Search Results (143)

This study investigates the antioxidant, enzyme inhibitory, and antimicrobial activities of water (WEHL) and ethanol (EEHL) extracts of hop (Humulus lupulus) cones. Phytochemical analyses revealed higher total phenolic content in EEHL (271.52 ± 0.13 mg GAE/g) than in WEHL (251.84 ± 0.06 mg GAE/g), as well as higher total flavonoid content (182.56 ± 0.45 mg QE/g for EEHL versus 179.39 ± 0.46 mg QE/g for WEHL). Antioxidant activity, determined by DPPH and ABTS assays, showed that EEHL had stronger radical scavenging capacity with IC₅₀ values of 19.13 ± 4.66 μg/mL (DPPH) and 12.66 ± 1.94 μg/mL (ABTS), compared to WEHL (DPPH: 20.90 ± 2.39 μg/mL; ABTS: 32.41 ± 4.29 μg/mL). In reducing assays, EEHL also showed better absorbance values in FRAP (0.77 ± 0.01), CUPRAC (2.09 ± 0.05), and Fe³⁺ reducing (1.95 ± 0.01) tests. EEHL likely outperformed WEHL due to solvent polarity and extraction efficiency. Moderately polar ethanol extracts a broader range of phenolics and flavonoids, including fewer polar bioactive compounds that contribute to antioxidant capacity and enzyme inhibition. This matches higher TPC/TFC in EEHL and explains stronger radical scavenging, reducing power, and multi-enzyme inhibition. Enzyme inhibition studies revealed that EEHL inhibited acetylcholinesterase (IC₅₀: 26.06 μg/mL), butyrylcholinesterase (IC₅₀: 44.00 μg/mL), α-glycosidase (IC₅₀: 119.31 μg/mL), and carbonic anhydrase isoenzymes hCA I (IC₅₀: 59.78 μg/mL) and hCA II (IC₅₀: 21.19 μg/mL). LC–MS/MS analysis identified major phenolic compounds such as isoquercitrin (3.14 ng/mL), rutin (0.60 ng/mL), and hesperidin (0.43 ng/mL) in EEHL. Antimicrobial screening showed selective activity against Staphylococcus aureus with an inhibition zone of 18.50 ± 0.58 mm, while no inhibition was observed against Escherichia coli and Candida albicans. These findings provide a solvent-dependent in vitro profile that can guide extraction strategies, support antioxidant and multi-enzyme screening (including hCA I and II), and identify candidates for selective antimicrobial evaluation and further preclinical investigation. Despite extensive use of hop extracts, comparative solvent-dependent profiling that links LC–MS/MS phenolic composition with a broad multi-enzyme inhibition panel, including the less frequently evaluated hCA I/II isoenzymes, remains limited. Therefore, the objective of this study was to systematically compare WEHL and EEHL in terms of phytochemical content and in vitro antioxidant, enzyme inhibitory, and antimicrobial activities. Overall, these results provide a solvent-dependent, comparative in vitro profile of WEHL vs. EEHL that can support antioxidant, multi-enzyme screening (including hCA I and II), and selective antimicrobial assays. Full article

The increasing interest in valorizing agricultural by-products has positioned grape pomace as a rich source of bioactive compounds. This study developed an effect-directed extraction (EDE) approach guided by bioactivity quantification on thin layer chromatography (TLC). Twelve grape pomaces were screened based on antioxidant and tyrosinase inhibitory properties. Using hydroalcoholic solvent (ethanol:water, 1:1), the two most promising sources (Malbec from San Rafael) were subjected to response surface methodology (RSM) to optimize extraction of anti-browning and antioxidant compounds visualized as TLC spots. Temperature and time were optimized (76 °C, 45 min), and samples were analyzed using TLC coupled with DPPH and laccase inhibition bioautography. Antioxidant compounds showed retention factor values on TLC plates of 0.37 and 0.75 (DPPH/ABTS-active), while laccase inhibition occurred at Rf 0.35, coinciding with the primary tyrosinase inhibition zone. However, subsequent bioassay-guided HPLC fractionation and HRMS/MS analysis revealed that tyrosinase and laccase inhibitions are mediated by distinct compounds within this bioactive zone, highlighting a synergistic multi-target effect in the optimized extract that is retained throughout the process. The primary tyrosinase inhibitor at Rf ~0.35 was tentatively elucidated as an acylated anthocyanin, consistent with malvidin-3-O-(p-coumaroyl)glucoside. Optimized extracts were evaluated on Pink Lady apple slices at different timepoints. The browning index was reduced by 25% versus the control at 15 h, confirmed by significantly lower ΔE values (p < 0.05). The process requires only food-grade solvents and conventional equipment, facilitating scale-up for grape pomace generated worldwide. Validating the EDE strategy, this TLC-guided approach successfully tracked and preserved the primary anti-tyrosinase activity from the crude waste matrix down to the tentatively identified molecule, contributing to circular economy objectives in the wine industry. Full article

Endophytic fungi represent an extensive source of chemically diverse and bioactive polyketides. Herein, an HSQC-based DeepSAT-guided strategy was employed for the scaffold-prioritized isolation of metabolites from Diaporthe kyushuensis ZMU-48-1, an endophyte isolated from Acacia confusa. DeepSAT analysis of the semi-purified fractions identified an α-pyrone chemotype, which facilitated the targeted isolation of thirteen pyranone-type polyketides, including eight previously undescribed analogues, diaporthopyranone A–H (1–8). The structures of the new compounds were rigorously elucidated via comprehensive spectroscopic analysis (1D and 2D NMR and HRESIMS), while their absolute configurations were established by comparing experimental and TDDFT-calculated ECD data. All isolates (1–13) were screened for antifungal activity against nine plant pathogens. While most metabolites were inactive at 200 μg/mL, compound 4 inhibited Alternaria alternata and Valsa mali (MICs = 100 and 80 μg/mL, respectively), and compounds 6 and 8 exhibited selective inhibition against Colletotrichum musae (MICs = 60 and 80 μg/mL). These results expand the pyranone repertoire of the genus Diaporthe and underscore the utility of the HSQC–DeepSAT platform for the streamlined discovery of specific natural product scaffolds. Full article

Background/Objectives: This study aimed to develop and formulation-design curcumin-loaded buccal films using a green deep eutectic solvent (DES) to improve drug solubility and support localized mucosal delivery, with the help of a Design of Experiments (DoE) approach. Methods: Various DESs with different components and molar ratios were prepared, characterized, and the optimal DES was selected. Curcumin-loaded buccal films were prepared by solvent casting, employing the optimal DES as the solvent system. A three-factor and five-level central composite design was applied to systematically investigate the amounts of HPMC K100, Kollicoat^® IR, and DES in buccal films, and mucoadhesive strength, elongation (%), swelling index, swelling time, and thickness were identified as critical responses. Based on these responses, characterization, in vitro release, ex vivo permeation, and in vitro biological activity studies were performed on the model-predicted optimal formulations. Results: Choline chloride: propylene glycol (1:4 molar ratio) was selected as the optimal DES due to its viscosity, pH, organoleptic properties, and the highest curcumin solubility (11.90 ± 0.15 mg/mL). While DES increased curcumin solubility, buccal films were successfully obtained. Six formulations identified through model-based DoE optimization were advanced to detailed experimental evaluation. The drug release exhibited sustained curcumin release profiles over 24 h, and ex vivo studies showed <2% mucosal permeation. The lead formulations demonstrated in vitro cell compatibility, anti-inflammatory and antioxidant activities, and enhanced wound-healing-related bioactivity. Conclusions: Curcumin-loaded buccal films containing DES and developed using a DoE-guided formulation strategy successfully demonstrated the acceptable formulation properties and screening-level in vitro biological activities, offering a promising formulation platform for localized buccal delivery applications. Full article

A species of the genus Tetracera has been used as herbal medicine in traditional Indian Tetracera loureiri medicine. Tetracera loureiri, a plant from the Dilleniaceae family is considered one of the most valuable herbs in Thailand and is native to Southeast Asia. However, the anti-obesity effects of Tetracera loureiri extract have not been reported. In this study, we screened the effect of EtOH extract on lipid accumulation in a 3T3-L1 adipocyte model at various concentrations using Oil Red O staining, and the results were visualized under a light microscope. The fractionation of the soluble CH₂Cl₂ and EtOAc fractions from the EtOH extract revealed that both fractions significantly inhibited lipid accumulation in adipocytes at 2.5, 5, and 10 μg/mL, compared to n-hexane, n-BuOH, and aqueous extracts. Bioactivity-guided fractionation of the CH₂Cl₂ and EtOAc extract led to the phytochemical investigation of 10 secondary metabolites (1–10), and the structure of these compounds was identified using various spectroscopic methods. All isolated compounds were evaluated for their ability to inhibit adipogenesis at a concentration of 2.5, 5, and 10 μM compared with positive control (Orlistat 100 μg/mL); in particular, compounds 1–3, 5, and 7–8 showed 57.39 ± 6.98, 19.35 ± 4.53%, 75.81 ± 1.75%, 17.61 ± 1.62%, 19.83 ± 5.27 and 14.66 ± 3.85% reduction in fat accumulation at 10 μMm in 3T3-L1 adipocytes, respectively. The activity of these compounds also inhibited the secretion of adiponectin and leptin in 3T3-L1 adipocytes, suggesting their role in disrupting adipocyte function and metabolic regulation. Therefore, the results herein provide experimental evidence supporting the potential of Tetracera loureiri extracts as an anti-obesity therapeutic agent. Full article

Background/Objectives: Capric acid (CA)–therapeutic deep eutectic systems (THEDES) are emerging as a distinct class of biofunctional matrices capable of reshaping drug solubilization, permeability, and bioactivity. Methods: Relevant studies on CA–THEDES were identified through targeted database searches and screened for evidence on their design, mechanisms, and pharmaceutical performance. Results: This review synthesizes current evidence on their structural design, mechanistic behavior, and pharmaceutical performance, revealing several unifying principles. Across multiple drug classes, CA consistently drives strong, directional hydrogen bonding and drug amorphization, resulting in marked solubility enhancement and stabilization of non-crystalline or supersaturated states relative to crystalline drugs or conventional solvent systems. Its amphiphilic C10 chain further contributes to membrane fluidization, which explains the improved transdermal and transmucosal permeation repeatedly observed in CA-THEDES. Additionally, synergistic antimicrobial and anticancer effects reported in several systems confirm that CA acts not only as a solvent component but as a bioactive co-therapeutic. Collectively, the reviewed data show that CA serves as a structurally determinant element whose dual hydrogen-bonding and membrane-interacting roles underpin the high pharmaceutical performance of these systems. However, gaps remain in long-term stability, toxicological profiling, and regulatory classification. Emerging Artificial Intelligence (AI) and Machine Learning (ML)-guided predictive approaches offer promising solutions by enabling rational selection of eutectic partners, optimal ratios, and property optimization through computational screening. Conclusions: Overall, CA-THEDES represent a rationally designable platform for next-generation drug delivery, where solvent functionality and therapeutic activity converge within a single, green formulation system. Full article

Type 2 diabetes mellitus (T2DM) poses a critical global health burden, necessitating safer multi-target therapies. We pioneer the exploration of novel bioactive peptides from Tenebrio molitor larvae—an underexplored, sustainable, and edible insect protein—through proteomics-guided screening and bioassays. Six unique peptides (DK-7, WK-6, GR-7, FK-8, SK-6, and DK-8) demonstrated significant α-glucosidase and dipeptidyl-peptidase IV (DPP-IV) inhibitory effects, and significant glucose consumption enhancement in insulin-resistant HepG2 cells. Molecular docking revealed a binding topology where peptides interacted with α-glucosidase at its active sites (Glu271, Arg643, Arg647, Arg653, Tyr733, Lys765, and Glu767) and with DPP-IV at active residues (Phe357, Tyr547, Trp629, Asp729, and Gln731) through dual hydrogen-bond networks and hydrophobic interactions, establishing a novel inhibition mechanism. We wish to propose that insect-derived biopeptides have potential value as next-generation therapeutics, simultaneously advancing sustainable drug discovery and approximating functional food bioresources to biomedicine. Full article

Sweet potato leaves (SPL) are increasingly recognized as a significant source of nutritionally and pharmacologically important bioactive compounds. This systematic review critically synthesizes current in vitro, in vivo, and preclinical data to evaluate the cancer preventive properties of SPL, with emphasis on their phytochemical composition, molecular mechanisms, and therapeutic relevance. A comprehensive literature search across major scientific databases (2015–2025), guided by PRISMA methodology, initially identified 29,416 records. After applying pre-specified inclusion and exclusion criteria and screening titles, abstracts, and full-texts, 38 eligible studies were included. The compiled evidence demonstrates that SPL contains high concentrations of phenolic acids, flavonoids, peptides, carotenoids, and dietary fiber, all of which contribute to diverse anticancer activities. Reported mechanisms include apoptosis induction, cell-cycle arrest, limitation of tumor propagation and metastatic activity, regulation of oncogenic pathways (PI3K/Akt, MAPK, NF-κB), modulation of inflammatory mediators, and suppression of angiogenesis. These effects were observed across multiple cancer models, including liver, colon, breast, lung, and prostate cancers. In addition, SPL represents a promising natural source of anticancer agents, significant gaps remain, particularly regarding standardized extraction procedures, phytochemical characterization, bioavailability, and human clinical validation. Overall, this review underscores SPL as a sustainable and underutilized plant resource with potential applications in functional foods, nutraceuticals, and adjunctive cancer therapy, while highlighting the need for mechanistic studies, pharmacokinetic investigations, and well-designed clinical trials to support future translational development. Full article

Fritillaria pallidiflora Schrenk ex Fisch. & C.A.Mey. (Yi Beimu) is a culturally significant Beimu drug in Northwest China, officially listed in the Chinese Pharmacopoeia and traditionally used to clear heat, moisten the lung, resolve phlegm, and relieve cough and wheeze. This narrative, critical review synthesizes current evidence on ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics/toxicology, and conservation of F. pallidiflora to support sustainable, evidence-based development. Literature was retrieved from major English and Chinese databases and screened for studies that unambiguously involved Yi Beimu or its key constituents. Ethnomedicinal records consistently support antitussive, expectorant, and anti-asthmatic use in Xinjiang and the Ili River Valley. Chemically, F. pallidiflora is rich in cevanine-type steroidal alkaloids (e.g., imperialine, peimine, yibeinones), steroidal saponins (pallidiflosides), polysaccharides, and minor phenolics. Preclinical data show that alkaloids relax airway smooth muscle, suppress inflammatory mediators, and contribute to antitussive and anti-asthmatic effects, while polysaccharides and total alkaloid extracts exhibit antioxidant and cytoprotective activity in cell and animal models of airway injury. Additional studies report cytotoxic saponins and seed-derived antimicrobial peptides. Pharmacokinetic work highlights low to moderate and variable oral bioavailability, shaped by P-glycoprotein efflux and CYP-mediated metabolism, and reveals potential hERG channel inhibition for peimine as a cardiac safety concern. Overharvesting and habitat loss have reduced wild resources, underscoring the need for conservation, cultivation, and marker-guided quality control. Overall, Yi Beimu shows credible ethnopharmacological rationale and promising multi-target pharmacology for respiratory disorders, but translation will require bioactivity-guided isolation coupled with PK–PD-guided in vivo studies, rigorous safety evaluation, and conservation-aware cultivation to move from traditional remedy toward validated therapeutic resource. Full article

Euryops floribundus has traditionally been recognized for its therapeutic benefits, although its pharmacological potential has not been fully explored. This study investigated the leaves of E. floribundus for volatile compounds, in vitro anticancer potential, antioxidant activity, and phytochemical composition using standard methods. Terpenoids, flavonoids, glycosides, tannins, saponins, and steroids were identified using qualitative screening. FTIR analysis verified that the functional groups corresponded to bioactive substances. Methanol, ethanol, and aqueous extracts showed dose-dependent 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. Nitric oxide scavenging activity ranged from 7.2% to 22.5% at 2500 μg/mL. GC-MS profiling of essential oils revealed monoterpenes as the primary constituents (60%), with sabinene (27.86%) and terpinen-4-ol (13.63%) as major chemicals. Significant antiproliferative effects were shown by ethanol and methanol extracts against DU-145, PC-3, and SK-UT-1 cancer cell lines with cell viability inhibition ranging from 82.6% to 85.6%, and IC₅₀ values ranging from 1.7 ± 0.02 to 2.7 ± 0.03 µg/mL. These findings support the potential therapeutic uses of E. floribundus leaves and necessitate additional bioassay-guided research since they indicate that the leaves are rich in bioactive phytochemicals with antioxidant and anticancer activities. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a multifactorial condition requiring multi-target therapeutic strategies beyond traditional single-marker approaches. In this work, we present a fully in silico nutraceutical screening pipeline that integrates molecular prediction, systemic aggregation, and technological design. A curated panel of ten MASLD-relevant targets, spanning nuclear receptors (FXR, PPAR-α/γ, THR-β), lipogenic and cholesterogenic enzymes (ACC1, FASN, DGAT2, HMGCR), and transport/regulatory proteins (LIPG, FABP4), was assembled from proteomic evidence. Bioactivity records were extracted from ChEMBL, structurally standardized, and converted into RDKit descriptors. Predictive modeling employed a stacked ensemble of Random Forest, XGBoost, and CatBoost with isotonic calibration, yielding robust performance (mean cross-validated ROC-AUC 0.834; independent test ROC-AUC 0.840). Calibrated probabilities were aggregated into total activity (TA) and weighted TA metrics, combined with structural clustering (six structural clusters, twelve MOA clusters) to ensure chemical diversity. We used physiologically based pharmacokinetic (PBPK) modeling to translate probabilistic profiles into minimum simulated doses (MSDs) and chrono-specific exposure (%T>IC50) for three prototype concepts: HepatoBlend (morning powder), LiverGuard Tea (evening aqueous form), and HDL-Chews (postprandial chew). Integration of physicochemical descriptors (MW, logP, TPSA) guided carrier and encapsulation choices, addressing stability and sensory constraints. The results demonstrate that a computationally integrated pipeline can rationally generate multi-target nutraceutical formulations, linking molecular predictions with systemic coverage and practical formulation specifications, and thus provides a transferable framework for MASLD and related metabolic conditions. Full article

Marine diatoms are prolific producers of bioactive metabolites, but Arctic species remain underexplored as sources of antibacterial and antibiofilm agents. Here, seven species were grown in photobioreactors (PBRs) and systematically screened for antibacterial, antibiofilm, and cytotoxic activities. All strains inhibited Gram-positive bacteria, and four reduced Staphylococcus epidermidis biofilm formation. Porosira glacialis emerged as a lead species, combining potent antibiofilm activity with favourable traits for large-scale cultivation, and no detectable cytotoxicity. Bioactivity-guided fractionation of P. glacialis yielded two antibiofilm compounds: methyl 3-hydroxyoctadecanoate, the first time reported in diatoms and newly associated with antibiofilm bioactivity, and pheophorbide a, a chlorophyll degradation product. Both inhibited S. epidermidis biofilm formation without any observed cytotoxicity. Notably, Cylindrotheca closterium exhibited cultivation-dependent antibiofilm activity, underscoring the importance of growth conditions for metabolite production. These findings highlight the potential of Arctic diatoms as a sustainable source of antibiofilm agents and support further exploration of their metabolites for antimicrobial and industrial applications. Full article

The fruits of Piper longum L. (long pepper), a spice and medicinal plant of the family Piperaceae, are widely used in South and Southeast Asian cuisine and traditional medicine, valued for their pungent flavor and aroma. The metabolomic profiling of P. longum using UPLC-qTOF-MS/MS provided a comprehensive chemical characterization of this traditional medicinal plant, revealing that lignans and amide alkaloids are the major classes of secondary metabolites. To further investigate its pharmacological potential, the bioactive ethyl acetate fraction was subjected to a SIRT1-targeted chemical investigation. This led to the isolation and structural elucidation of three previously undescribed compounds, a cadinene-type sesquiterpene (1) and two oxo-neolignan (2 and 5), along with four known compounds 3, 4, 6, and 7. Compounds (1–7) were evaluated for their ability to modulate p53-dependent transcriptional activity via SIRT1 activation using a luciferase reporter cell-based assay. SIRT1, a NAD⁺-dependent deacetylase, is a crucial regulator of longevity, metabolism, and cellular stress resistance, making it a key target for the treatment of age-related diseases. Compounds 2–7 exhibited significant SIRT1 activation, with compound 6 displaying particularly high efficacy, comparable to resveratrol, the most well-known natural SIRT1 activator. This study demonstrates that the discovery of novel chemical scaffolds through bioactivity-guided screening highlights the value of combining advanced metabolomics with pharmacological evaluation. The results support the traditional medicinal use of long pepper and its potential for development into functional foods or pharmaceuticals for healthy aging. Full article

Molecular docking has emerged as a pivotal computational approach in agri-food research, offering a rapid and targeted means to discover bioactive molecules for crop protection and food safety. Its ability to predict and visualize interactions between natural or synthetic compounds and specific biological targets provides valuable opportunities to address urgent agricultural challenges, including climate change and the rise in resistant crop pathogens. By enabling the in silico screening of diverse chemical entities, this technique facilitates the identification of molecules with antimicrobial and antifungal properties, specifically designed to interact with critical enzymatic pathways in plant pathogens. Recent advancements, such as the integration of molecular dynamics simulations and artificial intelligence-enhanced scoring functions, have significantly improved docking accuracy by addressing limitations like protein flexibility and solvent effects. These technological improvements have accelerated the discovery of eco-friendly biopesticides and multifunctional nutraceutical agents. Promising developments include nanoparticle-based delivery systems that enhance the stability and efficacy of bioactive molecules. Despite its potential, molecular docking still faces challenges related to incomplete protein structures, variability in scoring algorithms, and limited experimental validation in agricultural contexts. This work highlights these limitations while outlining current trends and future prospects to guide its effective application in agri-food biotechnology. Full article

Francisella tularensis is a pathogenic bacterium and the causative agent of the disease tularemia. Because of the virulence of this bacterium and the potential for weaponization, the Centers for Disease Control and Prevention (CDC) has classified F. tularensis as a Category A Bioterrorism Agent. Therefore, the need for new treatments for tularemia is critical. In this work, we screened a cataloged library of natural extracts to identify those that inhibit the growth of F. tularensis only during infection of THP-1 monocyte cells. One of the most promising extracts identified in this screen was derived from Foeniculum vulgare (fennel). Using bioassay-guided fractionation, the fennel extract was fractionated, and the bioactive compound was isolated and structurally elucidated as the phenylpropanoid dillapiole. We subsequently confirmed that dillapiole alone could limit the replication of F. tularensis in infected THP-1 cells, but not outside of this infection model. Investigations on host responses suggested that dillapiole was not substantially augmenting the immunity of these THP-1 cells. We then investigated the potential virulence modulation activity of dillapiole. To test this hypothesis, RNA-seq analysis was carried out on F. tularensis bacteria that were treated with dillapiole. This showed that dillapiole caused a significant downregulation of genes controlled by the transcriptional regulators MglA and SspA, including those encoded in the Francisella pathogenicity island. Western blotting validated these findings as both IglA and IglC expression was diminished in F. tularensis LVS bacteria treated with dillapiole. Because dillapiole dampens the virulence gene expression of F. tularensis, we concluded that this compound has potential to be used as a novel therapeutic for tularemia with a unique mechanism of action. Full article