Acta Pharmaceutica最新文献

This study evaluates the antihyperlipidemic (pancreatic lipase inhibition assay), antiglycation (inhibition of bovine serum albumin glycation, BSA glycation), and antioxidant activity (ABTS, DPPH and FRAP assays) of ethanolic extracts from flowering parts of five widely distributed plant species in Croatia - Crocus heuffelianus Herb. (tepals), Nicotiana tabacum L. (petals), Malva sylvestris L. (petals), Calendula officinalis L. and Helianthus annuus L. (both sterile ligulate flowers). An in vitro-simulated system of human digestion was employed to assess the bioaccessibility of the selected phenolics and the stability of the extracts' antioxidant, hypolipi demic, and antiglycation potential following each digestion phase. The concentrations of l-ascorbic acid, individual flavonoids, and phenolic acids were determined using RP-HPLC analysis. Principal component analysis revealed significant differences in the content of bioactive compounds and their biological activity among the investigated plant species. All original extracts exhibited high antioxidant capacity (> 70 %) in at least one assay, with N. tabacum and H. annuus demonstrating the strongest anti-oxidant capacity throughout digestion. H. annuus contained the highest levels of total identified phenolic acids, total identified phenols, and total identified compounds, while N. tabacum and C. heuffelianus exhibited the highest total flavonoid content. Among individual compounds, protocatechuic acid, quercetin, and ferulic acid significantly contributed to antioxidant activity. N. tabacum had the strongest antihyperlipidemic potential in the original extracts, as well as in the most digestion phases. Strong BSA glycation inhibition (70-100 %) was observed in all plant extracts across various digestion phases, with the exception of C. heuffelianus, which exhibited mode rate inhibitory effects. These findings suggest that the analyzed flower-derived plant materials, some of which are often considered agricultural waste, can serve as sustainable and valuable resources of bioactive compounds for functional food, dietary supplements, and pharmaceutical applications.

The current research brings introductory data to phytochemical composition and biological potential of the methanolic extract derived from the aerial parts of Aaronsohnia factorovskyi. In vitro testing was conducted to evaluate its antioxidant, anti-inflammatory and antidiabetic activities. The total phenolics and total flavonoids contents of the extract were estimated as 52.46 ± 5.93 mg GAE g^-1 and 19.01 ± 2.50 mg QE g-1, resp. UPLC-ESI-MS analysis disclosed 14 chromatographic peaks corresponding to 19 putatively identified compounds, including flavonoids, sesquiterpenes, lignans, saponins and fatty acids. The antioxidant efficacy was evaluated using DPPH and phosphomolybdenum assays, as total antioxidant capacity equals to 12.31 ± 2.33 mg g^-1 and 17.40 ± 0.96 mg g^-1, resp. In vitro testing of the anti-inflammatory activity demonstrated characteristic concentrations for 50 % inhibition of cyclooxygenase enzymes of 20.85 ± 0.73 µg mL^-1 and 8.25 ± 0.29 µg mL^-1 against COX-1 and COX-2, resp. Moreover, the extract displayed strong inhibition of α-glucosidase and α-amylase enzymes with concentration for 50 % inhibition of 0.243 ± 0.009 mg mL^-1 and 0.275 ± 0.01 mg mL-1, resp. Molecular docking studies further supported these findings highlighting the strong binding of yamogenin 3-O-neohesperidoside, convallasaponin A and baicalin to α-glucosidase and α-amylase active sites, as evidenced by their high binding affinities that are comparable to that of the co-crystallized ligands. Altogether, these findings recommend A. factorovskyi as a promising source for bioactive constituents.

Hydroxypropyl methylcellulose (HPMC)-based formulations are commonly used in nasal sprays due to their gelling and viscosity-enhancing properties. However, data on in vitro studies that mimic patient use remain limited. This study investigated two commercial HPMC-based aqueous formulations and HPMC-based powder formulations to provide an understanding of the relationship between the physical properties, their performance, and the stability of nasal products. Physical properties, quality tests focused on shot mass and shot volume were assessed. The coverage area within the nasal cavity was examined at various angles of actuation (15°, 30°, 45°, and 80°) using a simulated inhalation model. The 45° spray angle exhibited the highest coverage area (%) within the nasal cavity. Devices containing liquid formulations demonstrated more reproducible shot mass and shot volume compared to dry powder preparations. These findings provide valuable insights for patients and manufacturers, leading to a better understanding of optimal usage and formulation effectiveness.

Aloe vera has a long history of medicinal use due to its diverse biological activities, including antioxidant, anti-inflammatory and antimicrobial. This study investigates the physicochemical and ADME (absorption, distribution, metabolism, excretion) properties of two primary anthraquinones from Aloe vera, aloin A and aloe-emodin. The focus of this research was to evaluate the lipophilicity, solubility, and pharmacokinetic profiles of aloin A and aloe-emodin through a combination of computational predictions, the shake-flask method, and chromatographic techniques. The optimised shake-flask method was successfully employed to determine the log P values of phyto-chemicals. Aloin A was found to be more hydrophilic than aloe-emodin, likely due to the presence of an attached β-d-glucopyranosyl unit. All RP-TLC and RP-HPLC lipophilicity indices were higher for aloe-emodin compared to aloin A, aligning with their log P values (obtained through in silico and shake-flask methods). IAM (immobili sed artificial membrane)-HPLC results suggest that unlikely partitioning in the n-octanol/water system or C18 chains, partition into phospholipids involves not only hydrophobic intermolecular recognition forces but also electrostatic interactions. The presence of a sugar moiety (β-d-glucopyranosyl unit) at the C-10 position of aloin A considerably enhanced its affinity to phospholipids compared to its affinity to alkyl chains. HSA (human serum albumin)-HPLC and AGP (α1-acid glycoprotein)-HPLC data confirmed aloe-emodin's stronger affinity to plasma proteins. The integration of computational and experimental approaches provided a detailed understanding of aloin A and aloe-emodin physicochemical and ADME properties.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder that has become a global health challenge. With the lack of effective FDA-approved treatments, alternative therapies are being explored. Astragaloside IV (AS-IV), a bio-active compound derived from the plant Astragalus membranaceus (Fisch. ex Bunge) (Fabaceae/Leguminosae), native to Inner Mongolia and Siberia, has shown significant therapeutic potential in NAFLD. This review discusses the pharmacological effects and molecular mechanisms of AS-IV, highlighting its role in improving insulin resistance, regulating lipid metabolism, reducing oxidative stress and modulating inflammation. AS-IV acts through key molecular pathways, such as AMPK, Nrf2 and SREBP-1c, to mitigate liver steatosis and inflammation. Additionally, AS-IV influences gut microbiota and bile acid metabolism, contributing to its therapeutic effects. Despite promising results from preclinical studies, clinical data supporting AS-IV's efficacy in NAFLD treatment are limited. Future research should focus on clinical trials, pharmacokinetics, and the combination of AS-IV with other therapeutic agents to optimise its therapeutic potential and reduce side effects.

This study successfully generated magnetic N-doped carbon dots (CDs-MNPs) that exhibit two distinct functions: pH-responsive targeted drug delivery and powerful antioxidant action. The structural integrity, magnetic characteristics, and thermal stability of the samples were confirmed using comprehensive characterisation techniques, such as scanning electron microscopy, superconducting quantum interference device, Fourier Transform Infrared Spectroscopy, X-ray diffraction, continuous-wave electron para-magnetic resonance, X-ray photoelectron spectroscopy, surface porosity and thermogravimetric analysis. The CDs-MNPs displayed pH-dependent drug release profiles that conformed to zero-order, Higuchi, and Peppas models, demonstrating their ability to provide regulated release. The antioxidant activity of the carbon dots was assessed using the DPPH assay, where the radical scavenging capacity exceeded 80 %. This high level of activity was attributed to the synergistic effects of nitrogen doping and the functional groups present on the carbon dots. The biocompatibility of the specimen (up to 100 mg mL^-1), which is essential for biomedical applications, was confirmed by MTT assays. This study highlights the potential of CDs-MNPs as an effective option for therapeutic interventions, providing customised drug delivery and antioxidant advantages. The antibacterial activity of CDs-MNPs was evaluated against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacterial strains, demonstrating significant efficacy. These results highlight the potential of CD-based nanobactericides for applications in biomedical and food monitoring.

The aim of this study was to investigate the potential antidepressant-like effect of combined subthreshold and effective doses of chrysin and fluoxetine in adult male Wistar rats and their potential effects on the serotonergic and noradrenergic systems. Seventy rats were divided into seven experimental groups: vehicle (10 % dimethyl sulfoxide solution, DMSO), chrysin (4 or 20 µmol kg^-1), fluoxetine (1.6 and 3.2 µmol kg^-1), and their combinations. The treatments were administered for 28 consecutive days, and the effects were evaluated in the locomotor activity test (LAT) and forced swim test (FST). The results showed that the treatments did not significantly affect crossings in the LAT. Chrysin, alone or combined, reduced immobility time, increased latency to first immobility and prolonged swimming in the FST, similar to fluoxetine. However, only chrysin (20 µmol kg^-1) and its combination with fluoxetine (1.6 µmol kg^-1) enhanced climbing behaviour in the FST. Chrysin showed an anti-depressant effect, possibly related to enhanced serotonergic and noradrenergic neurotransmission, by increasing climbing and swimming time in the FST. This dual effect suggests a promising antidepressant prototype with different mechanisms of action, allow ing the use of subthreshold doses, which could reduce side effects.

The main protease 3CL^pro of the SARS-CoV-2 virus is a well--established therapeutic target for the treatment of COVID-19. In this study, we screened an in-house compound library and identified a series of α-heteroarylthiomethyl ketones as inhibitors of 3CL^pro. Among these, analogues 31 and 33 emerged as the most interesting candidates with IC ₅₀ values of 95.4 ± 3.1 and 95.0 ± 6.9 µmol L^{- 1}, respectively. Preliminary in vitro studies suggest a potential covalent mode of inhibition, although further studies are required to confirm this mechanism. These findings provide a new chemical scaffold for the development of 3CL^pro-targeting inhibitors.

The apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) proteins belong to a family of cytidine deami nases responsible for DNA and RNA sequence editing, playing pivotal roles in a wide range of biological processes, including immune responses, antiviral properties, and genetic mutations. In this work, we investigated the effect of SARS-CoV-2 structural proteins - Envelope (E), Spike (S), Nucleocapsid (N), Membrane (M) and protein ORF6 - on the expression of cytokines Interleukin 8 (IL-8) and Tumor Necrosis Factor-alpha (TNF-α), and APOBEC3s proteins (APOBEC3B and APOBEC3F) genes in Huh-7 and A549 human cell lines. While there is plenty of scientific evidence about the effects of SARS-CoV-2 on the inflammatory cascade, the current literature regarding the impact of SARS-CoV-2 on APOBEC expression is scarce. Our findings reveal a complex relationship between SARS-CoV-2 structural proteins and the host immune response, as certain viral structural proteins (S, M, E) modulate cytokine expression, potentially contributing to the dysregulated immune responses seen in COVID-19 patients. Additionally, our research uncovered interactions between viral proteins and APOBEC genes. This study contributes to a better understanding of the host-virus interactions in the context of SARS-CoV-2 infection and provides some insights into potential therapeutic targets for mitigating the immunopathological consequences of the disease.

A significant amount of data about the different pharmacological activities of the established antimicrobial compound nitroxoline (8-hydroxy-5-nitroquinoline) is available in the scientific literature. On the other hand, its regioisomer 8-hydroxy-6-nitroquinoline was never characterised biochemically and the same also applies to their 1,2,3,4-tetrahydroquinoline analogues. Herein, we determined the influence of pyridine ring saturation and the position of the nitro group on various biochemical characteristics of compounds, such as metal-chelating properties, inhibition of methionine aminopeptidases (MetAPs) from Mycobacterium tuberculosis and human MetAP2, as well as antibacterial activities on Escherichia coli, Staphylococcus aureus, and Mycobacterium smegmatis. In addition, inhibition of endopeptidase and exopeptidase activities of cathepsin B was determined, together with the ability of new nitroxo-line analogues to reduce intracellular collagen IV degradation. Substantially different biological activities were observed for the 6-nitro regioisomer of nitroxoline, as well as for both of their partially saturated counterparts.