Search Results (1,475)

Recently, essential rose oils and rose products have gained increasing importance in both the cosmetic and food industries, as well as in the composition of medicinal products. We investigated the in vitro antiviral activity of essential oil and floral water from Rosa damascena Mill against herpes simplex virus type 1 (HSV-1) infection in rabbit retinal cells (RRCs). The composition of the main chemical components in the rose essential oil was determined by means of gas chromatographic analysis. The effect on the viral replication cycle was determined using the cytopathic effect (CPE) inhibition assay. The virucidal activity, the effect on the adsorption stage of the virus to the host cell, and the protective effect on healthy cells were evaluated using the endpoint dilution method. The effects were determined as deviation in the viral titer, Δlg, for the treated cells from the one for the untreated viral control. The identified main active components of rose oil are geraniol (28.73%), citronellol (21.50%), nonadecane (13.13%), nerol (5.51%), heneicosane (4.87%), nonadecene (3.93), heptadecane (2.29), farnesol (2.11%), tricosane (1.29%), eicosane (1.01%), and eugenol (0.85%). The results demonstrated that both rose products do not have a significant effect on the virus replication but directly affect the viral particles and reduce the viral titer by Δlg = 3.25 for floral water and by Δlg = 3.0 for essential oil. Significant inhibition of the viral adsorption stage was also observed, leading to a decrease in the viral titers by Δlg = 2.25 for floral water and by Δlg = 2.0 for essential oil. When pretreating healthy cells with rose products, both samples significantly protected them from subsequent infection with HSV-1. This protective effect was more pronounced for the oil (Δlg = 2.5) compared to the one for the floral water (Δlg = 2.0). We used the in silico molecular docking method to gain insight into the mechanism of hindrance of viral adsorption by the main rose oil compounds (geraniol, citronellol, nerol). These components targeted the HSV-1 gD interaction surface with nectin-1 and HVEM (Herpesvirus Entry Mediator) host cell receptors, at N-, C-ends, and N-end, respectively. These findings could provide a structural framework for further development of anti-HSV-1 therapeutics. Full article

Background: Avian pathogenic Escherichia coli (APEC) is a leading cause of colibacillosis in poultry. Piper betle L. is a medicinal plant rich in bioactive compounds including hydroxychavicol that possess potent antibacterial activity. This study aimed to investigate the efficacy of a P. betle L. leaf nanoemulsion (NEPE) and hydroxychavicol against multidrug-resistant APEC isolates. Methods: In vitro and in silico analysis of NEPE and hydroxychavicol against APEC were determined. Results: The nanoemulsion exhibited potent antibacterial activity, with MIC and MBC values of 0.06–0.25% v/v and 0.125–0.25% v/v, respectively. The MIC and MBC values of hydroxychavicol against isolates ranged from 0.25 to 1.0 mg/mL. A time–kill assays revealed rapid bactericidal effects of both compounds, achieving a ≥3-log reduction within 4 h at 4 × MIC. Scanning electron microscopy demonstrated that APEC cells treated with hydroxychavicol exhibited filamentous cells with incomplete septa. Molecular docking and dynamics simulations of hydroxychavicol against APEC cell division proteins were investigated. According to the binding energy, hydroxychavicol exhibited the highest affinity with ZapE, FtsW, FtsX, FtsZ, and FtsA, respectively. However, the FtsA protein showed the least protein conformational change throughout the 5000 ns simulation, reflecting a highly stable conformation. Conclusions: These confirm the potential stability of protein and ligand, as supported by molecular dynamics simulation. The results suggested the potential of NEPE and hydroxychavicol, which may have promising antibacterial potential that can be used to inhibit APEC growth. Full article

Allergic contact dermatitis (ACD) is an immunologic reaction to a dermal chemical exposure that, once triggered in an individual, will result in an allergic response following subsequent encounters with the allergen. Air Force epidemiological consultations have indicated that aircraft structural maintenance workers may experience ACD at elevated rates compared to other occupations. We aimed to better understand the utility of non-animal testing methods in characterizing the sensitization potential of chemicals used during Air Force operations by evaluating the skin sensitization hazard of Air Force-relevant chemicals using new approach methodologies (NAMs) in a case study. We also evaluated the use of NAM data to develop preliminary candidate surface guidelines (PCSGs, maximum concentrations of chemicals on workplace surfaces to prevent induction of dermal sensitization) for chemicals identified as sensitizers. NAMs for assessing skin sensitization, including in silico models and experimental assays, were leveraged into an integrated approach to predict sensitization hazard for 19 chemicals. Local lymph node assay effective concentration values were predicted from NAM assay data via previously published quantitative models. The derived values were used to calculate PCSGs, which can be used to compare the presence of these chemicals on work surfaces to better understand the risk of Airmen developing ACD from occupational exposures. Full article

Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI₅₀ < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC₅₀ of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. Full article

With the increasing detection of artemisinin resistance to front-line antimalarials in Africa and notwithstanding the planned roll-out of RTS’S and R21 in Africa, the search for new vaccines with high efficacy remains an imperative. Towards this endeavour, we performed in silico screening to identify Plasmodium falciparum gametocyte stage genes that could be targets of protection or diagnosis. Through the analysis we identified a gene, Pf3D7_1105800, coding for a Plasmodium falciparum subtilisin-like domain-containing protein (PfSDP) and thus dubbed the gene Pfsdp. Genetic diversity assessment revealed the Pfsdp gene to be relatively conserved across continents with signs of directional selection. Using RT qPCR and Western blots, we observed that Pfsdp is expressed in all developmental stages of the parasite both at the transcript and protein level. Immunofluorescence assays found PfSDP protein co-localizing with PfMSP-1 and partially with Pfs48/45 at the asexual and sexual stages, respectively. Further, we demonstrated that anti-PfSDP peptide-specific antibodies inhibited erythrocyte invasion by 20–60% in a dose-dependent manner, suggesting that PfSDP protein might play a role in merozoite invasion. We also discovered that PfSDP protein is immunogenic in children from different endemic areas with antibody levels increasing from acute infection to day 7 post-treatment, followed by a gradual decay. The limited effect of antibodies on erythrocyte invasion could imply that it might be more involved in other processes in the development of the parasite. Full article

Iridoids are compounds recognized for their neuroprotective properties and their potential application in the treatment of neurodegenerative diseases. Geniposide (GP) and asperuloside (ASP) are iridoids that have demonstrated some biological activities. In this study, the potential neuroprotective effects of these iridoids were evaluated through in silico and in vivo assays, using Caenorhabditis elegans (C. elegans) strains CF1553 (sod-3::GFP), GA800 (cat::GFP), and CL2166 (gst-4::GFP). The results suggested that neither compound appears to have good passive permeability through the blood–brain barrier (BBB). However, an active transport mechanism involving the glucose transporter GLUT-1 may be present, as both compounds contain glucose in their molecular structure. In addition, they can inhibit the activity of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). GP at 1 and 2 mM reversed the H₂O₂-induced increase in sod-3 expression, while ASP at 1 and 2 mM reversed the increase in gst-4 expression. Worm survival was more adversely affected by higher concentrations of GP than ASP, although both similarly reduced acetylcholinesterase activity. These findings suggest that GP and ASP exhibit very low toxicity both in silico and in vivo in C. elegans, and positively modulate key enzymes involved in antioxidant pathways, highlighting their potential for neuroprotective applications. Full article

Background/Objectives: In the last few decades, the dengue virus, a prevalent flavivirus, has demonstrated various epidemiological, economic, and health impacts around the world. Dengue virus serotype 2 (DENV2) plays a vital role in dengue-associated mortality. The RNA-dependent RNA polymerase (RdRp) of DENV2 is a charming druggable target owing to its crucial function in viral reproduction. In recent years, streptomycetes natural products (NPs) have attracted considerable attention as a potential source of antiviral drugs. Methods: Seeking prospective inhibitors that inhibit the DENV2 RdRp allosteric site, in silico mining of the Streptome database was executed. AutoDock4.2.6 software performance in predicting docking poses of the inspected inhibitors was initially conducted according to existing experimental data. Upon the assessed docking parameters, the Streptome database was virtually screened against DENV2 RdRp allosteric site. The streptomycetes NPs with docking scores less than the positive control (68T; calc. −35.6 kJ.mol⁻¹) were advanced for molecular dynamics simulations (MDS), and their binding affinities were computed by employing the MM/GBSA approach. Results: SDB9818 and SDB4806 unveiled superior inhibitor activities against DENV2 RdRp upon MM/GBSA//300 ns MDS than 68T with ΔG_binding values of −246.4, −242.3, and −150.6 kJ.mol⁻¹, respectively. A great consistency was found in both the energetic and structural analyses of the identified inhibitors within the DENV2 RdRp allosteric site. Furthermore, the physicochemical characteristics of the identified inhibitors demonstrated good oral bioavailability. Eventually, quantum mechanical computations were carried out to evaluate the chemical reactivity of the identified inhibitors. Conclusions: As determined by in silico computations, the identified streptomycetes NPs may act as DENV2 RdRp allosteric inhibitors and mandate further experimental assays. Full article

Claoxylon longifolium (Euphorbiaceae) is an indigenous vegetable that has been used in southern Thai traditional medicine and cuisine. A bioassay-guided approach was adopted to investigate the phytochemicals and chemopreventive potential of C. longifolium leaves and stems. Phytochemical investigation of the active MeOH fractions afforded six known compounds, including caffeic acid (1), isovitexin (2), and vicenins 1–3 (3–5) from leaves and hexadecanoic acid methyl ester (6) from stems. Their structures were determined by spectroscopic means. Ten constituents were tentatively identified from the oily fractions of stems by GC-MS. Non-cytotoxic concentrations of compounds 1–6 were identified using the MTT cell viability assay. The ability of compounds 1–6 at non-cytotoxic concentrations to induce Nrf2 activation, correlating to their potential chemopreventive properties, was determined using a luciferase reporter assay in the AREc32 cell line. Only vicenin 1 (3) was considered to be a potent chemopreventive compound, as it increased luciferase activity by 2.3-fold. In silico studies on compounds 2–5 and vitexin (16) revealed the potential of these compounds as cancer chemopreventive and chemotherapeutic agents. This study provides the first report on the chemopreventive properties of C. longifolium. All identified and isolated compounds are reported here for the first time from this species. Full article

Skin aging is a natural biological process that can be accelerated by free radical induction, leading to a reduction in skin elasticity and the formation of wrinkles due to the depletion of elastin. Eugenia uniflora (dewandaru) is a promising plant believed to possess anti-aging properties, primarily attributed to its major constituents, myricitrin and quercetin. This study aimed to investigate the anti-elastase and antioxidant properties of Eugenia uniflora stem bark, ripe fruit, and seed extracts. Extracts were obtained using an ultrasound-assisted extraction (UAE) method with 70% ethanol. Quantitative phytochemical analysis involved measuring the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity. Bioactive constituents were identified using LC-MS analysis, and their interactions with target enzymes were further evaluated through in silico molecular docking. The results demonstrated that the E. uniflora seed extract exhibited the highest antioxidant activity, with an IC₅₀ of 5.23 µg/mL (DPPH assay) and a FRAP value of 3233.32 µmol FeSO₄/g. Furthermore, the ethanolic seed extract showed significant anti-elastase activity with an IC₅₀ of 114.14 µg/mL. Molecular docking predicted strong potential for several compounds as pancreatic elastase inhibitors, including 5-phenylvaleric acid, 2-(3-phenylpropyl)phenol, n-amylbenzene, 2-aminoadipic acid, and traumatin, each showing a prediction activity (PA) value exceeding 0.6. Notably, these compounds also exhibited inhibitory activity against tyrosinase. These findings collectively underscore the significant promise of E. uniflora seed extract as a novel and natural candidate for pharmacocosmeceutical product development, particularly for anti-aging applications. Full article

The potential of a protein to cause an allergic reaction is often assessed using a variety of computational techniques. Leveraging advances in high-throughput protein sequence data coupled with in silico or computational methods can be used to systematically analyze large proteomes for allergenic potential. Despite mango’s widespread consumption and growing clinical reports of hypersensitivity, the full extent of their allergenicity is yet unknown. In this study, for the first time, we conducted a genome-wide in silico analysis by analyzing a total of 54,010 protein sequences to identify the complete spectrum of potential mango allergens. These proteins were analyzed using various bioinformatics tools to predict their allergenic potential based on sequence similarity, structural features, and known allergen databases. In addition to the known mango allergens, including Man i 1, Man i 2, and Man i 3, our findings demonstrated that several isoforms of cysteine protease, non-specific lipid-transfer protein (LTP), legumin B-like, 11S globulin, vicilin, thaumatin-like protein, and ervatamin-B family proteins exhibited strong allergenic potential, with >80% 3D epitope identity, >70% linear 80 aa window identity, and matching with >80 known allergens. Thus, a genome-wide in silico study provided a comprehensive profile of the possible mango allergome, which could help identify the low-allergen-containing mango cultivars and aid in the development of accurate assays for variety-specific allergic reactions. Full article

Background: snoRNAs have traditionally been known for their role as guides in post-transcriptional rRNA modifications. Previously, our research group identified several RNAs that may bind to PIP2 with LIPRNA-seq. Among them, snR191 stood out due to its potential specific interaction with this lipid, distinguishing itself from other snoRNAs. However, a detailed study is needed to define the molecular interactions between RNA and lipids, which remain unknown but may serve as a mechanism for transport or liquid–liquid phase separation. This study aimed to determine the interaction between a snoRNA called snR191 and PIP2. Method: A novel methodology for RNA-PIP2 interaction was carried out. Total RNA from Saccharomyces cerevisiae was incubated with PIP2-bound nitrocellulose membranes and RT-PCR reactions. We performed the prediction of snR191-PIP2 interaction by molecular docking and in silico mutations of snoR191. Results: From LIPRNA-seq analysis, we identified that PIP2-bound RNAs were significantly enriched in diverse biological processes, including transmembrane transport and redox functions. Our RNA-PIP2 interaction approach was successful. We demonstrated that snR191 specifically interacts with PIP2 in vitro. The elimination of DNA ensured that the interaction assay was RNA-specific, strengthening the robustness of the experiment. PIP2 was docked to snR191 in a stem–loop–stem motif. Six hydrogen bonds across four nucleotides mediated the PIP2-snR191 interaction. Finally, mutations in snR191 affected the structural folding. Conclusions: In this study, we demonstrate the effectiveness of a new methodology for determining RNA–lipid interactions, providing strong evidence for the specific interaction between snR191 and PIP2. Integrating biochemical and computational approaches has allowed us to understand the binding of these biomolecules. Therefore, this work significantly broadens our understanding of snR191-PIP2 interactions and opens new perspectives for further research. Full article

The present study investigated the neuroprotective potential of the Murraya carbazole derivatives murrayanol, mahanimbine, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde using in silico and in vitro assays. The pharmacokinetic properties and potential toxicity (ADME/T) of the carbazole derivatives were assessed to evaluate their prospects as up-and-coming drug candidates. Molecular docking was used to investigate the interactions of the compounds with Aβ (PDB: 1IYT, 2BEG, and 8EZE) and AChE receptors (PDB: 4EY7 and 1C2B). The results from the in vitro assays were used to validate and support the findings from the in silico assays. The compounds demonstrated significant inhibition of acetylcholinesterase (AChE), a key target in neurodegenerative disorders. Murrayanol and mahanimbine presented superior inhibitory activity (IC₅₀ ~0.2 μg/mL), outperforming the reference drug, galantamine. The inhibition mechanisms were competitive (murrayanol, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde) and non-competitive (mahanimbine), supported by low Ki values and strong docking affinities. The compounds also proved effective in reducing Aβ fibrillization (murrayanol: 40.83 ± 0.30%; murrayafoline A: 33.60 ± 0.55%, mahanimbine: 27.68 ± 2.71%). These findings highlight Murraya carbazoles as promising scaffolds for multifunctional agents in AD therapy. Further optimization and mechanistic studies are warranted to advance their development into clinically relevant neuroprotective agents. Full article

Background/Objectives: Curcumin is a promising therapy for glioblastoma but is limited by poor water solubility, rapid metabolism, and low blood–brain barrier penetration. This study aimed to evaluate curcumin and six curcumin derivatives with improved activity against a glioblastoma cell line and favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Methods: Twenty-one curcumin derivatives were assessed and subjected to in vitro MTT cytotoxicity assays in SF268 glioblastoma and Vero cells. On the basis of the cytotoxicity results, six derivatives with the most favorable characteristics were selected for additional mechanistic studies, which included microtubule depolymerization, mitochondrial membrane potential (ΔΨm), and BAX activation assays. ADMET properties were determined in silico. Results: Compounds 2–4, 6, and 11 demonstrated better activity (IC₅₀: 0.59–3.97 µg/mL and SI: 3–20) than curcumin (IC₅₀: 6.3 µg/mL; SI: 2.5). Lead derivatives destabilized microtubules, induced ΔΨm collapse, and activated BAX. In silico ADMET prediction analysis revealed that compounds 4 and 6 were the most promising for oral administration from a biopharmaceutical and pharmacokinetic point of view. Conclusions: Strategic modifications were made to one or both hydroxyl groups of the aromatic rings of curcumin to increase its physicochemical stability and activity against glioblastoma cell line SF268. Compound 4, bearing fully protected aromatic domains, was identified as a prime candidate for in vivo validation and formulation development. Full article

The sustainable production of plant bioactive compounds is increasingly important as natural habitats decline. This study investigates whether in vitro cell cultures of Eryngium planum, Lychnis flos-cuculi, and Kickxia elatine can serve as alternative sources of biologically active biomass with antimicrobial and anti-Acanthamoeba properties. Callus cultures were established under optimized and controlled conditions, and metabolomic profiling was completed using UPLC-HRMS/MS. In silico analysis, using a molecular docking approach, was applied to understand the interaction between target compounds and Acanthamoeba profilin and identify possible targets for antimicrobial properties. Untargeted metabolomic analysis confirmed the presence of valuable compounds in the callus cultures of the studied species. Biological activity was assessed through anti-Acanthamoeba and antimicrobial assays. Lychnis flos-cuculi and Kickxia elatine callus extracts showed significant inhibitory effects on Acanthamoeba trophozoites, with 87.5% and 80.1% inhibition at 10 mg/mL, respectively. In contrast, E. planum extract stimulated amoebic growth. The anti-Acanthamoeba activity correlated with the presence of ferulic acid and p-coumaric acid in L. flos-cuculi extract, and acteoside in K. elatine extract. Antibacterial testing revealed moderate activity of E. planum and K. elatine extracts against Staphylococcus spp., while Gram-negative bacteria and fungi were largely resistant. These findings highlight the potential of in vitro cultures—particularly those from L. flos-cuculi and K. elatine—as promising, sustainable sources of anti-Acanthamoeba and antimicrobial agents, warranting further investigation into their pharmacologically active constituents. Full article

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article