Search Results (396)

Skeletal muscle atrophy underlies sarcopenia, frailty, and muscular dystrophies, but the molecular mechanisms linking oxidative stress to muscle degeneration remain incompletely understood. We previously identified protein complex formation between transient receptor potential canonical 3 (TRPC3) and NADPH oxidase 2 (Nox2) as a key driver of anthracycline-induced myocardial atrophy. Here, we investigated whether this complex also contributes to skeletal muscle wasting. In skeletal muscle from sciatic nerve transection model mice and Duchenne muscular dystrophy (mdx) mice, TRPC3-Nox2 complex formation was enhanced. TRPC3 deletion significantly attenuated denervation-induced soleus atrophy and reduced reactive oxygen species (ROS) production. TRPC3-Nox2 complex formation was upregulated in the soleus muscle (SM) of mdx mice. Pharmacological disruption of the TRPC3-Nox2 interaction improved muscle size and strength and reduced plasma creatine kinase in mdx mice. A recombinant adeno-associated virus (AAV) encoding a TRPC3 C-terminal peptide was used to suppress TRPC3-Nox2 complex formation in vivo. AAV-mediated expression of TRPC3 C-terminal peptide mitigated muscle wasting (CSA) in mdx mice, while muscle strength and plasma CK were not significantly improved. Thus, TRPC3-Nox2 complex formation may be a pivotal driver of oxidative stress-mediated skeletal muscle atrophy. Targeting this protein–protein interaction represents a promising therapeutic strategy for Duchenne muscular dystrophy (DMD) and other intractable muscle-wasting disorders. Full article

Aim: to study the level of immunoglobulin FLC in patients with myocarditis in comparison with non-inflammatory heart diseases, and FLC’s correlation with the severity of CHF. Methods: Ninety-nine patients (41 women, 59.6 ± 14.6 y.o.) were included in the study: 50 patients with myocarditis [confirmed by myocardial biopsy (n = 20) and/or cardiac MRI]; 49 patients with non-inflammatory heart disease. CHF was diagnosed in 66% and 65% of patients, respectively. The levels of FLC were determined using the ‘Cloneus S-FLC-K TIA Kit’ and ‘Cloneus S-FLC-L TIA Kit’ reagents. Results: Elevated FLC levels were found in 56% of patients with myocarditis and in 67% of comparison group patients (p > 0.05). Mean FLC kappa levels were 13.4 [11.7; 16.7] and 16.0 [11.3; 23.7] mg/L, FLC lambda 22.7 [16.7; 32.4] and 24.7 [18.1; 39.1] mg/L, FLC kappa/lambda ratio 0.62 [0.50; 0.73] and 0.65 [0.56; 0.76] in myocarditis and comparison groups, respectively; there were no significant differences between groups. Both groups showed correlations of FLC levels with levels of CRP and leukocytes, as well as with glomerular filtration rate, CHF NYHA class, and left ventricular ejection fraction. Only in patients with myocarditis did we observe a significant correlation between both kappa and lambda FLC and NT-proBNP (r = 0.528, p = 0.004, and r = 0.756, p < 0.001) and high-sensitivity troponin (r = 0.829, p = 0.042) levels. Conclusions: Increased FLC level may be considered an important pathogenetic link reflecting both specific mechanisms of myocarditis and severity of CHF. The determination of FLC can be used as an additional diagnostic marker, as well as one predictor of the decompensated course of myocarditis. Full article

Background: The senescence of testicular Leydig cells (LCs) is a key cause of age-related testosterone deficiency, in which oxidative stress (OS) and mitochondrial dysfunction are critical driving mechanisms. We explore whether the bioactive peptide C248 of PRDX4, an intracellular antioxidant, exerts mitochondrial protection to ameliorate LCs’ function. Methods: Based on the antioxidant domains of the PRDX4 protein, small molecular peptides were designed, and bioactive peptide C248 stood out from the crowd. An OS-induced senescence model of LCs was constructed by treating the MLTC-1 cell line with hydrogen peroxide (H₂O₂). C248 peptide or nicotinamide mononucleotide (NMN), as the positive control, was administered in the culture medium. The cellular function-related indicators, including DPPH free radical scavenging rate, cell viability, testosterone level, hydrogen peroxide (H₂O₂) content, senescence-associated β-galactosidase (SA-β-gal) activity, 8-hydroxy-2′-deoxyguanosine (8-OHDG) level, and 4-hydroxynonenal (4-HNE) level, were evaluated. The mitochondrial function and structural indicators, such as mitochondrial membrane potential, ATP production, mitochondrial morphology, and mitochondrial DNA (mtDNA) copy number, were subsequently tested. Results: In vitro experiments confirmed that C248 could scavenge DPPH free radicals in a dose-dependent manner, reduce the levels of reactive oxygen species, and increase antioxidant enzyme activity in LCs (p < 0.01). Both C248 and NMN increased testosterone secretion and improved cell viability (p < 0.01). Both C248 and NMN increased mitochondrial morphology and quantity, mitochondrial membrane potential (p < 0.01), ATP production (p < 0.01), and mitochondrial DNA (mtDNA) copy number (p < 0.01). Conclusion: This study reveals that the small molecular C248, a bioactive peptide of PRDX4, is a new candidate molecule for intervening in LC senescence and confirms that mitochondrial protection is a key strategy for improving age-related testicular dysfunction. Full article

Airborne particulate matter (PM) is a major environmental pollutant that accelerates skin aging, inflammation, and barrier impairment. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has shown anti-inflammatory and cytoprotective effects, yet its role in protecting full-thickness human skin from pollution-induced damage remains unclear. In this study, human full-thickness ex vivo skin explants were topically exposed to PM (0.54 mg/cm²) and treated with CBD (6.4 mM) administered via the culture medium for 48 h. Proinflammatory mediators (interleukin-6, IL-6; matrix metalloproteinase-1, MMP-1; cyclooxygenase-2, COX-2), oxidative stress markers (reactive oxygen species, ROS; 8-hydroxy-2′-deoxyguanosine, 8-OHdG), the xenobiotic sensor aryl hydrocarbon receptor (AhR), extracellular matrix proteins (procollagen type I C-peptide, PIP; fibrillin), and the barrier protein filaggrin were quantified using ELISA and immunofluorescence. PM exposure triggered significant inflammation, oxidative stress, AhR induction, extracellular matrix degradation, and barrier disruption. CBD selectively counteracted these effects by reducing IL-6, MMP-1, COX-2, ROS, and 8-OHdG levels, downregulating AhR expression, and restoring PIP, fibrillin, and filaggrin expression. No measurable effects were observed in unstressed control tissues. These results demonstrate that CBD protects human skin from PM-induced molecular damage and supports its potential as a functional bioactive ingredient for anti-pollution applications. Full article

Psoriasis vulgaris is a T-cell-mediated skin disease that may involve an autoimmune response against melanocytes. It develops through still unexplained pathomechanisms. Streptococcal tonsillopharyngitis is a major trigger of psoriasis onset and relapses. HLA-C*06:02 is the main psoriasis risk gene. Here we find that B cells isolated from streptococci-infected tonsils or peripheral blood of HLA-C*06:02⁺ psoriasis patients stimulate an HLA-C*06:02-restricted melanocyte-reactive Vα3S1/Vβ13S1 T-cell receptor (TCR) from a lesional psoriatic CD8⁺ T cell clone in an IFN-γ-enhanced manner. Patients’ B cells furthermore induce proliferation of autologous blood CD8⁺ T cells. We identify several HLA-C*06:02-presented self-peptides in the immunopeptidomes we had isolated from four HLA-C*06:02 homozygous B-cell lines that stimulate the Vα3S1/Vβ13S1 TCR and differ from the melanocyte autoantigen recognized by this TCR. These data suggest that the proinflammatory environment of streptococcal tonsillopharyngitis may enable B cells to activate autoreactive CD8⁺ T cells that, owing to the polyspecificity of T-cell receptors, recognize several B-cell self-peptides presented by HLA-C*06:02 and subsequently cross-react against melanocytes in the skin, thereby triggering psoriasis. The capacity of B cells to stimulate a cross-reactive autoimmune response through HLA class I-presented B-cell peptides is a previously unknown mechanism in the induction of autoimmunity that could explain psoriasis onset and persistence. Full article

Chronic low-grade inflammation is a central contributor to the development of cardiovascular disease, metabolic dysfunction, autoimmune disorders, and cognitive decline. Blood-based biomarkers, such as C-reactive protein (CRP), ferritin, homocysteine, white blood cell (WBC) count, and anti-thyroid peroxidase (anti-TPO) antibodies enable quantification and monitoring of systemic inflammation over time. We aimed to evaluate the impact of a 12-week personalized, biomarker-guided supplementation program including micronutrients, hormone support, and peptides on inflammatory and immune-related biomarkers across age- and sex-stratified adult cohorts. Participants (n = 48; 8 per group) were stratified by sex and age (40–49, 50–59, 60–69 years) and underwent blood testing at baseline and 12 weeks. Personalized protocols were developed based on individual biomarker profiles and included targeted interventions with vitamin D, omega-3 fatty acids, B vitamins, zinc, selenium, hormone optimization, and other supportive agents. Primary outcomes were percent changes in CRP, ferritin, homocysteine, WBC count, and anti-TPO antibody levels. CRP levels decreased by 33–46% across all groups, with similarly consistent declines in homocysteine (29–37%) and WBC count (22–28%). Ferritin reductions were most notable in men, particularly in older age groups (up to 48%), while anti-TPO antibody levels declined more prominently in women (up to 22%). These changes are consistent with reduced systemic inflammation, improved methylation status, and potential modulation of autoimmune activity. This biomarker-guided, personalized supplementation protocol was associated with clinically meaningful reductions in key markers of inflammation and immune dysregulation. These findings are suggestive of potential efficacy for precision-based health optimization programs and highlight the need for larger randomized controlled trials (RCTs) to confirm causal effects. Full article

Background: Systemic inflammation plays a pivotal role in heart failure (HF) progression, yet no meta-analysis has synthesized prospective cohort data on interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and neutrophil-to-lymphocyte ratio (NLR) as prognostic biomarkers. Objectives: To quantify the independent prognostic value of IL-6, hs-CRP, and NLR for mortality and HF-related outcomes across HF phenotypes. Methods: Following PRISMA and MOOSE guidelines, we searched PubMed, Embase, Scopus, Web of Science, and CENTRAL from January 2014 to October 2025 for prospective cohorts reporting adjusted hazard ratios (HRs). Random-effects meta-analysis pooled HRs; heterogeneity was assessed via I² statistic, with subgroup and sensitivity analyses for robustness. Quality was evaluated using Newcastle–Ottawa Scale (NOS) and GRADE. Results: Thirteen cohorts (n ≈ 19,000) were included. Elevated IL-6 (five studies) was associated with increased all-cause mortality and composite outcomes (low-moderate heterogeneity, I² < 35%). hs-CRP (five studies) showed similar prognostic strength, with trajectories amplifying risk. NLR (three studies) independently predicted adverse events with negligible heterogeneity. Associations persisted across HFrEF and HFpEF, acute/chronic settings, and geographic regions, independent of natriuretic peptides and comorbidities (NOS median 8/9; GRADE moderate-to-high). Conclusions: IL-6, hs-CRP, and NLR are robust, independent prognostic biomarkers in HF, supporting their integration into clinical risk stratification and inflammation-targeted therapies. PROSPERO: CRD420251207035. Full article

Background: Inflammation plays a key role in the pathogenesis of type 2 diabetes (T2D) and the associated cardiovascular complications. High-sensitivity C-reactive protein (hsCRP) is a widely used marker of systemic inflammation as well as a predictor of cardiovascular risk. Objective: There is increasing evidence that glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, may have effects on hsCRP levels, independent of their effects on glycemic control and body weight loss. This purpose of our study is to explore the effect of semaglutide on hsCRP levels in patients with type 2 diabetes. Additionally, we aimed to determine whether the observed effect of semaglutide on hsCRP is fully mediated by changes in HbA1c and body weight, or whether there is a direct effect suggesting the presence of an independent anti-inflammatory mechanism. Methods: The study included 70 outpatients with diagnosed type 2 diabetes undergoing therapy with metformin and/or a sulfonylurea. Semaglutide was added to the existing therapeutic regimen. All participants were followed up after a 6-month a period. At the beginning and at the end of the study, the hsCRP values, some selected indicators of glycemic control, and the anthropometric measurements were recorded. Results: The mean hsCRP value at baseline was 4.90 ± 1.21 mg/L, while after six-month therapy, it dropped to 2.23 ± 2.21 mg/L. Conclusions: The results of the analysis have a good potential to contribute to a better understanding of the pleiotropic effects of GLP-1 RAs and support the hypothesis of a direct anti-inflammatory role of semaglutide, which could have clinical significance in the context of cardiometabolic risk management in patients with type 2 diabetes. Full article

Objective: Obesity is characterized by chronic inflammation and gut dysbiosis, yet circulating markers reflecting intestinal immune activation remain limited. Regenerating islet-derived protein 3 alpha (REG3α), an antimicrobial peptide secreted by intestinal Paneth cells, plays a pivotal role in mucosal defense and mirrors microbial–epithelial interactions. In this cross-sectional study, we aimed to examine circulating REG3α levels in infection-free adults with obesity, overweight, and normal weight, and to explore their associations with vitamin D supplementation and biomarkers of inflammation and dysbiosis. Methods: Sixty-nine participants were stratified into control, overweight, and obesity groups. Serum REG3α, interleukin-6 (IL-6), β-defensin-2, high-sensitivity c-reactive protein, ferritin, and presepsin were assessed. Vitamin D status and supplementation history were recorded. Multivariable linear regression, principal component analysis (PCA), and bootstrap mediation models were applied to explore associations and potential indirect effects. Results: REG3α concentrations were higher in overweight and obesity compared to controls (646 ± 217 vs. 521 ± 311 ng/mL); however, the difference was not significant (p = 0.15). Vitamin D supplementation was inversely associated with REG3α (p = 0.06), and this effect appeared weaker in obesity. REG3α correlated positively with IL-6 (ρ = 0.28) and β-defensin-2 (ρ = 0.43). PCA revealed a shared inflammatory–mucosal activation component that predicted REG3α levels. Exploratory mediation suggested a partial indirect effect of vitamin D via reduced inflammatory activity. Conclusions: Circulating REG3α shows associations with indicators of inflammation and vitamin D supplementation in individuals with overweight and obesity. Although differences between groups did not reach statistical significance, the observed trends suggest possible links between mucosal immune activity and metabolic status. These exploratory results warrant validation in larger, longitudinal studies before any biomarker role can be established. Full article

Background: Ginseng oligopeptides (GOPs), small bioactive peptides with potent antioxidant capacity and high bioavailability, have shown promise in promoting healthy aging; however, their underlying molecular mechanisms remain largely unexplored. Methods: Using the model organism Caenorhabditis elegans (C. elegans), we comprehensively evaluated the anti-aging effects of GOPs on lifespan, locomotion, oxidative stress, and gene expression. Integrated phenotypic assays and transcriptomic analyses were conducted to elucidate GOP-mediated molecular mechanisms. The transgenic strain TJ356 (DAF-16::GFP) and the loss-of-function mutant CF1038 [daf-16(mu86)] were employed to functionally validate the role of the DAF-16/FOXO pathway. Results: GOP supplementation significantly extended median lifespan by approximately 11.5% and improved age-related locomotion decline in C. elegans. Transcriptomic profiling identified 1928 differentially expressed genes (DEGs) enriched in metabolic, antioxidant defense, and longevity-regulating pathways. GOPs upregulated key antioxidant and stress-response genes (gst-4, sod-5, mtl-1) and longevity-related regulators (daf-16, lin-31, Y51B9A.9, and daf-12), while downregulating ins-7, an insulin-like peptide. Moreover, GOPs enhanced cytochrome P450–related detoxification and vitamin-dependent (retinol, ascorbate, and riboflavin) metabolic pathways, establishing a multidimensional antioxidant defense network. Phenotypic validation confirmed that GOPs markedly reduced reactive oxygen species (ROS) levels and lipofuscin accumulation (p < 0.001). Notably, GOPs promoted DAF-16 nuclear translocation in TJ356 worms, whereas the lifespan-extending effects were abolished in CF1038 mutants, highlighting the essential role of DAF-16/FOXO in mediating GOP effects. Conclusions: GOPs delay aging in C. elegans by activating the DAF-16/FOXO signaling cascade and reinforcing antioxidant networks, thereby maintaining redox and metabolic homeostasis. These findings provide novel mechanistic evidence supporting GOPs as promising dietary antioxidants for promoting healthy aging through modulation of conserved redox and longevity pathways. Full article

GV1001, a multifunctional peptide, has shown numerous biomedical activities, including antioxidant, anti-inflammatory, anti-Alzheimer’s, and anti-atherosclerotic effects, and protects mitochondria from cytotoxic agents. Cisplatin is a widely used chemotherapeutic agent against cancers, but its clinical utility is limited by nephrotoxicity driven by mitochondrial dysfunction in renal epithelial cells. Here, we investigated whether GV1001 protected against cisplatin-induced nephrotoxicity (CIN) in vivo and preserved mitochondrial integrity in human renal epithelial cells in vitro. In mice, GV1001 substantially mitigated CIN by significantly reducing histological damage, kidney injury marker expression, macrophage infiltration, endothelial-to-mesenchymal transition, inflammation, and apoptosis. In cultured renal epithelial cells, GV1001 maintained mitochondrial membrane potential, preserved ATP production, and prevented mitochondrial membrane peroxidation possibly by binding to cardiolipin. GV1001 also reduced the level of reactive oxygen species (ROS), suppressed cytochrome c release into the cytosol, and inhibited activation of apoptosis-related pathways elicited by cisplatin. Collectively, these findings demonstrated that GV1001 might protect kidney from cisplatin through maintaining mitochondrial structure and function and suppressing downstream injury cascades in renal epithelial cells. By directly targeting the mitochondrial mechanisms underlying cisplatin toxicity, GV1001 represents as a promising therapeutic strategy to mitigate CIN and improve the safety of cisplatin-based chemotherapy. Full article

African swine fever virus (ASFV) is the only member of the family Asfarviridae and can cause African swine fever, a disease with a consistently high mortality rate. The pE248R protein, a myristoylated integral membrane protein of ASFV, is required for virus infectivity and some early postentry event, making it a key target for studying the prevention and treatment of ASFV. In this study, BALB/c mice were immunized with purified recombinant pE248R protein, leading to the generation of five monoclonal antibodies (mAbs). Selected mAbs were subsequently subjected to further characterization. By identifying the reactivity of different pE248R protein peptide segments with these monoclonal antibodies, we screened and identified a linear B cell epitope (⁸⁷QEVALTQWMDAG⁹⁸) on the pE248R protein. These results provide a new theoretical basis for analyzing the structure and function of pE248R protein, particularly contributing to the construction of a comprehensive B-cell epitope map for ASFV immunogens. Full article

Cardiovascular diseases (CVDs) remain a leading cause of mortality worldwide. According to the WHO, every year, there is an increase in the rate of death globally due to CVDs, stroke, and myocardial infarction. Several risk factors contribute to the development of CVDs, one of which is hypoxia, defined as a reduction in oxygen levels. This major stressor affects aerobic species and plays a crucial role in the development of cardiovascular disease. Research has uncovered the “hypoxia-inducible factors (HIFs) switch” and investigated the onset, progression, acute and chronic effects, and adaptations of hypoxia, particularly at high altitudes. The hypoxia signalling pathways are closely linked to natural rhythms such as the circadian rhythm and hibernation. In addition to genetic and evolutionary factors, epigenetics also plays an important role in postnatal cardiovascular responses to hypoxia. Oxidized LDL-C initiates atherosclerosis amidst oxidative stress, inflammation, endothelial dysfunction, and vascular remodelling in CVD pathogenesis. Anti-inflammatory and antioxidant biomarkers are needed to identify individuals at risk of cardiovascular events and enhance risk prediction. Among these, C-reactive protein (CRP) is a recognized marker of vascular inflammation in coronary arteries. Elevated pro-atherogenic oxidized LDL (oxLDL) expression serves as an antioxidant marker, predicting coronary heart disease in apparently healthy men. Natural antioxidants and anti-inflammatory molecules protect the heart by reducing oxidative stress, enhancing vasodilation, and improving endothelial function. For instance, the flavonoid quercetin exerts antioxidant and anti-inflammatory effects primarily by activating the Nrf2/HO-1 signaling pathway, thereby enhancing cellular antioxidant defense and reducing reactive oxygen species. Carotenoids, such as astaxanthin, exhibit potent antioxidant activity by scavenging free radicals and preserving mitochondrial integrity. The alkaloid berberine mediates cardiovascular benefits through activation of AMO-activated protein kinase (AMPK) and inhibition of nuclear factor kappa B [NF-kB] signalling, improving lipid metabolism and suppressing inflammatory cytokines. Emerging evidence highlights microRNAs (miRNAs) as potential regulators of oxidative stress via endothelial nitric oxide synthase (eNOS) and silent mating-type information regulation 2 homolog (SIRT1). While the exact mechanisms remain unclear, their benefits are likely to include antioxidant and anti-inflammatory effects, notably reducing the susceptibility of low-density lipoproteins to oxidation. Additionally, the interactions between organs under hypoxia signalling underscore the need for a comprehensive regulatory framework that can support the identification of therapeutic targets, advance clinical research, and enhance treatments, including FDA-approved drugs and those in clinical trials. Promising natural products, including polysaccharides, alkaloids, saponins, flavonoids, and peptides, as well as traditional Indian medicines, have demonstrated anti-hypoxic properties. Their mechanisms of action include increasing haemoglobin, glycogen, and ATP levels, reducing oxidative stress and lipid peroxidation, preserving mitochondrial function, and regulating genes related to apoptosis. These findings emphasise the importance of anti-hypoxia research for the development of effective therapies to combat this critical health problem. A recent approach to controlling CVDs involves the use of antioxidant and anti-inflammatory therapeutics through low-dose dietary supplementation. Despite their effectiveness at low doses, further research on ROS, antioxidants, and nutrition, supported by large multicentre trials, is needed to optimize this strategy. Full article

Background and Objectives: Left ventricular diastolic dysfunction (LVDD) is a known precursor of heart failure with preserved ejection fraction (HFpEF), particularly in patients with metabolic comorbidities. Acute coronary syndrome (ACS) and percutaneous coronary interventions (PCI) may exacerbate LVDD via systemic inflammation. This study aimed to explore the association between post-procedural systemic inflammation and the severity of diastolic dysfunction in patients with ACS and metabolic comorbidities. Materials and Methods: A retrospective observational study was conducted in 181 patients with ACS who underwent PCI. Inflammatory markers (leukocytes, neutrophils, and C-reactive protein [CRP]) measured at 24–48 h post-intervention were analyzed in relation to diastolic dysfunction, assessed by echocardiography. Multivariable ordinal logistic regression and correlation analyses were performed. Results: CRP showed a non-significant trend toward association with more advanced diastolic dysfunction (p = 0.081). Hypertension had a positive but nonsignificant coefficient. Other metabolic comorbidities (diabetes, dyslipidemia, and obesity) were not significantly associated. The correlation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin was exploratory. NT-proBNP was the only marker significantly correlated with high-sensitivity troponin (TrHS) at 48 h, indicating a link between myocardial injury and wall stress. Conclusions: CRP may be weakly associated with the severity of diastolic dysfunction post-PCI. However, classical metabolic comorbidities were not independently predictive. Post-PCI inflammation showed only modest, non-significant trends toward diastolic impairment, warranting confirmation in larger prospective studies. Full article

A growing scientific interest in bioactive compounds from sea cucumbers is contributing to a broader recognition even in regions where their consumption is not common. This study evaluated the biological potential of a Holothuria forskali extract obtained through different extraction methods, including water extraction, ethanol–water extraction, and enzymatic hydrolysis. The hydrolysate (H), rich in low-molecular-weight peptides, yielded the highest antioxidant (30.6 ± 0.6 mg VitC Eq/g sample for ABTS and 10.7 ± 0.1 mg GAEs/g sample for Folin-reactive substances) and ACE-inhibitory (82.6%) activities. Based on these results, the hydrolysate was selected for encapsulation in two nanostructured delivery systems for comparative purposes: chitosan nanoparticles (NPs) and rapeseed lecithin liposomes (LPs). Both nanostructures were characterized in terms of size, ζ-potential, and polydispersity and subjected to simulated in vitro gastrointestinal digestion (GIDv) to assess their stability and mucoadhesive properties. After digestion, antioxidant activity increased in both systems, particularly in liposomes. Although encapsulation initially reduced ACE-inhibitory activity, gastrointestinal digestion restored or enhanced it, especially in liposomal formulations (≈37% inhibition). The mucoadhesive potential of the nanostructures after DGIv, focusing on their interactions with mucin, was assessed. Liposomal digests significantly increased viscosity in the presence of mucin, while chitosan nanoparticles decreased it, suggesting the formation of soluble complexes with reduced hydrodynamic volume. Electrostatic and hydrogen bonding interactions between chitosan and mucin were particularly evident in the NPH formulation. The rheological synergism parameter (Δη) revealed more negative values for NPs and NPHs, indicating stronger mucoadhesive interactions compared to controls and suggesting their suitability for mucosal delivery. These findings support the use of H. forskali hydrolysates as a source of functional bioactive compounds and highlight the potential of chitosan-based nanocarriers for enhancing their stability, bioaccessibility, and mucoadhesive properties in functional food or nutraceutical applications. Full article