Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disorder whose core pathological hallmarks include Aβ aggregation, tau hyperphosphorylation, chronic neuroinflammation, oxidative stress, mitochondrial dysfunction, and gut microbiota dysbiosis. Lignans, a class of naturally occurring polyphenolic dimers widely distributed in medicinal plants and diet, exhibit multi-target neuroprotective effects with low toxicity. This review provides a systematic synthesis of the anti-AD pharmacological mechanisms underlying nine structurally distinct lignan subtypes-dibenzocyclooctadiene, tetrahydrofuran, bisepoxy, benzofuran, and biphenyl types-emphasizing scaffold-dependent structure-activity relationships. Key mechanistic pathways encompass direct inhibition of Aβ aggregation and tau phosphorylation, activation of the Nrf2 antioxidant signaling axis and PI3K/Akt pro-survival pathways, suppression of NF-κB-mediated neuroinflammation, restoration of cholinergic function, protection of mitochondria via SIRT3, inhibition of ferroptosis through Gsk3β/Nrf2/GPX4 signaling, and modulation of the gut-brain axis via microbiota-mediated conversion to enterolactone. This review addresses key pharmacokinetic limitations such as low oral bioavailability, rapid metabolism, and limited brain exposure, alongside strategies including structural modification, brain-targeted delivery systems, and gut microbiota modulation. Despite promising preclinical evidence, clinical translation remains limited. Future research priorities should focus on direct target validation, network pharmacology, optimized formulations, and well-designed clinical trials to develop lignans into next-generation anti-aging and anti-AD therapeutics.
Skin aging is a multidimensional biological process driven by intrinsic chronological changes, exposomal stress, endocrine-metabolic shifts, extracellular matrix remodeling, inflammaging, oxidative injury, barrier impairment, and microbiome dysbiosis. This review integrates current evidence on the endocrine-microbiome-skin axis and evaluates microbiome-directed bioactive strategies for preserving cutaneous homeostasis during aging. Particular attention is given to probiotics, prebiotics, postbiotics, synbiotics, phytoestrogens, polyphenols, bioactive peptides, antioxidants, mitochondrial protectors, adaptogens, and metabolic modulators. Their mechanisms are discussed in relation to collagen homeostasis, mitochondrial function, lipid barrier integrity, immune regulation, microbial metabolite signaling, and systemic endocrine-metabolic status. The review also examines advanced delivery platforms, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanocarriers, nanoemulsions, encapsulated microbiome-active systems, and stimuli-responsive carriers, emphasizing their potential to improve compound stability, skin retention, controlled release, and target-site precision. Translational limitations are critically addressed, including strain and formulation specificity, insufficient long-term safety data, incomplete nanocarrier toxicology, regulatory ambiguity, and the need for personalization according to hormonal, metabolic, and microbiome profiles. Overall, microbiome-directed bioactive compounds combined with precision delivery systems represent a promising, but still evolving, strategy for delaying skin aging and restoring cutaneous homeostasis.
Ziziphi Spinosae Semen (ZSS) is a traditional East Asian sedative-hypnotic herb with over 2000 years of clinical application. Spinosin (SPI), a characteristic flavone-C-glycoside, is the official quality marker and principal bioactive constituent of ZSS. Despite extensive research on SPI in recent years, a timely, comprehensive review integrating its pharmacological mechanisms, pharmacokinetic barriers, and translational strategies remains absent. Herein, a systematic literature search was conducted up to 31 May 2026, and we synthesize all available evidence on SPI's chemical properties, natural sources, pharmacology, pharmacokinetics, toxicology, structural derivatives, and advanced drug delivery systems. Our analysis reveals that SPI exerts broad-spectrum pharmacological activities via multi-target modulation of serotonergic/GABAergic neurotransmission, the ERK/CREB/BDNF axis, and the Nrf2/HO-1 pathway. However, its clinical translation is severely hindered by extremely low oral bioavailability (<1%) and limited blood-brain barrier penetration due to poor aqueous solubility and P-glycoprotein-mediated efflux. Novel formulations have achieved up to 5-fold enhancement in oral bioavailability in preclinical models. While toxicological studies support a favorable safety profile, long-term toxicity and human pharmacokinetic data are lacking. This review critically discusses key translational bottlenecks and proposes evidence-based future directions to advance SPI as a natural neurotherapeutic agent.
Emerging contaminants (ECs) represent a growing environmental problem due to their presence in various environmental matrices. In Mexico, research on ECs remains limited. This scoping review, conducted in accordance with the PRISMA-ScR guidelines, analyzes their environmental fate during the period 2004-2025, considering their distribution in surface and groundwater, sediments, and influents and effluents from wastewater treatment plants (WWTPs). The reviewed studies demonstrate the presence of pharmaceutically active compounds (PhACs), endocrine-disrupting compounds (EDCs), personal care products, phthalates, bisphenols, pesticides, illicit drugs, xanthines, perfluoroalkyl and polyfluoroalkyl substances (PFAS), metabolites, and industrial compounds. The Apatlaco, Cuautla, and Santa Catarina rivers exhibit the greatest diversity of ECs, while groundwater shows evidence of infiltration of PhACs, phthalates, bisphenols, and triclosan, associated with urban, industrial, and tourist discharges. In sediments, PhACs and EDCs accumulate at concentrations in the ng/g range, while phthalates reach concentrations of thousands of ng/g, indicating their affinity for the solid phase. At Mexican wastewater treatment plants, conventional treatment methods do not completely remove ECs, allowing residual amounts to be discharged into receiving bodies of water. Overall, national monitoring should be expanded to include metabolites, transformation products, and advanced treatment assessment.
Bovine milk contains bioactive proteins and encrypted peptide sequences whose abundance and availability may change during mammary or systemic inflammation. This narrative review critically evaluates evidence associated with subclinical mastitis, lameness-causing claw disorders, and periparturient metabolic disorders. Direct milk-level evidence is strongest for mastitis: increased somatic cell count and intramammary inflammation are generally associated with higher concentrations of milk haptoglobin, milk serum amyloid A (including mammary-associated serum amyloid A3, when isoform-resolved), lactoferrin, cathelicidins, and immunoglobulins, together with accelerated casein proteolysis. For lameness and metabolic disorders, evidence is substantially weaker and derives mainly from systemic acute-phase responses, broad milk metabolomic or compositional changes, and mechanistic hypotheses involving blood-milk barrier permeability and protease regulation. The review explicitly separates direct disease-defined milk evidence from systemic, broad omics, and mechanistic evidence. These alterations may influence biomarker performance, whereas processing consequences are best-established for mastitic milk. Their persistence after processing and digestion, and their biological effects in human consumers, remain largely unresolved. Future studies should combine diagnosis-specific cow health monitoring with milk proteomics and peptidomics. They should also assess the stability, bioaccessibility, and functionality of altered proteins and peptides during processing and digestion.
Given the scarce data in the literature regarding the lanthanide content of Greek monofloral honey, Sc (Scandium), Y (Yttrium), La (Lanthanum), Ce (Cerium), Pr (Praseodymium), Nd (Neodymium), Sm (Samarium), Eu (Europium), Gd (Gadolinium), Tb (Terbium), Dy (Dysprosium), Ho (Holmium), Er (Erbium), Tm (Thulium), Yb (Ytterbium), Lu (Lutetium) and Th (Thorium) were determined in honeydew and nectar honey, using inductively coupled plasma mass spectrometry (ICP-MS). Results showed that, in general, honeydew honey had a higher lanthanide content than nectar honey, even though the determined values were below the limit of quantification. Preliminary reference values in this case for pine honey were Ce (26.82 ± 21.49 ng/L) and La (15.25 ± 11.82 ng/L). Adulteration testing was also performed using elemental analysis coupled to isotope ratio mass spectrometry (EA-IRMS), where no adulteration with cheap sugars was detected. Factor analysis identified the principal lanthanides related to honey botanical origin, basically Ce, and the k-NN algorithm classified the samples, achieving a training classification rate of 81.8% and a hold-out classification rate of 76.5%. Even in low amounts, lanthanides may contribute to the botanical origin identification of monofloral honey.
Silybum marianum (SM) is a rich source of flavonolignans with promising antioxidant and antidiabetic properties; however, its therapeutic application is limited by poor stability and bioavailability. This study combined experimental and computational approaches to develop and evaluate SM-loaded chitosan nanoparticles (CS-SM nanoparticles). Microwave-assisted extraction followed by LC-MS/MS profiling identified eleven metabolites, including major flavonolignans characteristic of SM. Nanoparticles prepared by ionic gelation exhibited favorable physicochemical properties, including a particle size of 173-189 nm, a polydispersity index of 0.23, a zeta potential of +41.5 mV, an encapsulation efficiency of 98%, and a drug loading capacity of 50%, indicating the formation of a stable colloidal delivery system. CS-SM nanoparticles showed enhanced antioxidant, anti-inflammatory, and α-amylase inhibitory activities compared with crude extracts. The formulation exhibited an α-amylase IC50 value of approximately 0.40 mg/mL and maintained low hemolytic activity, suggesting favorable preliminary biocompatibility. Molecular docking demonstrated favorable interactions of neosilyhermin A, silibinin, and silyhermin with α-amylase and α-glucosidase active sites. Short-timescale molecular dynamics simulations revealed ligand-dependent behavior within the chitosan-TPP matrix, indicating different release tendencies among the investigated flavonolignans. Overall, the results support CS-SM nanoparticles as a promising platform for the delivery of bioactive phytochemicals with antioxidant and antidiabetic potential.
Glucagon-like peptide-1 (GLP-1) analogues are a major class of peptide therapeutics used to treat metabolic diseases. GLP-1-derived peptides are characterized by dynamic conformational ensembles in which folding, intermolecular assembly, and aggregation are strictly coupled processes. This study focused on the effects of sequence modifications, such as helix-promoting residues and backbone constraints on the helix-coil equilibrium, as well as lipidation, which creates competing equilibria among monomeric, oligomeric, and albumin-bound forms. These coupled equilibria simultaneously enhance pharmacokinetic properties and modulate conformational stability. We also explored how environmental conditions such as ionic concentration and temperature affect conformation, and emphasize how manufacturing processes act as external perturbations that could impact structural integrity. Moreover, we focus on the increasingly emerging new multi-agonist peptides, noting that their increased sequence complexity broadens conformational diversity and poses challenges to existing design methods. Despite significant experimental progress, predictive models capable of mapping the intricate interconnections among peptide sequences, lipidation patterns, and aggregation pathways remain critically limited. This highlights the importance of integrating biophysics, computation, and process science. The review points out that designing effective GLP-1 therapeutics rationally depends on managing conformational distributions across complex energy landscapes, not just stabilizing individual structures, in order to offer a new framework for developing the next generation of peptide drugs.
Organoselenium chemistry has progressed from the early synthesis of simple selenoorganic molecules in the 20th century to advanced methodologies aligned with the principles of green chemistry. Conventional synthetic approaches, frequently dependent on hazardous reagents and organic solvents, are increasingly being replaced by environmentally benign strategies, including solvent-free reactions, aqueous and bio-based solvent systems, microwave-assisted synthesis, and mechanochemical techniques. These sustainable methodologies offer significant advantages, such as enhanced reaction efficiency, higher or comparable yields, reduced waste generation, improved safety, and lower environmental impact. In parallel, evolving regulatory standards and industrial practices are encouraging the adoption of greener synthetic protocols to minimize hazardous waste and support safer pharmaceutical manufacturing. This review systematically categorizes organoselenium compounds, highlighting their synthetic methodologies, structural characteristics, and biological activities. Overall, recent advances emphasize the therapeutic potential of organoselenium compounds and demonstrate the essential role of sustainable synthetic chemistry in the development of future medicinal agents.
A convenient one-pot strategy was adopted to fabricate Cu-4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) nanosheets through the coordination of HEPES with copper ions under alkaline conditions, and the obtained nanosheets possessed dual laccase-mimetic and oxidase-mimetic activities for phenolic pollutant analysis and show potential for dye decolorization/removal. The Cu-HEPES nanosheets displayed significant dual enzyme-mimetic activities, effectively catalyzing the oxidation conversion for phenolic compounds, specifically 2,4-dichlorophenol (2,4-DCP), to yield quinone imine products characterized by a unique absorption signal at 500 nm. Meanwhile, Cu-HEPES nanosheets also facilitated the conversion of 3,3',5,5'-tetramethylbenzidine to yield a yellow-green substance with a distinctive absorption signal at 458 nm. The Cu-HEPES nanosheets displayed a satisfactory affinity (Km = 23.2 μM) for 2,4-DCP, facilitating its use in accurately detecting 2,4-DCP (linear range from 3.3 to 16.6 µM) with a detection limit of 0.3 µM. Subsequently, the devised colorimetric sensing platform was applied to measure 2,4-DCP levels in real tap water samples, yielding satisfactory spiked recoveries ranging from 92.7% to 106.9%. Finally, the synthesized Cu-HEPES nanosheets were preliminarily evaluated for the simultaneous decolorization/removal of malachite green and Congo red, suggesting their potential applicability in aqueous systems containing multiple organic dyes.
The effect of the chlorine atom in the sixth position and methyl group in the third position of the uracil ring on the structural parameters, NBO charge distribution, and molecular properties of the 6-chloro-3-methyluracil (M6CU) biomolecule was analyzed in the isolated state, solid-state arrangement and within a double-stranded RNA microhelix. This effect, which was also compared to those with uracil and several uracil derivatives, leads to higher reactivity and the special properties of this pharmaceutical compound. Several correlations were established using MP2 and several DFT methods. The structural characterization of M6CU and a detailed analysis of the experimental FT-IR and FT-Raman spectra in the solid state was another aim studied in detail. For an accurate assignment, a simple approximation to a crystalline unit cell was optimized using a trimer form and the wavenumbers were subsequently corrected using several scaling procedures. The modified nucleobase M6CU forms base pairs with the complementary adenine and, therefore, it could replace uracil in the helix; based on our calculations, it leads to a noticeable helix deformation. This computational finding suggests its possible potential effect by binding to cancer-related or viral RNA helices. Molecular docking also revealed that M6CU could act as an active ligand within the 1JPW active site of the target β-catenin/Tcf4 protein complex.
This work examines the utilization of the natural product shilajit resin, sourced from the Himalayas, for the extraction of diverse components suitable to the synthesis of gold nanoparticles (AuNPs) and selenium nanoparticles (SeNPs). The study evaluated the extraction efficiency of Uro-A, a polar phenolic component, from shilajit samples utilizing various solvent systems, followed by the eco-friendly synthesis and characterization of AuNPs and SeNPs. The LC-MS/MS analysis demonstrated that the methanol/ethyl acetate (MeOH/EA) extract was particularly effective and contained the highest concentration of Uro-A. A robust positive association was discovered between Uro-A content in shilajit and the efficiency of nanoparticle production. Sample 2, with 0.002 ppm Uro-A, produced suboptimal yields (15% for AuNPs; 34% for SeNPs), while sample 1, with 2.504 ppm Uro-A, noticeably enhanced the yields to 90% (AuNPs) and 96% (SeNPs). The synthesized AuNPs and SeNPs were characterized using SEM, EDS, PSD, ZP, XRD, FTIR, and XPS techniques, demonstrating spherical particles with an average diameter of around 100 nm. XPS spectra confirmed the elemental form of the obtained AuNPs and SeNPs. Antimicrobial studies revealed that SeNPs exhibit moderate efficacy (MIC = 0.125-1 mg/mL) against bacteria (e.g., Bacillus subtilis, Staphylococcus aureus) and fungi (e.g., Penicillium italicum, Mucor mucedo), but higher in comparison to AuNPs (MIC 0.25-5 mg/mL).
While anti-tumor drugs markedly improve patient survival, dose-limiting toxicities remain major constraints on clinical efficacy and quality of life. Conventional management strategies lack timeliness and precision. Traditional Chinese medicine (TCM) and its active ingredients offer unique potential for mitigating anti-tumor drug toxicities through multi-component and multi-target regulation. However, the transformation of TCM is hampered by poor bioavailability and targeting. This review summarizes and evaluates an integrated strategy combining TCM with nanotechnology to develop novel nanomedicines. It elucidates the distinct toxicity mechanisms of chemotherapy drugs, targeted drugs, and immunotherapy drugs, revealing toxicopathological transitions from non-specific killing to microenvironment disruption and immune imbalance. Subsequently, it discusses the intervention mechanisms and research progress of TCM and its active ingredients targeting different categories of anti-tumor drug toxicity. To overcome delivery challenges, this review explores construction strategies for diverse nanodelivery systems, including carrier-free self-assembled nanomedicines, physically loaded nanomedicines, and chemically coupled nanomedicines, highlighting their value in organ-specific accumulation and controlled release. Finally, it objectively analyzes challenges in the clinical translation of these nanomedicines, encompassing safety and industrialization, while prospecting future trends, aiming to contribute to a new therapeutic paradigm focused on “toxicity attenuation and efficacy potentiation” and steer cancer treatment toward greater precision and intelligence.
Broccoli processing generates large quantities of leaves that remain underutilized despite being rich in bioactive compounds. Their valorization as a functional ingredient aligns with sustainable food production and offers an opportunity to enhance the nutritional quality of cereal-based foods. This study evaluated the impact of broccoli leaf powder (BLP) fortification (2.5 and 5%) on the phytochemical composition and functional properties of durum pasta under three drying regimes. BLP introduced glucosinolates, flavonols, carotenoids, and chlorophylls that were absent in the control samples, and their contents increased proportionally with the fortification level. The drying regime modulated compound stability, with low-temperature drying generally favoring retention, whereas cooking caused up to a 50% loss of glucosinolate, depending on the processing conditions. Functional properties were markedly enhanced by BLP addition. The 5% fortification level showed the greatest improvement, resulting in the highest antioxidant activity, antiglycation potential, and angiotensin-converting enzyme (ACE)-inhibitory activity compared to the control pasta. Antioxidant, antiglycation, and ACE-inhibitory activities increased proportionally with the fortification level, and although drying reduced some activities, the fortified pasta consistently outperformed the control. Among the tested formulations, pasta enriched with 5% BLP showed the most favorable overall functional and bioactive compound profiles. Overall, broccoli leaves represent a valuable by-product for developing nutritionally enriched pasta, and the processing conditions play a key role in shaping the stability and bioactivity of the incorporated compounds.
Biomass-derived porous carbons are promising sustainable adsorbents for wastewater treatment. However, most reported materials require chemical activation, while the relationships between biomass precursor, pore structure, adsorption mechanism, and regeneration remain insufficiently understood. In this work, non-activated carbon materials were prepared from Juglans regia (JR) and Allium sativum (AS) biomass by pyrolysis at 400 and 900 °C and evaluated for the removal of methylene blue (MB), rhodamine B (RB), crystal violet (CV), and malachite green (MG). Carbonization at 900 °C markedly enhanced porosity, yielding a surface area of 790 m2 g-1 for JR900 and 177 m2 g-1 for AS900, together with predominantly microporous structures and negatively charged surfaces at neutral pH. The pseudo-second-order model best described adsorption kinetics, while intraparticle diffusion analysis indicated a multistep adsorption process. Equilibrium data were well fitted by both Langmuir and Freundlich isotherm models. JR900 exhibited the highest adsorption capacities for MB (321 mg g-1) and RB (304 mg g-1), whereas AS900 showed superior performance toward MG (278 mg g-1). Stable dynamic filtration, efficient regeneration, and nearly complete dye recovery demonstrate the potential of these non-activated biomass-derived carbons for sustainable dye removal and recovery from water.
To investigate the influence of manufacturing process on the flavor of Chinese dark tea, the volatile profiles of five varieties (Fuzhuan, Pu-erh, Liubao, Bailiang, and Tianjian) were analyzed using gas chromatography-mass spectrometry/olfactometry (GC-MS/O). A total of 178 volatile compounds were identified by GC-MS, among which linalool and its oxides were the most abundant aroma-active components, particularly in Pu-erh tea, which underwent the longest fermentation. GC-O analysis revealed 11 compounds with relative odor activity values (ROAVs) greater than 1, including β-gulonic aldehyde, (E,Z)-2,6-nonadienal, β-isopropenyl, (Z)-4-hexenal, 3-methylbutanal, (E,Z)-2,4-decadienal, (E,E)-2,4-decadienal, hexanal, linalool, and (R/Z)-linalool oxide. These were considered the key aroma-active compounds contributing to the overall aroma of dark tea. Principal component analysis further indicated that the distinctive woody and aged notes of Pu-erh tea were associated with linalool, (E/Z)-linalool oxide, 1,2,3-trimethylbenzene, β-gulonic aldehyde, benzaldehyde, and citronellol. In contrast, α/β-ionone and a series of fatty acid derivatives such as (E,Z)-2,6-nonadienal, (Z)-4-heptenal, (E,Z)-2,4-dodecadienal, (E,E)-2,4-dodecadienal, and hexanal were mainly responsible for sweet, grassy, and herbal notes. These substances are particularly prominent in Fuzhuan and Bailiang teas. Our findings demonstrate that processing techniques significantly affect the aroma quality of dark tea, providing a valuable reference for variety discrimination and process optimization.
A strategy for the selective C-H silylation of 7-phenyl-1H-indoles has been established via palladium(II)/norbornene cooperative catalysis. This method employs norbornene (NBE) as both a C-H activation mediator and an alkylating agent to access arylsilanes with exceptional selectivity. Kinetic isotope effect (KIE) studies revealed that C-H cleavage is the rate-determining step, consistent with a mechanism proceeding through an eight-membered palladacycle.
Background: Conventional tyrosinase (TYR) inhibitors irritate skin and trigger rebound pigmentation, necessitating safer and more effective depigmenting agents. Methods: Biocompatibility was assessed by cell viability. Melanin content and TYR activity were measured spectrophotometrically. Reactive oxygen species (ROS), adenosine triphosphate (ATP), and inflammatory cytokines were detected by fluorescence, luminescence, and ELISA. Western blot and RT-qPCR assessed oxidative stress, inflammatory, and melanogenic targets. Molecular docking simulated Ganoderic Acid A (GAA) interactions with key proteins. Results: GAA exhibits good biocompatibility, inhibits melanin synthesis and TYR activity in B16-F10 cells, and reverses ultraviolet B-induced pigmentation. Mechanistically, GAA restores mitochondrial homeostasis by scavenging ROS, replenishing ATP, activating the nuclear factor erythroid 2-related factor 2 (Nrf2) axis, and inhibiting nuclear factor kappa-B (NF-κB) and cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to regulate the inflammatory microenvironment. This synergistic regulation inhibits the mitogen-activated protein kinase (MAPK) signaling pathway and down-regulates the microphthalmia-associated transcription factor (MITF) transcriptional network and the expression of TYR, tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). Conclusion: GAA eliminates ultraviolet B-induced hyperpigmentation through a multi-target mechanism of mitochondrial repair, inflammation inhibition, and direct binding to tyrosinase, and is a potential natural candidate drug for the treatment of skin diseases.
Micromelum falcatum (Lour.) Tanaka is a medicinal plant widely utilized in traditional Chinese medicine. In this study, the essential oil (EO) was isolated by hydrodistillation using a Clevenger-type apparatus, and its chemical composition and biological activities were systematically investigated. A total of 63 constituents were identified by GC-MS and GC-FID, with bicyclogermacrene (20.52%), γ-palmitolactone (18.16%), humulene (10.55%), caryophyllene (10.09%), and spathulenol (4.50%) representing the major components. Antioxidant capacity was evaluated using DPPH (IC50 = 15780 ± 1490 μg/mL), ABTS (IC50 = 3440 ± 40 μg/mL), and FRAP assays (Trolox equivalent antioxidant concentration: 734.47 ± 6.82 μmol/g), in which the EO exhibited relatively moderate radical-scavenging and ferric-reducing activities. In addition, the EO demonstrated notable β-lactamase inhibitory activity (IC50 = 25.59 ± 4.99 μg/mL). Molecular docking analysis further suggested that compounds such as isospathulenol, globulol, and spathulenol may interact with the enzyme's active site via hydrogen bonds. These findings indicate that M. falcatum EO represents a promising natural source of bioactive compounds with antioxidant and enzyme-inhibitory potential, warranting further pharmacological investigation.
