Search Results (28)

Piperine (PIP), a plant alkaloid with anti-inflammatory and antioxidant effects, has poor solubility and bioavailability, limiting its therapeutic potential in macrophage-mediated inflammatory and oxidative stress conditions. Despite various nanocarrier systems being explored for bioactive compounds, the specific combination of mannose-functionalized chitosan with dual stabilizers (TPGS and Tween 80) for enhanced macrophage targeting and piperine delivery has not been investigated. We hypothesized that this novel formulation would significantly enhance piperine solubility, macrophage uptake, and anti-inflammatory/antioxidant effects compared to conventional systems, while modulating apoptosis-related pathways. This study evaluated targeted and non-targeted nanoparticles synthesized by ionic gelation and emulsification using RAW 264.7 and THP-1 macrophages. FTIR, UV–Vis, XRD, and CHNS confirmed mannose conjugation, while SEM, TEM, and AFM revealed morphology. Physicochemical properties were assessed by DLS, encapsulation efficiency (EE%), drug loading (DL%), and stability. Biological evaluations included drug release, cytotoxicity (MTT), apoptosis analysis (Annexin V–FITC/PI staining), cellular uptake (fluorescence microscopy with coumarin-6), anti-inflammatory assays (extracellular and intracellular NO inhibition, cytokine suppression), antioxidant activity (DPPH, ABTS, FRAP, TAC), intracellular ROS/RNS, and apoptosis-related markers. Targeted nanoparticles showed larger mean size (162 nm) versus non-targeted ones (78 nm). EE% was 82% (targeted) and 92% (non-targeted). Both demonstrated sustained 72 h release. Cellular uptake was significantly greater for targeted nanoparticles. Both formulations reduced NO and pro-inflammatory cytokines, regulated apoptosis-associated markers, and induced controlled apoptosis at higher concentrations, with stronger effects observed for targeted particles. Antioxidant activity increased dose-dependently, with targeted nanoparticles showing superior intracellular ROS/RNS suppression. This novel multi-functional platform efficiently encapsulates PIP, enhances macrophage targeting, modulates apoptosis pathways, and demonstrates superior therapeutic promise for inflammation-related disorders. Full article

To address yttrium (Y) contamination from ion adsorption mining, this study developed a combined microbial phytoremediation strategy for dual objectives: ensuring crop safety in Lactuca sativa and enhancing Y recovery by Solanum nigrum. Two specific microbial consortia were constructed from rare earth tailings isolates: inoculant I (bacterial: Enterobacter sp., Serratia sp., Bacillus sp.) applied to L. sativa, and inoculant II (fungal: Penicillium sp., Aspergillus sp., Talaromyces sp.) applied to S. nigrum. Inoculant I increased L. sativa biomass by 26% while reducing Y content in roots and rhizosphere soil solution by 47% and 56%, respectively, potentially through down-regulation of amino acid metabolites. Inoculant II increased Y content in the S. nigrum rhizosphere soil solution by 89%, linked to up-regulation of organic acids and coumarin derivatives. Both consortia reduced plant stress markers and enhanced soil enzyme activities. These findings demonstrate that specialized microbial consortia can differentially regulate Y behavior in the rhizosphere—immobilizing it in a crop for food safety, while enhancing its bioavailability for a hyperaccumulator—offering a targeted strategy for managing rare earth element-contaminated agricultural soils. Full article

Coumarin-based compounds are recognized for their chemical versatility and diverse biological activities, yet clinical applications remain largely confined to 4-hydroxycoumarin anticoagulants. To bridge this translational gap, coumarin scaffolds have been increasingly employed in prodrug design to enable controlled activation, targeted delivery, and theranostic functionality. This review critically evaluates whether coumarin-based prodrugs fulfill their therapeutic promise or remain primarily preclinical tools across oncology, inflammation, infectious diseases, and cardiovascular disorders. Strategies including enzymatic-, pH-, redox-, and light-triggered activation, as well as subcellular targeting and multifunctional hybrids, are discussed. Preclinical studies demonstrate improved bioavailability, reduced off-target toxicity, and real-time fluorescence monitoring, yet most compounds remain at the in vitro or small-animal model stage. Despite their mechanistic and conceptual potential, clinical translation is constrained by molecular complexity, pharmacokinetics, safety, and regulatory challenges. Overall, coumarins constitute a versatile multifunctional platform whose therapeutic impact relies on rigorous in vivo validation and strategic optimization. Full article

Background/Objectives: Commiphora gileadensis (Balm of Gilead) is an aromatic medicinal plant with a history of traditional use in ancient and Arabic medicine. It has been used traditionally to treat inflammation, infections, and wounds. Despite its long-standing cultural and economic importance, modern pharmacological validation requires a comprehensive synthesis of current scientific data. This review aims to provide a thorough comparative summary of the phytochemical composition and biological activities of its diverse products. Methods: An updated literature search was conducted using databases such as ScienceDirect, PubMed, Scopus, and Google Scholar, covering publications from approximately 2000 to 2025. The review included English-language peer-reviewed articles, books, and reports providing phytochemical analyses or biological evaluations. Data were manually extracted and categorized by plant parts (resin, leaves, bark, stems), major constituents, and specific pharmacological activities. Results: The review identified ten diverse chemical groups, mainly terpenoids (mono-, sesqui-, di-, and triterpenes) and flavonoids. Other remarkable classes included phenolic acids, phytosterols, lignans, coumarins, and fatty acids. However, the essential oil chemical profile is highly variable, influenced by geographical origin and preparation technique. Pharmacological studies demonstrated a wide spectrum of bioactivities, in particular antioxidant, anti-inflammatory, antimicrobial, anticancer, antidiabetic, and wound-healing properties. Toxicological studies classified the plant as generally non-toxic; however, there is a notable lack of clinical and pharmacokinetic data. Conclusions:C. gileadensis possesses a rich and diverse secondary metabolite profile, validating its traditional ethnobotanical applications. Future research should prioritize pre-clinical and clinical trials to establish its safety, bioavailability, and metabolic fate for its successful integration into modern medicine. Full article

Copper(II) coordination complexes with coumarin-derived heterocyclic ligands are promising in inorganic therapeutics for anticancer and antimicrobial applications. To establish quantitative structure–activity relationships for lead design, we studied six copper(II) complexes (Cu1–Cu6)with four- and five-coordinate geometries using Density Functional Theory, Conceptual Density Functional Theory, and visualization analyses. Geometry optimization at M06/6-31G(d)+DZVP revealed distorted coordination environments from $d^9$ Jahn–Teller effects. Tridentate $N_{2}O$-chelatedcomplexes (Cu4–Cu6) showed greater aqueous stability ($\Delta G_{solv}=-43$ to $-50$ kcal·mol⁻¹) than four-coordinate analogs ($-29$ to $-31$ kcal·mol⁻¹). CDFT global descriptors contrasted reactivity: four-coordinate Cu1–Cu2 had higher electron affinity (>4.2 eV) and electrophilicity (>5.7 eV), suggesting propensity for redox cycling and for undergoing nucleophilic attack by DNA bases, whereas Cu4–Cu6 displayed increased chemical hardness (3.43–3.54 eV) and lower electrophilicity (≈3.8 eV), implying enhanced kinetic stability and bioavailability. Frontier orbital analysis indicated ligand-to-metal charge transfer via a LUMO delocalized over the $\pi$-conjugated coumarin, facilitating intercalation by $\pi$-$\pi$ stacking. The visualization showed strong covalent bonds (blue isosurfaces) stabilizing the metal and dispersive $\pi$ interactions (green surfaces) on the ligand, enabling solvent interactions and biomolecular recognition. Tridentate $N_{2}O$ coordination thus balances electronic stability and biological reactivity, making Cu4–Cu6 promising for further study. Full article

FABP4 (fatty acid-binding protein 4) is a lipid chaperone and secreted adipokine linking dysregulated fatty acid handling with inflammation, cellular stress, and insulin resistance in obesity. By modulating nuclear receptor signaling (notably PPARγ) and enhancing NF-κB/MAPK activation in adipocytes and macrophages, FABP4 contributes to maladaptive adipose remodeling and systemic metabolic decline. This review critically summarizes recent preclinical evidence on natural bioactive compounds that regulate FABP4 expression and associated adipogenic programs in models of adipogenesis and diet-induced obesity. Data from 3T3-L1/OP9 adipocytes, rodent studies, and selected alternative models indicate that many plant-derived extracts and phytochemicals (e.g., polyphenols, saponins, coumarins, terpenoids, and fermented products) down-regulate FABP4 at mRNA and/or protein levels. These effects are frequently accompanied by suppression of PPARγ/C/EBPα/SREBP1c signaling, activation of AMPK-related pathways, reduced lipid accumulation, and improved metabolic outcomes including lower weight gain, reduced adipocyte hypertrophy, improved steatosis, and favorable serum lipid profiles. Natural compounds from non-plant sources (animal- and microbe-derived metabolites) further broaden FABP4-targeting strategies, supporting FABP4 as a cross-class therapeutic node. Key translational barriers include poor extract standardization, incomplete identification of active constituents, limited oral bioavailability, microbiome-dependent variability, and scarce clinical validation. Future work should prioritize well-characterized lead scaffolds, targeted delivery, rational combinations, and standardized, adequately powered clinical trials assessing dose, durability of FABP4 suppression, and cardiometabolic safety. Full article

Introduction: Globally, microbial infections are projected to be among the leading causes of death by 2050 due to rising drug resistance. Antimicrobials are vital for treating both animals and humans worldwide. However, their overuse and misuse accelerate drug resistance, posing a serious threat to public health. Coumarin is a naturally occurring compound contributing health-beneficial features in drug discovery. Its high solubility in organic solvents, high bioavailability, simple structure, low toxicity, and low molecular weight make it an ideal candidate for combining with other pharmacophores to develop new therapeutic agents. This compound exhibits several biological activities, including antimicrobial, anticancer, anti-inflammatory, antidiabetic, neuroprotective, and anticoagulant effects, motivating medicinal researchers to hybridize it with other compounds to enhance its pharmacological efficacy. Hybridization of different pharmacophores via suitable linkers, including cleavable and non-cleavable ones, is a promising approach in drug development, resulting in new therapeutics with improved biological activity. Therefore, the hybridization of coumarin with other pharmacophores has become an interesting paradigm for medicinal scientists. Aim: This review aims to summarize the existing scientific literature on coumarin-based hybrid compounds with antimicrobial capabilities and discuss the structure–activity relationship (SAR) of these hybrids to potentially guide future research on and development of coumarin-based drugs for microbial treatment. Material and Methods: The review focuses on open-access literature about coumarin hybrid drugs available through searching tools such as Google, Google Scholar, ScienceDirect, and Scopus, published from 2024 to 2025. Results: Coumarin hybrids exhibit promising antimicrobial activity, particularly against S. aureus and C. albicans. The SAR reveals that halogenation, bulky aromatics, nitro, and hydroxyl groups enhance the interaction of the coumarin rings with amino acid residues. Conclusions: The reported coumarin hybrids showed a promising antimicrobial activity, with structural modifications influencing their activity. Hence, more studies, including more pre-clinical and clinical evaluations, are recommended for these hybrid compounds. Full article

Background/Objectives: Palmitoylethanolamide (PEA) is an endogenous lipid mediator with endocannabinoid-like activity. Despite its therapeutic potential in muscle-related inflammatory disorders, including sarcopenia, its clinical use is limited by poor solubility and bioavailability. To overcome these issues, we developed hybrid nanoparticles combining poly(lactic-co-glycolic acid) (PLGA) and lipids to enhance PEA encapsulation and ok delivery. Methods: PEA-loaded hybrid nanoparticles (PEA-Hyb-np) were produced via a modified single-emulsion solvent evaporation method using stearic acid and Gelucire^® 50/13 as lipid components. Characterization included particle size, morphology, PDI, and zeta potential, as well as DSC, FT-IR, and XRD analyses. For the biological evaluation in a C2C12 myoblasts cell culture, coumarin-6-labeled nanoparticles were employed. Results: PEA-Hyb-np showed mean particle sizes of ~150 nm, with internal lipid–polymer phase separation. This structure enabled high encapsulation efficiency (79%) and drug loading (44.2 mg/g). Drug release in physiological and non-physiological media was enhanced due to drug amorphization, confirmed by DSC, FT-IR, and XRD analyses. Cytocompatibility studies showed no toxicity and improved cell viability compared to unloaded nanoparticles. Cellular uptake studies by confocal microscopy and flow cytometry demonstrated efficient and time-dependent internalization. Conclusions: PEA-Hyb-np represent a promising delivery platform to improve the solubility, bioavailability, and therapeutic efficacy of PEA for muscle-targeted applications. Full article

The recent COVID-19 pandemic highlighted the significant challenge of insufficient antiviral pharmacological options. Edible plants offer a promising avenue for developing novel antiviral drugs. Etrog citron (Citrus medica L.), which is a valuable edible and medicinal plant, contains various antiviral phytochemicals, mainly flavonoids, coumarins, and terpenes. However, the therapeutic application of these compounds remains limited by factors such as poor solubility, limited bioavailability, and unclear mechanisms of action. The aim of the present article is to offer a comprehensive analysis of the antiviral phytochemicals extracted from various parts of Citrus medica, emphasizing their mode of action and delivery strategies that may allow turning these compounds into new antiviral drugs. Full article

Inonotus obliquus, a medicinal mushroom valued for its bioactive compounds, has not been previously characterized from Romanian sources. This study presents the first comprehensive chemical and biological screening of I. obliquus, introducing novel polymer-based encapsulation systems to enhance the stability and bioavailability of its bioactive constituents. Two distinct delivery systems were designed to enhance the functionality of I. obliquus extracts: (i) microencapsulation in maltodextrin (MIO) and (ii) a sequential approach involving preparation of silver nanoparticle-loaded I. obliquus (IO–AgNPs), followed by microencapsulation to yield the hybrid MIO–AgNP system. Comprehensive metabolite profiling using GC–MS and ESI–QTOF–MS revealed 142 bioactive constituents, including terpenoids, flavonoids, phenolic acids, amino acids, coumarins, styrylpyrones, fatty acids, and phytosterols. Structural integrity and successful encapsulation were confirmed by XRD, FTIR, and SEM analyses. Both IO–AgNPs and MIO–AgNPs demonstrated potent antioxidant activity, significant acetylcholinesterase inhibition, and robust antimicrobial effects against Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli. Cytotoxicity assays revealed pronounced activity against MCF-7, HCT116, and HeLa cell lines, with MIO–AgNPs exhibiting superior efficacy. The synergistic integration of maltodextrin and AgNPs enhanced compound stability and bioactivity. As the first report on Romanian I. obliquus, this study highlights its therapeutic potential and establishes polymer-based nanoencapsulation as an effective strategy for optimizing its applications in combating microbial resistance and cancer. Full article

Coumarins are natural organic compounds widely found in plants that show promising anticancer properties. This article reviews the current research on the mechanisms of action of coumarins in cancer therapy, including the induction of apoptosis, inhibition of tumor cell proliferation, modulation of oxidative stress, and inhibition of angiogenesis and metastasis. Examples of coumarins with demonstrated anticancer activity, such as scopoletin, umbeliferon, esculetin and their synthetic derivatives, are also presented. The results of preclinical studies, the potential use of coumarins as stand-alone drugs and their role in combination therapy with chemotherapy are discussed. In addition, challenges related to bioavailability, safety and potential interactions with other drugs are highlighted. This review concludes by pointing out future research directions, such as the design of new coumarin analogs and the use of nanotechnology to enhance their efficacy in cancer treatment. Full article

Chenopodium quinoa sprouts possess a superior nutritional profile relative to conventional quinoa seeds, which is mainly attributable to their germination process. Sprouting quinoa is able to preserve its substantial nutritional value while enhancing its bioavailability and digestibility. The aim of this study was to evaluate the gastroprotective effects of hydroalcoholic extracts of three varieties of quinoa sprouts (pasankalla, yellow maranganí, and black coito). The chemical compounds were determined using LC-MS (Liquid Chromatography–Mass Spectrometry). Antioxidant activity was determined using two analytical methods, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). To evaluate the gastroprotective effects of these hydroalcoholic extracts in Holtzman male rats, a gastric lesion was induced with 96% ethanol after the administration of the hydroalcoholic extract of the three varieties of C. quinoa sprouts. Our phytochemical analysis results reveal the presence of amino acids (valine, leucine, isoleucine, phenylalanine, tryptophane, proline, tyrosine, and arginine, among others) and their derivatives, organic acids, monosaccharides, lipids, nucleobases/nucleosides, steroids, triterpene saponins, and coumarins. The pasankalla, yellow maranganí, and black coito varieties exhibited antioxidant capacities of 36.70, 32.32, and 34.63 µmol Trolox equivalent (TE)/mg of extract for the DPPH radical and 56.61, 41.56, and 52.09 µmol TE/mg of extract for the ABTS radical, respectively. The percentage of antisecretory efficiency at a dose of 500 mg/kg for the pasankalla, yellow maranganí, and black coito varieties was 34.13%, 30.67%, and 26.67%, respectively, and the anti-ulcer effect, expressed as a percentage of inhibition of ulcer formation, was 74.7%, 67.4%, and 69.5%, respectively. In contrast, the groups treated with ranitidine and sucralfate exhibited percentages of 59.0% and 67.4%, respectively. The pasankalla quinoa exhibits more significant antioxidant activity and a stronger gastroprotective effect compared to the other varieties examined in this study. In conclusion, the hydroalcoholic extracts of the three varieties of C. quinoa sprouts exhibited a gastroprotective effect, and the pasankalla variety at a dose of 500 mg/kg exhibited a stronger protective effect on the gastric mucosa of the rats. Full article

Although COVID-19 is not a pandemic anymore, the virus frequently mutates, resulting in new strains and presenting global public health challenges. The lack of oral antiviral drugs makes it difficult to treat him, which makes the creation of broadly acting antivirals necessary to fight current and next epidemics of viruses. Using the molecular docking approach, 118 compounds derived from marine organisms and 92 previously synthesized compounds were screened to assess their binding affinity for the main protease and papain-like protease enzymes of SARS-CoV-2. The best candidates from the xanthene, benzoxazole, and coumarin classes were identified. Marine-derived compounds showed slightly better potential as enzyme inhibitors, though the binding affinities of synthesized compounds were similar, with the best candidates displaying affinity values between 0.2 and 0.4 mM. Xanthenes, among both marine origin and synthesized compounds, emerged as the most promising scaffolds for further research as inhibitors. The papain-like protease was found to be more druggable than the main protease. Additionally, all top candidates met the criteria for various drug-likeness properties, indicating good oral bioavailability and low risk of adverse effects. This research provides valuable insights into the comparative affinities of marine origin and synthesized compounds from the xanthene, coumarin, and benzoxazole classes, highlighting promising candidates for further in vitro and in vivo studies. Full article

Background/Objectives: Glucagon-like peptide-1 (GLP-1) receptor is currently one of the most explored targets exploited for the management of diabetes and obesity, with many aspects of its mechanisms behind cardiovascular protection yet to be fully elucidated. Research dedicated towards the development of oral GLP-1 therapy and non-peptide ligands with broader clinical applications is crucial towards unveiling the full therapeutic capacity of this potent class of medicines. Methods: This study describes the virtual screening of a natural product database consisting of 695,133 compounds for positive GLP-1 allosteric modulation. The database, obtained from the Coconut website, was filtered according to a set of physicochemical descriptors, then was shape screened against the crystal ligand conformation. This filtered database consisting of 26,325 compounds was used for virtual screening against the GLP-1 allosteric site. Results: The results identified ten best hits with the XP score ranging from −9.6 to −7.6 and MM-GBSA scores ranging from −50.8 to −32.4 and another 58 hits from docked pose filter and a second round of XP docking and MM-GBSA calculation followed by molecular dynamics. The analysis of results identified hits from various natural products (NPs) classes, to whom attributed antidiabetic and anti-obesity effects have been previously reported. The results also pointed to β-lactam antibiotics that may be evaluated in drug repurposing studies for off-target effects. The calculated ADMET properties for those hits revealed suitable profiles for further development in terms of bioavailability and toxicity. Conclusions: The current study identified several NPs as potential GLP-1 positive allosteric modulators and revealed common structural scaffolds including peptidomimetics, lactams, coumarins, and sulfonamides with peptidomimetics being the most prominent especially in indole and coumarin cores. Full article

The increasing cases of drug resistance and high toxicity associated with the currently used antifungal agents are a worldwide public health concern. There is an urgent need to develop new antifungal drugs with unique target mechanisms. Plant-based compounds, such as carvacrol, eugenol, coumarin, cinnamaldehyde, curcumin, thymol, etc., have been explored for the development of promising antifungal agents due to their diverse biological activities, lack of toxicity, and availability. However, researchers around the world are unable to fully utilize the potential of natural products due to limitations, such as their poor bioavailability and aqueous solubility. The development of hybrid molecules containing natural products is a promising synthetic approach to overcome these limitations and control microbes’ capability to develop resistance. Based on the potential advantages of hybrid compounds containing natural products to improve antifungal activity, there have been different reported synthesized hybrid compounds. This paper reviews different literature to report the potential antifungal activities of hybrid compounds containing natural products. Full article