (PUFAs), particularly omega-3 long-chain fatty acids, in the prevention of allergic diseases during early life. Methods: A scoping literature review and consensus process were conducted to map biological mechanisms and clinical evidence linking omega-3 PUFAs with allergic disease prevention. This document analyzed experimental, observational, and randomized controlled studies evaluating maternal prenatal/lactational omega-3 exposure. The clinical evidence was qualitatively appraised using study-design-specific Joanna Briggs Institute (JBI) Critical Appraisal Tools. Particular attention was given to immune modulation, inflammatory pathways, epithelial barrier function, gut microbiota interactions, and the ferroptosis–immune–metabolic axis. Results: Omega-3 PUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert immunomodulatory and anti-inflammatory effects through multiple mechanisms, including specialized pro-resolving mediator production, regulation of T-helper cell responses, cytokine modulation, maintenance of epithelial barrier integrity, and microbiota interaction. Emerging evidence also supports their involvement in oxidative stress and ferroptosis regulation. Current clinical evidence, particularly from higher-quality prenatal randomized trials and evidence syntheses, suggests that adequate maternal omega-3 intake during pregnancy and lactation may reduce the risk of respiratory allergic outcomes, especially wheezing and asthma, in selected offspring. Conclusions: Adequate omega-3 PUFA intake, such as 2 g/die, during critical windows of immune maturation may represent a valuable strategy for the primary prevention of allergic diseases. Current evidence most strongly supports supplementation during pregnancy and lactation, particularly in populations with low dietary omega-3 intake or increased allergic risk. Omega-3 supplementation should be considered within a broader multifactorial preventive approach aimed at promoting immune tolerance and reducing the future burden of allergic diseases. Full article

Background/Objectives: Obesity is a major public health problem associated with chronic inflammation and functional alterations in multiple organs and systems. Few studies have examined colostrum from obese mothers, particularly with respect to macrophage function, enzyme and cytokine concentrations, and the role of melatonin in immune modulation. This study aimed to evaluate melatonin levels and their effects on macrophage polarization, cytokine concentrations, nitric oxide synthase [iNOS], and arginase in colostrum from obese mothers. Colostrum samples were collected from eutrophic mothers [BMI: 18.5–24.9 kg/m²] and obese mothers [BMI: ≥30 kg/m²]. Methods: Macrophages were isolated by density gradient and treated with melatonin. The expression of M1 and M2 macrophages and cytokine concentrations were assessed by flow cytometry, while melatonin levels in colostrum supernatants, iNOS, and arginase in cell lysates were determined by ELISA. Results: An endogenous increase in melatonin was also observed in the colostrum of obese mothers. Maternal obesity has been shown to reduce M1 and M2 macrophage expression, increase nitric oxide synthase [NOS] activity, and elevate interleukin-6 [IL-6] and interleukin-17 [IL-17] levels. However, melatonin treatment restored M1 and M2 macrophage levels and reduced inducible nitric oxide synthase [iNOS] and arginase production to levels similar to those observed in mothers of healthy weight. Conclusions: these findings suggest that maternal obesity creates a pro-inflammatory environment in colostrum, characterized by altered macrophage polarization, altered cytokine secretion, and an imbalance in the enzymatic activities of iNOS and arginase within the L-arginine metabolic pathway. Both natural and supplemental melatonin exhibited immunomodulatory, antioxidant, and anti-inflammatory effects, helping to restore immune balance in colostrum. These results emphasize the potential benefits of melatonin as an immunometabolic modulator and its contribution to understanding immunometabolic regulation in obese mothers. Full article

Plant polysaccharides, such as Astragalus polysaccharide (APS) and Glycyrrhiza polysaccharide (GPS), have potential as functional feed additives. This study investigated the effects of dietary APS and GPS on growth-related traits, serum biochemical and immune indices, antioxidant capacity, intestinal health, and microbial diversity in early-weaned squabs. A total of 192 15-day-old Silver King squabs were randomly divided into four groups: the control group (CK), the 800 mg/kg APS group, the 450 mg/kg GPS group, and the APS + GPS combination group (AG group), with 12 replicates per group and 4 squabs per replicate. The experiment lasted for 28 days. The results showed that final body weight tended to be higher in the APS, GPS, and AG groups, whereas breast width and breast depth were significantly increased in the GPS and AG groups (p < 0.01). The GPS and AG groups exhibited increased serum immunoglobulin A (IgA; p < 0.05) and immunoglobulin G (IgG; p < 0.01) levels, as well as reduced levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α; p < 0.01). All treatments increased serum total antioxidant capacity (T-AOC; p < 0.01), while the AG group reduced malondialdehyde (MDA) levels and increased total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities (p < 0.01). Duodenal and jejunal T-AOC increased in all treatment groups (p < 0.01), and APS and AG increased ileal T-AOC (p < 0.01). However, intestinal MDA concentrations increased in several segments, indicating a complex and segment-specific oxidative response. The AG group also increased jejunal lipase activities (p < 0.05). Microbiome analysis suggested that Helicobacter was correlated with immune-related indicators, while Lactobacillus was identified as an important core genus in the microbial co-occurrence network. These findings suggest that dietary APS and GPS may regulate immune function, oxidative–antioxidant responses, intestinal function, and gut microbial composition, thereby supporting physiological adaptation in early-weaned squabs. Full article

Ovarian granulosa cells (GCs) ensure proper follicular development and oocyte maturation through gap-junction-mediated intercellular communication. Zearalenone (ZEA), a mycotoxin with estrogen-like activity, specifically targets and impairs ovarian function. Most existing studies have focused on ZEA-induced apoptosis in GCs, but whether ZEA disrupts gap junctions in ovarian GCs remains unclear. Therefore, the aim of this study was to investigate whether and how ZEA induces gap junction injury in ovine ovarian GCs, with a particular focus on the roles of G protein-coupled receptor 30 (GPR30), oxidative stress, and the NLRP3 inflammasome. In the present study, primary ovine ovarian GCs were isolated, cultured, and treated with different concentrations of ZEA to establish a gap junction injury model, and specific inhibitors/antagonists were used to investigate the underlying mechanisms. The results showed that ZEA decreased granulosa cell viability and significantly inhibited the expression of the gap junction proteins Connexin 43 (Cx43) and Connexin 37 (Cx37) in a concentration-dependent manner. ZEA treatment also significantly upregulated the expression of the NOD-like receptor familypyrindomain containing 3 (NLRP3) inflammasome-related proteins (NLRP3, ASC, Cleaved Caspase-1, and the downstream pro-inflammatory cytokine IL-1β) in a concentration-dependent manner. Pretreatment with the NLRP3-specific inhibitor MCC950 significantly reversed ZEA-induced downregulation of Cx43 and Cx37 and effectively blocked NLRP3 inflammasome activation, indicating that NLRP3 is a key target in ZEA-induced gap junction injury. Further experiments confirmed that ZEA treatment significantly increased oxidative stress levels in granulosa cells; pretreatment with the reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) restored the ZEA-induced downregulation of Cx43 and Cx37 and suppressed NLRP3 inflammasome activation, suggesting that ROS acts as an upstream regulator of NLRP3 inflammasome activation. Moreover, ZEA treatment altered GPR30 expression levels, and pretreatment with the GPR30 antagonist G15 effectively inhibited ZEA-induced ROS production, NLRP3 inflammasome activation, and downregulation of Cx43/Cx37, indicating that ZEA exerts its effects through functional activation of GPR30. Collectively, ZEA activates the GPR30 receptor, induces ROS accumulation in granulosa cells, and subsequently triggers NLRP3 inflammasome activation, ultimately leading to downregulation of Cx43 and Cx37 and gap junction dysfunction. This study reveals a previously unrecognized molecular mechanism by which ZEA induces gap junction injury in ovarian GCs, providing potential therapeutic targets and a theoretical basis for preventing ZEA-induced ovarian dysfunction and improving animal reproductive health. Full article

Background/Objectives: Metabolic-dysfunction-associated steatotic liver disease (MASLD) and its progressive inflammatory/fibrotic form, metabolic-dysfunction-associated steatohepatitis (MASH), represent a growing global health burden. This progression is driven by complex mechanisms involving metabolic dysregulation, chronic inflammation, oxidative stress, and progressive fibrosis. To date, effective pharmacological therapies remain limited. Pentacyclic triterpenes have attracted increasing attention due to their broad biological activities and ability to modulate multiple molecular pathways implicated in chronic liver disease. This review aims to provide a mechanistic overview of the potential role of pentacyclic triterpenes in MASLD and MASH. Methods: A literature review was conducted using major scientific databases (PubMed and Web of Science) to identify experimental studies investigating pentacyclic triterpenes in metabolic liver diseases. Selected studies were analyzed according to triterpene structural classification, reported bioactivities, molecular targets, and experimental evidence from in vitro and in vivo models of MASLD/MASH or related pathogenic processes. Results: Pentacyclic triterpenes, especially ursolic acid, oleanolic acid, and glycyrrhizin, exhibit hepatoprotective effects including regulation of lipid metabolism, attenuation of oxidative and endoplasmic reticulum stress, suppression of pro-inflammatory signaling, inhibition of inflammasome activation, and reduction in hepatic stellate cell activation and extracellular matrix deposition. These effects involve modulation of signaling pathways, including AMPK, NF-κB, NLRP3, TGF-β, FXR, and MAPK. Preclinical evidence demonstrates improvements in steatosis, inflammation, and fibrosis in experimental models. Conclusions: Pentacyclic triterpenes emerge as multitarget modulators of MASH pathophysiology. However, translating preclinical evidence into well-designed clinical trials is necessary to validate their safety and efficacy in humans. Full article

The incidence of liver injury has been increasing year by year, potentially progressing to liver fibrosis, cirrhosis, and even hepatocellular carcinoma, posing a threat to human health. Gardenia, Astragalus, and Hawthorn are commonly used natural products with dual purposes as both medicine and food. While extensive research has been conducted on their individual pharmacological activities, systematic studies on the synergistic effects and efficacy evaluation of their combined use in liver protection are still lacking. This study aimed to investigate the protective effects and underlying mechanisms of the compound Gardenia and Scutellaria extract (GACE) on CCl4-induced liver injury in mice. The composition and content of GACE were analyzed by HPLC. Serum biochemical, inflammatory, and hepatic oxidative stress indicators were detected using assay kits. Liver pathological changes were examined by HE staining, while apoptosis was observed via TUNEL staining. Transcriptomic and metabolomic sequencing were employed to analyze the potential mechanisms of CCl4 in alleviating liver injury. Finally, Western blotting was performed to validate the analytical results. The results demonstrated that CCl4 significantly upregulated the levels of pro-inflammatory cytokines IL-6, IL-12 and IL-2 (p < 0.05), downregulated the level of anti-inflammatory cytokine IL-10 (p < 0.05), and caused markedly elevated serum ALT and AST levels (p < 0.01). The hepatic lobule structure was nearly obliterated in liver tissue, with disordered arrangement of hepatic cords and numerous vacuoles appearing in hepatocytes. The TUNEL staining positive cell rate increased significantly compared with the blank group (p < 0.001). Meanwhile, CCl4 also significantly inhibited SOD and GSH-Px activities in liver tissue (p < 0.05), while markedly increasing MDA levels (p < 0.05). GACE significantly alleviated liver tissue damage and reduced hepatocyte apoptosis (p < 0.05). It markedly enhanced SOD and GSH-Px activities in liver tissue while decreasing ALT, AST, MDA, IL-6, IL-12, and IL-2 levels (p < 0.05), thereby mitigating hepatic oxidative damage and inflammatory responses. Integrated transcriptomic and metabolomic analyses revealed that the PI3K-Akt and MAPK signaling pathways play crucial roles in mediating GACE’s therapeutic effects against liver injury. Further validation demonstrated that GACE can attenuate CCl4-induced liver injury by inhibiting the PI3K-Akt and MAPK pathways. Full article

Selenium (Se), a vital trace element, plays a significant role in maintaining vascular health and may offer protective effects against atherosclerosis. Its actions are mediated through Se-dependent selenoenzymes and selenoproteins, which enhance antioxidant defense, modulate inflammatory responses, and promote autophagy. These processes collectively help prevent cellular senescence—a state associated with age-related vascular decline characterized by oxidative stress, DNA damage, pro-inflammatory activity, and endothelial dysfunction. Epidemiological evidence consistently shows that low Se status is associated with increased risk of atherosclerotic cardiovascular disease within a narrow concentration range. However, clinical trials have not demonstrated clear reductions in cardiovascular events or mortality with Se supplementation alone. Overall, current evidence indicates that Se modulates key mechanisms involved in vascular aging and atherosclerosis, particularly redox balance, immune activation, and vascular cell homeostasis. This comprehensive review summarizes current epidemiological, clinical, and experimental research on the role of Se in cardiovascular health. It underscores Se’s potential as a promising strategy for the prevention and treatment of atherosclerosis, while also acknowledging the complexities and nuances of its effects on vascular health. A deeper understanding of the cellular and molecular mechanisms involved could pave the way for targeted interventions aimed at reducing the burden of atherosclerotic cardiovascular disease. Full article

Background/Objectives: Non-alcoholic steatohepatitis (NASH) represents a worldwide health challenge with limited currently available effective treatment. The present analysis was designed to examine possible therapeutic advances of Ambrisentan (AMB) targeting multiple features of hepatic damage in dexamethasone (DEXA)-provoked nonalcoholic steatohepatitis (NASH) in rats. Methods: Rats were randomly divided into four groups: a control group; a DEXA group; and two AMB-treated groups that received AMB (5 or 10 mg/kg/day orally for a week) before and concomitantly with DEXA (8 mg/kg/day, i.p.) for 6 days. After completion of the experiment, serum markers of liver function and lipid profile were assessed, and hepatic histopathological alterations were examined. Results: AMB (mainly at 10 mg/kg/day) markedly ameliorated liver-function parameters, the lipid profile, and hepatic histopathological characteristics in DEXA-treated rats. MDA was reduced, whereas GSH, GPX4 and Nrf2 were heightened, indicating elevated oxidative damage. Moreover, AMB efficiently reinstated iron homeostasis and aggravated iron overload by altering serum iron, hepatic ferritin, transferrin and hepcidin. AMB decreased serum calcium and hepatic calcineurin A levels, followed by a reduction in hepatic autophagy biomarker Beclin-1. AMB downregulated pro-inflammatory biomarkers NF-κB, IL-6 and TGF-β1. Moreover, it notably repressed the hepatic gene expression of ferritinophagy biomarker NCOA4, with elevated FTH1 hepatic gene expression. Moreover, AMB ameliorated DEXA-induced changes in endothelial and vascular function by increasing hepatic PGI2 and cGMP and lowering ET-1 and iNOS. Conclusions: AMB improved DEXA-induced NASH, primarily through its action on endothelin pathways, with associated reductions in inflammation and the downstream processes of ferroptosis, ferritinophagy, lipophagy, and autophagy. Full article

Affective disorders, including anxiety, depression, and bipolar disorder (BD), represent a global mental health burden with complex, multifactorial etiopathogenesis. Increasing evidence implicates neuroinflammation, oxidative stress, and dysregulation of neurotrophic and neurotransmitter systems as central mechanisms driving these conditions. Flavonoids, a structurally diverse class of plant-derived polyphenolic compounds abundantly found in fruits, vegetables, tea, and other dietary sources, have emerged as promising modulators of these pathophysiological pathways. This narrative review synthesizes current preclinical and clinical evidence on the role of flavonoids and related natural compounds in modulating neuroinflammation and affective disorders. We describe the major flavonoid subclasses—flavones, flavonols, isoflavones, anthocyanins, flavanones, and flavan-3-ols—and analyze their mechanisms of action, including inhibition of the NF-κB/NLRP3 axis, reduction in pro-inflammatory cytokines, attenuation of oxidative stress via Nrf2 pathway activation, modulation of monoaminergic and GABAergic neurotransmission, promotion of Brain-Derived Neurotrophic Factor (BDNF)-mediated neuroplasticity, and regulation of the microbiota–gut–brain axis. Preclinical studies consistently demonstrate anxiolytic and antidepressant effects for compounds such as quercetin, luteolin, apigenin, and chrysin; however, clinical evidence remains limited and methodologically heterogeneous. Future research should prioritize bioavailability-enhanced formulations, standardized clinical trials, and biomarker-guided stratification to fully establish the therapeutic potential of flavonoids in affective disorders. Full article

Background: Muscle function determines overall health and is often impaired in metabolic syndrome and cancer, largely due to oxidative stress and inflammation. Olive mill wastewater (OMWW) is rich in bioactive polyphenols (e.g., hydroxytyrosol and verbascoside) that may hinder these potential pro-sarcopenic mechanisms, representing a potential nutraceutical to limit muscle health decline. Objective: To evaluate the effects of short-term supplementation with an OMWW-derived polyphenol extract (Oliphenolia^®, OMWW-OL) on muscle-related parameters and antioxidant biomarkers in adults at metabolic risk while maintaining dietary habits. Methods: This exploratory, hypothesis-driven secondary analysis was based on a single-arm longitudinal pilot study assessing patients at baseline (T0), after 30 days of supplementation (T1), and 30 days post-discontinuation (T2). Anthropometry, bioelectrical impedance, and biochemical assessments were performed. Results: Supplementation was associated with modest increases in skeletal muscle mass, muscle mass percentage, and wrist, arm, and calf circumferences. Fat mass decreased progressively, while total body water percentage and hydration status improved. Ferritin levels rose at T2, alongside increases in protein thiols (PSH) and Trolox equivalent antioxidant capacity (TEAC), suggesting improved iron status and reduced oxidative stress. Body weight and BMI decreased, as expected in a dietary intervention for metabolic syndrome, while muscle health showed a tendency toward improvement. Conclusions: Although the findings require cautious interpretation, short-term OMWW-OL supplementation was associated with modest but consistent directional changes in muscle-related and metabolic indicators in adults at metabolic risk. The results support hypothesis generation and highlight the need for larger studies to further explore the potential role of OMWW-OL in the context of cancer-associated sarcopenia. Full article