Search Results (120)

Background Despite many studies on polymer-incorporated nanocarriers for ophthalmic drug delivery, few have thoroughly explored the relationship between coating composition and performance. This study aimed to evaluate the effects of three commonly used cationic polymers—distearoyl phosphatidylethanolamine-polyethylene glycol 1000-poly(amidoamine) (DSPE-PEG1000-PAMAM), trimethyl chitosan (TMC), and (2,3-dioleoyloxypropyl) trimethylammonium chloride (DOTAP)—on the corneal behaviors and anti-cataract efficacy of diosmetin (DIO)-loaded micelles (D-M-P, D-M-T, and D-M-D, respectively). Methods The DIO-loaded micelles were prepared using the thin-film dispersion method and incorporated with the three polymers through hydrophobic interactions and electrostatic adsorption. Structural characterization was demonstrated by TEM imaging and particle size analyzer. In vitro release behavior was detected by the dialysis method. Cell viability of D-M-P, D-M-T, and D-M-D on L929 cells was detected by CCK-8 assays, with cellular uptake performed using coumarin 6 as the fluorescence indicator. Precorneal retention behaviors of these three vesicles were observed by In Vivo Imaging System. Transcorneal permeability was determined by modified Franz diffusion method and the permeation routes of the vesicles are investigated. Selenite-induced cataract model was established. The anti-cataract effects of three different DIO-loaded micelles were evaluated by the observation of lens opacity and antioxidant enzyme activities. Eye Irritation of the DIO in different preparations was estimated using the Draize test, along with H&E staining of the corneas. Results Structural characterization of DIO-loaded micelles revealed that the vesicles were spherical, with a uniform size distribution of around 28 nm, a similar surface potential of approximately 6.0 mV, and a high DIO entrapment efficiency of about 95%. Compared to the DIO suspension, all three formulations exhibited a significant sustained-release effect. They showed no signs of irritation and demonstrated increased IC50 values in L929 cells, indicating improved biocompatibility. Cellular uptake in human lens epithelial cells (HLECs) was assessed using confocal laser scanning microscopy. C-M-T displayed the highest fluorescence signals, with a cellular internalization 3.2 times greater than that of the solution group. Both C-M-T and C-M-P enhanced vesicle retention on the corneal surface by at least 47.8% compared to the Cou-6 solution. Furthermore, TMC facilitated the paracellular transport of vesicles into the deepest layers of the cornea and delivered DIO across the cornea, with a P_app value 3.11 times and 1.49 times those of D-M-D and D-M-P, respectively. In terms of therapeutic efficacy, D-M-T demonstrated the most significant attenuation of lens opacity, along with enhanced antioxidant enzyme activities and inhibition of lipid peroxidation. Conclusion The modification of micelle vesicles with different cationic polymers significantly influences their performance in ocular drug delivery. Among the tested formulations, D-M-T stands out due to its multiple advantages, including enhanced transcorneal drug delivery, therapeutic efficacy for DIO, and safety, making it the most promising candidate for ophthalmic applications. Full article

Background: Epizootics of largemouth bass ranavirus (LMBRaV) in largemouth bass (Micropterus salmoides) populations are associated with elevated mortality and significant financial losses. Given the lack of effective and safe medication to treat this disease, oral vaccination, which directly targets the intestinal mucosal immune system, is crucial for disease resistance. Methods: This study utilized carboxymethyl cellulose (CMC) to coat LMBRaV inactivated vaccine (LIV) (micro-CMC@LIV). The morphology and characteristics of the CMC microcapsules were determined. In vitro simulated gastric and intestinal conditions were used to validate that the microcapsules could tolerate gastric conditions and subsequently release their contents in the intestinal tract. This was confirmed using CMC-coated coumarin 6 (C6) fluorescence microcapsules. Results: After the oral administration of micro-CMC@LIV, the detection of LMBRaV major capsid protein confirmed effective antigen release and absorption in the midgut and hindgut. Neutralizing antibody titers were significantly higher (1:81.71) in the micro-CMC@LIV group compared to the uncoated vaccine group (1:21.69). The expression of genes linked to the innate and adaptive immune systems was upregulated post-micro-CMC@LIV treatment. Following the LMBRaV challenge, the micro-CMC@LIV group exhibited a relative percent survival (RPS) of 82.14%, significantly higher than the uncoated vaccine group (61.61%). Droplet digital PCR analysis revealed significantly lower viral loads in the liver, spleen, and head kidney of the micro-CMC@LIV group compared to the control group and the uncoated vaccine group. Conclusions: These results collectively suggest that the CMC-coated LIV can be effectively delivered to the intestinal tract and induce robust antibody and immune responses, providing a reliable method for preventing and controlling LMBRaV disease in the largemouth bass industry. Full article

The ageing of the world population has led to an increase in the incidence of neurodegenerative diseases. In this regard, plants have become an important source of bioactive principles that are able to act on multiple targets. Chamaemelum nobile (L.) All. is a perennial herb of the Asteraceae family, known as Roman chamomile, less studied in the scientific literature than the more common Matricaria chamomilla. Flavonoids and sesquiterpene lactones represent the main secondary metabolites. Among these, nobilin and its derivatives are considered the main components. With the aim of performing a phytochemical investigation, the extract of the fresh aerial parts of C. nobile was firstly analysed by LC-(+)ESI/QExactive/MS/MS, which guided the isolation of 15 compounds (coumarins, glucoside derivatives, flavonoids, and germacrane-type sesquiterpene lactones) characterised by 1D and 2D NMR spectroscopy. The presence of a derivative of nobilin, never been reported before, was highlighted. Moreover, for all isolated compounds, acetylcholinesterase and tyrosinase inhibitory activity were tested by spectrophotometric assays. The results showed that the tested compounds presented interesting tyrosinase (IC₅₀ values: 32.09–412.02 µM) and acetylcholinesterase inhibitory activity (IC₅₀ values: 181.58–387.99 µM). In detail, apigenin 7-O-rutinoside (6) showed the highest tyrosinase and AchE inhibitory activity, with IC₅₀ values of 32.09 and 181.58 µM, respectively. Full article

Arnebia euchroma (Royle) Johnst. has high medicinal and economic value, but in recent years, wild resources of this species have been depleted and the quality of artificially cultivated A. euchroma has been poor. The endophyte community of medicinal plants is rich, serving as an internal resource that promotes the growth of medicinal plants and the accumulation of secondary metabolites, and has important potential application value in improving the quality of medicinal materials. A. euchroma cultivars and wild varieties contain abundant endophyte communities and metabolites in different tissues. However, the relationships between A. euchroma endophytes and metabolites with different growth patterns and different tissue sites remain unclear. In this study, microbiome analysis and metabolomics were used to analyze the diversity of endophytes in the root and leaf tissues of cultivated and wild A. euchroma and their correlations with metabolites. The results revealed that the diversity of endophytes in A. euchroma was different from that in wild A. euchroma and that there was tissue specificity among different tissues. A species composition analysis revealed that the dominant endophytic fungi belonged to Ascomycota and Basidiomycota, and the dominant endophytic bacteria belonged to Proteobacteria and Cyanobacteria. A total of 248 metabolites, including quinones, flavonoids, alkaloids, organic acids, sugars, amino acids, coumarins, sterols, terpenoids, polyphenols, fatty ketones, and their derivatives, were identified in positive ion mode via LC–MS/MS. According to their different growth patterns and associated tissue parts, 9 differentially abundant metabolites were screened between AEZ-L (cultivated leaf tissue of A. euchroma) and AEY-L (wild leaf tissue of A. euchroma), 6 differentially abundant metabolites were screened between AEZ-R (cultivated root tissue of A. euchroma) and AEY-R (wild root tissue of A. euchroma), and 104 differentially abundant metabolites were screened between AEZ-R and AEZ-L. Eighty-two differentially abundant metabolites were screened between AEY-R and AEY-L. The contents of eight naphthoquinones in AEZ-R and AEY-R were determined via HPLC. The contents of β,β’-dimethylacrylylakanin in wild A. euchroma were greater than those in cultivated A. euchroma. A correlation analysis revealed that the dominant endophytes in the four groups were significantly correlated with a variety of metabolites, and the eight naphthoquinones in the root tissue were also significantly correlated with the dominant endophytes. The diversity of the A. euchroma endophyte community differed across different growth patterns and different tissue parts. There were significant differences in the relative contents of A. euchroma metabolites in different tissues. A correlation analysis verified the correlation between A. euchroma endophytes and metabolites. Full article

Smart fibers with tunable luminescence properties, as a new form of visual output, present the potential to revolutionize personal living habits in the future and are receiving more and more attention. However, a huge challenge of smart fibers as wearable materials is their stretching capability for seamless integration with the human body. Herein, stretchable thermochromic fluorescent fibers are prepared based on self-crystallinity phase change, using elastic polyurethane (PU) as the fiber matrix, to meet the dynamic requirements of the human body. The switching fluorescence-emitting characteristic of the fibers is derived from the reversible conversion of the dispersion/aggregation state of the fluorophore coumarin 6 (C6) and the quencher methylene blue (MB) in the phase-change material hexadecanoic acid (HcA) during heating/cooling processes. Considering the important role of phase-change materials, thermochromic fluorescent dye is encapsuled in the solid state via the piercing–solidifying method to avoid the dissolution of HcA by the organic solvent of the PU spinning solution and maintain excellent thermochromic behavior in the fibers. The fibers obtained by wet spinning exhibit good fluorescent emission contrast and reversibility, as well as high elasticity of 800% elongation. This work presents a strategy for constructing stretchable smart luminescence fibers for human–machine interaction and communications. Full article

An antiviral effect of extracts prepared from aerial parts of nine species and from leaves of two species of the genus Spiraea L. was investigated for potential antiviral activity toward influenza A (H1N1) virus. The toxicity of dry extracts was analyzed, and the most selective extract was identified in vitro. The study’s material was collected in the Asian part of Russia. The plant extracts were prepared via three-stage countercurrent repercolation involving a complete cycle. All 40%-ethanolic extracts from Spiraea manifested antiviral activity against influenza A (H1N1) virus, with a selectivity index (SI) ranging from 1 to 10. IC₅₀ values indicated that the S. salicifolia L. S15 leaf extract (5.9 µg/mL) has the most pronounced antiviral effect and the lowest toxicity (CC₅₀ = 57.6 µg/mL) among the studied samples. The SI of this extract was 10, which exceeded that of the antiviral agent rimantadine (SI = 6). Biologically active compounds in the extract with the highest antiviral activity were identified using UV spectrometry and high-performance liquid chromatography. The S. salicifolia leaf extract was found to contain phenolic acids (chlorogenic, gentisic, caffeic, ferulic, and cinnamic acids), flavonols (quercetin, quercetin-3-glucuronoside, hyperoside, isoquercitrin, rutin, spiraeoside, avicularin, quercitrin, kaempferol, nicotiflorin, astragalin, and isorhamnetin-3-rutinoside), flavones (orientin, luteolin-7-glucoside, and vitexin), and coumarin. Predominant biologically active compounds in the S. salicifolia S15 leaf extract were such flavonols as rutin (19.3 mg/g), isoquercitrin (16.6 mg/g), isorhamnetin-3-rutinoside (10.6 mg/g), and astragalin (9.5 mg/g). Extraction of S. salicifolia leaves by repercolation is a more suitable method for extracting active ingredients with an antiviral effect. Full article

Polyglutamine (polyQ)-mediated spinocerebellar ataxia (SCA), including SCA1, 2, 3, 6, 7, and 17, are caused by mutant genes with expanded CAG repeats, leading to the intracellular accumulation of aggregated proteins, the production of reactive oxygen species, and cell death. Among SCA, SCA3 is caused by a mutation in the ATXN3 (ataxin-3) gene. In a circumstance of polyQ aggregation, the autophagic pathway is induced to degrade the aggregated proteins, thereby suppressing downstream deleterious effects and promoting neuronal survival. In this study, we tested the effects of synthetic indole (NC009-1, -2, -3, -6) and coumarin (LM-022, -031) derivatives as chemical chaperones to assist mutant ATXN3-Q₇₅ folding, as well as autophagy inducers to clear aggregated protein. Among the tested compounds, NC009-1, -2, and -6 and LM-031 interfered with Escherichia coli-derived ATXN3-Q₇₅ aggregation in thioflavin T binding and filter trap assays. In SH-SY5Y cells expressing GFP-fused ATXN3-Q₇₅, these compounds displayed aggregation-inhibitory and neurite growth-promoting potentials compared to untreated cells. Furthermore, these compounds activated autophagy by increasing the phosphatidylethanolamine-conjugated LC3 (microtubule associated protein 1 light chain 3)-II:cytosolic LC3-I ratio in these cells. A biochemical co-immunoprecipitation assay by using a mixture of HEK 293T cell lysates containing recombinant ATXN3-Q₇₅-Venus-C-terminus (VC) or Venus-N-terminus (VN)-LC3 protein indicated that NC009-1 and -2 and LM-031 served as an autophagosome-tethering compound (ATTEC) to interact with ATXN3-Q₇₅ and LC3, and the interaction was further confirmed by bimolecular fluorescence complementation analysis in cells co-expressing both ATXN3-Q₇₅-VC and VN-LC3 proteins. The study results suggest the potential of NC009-1 and -2 and LM-031 as an ATTEC in treating SCA3 and, probably, other polyQ diseases. Full article

Melilotus officinalis has been traditionally used as an anti-inflammatory agent; nevertheless, a comprehensive evaluation of its efficacy and safety and comparison with standard drugs are lacking. Taking into consideration concerns with current therapies, like efficacy limitations, side effects, and resistance, we aimed to develop a natural gel and cream based on Melilotus officinalis extract and explore their anti-inflammatory potential. After the chemical analysis of the extract confirmed the presence of coumarin, p-coumaric acid, gallic acid, and quercetin, formulations were prepared and subjected to physical and chemical stability evaluations over 6 months. The safety potential was tested in rats, while the anti-inflammatory activity was assessed both via in silico tests and in a rat model of inflammation. The examined formulations showed stable physical characteristics at the defined storage conditions and did not exert any sign of adverse skin reaction. The gel formulation exhibited a remarkable effect in inflammation reduction comparable with hydrocortisone. The in silico results suggest that coumarin, p-coumaric, and gallic acid bind to COX-1 and COX-2 with a lower affinity compared to diclofenac. On the other hand, quercetin demonstrated comparable inhibitory activity and stronger interaction compared to the control drug. Our results indicate that the examined formulations are stable and safe and may be promising dermal products for the alleviation of inflammatory skin conditions. Full article

A new series of compounds planned by molecular hybridization of the nucleobases uracil and thymine, or the xanthine theobromine, with coumarins, and linked through 1,2,3-triazole heterocycles were evaluated for their in vitro anticancer activity against the human tumor cell lines: colon carcinoma (HCT116), laryngeal tumor cells (Hep-2), and lung carcinoma cells (A549). The hybrid compound 9a exhibited better activity in the series, showing an IC50 of 24.19 ± 1.39 μM against the HCT116 cells, with a selectivity index (SI) of 6, when compared to the cytotoxicity against the non-tumor cell line HaCat. The in silico search for pharmacological targets was achieved through molecular docking studies on all active compounds, which suggested that the synthesized compounds possess a high affinity to the Topoisomerase 1–DNA complex, supporting their antitumor activity. The in silico toxicity prediction studies suggest that the compounds present a low risk of causing theoretical mutagenic and tumorigenic effects. These findings indicate that molecular hybridization from natural derivative molecules is an interesting approach to seek new antitumor candidates. Full article

Pterocaulon polystachyum is a species of pharmacological interest for providing volatile and non-volatile extracts with antifungal and amebicidal properties. The biological activities of non-volatile extracts may be related to the presence of coumarins, a promising group of secondary metabolites. In the present study, leaves and inflorescences previously used for the extraction of essential oils instead of being disposed of were subjected to extraction with supercritical CO₂ after pretreatment with microwaves. An experimental design was followed to seek the best extraction condition with the objective function being the maximum total extract. Pressure and temperature were statistically significant factors, and the optimal extraction condition was 240 bar, 60 °C, and pretreatment at 30 °C. The applied mathematical models showed good adherence to the experimental data. The extracts obtained by supercritical CO₂ were analyzed and the presence of coumarins was confirmed. The extract investigated for cytotoxicity against bladder tumor cells (T24) exhibited significant reduction in cell viability at concentrations between 6 and 12 μg/mL. The introduction of green technology, supercritical extraction, in the exploration of P. polystachyum as a source of coumarins represents a paradigm shift with regard to previous studies carried out with this species, which used organic solvents. Furthermore, the concept of circular bioeconomy was applied, i.e., the raw material used was the residue of a steam-distillation process. Therefore, the approach used here is in line with the sustainable exploitation of native plants to obtain extracts rich in coumarins with cytotoxic potential against cancer cells. Full article

Chronic inflammation is driven by proinflammatory cytokines such as interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and chemokines, such as c-c motif chemokine ligand 2 (CCL2), CCL3, C-X-C motif chemokine ligand 2 (CXCL2), and CXCL10. Inflammatory processes of the central nervous system (CNS) play an important role in the pathogenesis of various neurological and psychiatric disorders like Alzheimer’s disease, Parkinson’s disease, and depression. Therefore, identifying novel anti-inflammatory drugs may be beneficial for treating disorders with a neuroinflammatory background. The G-protein-coupled receptor 55 (GPR55) gained interest due to its role in inflammatory processes and possible involvement in different disorders. This study aims to identify the anti-inflammatory effects of the coumarin-based compound KIT C, acting as an antagonist with inverse agonistic activity at GPR55, in lipopolysaccharide (LPS)-stimulated BV2 microglial cells in comparison to the commercial GPR55 agonist O-1602 and antagonist ML-193. All compounds significantly suppressed IL-6, TNF-α, CCL2, CCL3, CXCL2, and CXCL10 expression and release in LPS-treated BV2 microglial cells. The anti-inflammatory effects of the compounds are partially explained by modulation of the phosphorylation of p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK (ERK 1/2), protein kinase C (PKC) pathways, and the transcription factor nuclear factor (NF)-κB, respectively. Due to its potent anti-inflammatory properties, KIT C is a promising compound for further research and potential use in inflammatory-related disorders. Full article

Celery seeds contain various bioactive compounds and are commonly used as a spice and nutritional supplement in people’s daily lives. The quality of celery seeds sold on the market varies, and their regions of production are unclear. This study evaluated the metabolites of Chinese celery seeds from three production regions using HS-SPME-GC-MS, HS-GC-IMS, and UPLC-ESI-MS/MS. The results indicate that GC-IMS analysis obtained a metabolic profile different from that detected using GC-MS. Terpenoids, polyphenols, coumarins, and phthalides are the main bioactive compounds in celery seeds. The production region significantly affects the metabolic characteristics of celery seeds. Based on GC-MS data, GC-IMS data, and LC-MS data, the variation analysis screened 6, 12, and 8 metabolites as potential characteristic metabolites in celery seeds related to the production region, respectively. According to the aromatic characteristics of the characteristic metabolites, seeds from the HCQ region and HZC region have a strong herbal, woody, celery, and turpentine aroma. The concentration of secondary metabolites was highest in the seeds from the HCQ region followed by the HZC region, and it was the lowest in the JJC region. Altogether, this study investigates how geographical origins influence the metabolomic profile of celery seeds. The results can be used to guide the planting and harvesting of celery seeds in suitable regions. Full article

An experimental study is presented on the possibility of using the fluorescence from organic dyes as a broadband light source together with a monochromator for applications in excitation–emission matrix (EEM) fluorescence spectroscopy. A high-power single-chip light-emitting diode (LED) was chosen as an excitation source with a central output wavelength at 365 nm to excite a fluorescent solution of Coumarin 1 dye dissolved in ethanol. Two excitation configurations were investigated: direct excitation from the LED and excitation through an optical-fiber-coupled LED. A Czerny–Turner monochromator with a diffraction grating was used for the spectral tuning of the fluorescence. A simple method was investigated for increasing the efficiency of the excitation as well as the fluorescence signal collection by using a diffuse reflector composed of barium sulfate (BaSO₄) and polyvinyl alcohol (PVA). As research objects, extra-virgin olive oil (EVOO), Coumarin 6 dye, and Perylene, a polycyclic aromatic hydrocarbon (PAH), were used. The results showed that the light-emitting-diode-induced fluorescence was sufficient to cover the losses on the optical path to the monochromator output, where a detectable signal could be obtained. The obtained results reveal the practical possibility of applying the fluorescence from dyes as a light source for food system analysis by EEM fluorescence spectroscopy. Full article

In the frame of a systematic study on the sequestering ability of natural antioxidants towards metal cations, here the complexation of coumarin-3-carboxilic acid (HCCA) with Pb(II) and the overall stability constants of the resulting complexes, at 37 °C and in 0.16 M NaClO₄, are discussed. Reaction of Pb(ClO₄)₂ with HCCA in an aqueous medium at a pH range from 2 to 6 and various ratios (1:1–1:10) yielded the Pb–CCA complexes, which were characterized spectrometrically by laser desorption ionization mass spectrometry (LD-MS). LD-MS has provided the composition and structure of Pb–CCA species according to the speciation model proposed on the basis of the potentiometric data. The graphic representation of the complex’s concentration curves is given by the distribution diagram, which provides a whole depiction of the species present in the solution at the selected pH ranges. Full article

Drug resistance substantially compromises antibiotic therapy and poses a serious threat to public health. Fusidic acid (FA) is commonly used to treat staphylococcal infections, such as pneumonia, osteomyelitis and skin infections. However, Gram-negative bacteria have natural resistance to FA, which is almost restrained in cell membranes due to the strong interactions between FA and phospholipids. Herein, we aim to utilize the strong FA–phospholipid interaction to pre-form a complex of FA with the exogenous phospholipid. The FA, in the form of an FA–phospholipid complex (FA-PC), no longer interacts with the endogenous membrane phospholipids and thus can be delivered into bacteria cells successfully. We found that the water solubility of FA (5 µg/mL) was improved to 133 µg/mL by forming the FA-PC (molar ratio 1:1). Furthermore, upon incubation for 6 h, the FA-PC (20 µg/mL) caused a 99.9% viability loss of E. coli and 99.1% loss of P. aeruginosa, while free FA did not work. The morphology of the elongated bacteria cells after treatment with the FA-PC was demonstrated by SEM. The successful intracellular delivery was shown by confocal laser scanning microscopy in the form of coumarin 6-PC (C6-PC), where C6 served as a fluorescent probe. Interestingly, the antibacterial effect of the FA-PC was significantly compromised by adding extra phospholipid in the medium, indicating that there may be a phospholipid-based transmembrane transport mechanism underlying the intracellular delivery of the FA-PC. This is the first report regarding FA-PC formation and its successful reversing of Gram-negative bacteria resistance to FA, and it provides a platform to reverse transmembrane delivery-related drug resistance. The ready availability of phospholipid and the simple preparation allow it to have great potential for clinical use. Full article