Search Results (301)

The valorization of culinary by-products into functional bioactive resources represents a significant advancement in sustainable biotechnology. This study characterizes an extract derived from “battuto toscano” by-products, a traditional blend of garlic, onion, carrot, and celery trimmings, recovered through circular economy principles. Comprehensive antioxidant profiling was performed alongside biological evaluations on human cell lines and anti-glycation assays. Results from Folin–Ciocalteu, FRAP, and TEAC assays confirmed a high concentration of secondary metabolites with significant scavenging capacity. In vitro testing on primary human fibroblasts and HaCaT keratinocytes revealed a concentration- and time-dependent biological response, with lower concentrations showing better compatibility and transiently enhancing HaCaT metabolic activity. Furthermore, BTE reduced AGE-associated fluorescence in the BSA–glucose model, particularly at 5 mg/mL, supporting its potential anti-glycation activity. These findings establish “battuto toscano” by-products as a reservoir of sustainable biomolecules. This study offers a transformative resource for the pharma/nutraceutical sectors by bridging culinary tradition with biomedical innovation. Full article

Cyclocarya paliurus leaves, commonly consumed as “sweet tea”, remain underutilized after spring harvest. This pilot study investigated harvest month-associated changes in bioactivity-related properties and volatile profiles of mature leaves collected from May to September (Q5–Q9) at one site in 2024. Aqueous extracts were analyzed for TPC, TFC, TP, TSC, DPPH and ABTS•+ radical scavenging activities, and inhibition of advanced glycation end-products (AGEs) formation in glucose/fructose-BSA models, with aminoguanidine as a positive reference. Dried leaf powders were profiled by SPME-GC-MS for tentative VOC annotation. TPC, TFC, TP, and TSC ranged from 28.04 to 28.87, 15.42 to 40.22, 2.14 to 2.51, and 23.15 to 25.30 mg/g, respectively. Q9 showed the strongest radical scavenging response, with the lowest DPPH and ABTS•+ IC50 values (0.119 and 0.131 mg/mL), while Q6 also exhibited relatively strong activity. Furthermore, Q6 and Q9 exhibited superior advanced glycation end-product (AGE) inhibitory responses, with Q9 being particularly effective in the fructose-BSA model. VOC profiles varied markedly by month, shifting from alkene/terpene predominance in Q5–Q6 to alcohol enrichment in Q7 and renewed alkene/terpene predominance in Q9. Integrated heatmap and Pearson correlation analyses identified clear temporal co-variations and pairwise associations between distinct VOC classes and bioactivity indices. Collectively, these results provide preliminary, site- and year-specific evidence that harvest month is associated with changes in the bioactivity-related properties and aroma-related phytochemical profiles of mature C. paliurus leaves, offering a cautious reference for harvest-stage-oriented utilization. Full article

Background: N-Acetylneuraminic acid (Neu5Ac), the predominant form of sialic acid, exhibits potent antioxidant, anti-inflammatory, and anti-glycation properties in preclinical studies, suggesting potential dermatological benefits. However, robust clinical evidence supporting the efficacy of oral Neu5Ac supplementation on human skin conditions remains lacking. Methods: A randomized, double-blind, placebo-controlled trial was conducted with 55 Chinese women (40–65 years) who received 120 mg/day Neu5Ac (n = 27) or a matching placebo (n = 28) for 84 days. Skin pigmentation, hydration, biomechanical properties, and dermis echogenicity were evaluated at baseline, D28, D56, and D84 using standardized clinical and instrumental assessments. Results: Both clinical (Pantone color card) and instrumental (photographic) assessments showed that oral Neu5Ac supplementation significantly improved skin lightness on both pigmentary spots and surrounding normal skin compared with placebo at day 84. In addition, stratum corneum hydration and skin biologic extensibility were significantly increased in the Neu5Ac group. Dermal echogenicity showed numerical improvement but did not reach statistical significance. Self-assessment indicated that 100% of the Neu5Ac participants reported improvements in skin whiteness, radiance, elasticity, firmness, and hydration, with mean satisfaction scores of 9.1/10 versus 7.9/10 for placebo. Conclusions: Daily oral supplementation with 120 mg Neu5Ac for 84 days significantly promoted localized spot brightening, enhanced skin hydration, and improved skin elasticity, providing the first clinical evidence supporting Neu5Ac as a safe and effective oral cosmetic ingredient for skin anti-aging. Full article

Aloysia triphylla (lemon verbena, LV) herbal tea is a rich source of phenolic compounds with recognized antioxidant and antiglycoxidant properties, although their stability during digestion remains insufficiently understood. This study evaluated the impact of simulated gastrointestinal digestion on the phenolic composition and bioactivity of LV infusion using a standardized in vitro model. Total phenolic, flavonoid, and phenolic acid contents were determined spectrophotometrically, while individual compounds were analyzed by HPLC. Antioxidant activity was assessed using complementary assays (DPPH•, ABTS•, FRAP, ORAC, and nitric oxide scavenging), and antiglycation activity was evaluated using a BSA/D-ribose model. Digestion did not significantly affect total phenolic and phenolic acid contents, whereas flavonoids moderately decreased during the intestinal phase. Verbascoside underwent partial degradation, leading to increased levels of isoverbascoside and caffeic acid. Despite these transformations, antioxidant capacity was maintained or enhanced, particularly in ABTS and ORAC assays, suggesting a contribution of digestion-derived metabolites. Antiglycation activity remained stable after digestion. Pre-column HPLC analyses identified verbascoside and its derivatives as the main contributors to radical scavenging and methylglyoxal trapping activities. These findings indicate that LV infusion retains its bioactive potential after digestion and supports its relevance as a functional beverage. Full article

This study characterises the polyphenol profile (LC–MS), antiglycation (BSA–GLU, BSA–FRU, BSA–MGO), and antioxidant potential (ABTS, DPPH) of A. arguta (‘Scarlet September Kiwi’) and A. kolomikta (‘Lande’) fruit before and after extract purification. A total of 48 polyphenols belonging to 11 chemical groups were identified. Crude Scarlet extract showed higher TPI (1079.51 µg/g dw) than the crude Lande (761.13 µg/g dw), with quercetin glucoside accounting for 71% of TPI. Crude Lande extract was dominated by caffeic acid glucoside (39% TPI). Purification markedly increased TPI values to 4082.13 µg/g dw (Scarlet) and 2550.51 µg/g dw (Lande). The crude extracts more effectively inhibited glucose- and fructose-induced protein glycation (IC₅₀ = 1.81–7.71 mg/mL) than methylglyoxal-mediated glycation (IC₅₀ = 14.33–24.26). Purification significantly enhanced antiglycation efficacy in all models (IC₅₀ = 0.47–1.78), as well as antioxidant capacity (IC₅₀ = 0.10–0.67 mg/mL). Statistical analyses revealed a strong alignment between the glycation-inhibitory activity and the tested antioxidant potential. These findings suggest that targeted purification enhances the functional potential of Actinidia species, making them promising sources of bioactive compounds against oxidative stress and protein glycation-related disorders. Full article

Life expectancy in high-income countries is increasing, leading to a higher incidence of age-related neurodegenerative diseases. To address this urgent medical need, several molecular targets have been identified, including advanced glycation end products (AGEs) and tyrosinase. Given the well-established role of diet in counteracting degenerative processes, this study aimed to identify a potential food ingredient with combined anti-tyrosinase and anti-glycative properties. Acanthus mollis L. was selected based on its inclusion in the BelFrIt list and its known content of tyrosinase inhibitors, such as benzoxazinones and verbascoside. Extraction of A. mollis leaves was optimized using a design of experiments approach, comparing microwave- and ultrasound-assisted techniques. Optimal conditions were achieved using microwave-assisted extraction with ethanol 80%, 80 °C, one cycle, drug-to-solvent ratio of 10 mL/g. The optimized extract (at 5 mg/mL) inhibited tyrosinase activity by approximately 47%, increasing to 58% after chlorophyll removal. Moreover, the extract reduces AGEs formation in presence of methylglyoxal, with an activity at 1 mg/mL comparable with that of a well-known anti-glycative agent. A similar trend was observed in the reduction in methylglyoxal and glyoxal levels. Overall, these results support the potential of the optimized A. mollis extract as a functional food ingredient to counteract aging-related neurodegeneration. Full article

Background/Objective: With rising per capita sugar consumption, skin glycation-related issues including dullness, homeostasis disruption and accelerated wrinkling have gained widespread attention. However, globally standardized and rigorous evaluation criteria for anti-glycation efficacy remain lacking. This study aimed to establish stage-specific glycation injury cell models and elucidate the stage-dependent molecular mechanisms of glycation-induced fibroblast damage, providing a standardized reference for anti-glycation efficacy assessment. Methods: Three glycation injury models were constructed in human foreskin fibroblasts (HFF-1): early-stage (glucose-induced), intermediate-stage (glyoxal-induced), and late-stage (advanced glycation end products (AGEs)-induced). Core biomarkers including Nε-(carboxymethyl)lysine (CML), collagen type I (Col I) and elastin (ELN) were used to optimize modeling conditions via Cell Counting Kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA). Untargeted metabolomics based on ultra-high-performance liquid chromatography (UHPLC)-Q Exactive Orbitrap was applied to identify differential metabolites and perturbed pathways, following Metabolomics Standards Initiative (MSI) Level 2 identification criteria. Results: Optimal conditions were determined as 50 mmol/L glucose for 48 h, 0.5 mmol/L glyoxal for 48 h, and 200 μg/mL AGEs for 24 h. A total of 319, 34 and 148 differential metabolites were identified in the three groups, respectively. Six key pathways were significantly perturbed. Early and intermediate models shared similar mechanisms (purine metabolism disturbance), while the late model showed distinct alterations in pyrimidine, nicotinate, arachidonic acid and steroid hormone metabolism. Conclusions: Three stable stage-specific glycation models were successfully established in HFF-1 cells. Significant differences in metabolic profiles and mechanisms exist across the three stages, providing a rational basis for model selection and theoretical support for anti-glycation efficacy evaluation. Full article

The advanced glycation end products generated from protein glycation are associated with the development of diabetic complications. This study aimed to investigate the inhibitory mechanisms of isoliquiritigenin on protein glycation and compare its anti-glycation activity in PBS versus a macromolecular crowding environment. The results showed that in PBS, 500 μmol/L isoliquiritigenin showed an advanced glycation end product inhibition rate of 37.78%, outperforming aminoguanidine. Meanwhile, isoliquiritigenin inhibited the protein carbonylation process, reduced the generation of protein oxidation products, and inhibited the formation of β-crosslinking structures with a rate of 34.20%. Molecular docking results indicated that isoliquiritigenin bound to site I of bovine serum albumin, effectively blocked glycation reactions by occupying multiple arginine residues and contributed to stabilizing the secondary structure of bovine serum albumin. In addition, isoliquiritigenin exhibited significant hydroxyl radical scavenging and Fe²⁺-chelating abilities, achieving a 34.35% trapping efficiency for methylglyoxal. Isoliquiritigenin exerted its anti-glycation activity through multiple pathways, including scavenging free radicals, protecting protein structure, interacting with bovine serum albumin, and trapping methylglyoxal. However, in the crowding environment, the excluded volume effect and higher viscosity might lead to limited isoliquiritigenin binding to bovine serum albumin, reducing its inhibition of glycation and decreasing advanced glycation end product inhibition to 16.38%. This study realistically evaluated the inhibitory effects of isoliquiritigenin in complex crowding environments and provided a theoretical basis for isoliquiritigenin as a functional food ingredient for the prevention of diabetes complications. Future studies need to establish animal models to further explore its effects in vivo. Full article

Plants produce diverse metabolites with potential benefits for human health. However, the metabolomes of plant callus cultures—cell cultures analogous to stem cells—remain poorly characterized in terms of their functional relevance. This study aimed to systematically profile and functionally annotate metabolites from diverse plant callus cultures to better understand their potential biological activities and applications. We profiled the metabolomes of six plant calli: Acacia concinna (Shikakai), Daucus carota (carrot), Hibiscus sabdariffa (hibiscus), Linum usitatissimum (flax), Ocimum sanctum (tulsi), and the Nicotiana tabacum Bright-Yellow 2 (BY-2) cell line. To facilitate functional interpretation, we developed Metabolite2Function (M2F), a pipeline that annotates metabolites with biological functions using scientific literature and large language modeling. Untargeted metabolomics identified 177 metabolites, revealing clustering patterns independent of genetic relationships, culture age, or growth rate. Tulsi and carrot calli exhibited enrichment in metabolites relative to the tobacco reference line, whereas flax and hibiscus were comparatively depleted. Most metabolites varied across at least four calli, and 10% were unique to a single species. Using M2F, we annotated 87 metabolites with beneficial activities, including antioxidant, anti-glycation, anti-inflammatory, and anti-senescence functions, as well as skin-related effects such as collagen production and brightening. Notably, antioxidant and anti-senescence metabolite levels correlated with corresponding biological activities in human cells. Plant callus cultures generate distinct and functionally diverse bioactive metabolomes. M2F provides a scalable framework for systematic functional annotation relevant to human health and cosmetic applications. Full article

This study focused on the inhibitory effects of wheat bran feruloyl oligosaccharides (FOs) on the formation of AGEs in three bovine serum albumin (BSA)-based non-enzymatic glycation models, namely BSA-fructose, BSA-methylglyoxal (MGO), and BSA-glyoxal (GO). In the BSA-fructose model, FOs at 0.25 mg/mL achieved a 62% inhibition rate of fructosamine, equivalent to approximately 78% of the activity of the positive control aminoguanidine (AG), and reduced fluorescent AGEs by over 50% on day 12. Additionally, FOs suppressed the accumulation of α-dicarbonyl compounds, key intermediates in the glycation pathway. In the BSA-MGO and BSA-GO system, the decreased fluorescence intensity of tryptophan residues indicated that FOs bound to BSA, inducing conformational changes in the protein microenvironment; this binding also inhibited protein carbonyl formation and the loss of thiol groups, thereby modulating the protein glycation process. Compared with their precursors (ferulic acid, FA; xylooligosaccharides, XOS), FOs exhibited comparable or even superior inhibitory activity against specific AGE subtypes, suggesting a synergistic effect between the feruloyl and oligosaccharide moieties. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed that FOs reduced the band intensity of 90 kDa AGEs in the glycation system, indicating the inhibition of protein-fructose cross-linking. Fluorescence spectroscopy confirmed that FOs dynamically quenched BSA with a single binding site, and thermodynamic calculations demonstrated that the binding was spontaneous (ΔG < 0), primarily driven by hydrogen bonds and van der Waals forces (ΔH < 0, ΔS < 0). This study systematically investigated the anti-glycation activities of FOs and their precursors. The findings demonstrate that FOs are promising natural glycation inhibitors and provide important theoretical and experimental support for related research. Furthermore, this study establish a basis for the green and high-value utilization of agricultural by-products like wheat bran. Full article

In this study, the rank of multifaceted activity of catechin (C), epicatechin (EC), epigallocatechin (EGC), epicatechin-3-gallate (ECG) and epigallocatechin-3-gallate (EGCG) was addressed. Their antioxidant activity was determined by the differential pulse voltammetry (DPV), whereas their ability to inhibit angiotensin-converting enzyme (ACE) activity, acetylcholinesterase activity (AChE), and formation of the advanced glycation end-products (AGEs) was performed in a model system to show their importance against hypertension, Alzheimer-type dementia, and diabetic’s complication, respectively. The order of the antioxidant potential of catechins in comparision to gallic acid (GA) was EGCG > ECG > EC > EGC ≈ C > GA, whereas the order of the ACE inhibitory activity was EGCG > ECG > EGC > EC > C, thus indicating the importance of the structure–activity relationship. The correlation between IC₅₀ for ACE inhibition of catechins and their antioxidant activity had the value r = −0.60. The order of the AChE enzyme inhibitory activity was EGCG ≈ EGC > ECG > EC > C, and the weak positive correlation between IC₅₀ and the first anodic peak potential (E_pa1) values was noted (r = 0.67). The ranking of the anti-AGE activities was EGCG ≈ ECG > EGC > EC > C, and a negative correlation between the inhibitory activity of catechins against AGE formation and their antioxidant activity was r = −0.82, whereas a positive correlation (r = 0.88) was noted between their first anodic peak potential (E_pa1) values. The provided results expand our knowledge on the multifaceted activity of catechins, indicating EGCG and ECG as the most active antioxidants against inhibition of ACE and AChE as well as towards AGE formation. Full article

Oxidative stress and inflammation are interconnected pathological processes involved in the progression of neurodegenerative, cardiovascular, and metabolic diseases, highlighting the need for multifunctional therapeutic agents targeting multiple pathways. In this study, two novel hybrid compounds were designed and synthesized in three steps by conjugating butylated phenolic moieties derived from butylated hydroxytoluene and p-coumaric acid with proline and γ-aminobutyric acid (GABA). The aim was the combination of antioxidant, anti-inflammatory, and cytoprotective properties within a single molecular framework. The compounds were evaluated using a comprehensive panel of in vitro and in vivo assays to assess antioxidant, metal-reducing, iron-chelating, antiglycation, anti-inflammatory, and acetylcholinesterase inhibitory activities. Both compounds exhibited significant antioxidant activity, with compound 2 demonstrating superior radical scavenging ability against DPPH, ABTS·⁺ and hydrogen peroxide (IC₅₀ 86 μM, 25 μM and 104 μM, respectively), enhanced ferric-reducing capacity (up to 91% of trolox activity), and strong iron-chelating activity (61.3%). Compound 2 also showed potent inhibition of lipid peroxidation (IC₅₀ 17.5 μM) and moderate antiglycation effects (44%), indicating substantial cytoprotective potential. Furthermore, both compounds selectively inhibited COX-2 over COX-1 and demonstrated moderate lipoxygenase inhibition, while compound 2 exhibited significant in vivo anti-inflammatory activity (53%), exceeding that of ibuprofen. Moderate acetylcholinesterase inhibition was also observed. In summary, the results confirm the design rationale, indicating that compound 2 could be further optimized as a multi-targeting molecule directed against oxidative stress- and inflammation-mediated conditions. Full article

Background: Effective anti-aging requires dual strategies to stimulate regeneration and counteract damage. While the combination of hydroxypinacolone retinoate (HPR) and carnosine (CA) holds great promise, their effectiveness is hampered by instability and poor skin penetration. Methods: To overcome these challenges, this study developed HPR and CA co-encapsulated nanoliposomes (HC-NLPs) via high-pressure homogenization as an advanced epidermal/dermal delivery system. Results: HC-NLPs markedly improved skin retention of HPR (58.97%) and CA (111.36%) compared to the free combination (Free-HC). In cellular studies, HC-NLPs displayed excellent biocompatibility and demonstrated a 4.7-fold higher cellular uptake. This led to enhanced proliferative (EdU positive rate increased by 78.32%) and migratory (wound closure improved by 31.5%) capacities. Moreover, HC-NLPs effectively reinforced multiple skin-protective processes associated with aging, including enhanced resistance to oxidative and glycation-induced damage, suppressed inflammatory responses, and strengthened cellular barrier integrity. In 3D skin models, HC-NLPs promoted collagen deposition and improved tissue morphology compared to Free-HC. Their superior in vivo antioxidant and anti-aging effects were further validated in Zebrafish assays. HC-NLPs effectively co-deliver HPR and CA, markedly improving their stability, skin penetration, and cellular internalization. Conclusions: The formulation demonstrates comprehensive pro-regenerative, anti-inflammatory, antioxidative, and anti-glycation effects, representing a promising nano-delivery strategy for advanced anti-aging skincare. Full article

Carnosine (or β-alanyl-L-histidine) is an endogenous compound playing very important roles in human organisms as antiglycation and antioxidant agents, and, in addition, helping to mitigate illnesses such as cancer and neurodegenerative diseases. Aiming to explore the chelating ability of carnosine, based on its coordinating possibilities, we started to investigate the metal complexes of essential copper(II), zinc(II), and iron(II) ions coordinated to this dipeptide. Different compounds were isolated in the solid state by adding stoichiometric amounts of metal salts to carnosine at controlled pH or under a controlled atmosphere, with the formation of mono-, bi- and polynuclear species. These complexes were subsequently characterized mainly by spectroscopic techniques (UV–Vis, IR, EPR), in addition to elemental analysis. A binuclear species was isolated with copper(II) and had its structure determined by X-ray diffraction, improving previously reported data in the literature. Two insoluble correlated trinuclear species were isolated with zinc(II) ions, using perchlorate or chloride as counter-ions. In the case of iron, a mononuclear species was verified with Fe(II) ions, obtained under an inert atmosphere. Further, the antioxidant properties of free carnosine and the copper–carnosine complex were verified by their scavenging activity toward the ABTS^•+ radical, using Trolox as a reference, showing significant activity. The carnosine–metal complexes were also tested as potential antineoplastic agents, in comparison to the free ligand, after 24 h of incubation at 37 °C, using malignant HeLa, SKMEL 28 and SKMEL 147, and non-tumor fibroblast cells. Results indicated neglected or poor anti-proliferative properties of these metal complexes, when compared to other similar compounds described in the literature. Full article

Background/Objectives: Advanced glycation end products (AGEs) and oxidative stress increase with aging and are implicated in Alzheimer’s disease (AD). We developed an anti-glycation blend using LC-MS-based screening and assessed its effects on oxidative and glycation-related biomarkers in humans. Methods: Twelve candidate compounds were screened in a BSA–glucose model using LC-MS peptide mapping to quantify lysine glycation and rank inhibitory activity. The top candidates were combined into a three-compound blend (quercetin, rutin, genistein). In a randomized, double-blind, placebo-controlled 3-month trial, older healthy adults (n = 30) and individuals with AD (n = 30) received anti-AGE blend (n = 15 in older group and n = 15 in AD group) or placebo (n = 15 in older group and n = 15 in AD group). Serum malondialdehyde and urinary Nε-(carboxymethyl)lysine were measured pre–post intervention. Pre/post and between-arm comparisons within each population were performed using REML ANOVA with Tukey post hoc tests. Serum MDA (malondialdehyde) and urinary CML (Nε-(carboxymethyl)lysine) were prespecified biomarker outcomes and are reported here as co-primary biomarker endpoints. No formal a priori sample size calculation was performed; the study size was feasibility-based. Results: LC-MS screening identified genistein, quercetin, and rutin as the most consistent inhibitors of glucose-driven BSA glycation. In older healthy adults, serum MDA decreased after anti-AGE supplementation (p < 0.001) and differed from the placebo (p < 0.01), while no change was observed within the placebo group (ns). In the AD cohort, MDA did not change significantly from baseline within either arm (ns), but post-intervention MDA was lower in anti-AGE than in the placebo (p < 0.05). Urinary CML was unchanged in older healthy adults (ns in both arms), whereas in AD, it decreased after anti-AGE supplementation (p < 0.01) and differed from the placebo (p < 0.05). Conclusions: A screening-guided anti-glycation blend supplementation was associated with changes in selected biomarkers in humans: MDA decreased across cohorts, while CML decreased selectively in AD. Larger trials with extended biomarker panels and LC–MS/MS confirmation are warranted. Full article