Search Results (260)

Bilberry (Vaccinium myrtillus L.) fruits represent the recognized wellspring of bioactive compounds with various documented bioactivities. Although bilberry leaves are often treated as industrial by-products, they also represent a valuable source of phytochemicals with potential dermocosmetic applications. In this study, extracts of bilberry fruits and leaves were prepared using both conventional solvents (water and 50% ethanol) and natural deep eutectic solvents (NaDES) as green, biodegradable alternatives. The aim of this study was to examine the UV protective activity and inhibitory potential of those extracts against some enzymes (tyrosinase, hyaluronidase, collagenase) that are important in terms of skin conditioning and skin aging. The results of in vitro tests have shown the superiority of NaDES extracts compared to conventional extracts regarding all tested bioactivities. In addition, bilberry leaves extracts were more potent compared to fruit extracts in all cases. The most potent extract was bilberry leaf extract made with malic acid–glycerol, which exhibited strong anti-tyrosinase (IC₅₀ = 3.52 ± 0.26 mg/mL), anti-hyaluronidase (IC₅₀ = 3.23 ± 0.30 mg/mL), and anti-collagenase (IC₅₀ = 1.84 ± 0.50 mg/mL) activities. The correlation analysis revealed correlation between UV protective and anti-tyrosinase, UV protective and anti-collagenase as well as between anti-hyaluronidase and anti-collagenase activity. UV protection and anti-tyrosinase activity correlated significantly with chlorogenic acid and hyperoside contents in extracts. The extracts with the best activities also demonstrated a good safety profile in a 24 h in vivo study on human volunteers. Full article

In this study, the design and synthesis of a novel series of cinnamic acid and 1,2,4-triazole hybrids were reported, aiming to enhance antioxidant and lipoxygenase inhibitory activities through pharmacophore combination. Cinnamic acid derivatives and 1,2,4-triazoles exhibit a broad spectrum of biological activities; therefore, by synthesizing hybrid molecules, we would like to exploit the beneficial characteristics of each scaffold. The general synthetic procedure comprises three synthetic steps, starting from the reaction of appropriate substituted cinnamic acid with hydrazine monohydrate in acetonitrile with cyclohexane and resulting in the formation of hydrazides. Consequently, the hydrazides reacted with phenylisothiocyanate under microwave irradiation conditions. Then, cyclization proceeded to the 1,2,4-triazole after the addition of NaOH solution and microwave irradiation. All the synthesized derivatives have been studied for their ability (a) to interact with the free radical DPPH, (b) inhibit lipid peroxidation induced by AAPH, and (c) inhibit soybean lipoxygenase. The synthesized derivatives have shown significant antioxidant activity and have been proved to be very good lipoxygenase inhibitors. Compounds 4b and 4g (IC₅₀ = 4.5 μM) are the most potent within the series followed by compound 6a (IC₅₀ = 5.0 μM). All the synthesized derivatives have been subjected to docking studies related to soybean lipoxygenase. Compound 4g exhibited a docking score of −9.2 kcal/mol and formed hydrophobic interactions with Val126, Tyr525, Lys526, Arg533, and Trp772, as well as a π−cation interaction with Lys526. Full article

(1) Background: The highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b is an emerging threat that poses a great risk to the poultry industry. A few human cases have been linked to the infection with this clade in many parts of the world, including the USA. Unfortunately, there are no specific vaccines or antiviral drugs that could help prevent and treat the infection caused by this virus in birds. Our major objective is to identify/repurpose some (novel/known) antiviral compounds that may inhibit viral replication by targeting some key viral proteins. (2) Methods: We used state-of-the-art machine learning tools such as molecular docking and MD-simulation methods from Biovia Discovery Studio (v24.1.0.321712). The key target proteins such as hemagglutinin (HA), neuraminidase (NA), Matrix-2 protein (M2), and the cap-binding domain of PB2 (PB2/CBD) homology models were validated through structural assessment via DOPE scores, Ramachandran plots, and Verify-3D metrics, ensuring reliable structural representations, confirming their reliability for subsequent in silico approaches. These approaches include molecular docking followed by molecular dynamics simulation for 50 nanoseconds (ns), highlighting the structural stability and compactness of the docked complexes. (3) Results: Molecular docking revealed strong binding affinities for both sofosbuvir and GS441524, particularly with the NA and PB2/CBD protein targets. Among them, GS441524 exhibited superior interaction scores and a greater number of hydrogen bonds with key functional residues of NA and PB2/CBD. The MM-GBSA binding free energy calculations further supported these findings, as GS441524 displayed more favorable binding energies compared to several known standard inhibitors, including F0045S for HA, Zanamivir for NA, Rimantadine and Amantadine for M2, and PB2-39 for PB2/CBD. Additionally, 50 ns molecular dynamics simulations highlighted the structural stability and compactness of the GS441524-PB2/CBD complex, further supporting its potential as a promising antiviral candidate. Furthermore, hydrogen bond monitor analysis over the 50 ns simulation confirmed persistent and specific interactions between the ligand and proteins, suggesting that GS441524 may effectively inhibit the NA, and PB2/CBD might potentially disrupt PB2-mediated RNA synthesis. (4) Conclusions: Our findings are consistent with previous evidence supporting the antiviral activity of certain nucleoside analog inhibitors, including GS441524, against various coronaviruses. These results further support the potential repurposing of GS441524 as a promising therapeutic candidate against H5N1 avian influenza clade 2.3.4.4b. However, further functional studies are required to validate these in silico predictions and support the inhibitory action of GS441524 against the targeted proteins of H5N1, specifically clade 2.3.4.4b. Full article

Background/Objectives: Root canal infections represent a serious challenge to the success of endodontic treatment. The most commonly used antimicrobial irrigants, such as sodium hypochlorite (NaOCl), have certain limitations, while endodontic biofilms pose a significant microbiological complexity in the endodontic field. Silver nanoparticles (AgNPs) have emerged as a promising irrigant option in root canal treatments; however, few studies are focusing on endodontic biofilms. This work aimed to evaluate the antimicrobial and anti-adherence properties of AgNPs against clinically isolated bacteria taken directly from patients with various pulp and periapical diseases. Methods: AgNPs of two sizes were synthesized and characterized. The bactericidal and anti-adherence activities of AgNPs were evaluated through microbiological assays using experimental in vitro and ex vivo tests on oral biofilms taken from patients with symptomatic apical periodontitis (AAP) and pulp necrosis (PN). NaOCl solution was used as the gold standard. Results: The size of AgNPs was uniformly distributed (13.2 ± 0.4 and 62.6 ± 14.9 nm, respectively) with a spherical shape. Both types of nanoparticles exhibited good antimicrobial and anti-adherence activities in all microbiological assays, with a significant difference from NaOCl for in vitro and ex vivo models (p < 0.05). The inhibitory activity of AgNPs is mainly related to the type of microbiological sample and the exposure time. The antibacterial substantivity of both nanoparticle sizes was time-dependent. Conclusions: AgNPs may represent a promising antimicrobial option as an endodontic irrigant during conventional root canal treatments to prevent and control endodontic infections. Full article

This study aimed to evaluate the anti-inflammatory properties of Carthamus caeruleus L. root juice (CRJ), which is used in the traditional medicine of Algeria. The product was characterized by colorimetric assays (total polyphenols, flavonoids, and tannins) and by RP-HPLC-DAD analysis. Experiments were conducted in vitro to assess the ability of CRJ to stabilize human erythrocyte membranes under various stress conditions and inhibit albumin denaturation, a process linked to inflammation. An in silico study was also performed to investigate the inhibitory effects on cyclooxygenase-2 (COX-2) and assess the phenolic constituents with the highest activity. Moderate levels of polyphenols, flavonoids, and tannins were assessed; among these, 22 compounds were identified via chromatographic analysis. While present at low concentrations, some of these compounds, including myricetin, luteolin, and quercetin, are known to exhibit bioactivity at micromolar levels. CRJ provided erythrocyte membranes with notable protection against disruption caused by hypotonic NaCl solutions (protection levels of 90.51%, 87.46%, and 76.87% at NaCl concentrations of 0.7%, 0.5%, and 0.3%, respectively), heat stress (81.54%), and oxidative damage from HClO (75.43%). Additionally, a protection of 61.5% was observed against albumin denaturation. Docking analysis indicated favorable COX-2 binding for myricetin, luteolin, and quercetin. In conclusion, the root juice derived from C. caeruleus demonstrated potential anti-inflammatory activity in vitro and in silico. However, further studies, including in vivo investigations, are necessary to confirm efficacy and fully elucidate the mechanisms of action. Full article

Background: The development of cerebral organoids created from human pluripotent stem cells in 3D culture may greatly improve the discovery of neuropsychiatric medicines. Methods: In the current study we differentiated neural organoids from a human pluripotent stem cell line in vitro, recorded the development of neurophysiological activity using multielectrode arrays (MEAs) and characterized the neuropharmacology of synaptic signaling over 8 months in vitro. In addition, we investigated the ability of these organoids to display epileptiform activity in response to a convulsant agent and the effects of antiseizure medicines to inhibit this abnormal activity. Results: Single and bursts of action potentials from individual neurons and network bursts were recorded on the MEA plates and significantly increased and became more complex from week 7 to week 30, consistent with neural network formation. Neural spiking was reduced by the Na channel blocker tetrodotoxin but increased by the inhibitor of K_V7 potassium channels XE991, confirming the involvement of voltage-gated sodium and potassium channels in action potential activity. The GABA antagonists bicuculline and picrotoxin each increased the spike rate, consistent with inhibitory synaptic signaling. In contrast, the glutamate receptor antagonist kynurenic acid inhibited the spike rate, consistent with excitatory synaptic transmission in the organoids. The convulsant 4-aminopyridine increased spiking, bursts and synchronized firing, consistent with epileptiform activity in vitro. The anticonvulsants carbamazepine, ethosuximide and diazepam each inhibited this epileptiform neural activity. Conclusions: Together, our data demonstrate that neural organoids form inhibitory and excitatory synaptic circuits, generate epileptiform activity in response to a convulsant agent and detect the antiseizure properties of diverse antiepileptic drugs, supporting their value in drug discovery. Full article

This study investigated thermophilic bacterial communities from two Algerian hot springs: Hammam Debagh (94–98 °C), recognized as the second hottest spring in the world, and Hammam Bouhadjar (61–72 °C), one of the hottest in northwest Algeria. Thirty isolates were obtained, able to grow between 45 °C and 80 °C, tolerating pH 5.0–12.0 and NaCl concentrations up to 3%. Colonies displayed diverse morphologies, from circular and smooth to star-shaped and Saturn-like forms. All isolates were characterized as Gram-positive, catalase-positive rods or filamentous bacteria. Identification by MALDI-TOF, rep-PCR and 16S rRNA sequencing classified them mainly within Bacillus, Brevibacillus, Aneurinibacillus, Geobacillus, and Aeribacillus, with Geobacillus predominating. Rep-PCR provided higher resolution, revealing intra-species diversity overlooked by MALDI-TOF MS and 16S rRNA. A subset of six isolates, mainly Geobacillus spp., was selected based on phenotypic and genotypic diversity and tested for antimicrobial activity against thermophilic target isolates from the same hot spring environments. Strong inhibition zones (~24 mm) were observed, with Geobacillus thermoleovorans B8 displaying the highest activity. Optimization on Modified Nutrient Agar medium with Gelrite enhanced antimicrobial production and inhibition clarity. These findings highlight the ecological and biotechnological significance of thermophilic bacteria from Algerian geothermal ecosystems. While this study focused on microbial interactions within thermophilic communities, the promising inhibitory profiles reported here provide a foundation for future research targeting foodborne and antibiotic-resistant pathogens, as part of broader efforts in biopreservation and sustainable antimicrobial development. Full article

Cardiac glycosides (CGs), a class of plant- and animal-derived compounds historically used to treat heart failure, have garnered renewed interest for their diverse pharmacological properties beyond Na⁺/K⁺-ATPase (NKA) inhibition. Recent studies reveal that CGs modulate key signaling pathways—such as NF-κB, PI3K/Akt, JAK/STAT, and MAPK—affecting processes central to cancer, viral infections, immune regulation, and neurodegeneration. In cancer, CGs induce multiple forms of regulated cell death, including apoptosis, ferroptosis, pyroptosis, and immunogenic cell death, while also inhibiting angiogenesis, epithelial–mesenchymal transition, and cell cycle progression. They demonstrate broad-spectrum antiviral activity by disrupting viral entry, replication, and mRNA processing in viruses such as HSV, HIV, influenza, and SARS-CoV-2. Immunologically, CGs regulate Th17 differentiation via RORγ signaling, although both inhibitory and agonistic effects have been reported. In the nervous system, CGs modulate neuroinflammation, support synaptic plasticity, and improve cognitive function in models of Alzheimer’s disease, epilepsy, and multiple sclerosis. Despite their therapeutic potential, clinical translation is hindered by narrow therapeutic indices and systemic toxicity. Advances in drug design and nanocarrier-based delivery are critical to unlocking CGs’ full potential as multi-target agents for complex diseases. This review synthesizes the current knowledge on the emerging roles of CGs and highlights strategies for their safe and effective repurposing. Full article

Background/Objectives: Dental caries and candidiasis are major health problems worldwide. Dental caries is caused by cariogenic bacteria, especially those belonging to the Streptococcus genus, whereas candidiasis is caused by Candida species. In this study, the antimicrobial activity of a series of synthetic N-methyl-4-piperidone-derived monoketone curcuminoids (MKCs) against Candida albicans, C. krusei, and a representative panel of cariogenic bacteria was assessed. Methods: Fifteen MKCs were synthesized using an environmentally friendly base-catalyzed Claisen–Schmidt condensation between an aromatic aldehyde (R-PhCHO) and N-methyl-4-piperidone ethanol using NaOH as the catalyst. These compounds were evaluated for their antibacterial activity against a representative panel of cariogenic bacteria, along with their antifungal activity against Candida krusei and C. albicans. The antimicrobial activity was determined based on the Minimum Inhibitory Concentration (MIC) values. Results: Most of the compounds were obtained in about 2 h in yields ranging from 40 to 70%. None of the compounds displayed antifungal activity, even at 100 μg/mL, the highest tested concentration. Similarly, none of the compounds were active against Enterococcus faecalis. On the other hand, compounds 1 (R = H), 10 (R = 3,4,5-OMe), and 13 (R = 3-F) displayed moderate activity against Streptococcus mutans (13), S. salivarus (1), L. paracasei (1 and 10), S. mitis (1, 10, and 13), S. sanguinis (1, 10, and 13), and S. sobrinus (13), with MIC values of 250 μg/mL and 500 μg/mL. The presence of the N-methyl-4-piperidone ring was found to boost the antibacterial activity as compared to the corresponding acetone-derived MKCs. Moreover, the antibacterial activity of compounds 10 and 13 was associated with the presence and position of the fluor atom and the methoxy groups at the aromatic ring. Conclusions: This study contributed to a better understanding of the antimicrobial activity of MKCs, whose data in the literature are still scarce. Full article

The essence of coal spontaneous combustion lies in the existence of a large number of chemically active functional groups in the coal molecule, such as aldehyde group (-CHO) and methoxy group (-OCH₃) in the side chain structure of coal molecule, which can be easily oxidized, thus triggering the spontaneous combustion process. Retardant is a more widely used technology to prevent the spontaneous combustion of coal, but the research on the microscopic level of the mechanism of coal spontaneous combustion retardation has been weak for many years, so deepening the exploration in this field is crucial for the optimization of the retardation strategy. The inhibition effect of Li⁺, Na⁺, and K⁺ inhibitors was investigated through the programmed warming experiments, and the results showed that the carbon monoxide production and oxygen consumption of coal samples inhibited by Li⁺, Na⁺, and K⁺ inhibitors were reduced to different degrees compared with that of the original coal, which proved that it had an inhibitory effect on the spontaneous combustion of coal. In order to deeply investigate the interaction between the molecular structure properties of coal and alkali metal ions, the complexes formed by three typical alkali metal ions-Li⁺, Na⁺, and K⁺-with specific reactive groups (-CHO and -OCH₃) in coal were investigated with the help of the quantum chemical calculation software Gaussian 16W, and the following conclusions were made after analyzing the complexes: on the one hand, the complexes formed by Li⁺, Na⁺, and K⁺ with the reactive groups in coal can occupy the sites where the reactive groups bind with oxygen, reduce the chance of coal oxygen contact and inhibit its oxidation process; on the other hand, the coordinating action of alkali metal ions increases the maximum energy barrier that needs to be overcome for the reaction of the originally active groups, resulting in the coal molecules in the process of oxidation reaction, increasing the difficulty of the reaction, thus effectively curbing the tendency of spontaneous combustion of coal. Full article

Zuranolone (SAGE-217), the first FDA-approved oral neurosteroid (NAS), a positive allosteric modulator (PAM) of γ-aminobutyric acid type A (GABA_A) receptor for postpartum depression approved in 2023, has limitations such as short half-life, low bioavailability, and central inhibitory side effects. To address these, we designed novel C-21 modified derivatives of Zuranolone, identifying the triazolone scaffold as key for enhancing GABA_A activity. Here, we synthesized Zuranolone analogs with diverse triazolone substituents, finding that pyridine-derived modifications improved the activity correlated with LogP. The optimal derivative, S9 (2-(trifluoroethoxy)pyridine-triazolone, LogP 4.61), showed 2.5-fold greater potency (EC₅₀) and efficacy (Emax) than Zuranolone (LogP 4.78) at synaptic/extrasynaptic GABA_A receptors, attributed to stronger binding via molecular docking. In rats, S9 exhibited 5-fold longer plasma T_1/2, 6-fold higher AUC, 3-fold greater brain exposure, and 30% improved bioavailability. It also outperformed Zuranolone in pentylenetetrazole (PTZ)-induced seizure suppression and threshold dose for loss of righting reflex (LORR) in rats. The C21-pyridine-triazolone pharmacophore in S9 enhances receptor activity potency without increasing lipophilicity, optimizing pharmacokinetics and safety, which makes it a promising therapeutic candidate for depression and epilepsy. Full article

Natural polysaccharides (PSs) have shown inhibitory effects on differentiated cancer cells (DCCs), but their activity against cancer stem cells (CSCs) remains poorly understood. Here, we report that PSs from wheat cell cultures (WCCPSs) inhibit the proliferation of both DCCs and CSCs derived from HCT-116 colorectal cancer cells. Among them, NA and DC fractions showed the strongest anti-CSC activity. NA, rich in xylose, was effective at lower concentrations, while DC, enriched in xylose and galacturonic acid (GalUA), exhibited higher potency, with a lower IC₅₀ and preferential activity against CSCs at higher doses. WCCPSs reduced β-catenin levels, and some fractions also downregulated Ep-CAM, CD44, and c-Myc. Notably, DC increased caspase-3 without inducing cytochrome C and caspase-8 overexpression, suggesting a mechanism promoting CSC differentiation rather than apoptosis. Correlation analysis linked xylose content to reduced c-Myc expression, and GalUA levels to increased caspase-3. These results suggest that WCCPS bioactivity may be related to their monosaccharide composition. Overall, our findings support the potential of wheat-derived PSs as CSC-targeting agents that suppress self-renewal and promote differentiation, offering a promising approach to reduce tumor aggressiveness and recurrence. Full article

There are approximately 130 reported medicinal effects attributed to mushrooms. We investigated the anti-inflammatory effects of hot-water extracts of 66 wild and cultivated fungi species (both edible and poisonous) by analyzing the inhibition of platelet aggregation and interleukin-8 (IL-8) gene expression induced by sodium arachidonate (A-Na), platelet-aggregating factor (PAF), and adenosine diphosphate (ADP). All species exhibited inhibitory effects: 38.3–98.1%, 37.3–96.8%, and 41.0–96.6% species inhibited platelet aggregation induced by A-Na, PAF, and ADP, respectively, while 17.0–97.0% inhibited IL-8 expression. Gyromitra esculenta showed the highest inhibition rate in all assays. High inhibition (≥80%) of A-Na-, PAF-, and ADP-induced platelet aggregation was observed in 29 (43.9%), 29 (43.9%) and 31 (47.0%) species, respectively. Half (33) of the species exhibited high inhibition of IL-8 expression. Four (6.1%), five (7.6%), and seven (10.6%) species exhibited inhibition rates of <50% for A-Na-, PAF-, and ADP-induced platelet aggregation, while nine (13.6%) exhibited low inhibition of IL-8 expression. The majority (87.5–100%) of poisonous species exhibited high inhibition. Our findings suggest that anti-inflammatory effects are universal among fungi, with poisonous species showing particular potential as raw materials for drug discovery. It can be inferred that many fungi contain universal or pleiotropic compounds with anti-inflammatory activities. Full article

We report in this contribution the synthesis and in vitro biological evaluation of a novel class of chiral thiazoloisoindolinone scaffolds as potent inhibitors against human farnesyltransferase (FTase-h). The targeted products, sulfides (4), sulfoxides (5,6), and sulfones (7), containing up to three points of diversification, were obtained in a short-step sequence starting from the available and cost-effective L-cysteine hydrochloride (1), which is the source of N and S atoms and the chiral pool, and α-carbonyl benzoic acids (2), which are isoindolinone precursors. Concisely, the key ester intermediates (1) provide (a) sulfide-amides (4) by solvent-free amidation, (b) sulfoxides (5,6) by selective S-oxidation using NaIO₄, and (c) sulfones (7) by oxidation using MMPP. Finally, the obtained N,S-acetal systems have shown promising inhibitory activities on FTase-h in the nanomolar range with excellent half maximal inhibitory concentration (IC₅₀) values up to 4.0 nanomolar (for example, 25.1 nM for sulfide 4bI, 67.3 nM for sulfone 7bG, and more interesting of 4.03 nM for sulfoxide 5bG). Full article

This study optimized the extraction process of crude polysaccharides from Panax notoginseng leaves (PNLP) using the ultrasonic-assisted dual-enzyme method through a single-factor combined with response surface experiment. The crude polysaccharides were subsequently purified and isolated with DEAE-Cellulose 52, followed by structural analysis, evaluation of antioxidant activity, and examination of digestive enzyme inhibition. The hypoglycemic effects of the purified components were further clarified. The results indicated that the optimized crude polysaccharide had an extraction yield of 17.13 ± 0.29%. The purified fraction PNLP-3 (eluted with 0.3 M NaCl) was obtained through DEAE-Cellulose 52 chromatography, exhibiting a total sugar content of 81.2% and a molecular weight of 16.57 kDa. PNLP is primarily composed of arabinose, galactose, and galacturonic acid, with molar percentages of 20.24%, 33.54%, and 24.27%, respectively. PNLP-3 is mainly composed of arabinose and galactose, with molar percentages of 29.97% and 49.35%, respectively. In this study of hypoglycemic activity, the IC₅₀ values of PNLP-3 for α-glucosidase and α-amylase inhibition were 1.045 mg/mL and 9.53 mg/mL, respectively. Molecular docking results confirmed that PNLP-3 exhibits better inhibitory activity against α-glucosidase. Furthermore, PNLP-3 alleviated hyperglycemia in insulin-resistant HepG2 cells by enhancing glucose consumption and glycogen synthesis. The antioxidant activity of PNLP-3 exhibited a positive correlation with its concentration, potentially contributing to its hypoglycemic effects by reducing oxidative stress. These findings underscore the therapeutic potential of Panax notoginseng leaf polysaccharides in managing type 2 diabetes and offer new perspectives on the use of natural polysaccharides for regulating blood glucose. Full article