The aim. The study aimed to develop the composition of a gel-based pharmaceutical formulation containing an extract of Bidens pilosa hairy roots for local application to inflammatory processes in the oral mucosa and to investigate its pharmacotechnical properties, irritant potential, and anti-inflammatory activity. Materials and methods. Model gel bases with varying ratios of polymeric and humectant components were prepared to develop the pharmaceutical formulation. The optimal base was selected for its organoleptic characteristics, homogeneity, consistency, and ability to form a thin, evenly distributed layer. A 1% dry extract of Bidens pilosa hairy roots was incorporated into the selected gel base. The pharmacotechnological properties of the formulation were evaluated by determining pH and rheological characteristics at 25.0 ± 0.1°C and 37.0 ± 0.1°C. The total flavonoid content was determined spectrophotometrically and expressed as rutin equivalent. The anti-inflammatory activity was evaluated in vitro by measuring the ability of a 70% ethanolic extract obtained from the gel to inhibit 15-lipoxygenase activity during linoleic acid oxidation. Local tolerability was assessed in vitro using the HET-CAM method, with determination of the chorioallantoic membrane irritation index. Results of the study. For the first time, a pharmaceutical composition in the form of a gel containing 1% dry extract from “hairy” roots of Bidens pilosa was developed. The selected gel base was characterised by homogeneity, acceptable consistency, and uniform distribution on the model surface. The pH value of the developed composition was 5.97–6.00. It was established that the gel exhibited non-Newtonian pseudoplastic flow behaviour: as the shear rate increased from 10 to 500 s⁻¹, the dynamic viscosity decreased 13.1-fold at 25.0 ± 0.1°C and 11.0-fold at 37.0 ± 0.1°C. The total flavonoid content of the composition was 0.158%, expressed as rutin equivalents. It was demonstrated that the developed gel exhibits anti-inflammatory activity in vitro by inhibiting the enzyme 15-lipoxygenase through full competitive inhibition (Ki=2.06 µM; IC50=3.88 µM). It was found that the developed pharmaceutical composition in gel form is characterised by the absence of an irritating effect in the HET-CAM test (irritation index: 0.7 points). Conclusion. A pharmaceutical composition in the form of a gel, based on a 1% dry extract from the “hairy” roots of Bidens pilosa, was developed; it exhibits acceptable pharmacotechnical properties, pronounced anti-inflammatory activity in vitro, and no irritant potential in the HET-CAM test. The results obtained substantiate the feasibility of further investigation of the developed composition as a basis for developing a topical medicinal product with anti-inflammatory activity for application to the oral mucosal membrane
The aim. The multicomponent composition of plant extracts complicates the selection of chemical markers and biological targets relevant to the pharmaceutical and pharmacological development of combined medicinal products. The aim of the study was to investigate the chemical composition of Fumaria officinalis extract using the UHPLC-Q-TOF-MS/MS method and to analyze the potential pharmacological mechanisms of action of the identified compounds using artificial intelligence. Based on the obtained results and an assessment of scientific evidence, the study aimed to identify the most promising directions for further research, particularly the possibility of combining the extract with ibuprofen. Materials and methods. The chemical profile of the F. officinalis extract was investigated using the UHPLC-Q-TOF-MS/MS method. Based on the obtained results, a standardized set of 14 provisionally identified compounds was compiled and analyzed using three large language models: GPT-5.6 Luna, Claude Sonnet 5, and Grok 4.5. The artificial intelligence-based analysis included predictions without the use of external sources and with access to internet sources, independent assessment of scientific evidence using the E0–E5 matrix, and subsequent prioritization of pharmacological hypotheses based on scientific evidence. Results. UHPLC-Q-TOF-MS/MS analysis revealed numerous signals provisionally annotated as isoquinoline alkaloids and other components of the plant extract. The most reproducible predictions generated by large language models concerned the GABA-A receptor system, acetylcholinesterase (AChE), ion channels, particularly calcium channels, and mechanisms regulating redox processes. Predictions using internet sources enabled further refinement of hypotheses concerning NF-κB, PI3K/Akt, NLRP3, and HDAC6. An independent assessment of scientific evidence revealed experimental support at the individual compound level for several predicted mechanisms, particularly those associated with NF-κB/MAPK, COX-2/iNOS, AChE, NLRP3, and HDAC6. However, no direct experimental evidence confirming these mechanisms for the investigated extract was obtained. Conclusions. Combining the experimental investigation of the extract’s chemical profile with an analysis of the potential pharmacological properties of its components using artificial intelligence made it possible to formulate and prioritize mechanistic hypotheses for further studies of F. officinalis, particularly in the context of its potential combination with ibuprofen. Large language models can be used as an auxiliary tool for selecting promising molecular targets and directions for further computational and experimental research, but they do not replace such research
The aim. The aim of the study was to evaluate the tyrosinase inhibitory activity and phytochemical profile of Calendula officinalis flower extracts obtained with solvents of different polarity. Materials and methods. Chloroform, methanol, and water extracts of C. officinalis flowers were obtained by Soxhlet extraction. The extracts were studied by preliminary phytochemical screening, LC-MS analysis, spectrophotometric determination of total phenolic and flavonoid contents, and an in vitro mushroom tyrosinase inhibitory assay. Results. The highest extractive yield was obtained for the methanol extract. Phytochemical screening and LC-MS profiling showed that methanol and water extracts were richer in phenolic compounds and flavonoids, whereas the chloroform extract contained more lipophilic compounds, including sterols, triterpenoids, and carotenoids. The methanol extract had the highest total phenolic and flavonoid contents and demonstrated measurable mushroom tyrosinase inhibitory activity, with maximum inhibition of 24.5%. Conclusions. The results indicate that the methanol extract of C. officinalis flowers is the most promising among the studied extracts as a source of natural compounds with potential skin-whitening activity. Its activity is probably related to the presence of phenolic compounds and flavonoids. The data support further investigation of C. officinalis methanol extract as a component of complex plant-based cosmetic formulations for skin tone correction
The aim. To study the effect of synthetic dephosphorylated 2'-5'-triadenylate (2'-5'A₃) and its analogues on the calcium-binding properties of calmodulin and to evaluate the role of these compounds as potential conformational modifiers of the protein. Materials and methods. Synthetic dephosphorylated 2'-5'-oligoadenylates – specifically 2'-5'A₃, 2'-5'epoA₃, and 2'-5'cordA₃ – were used in the study. The binding of labeled ⁴⁵Ca²⁺ to calmodulin was determined using a radioisotopic method. The affinity of calcium binding to calmodulin and the maximum binding capacity were determined via Scatchard analysis. Results. It was shown that 2'-5'A₃ at concentrations of 20 and 100 µM significantly increased Ca²⁺ binding to calmodulin by 35% and 47%, respectively. Meanwhile, the epoxy analog increased Ca²⁺ binding by 53%, but only at a concentration of 20 µM. All the analogs tested increased the affinity of Ca²⁺ binding to calmodulin. Concurrently, they reduced the dissociation constant from 912 ± 34 nM in the control to 309 ± 76, 426 ± 140, and 348 ± 90 nM for 2'-5'A₃, 2'-5'epoA₃, and 2'-5'cordA₃, respectively. The most significant and pronounced effect was observed within the range of physiological free Ca²⁺ concentrations (10⁻⁷–10⁻⁶ M) characteristic of the cell. These data indicate an increased sensitivity of calmodulin to the calcium signal. The maximum calcium-binding capacity of calmodulin (expressed in pmol Ca²⁺/mg protein) was found to be 6154 ± 563* for the cordycepin analogue. The "Core" 2'-5'A3 and its epoxy analogue also significantly increased the maximum calcium-binding capacity to 5382 ± 359 and 4874 ± 351 pmol Ca²⁺/mg protein, respectively, whereas the control value was 4215 ± 196 pmol Ca²⁺/mg protein. Conclusions. We have demonstrated for the first time that dephosphorylated 2'-5'-oligoadenylates and their analogs act as conformational modifiers of calmodulin. They increase its affinity for calcium at physiological Ca²⁺ concentrations. This effect is most pronounced within the range of physiological intracellular calcium concentrations. Such an effect is characteristic of intracellular signaling operating within the free calcium concentration range of 10⁻⁶ to 10⁻⁷ M. This result suggests that calmodulin is a potential molecular target for the biological activity of dephosphorylated 2'-5'-oligoadenylates and their analogs, independent of the canonical action of their phosphorylated derivatives on RNase L
The aim: to conduct a comprehensive analysis of the implementation of the Managed Entry Agreement (MEA) framework in the public procurement of medicines in Ukraine and to identify the main trends in its development. Materials and methods: a retrospective descriptive study was conducted using official, publicly available national data from the Medical Procurement of Ukraine and the State Expert Center of the Ministry of Health of Ukraine. During the study, a unified database was created that includes medicines under consideration for MEAs as of July 2026. The analysis covered 58 indications corresponding to 48 international non-proprietary names. Methods of content analysis, classification, structural analysis, comparative analysis and summarizing analysis were applied. Data analysis was conducted using descriptive statistics. Results: oncology accounted for the largest share of indications considered for MEAs (31; 53.4%), followed by immunological and other systemic diseases (17; 29.3%) and rare and genetic diseases (10; 17.2%). All included medicines underwent the national Health Technology Assessment (HTA) procedure and received approval to begin negotiations. As of July 2026, MEAs had been signed for 23 indications (39.7%), a negative decision had been recorded for 1 indication (1.7%), and no final decision on conducting an MEA had been recorded for 34 indications (58.6%). Roche had the largest therapeutic portfolio (13 indications), while Takeda and Pfizer were represented in all three therapeutic areas. The number of national HTA recommendations supporting MEA consideration increased from 6 in 2021 to 21 in 2025, indicating a gradual expansion of the MEA framework in Ukraine. Conclusions: the MEA framework is gradually being integrated into the mechanism for public financing of high-cost innovative medicines in Ukraine. National HTA is a key prerequisite for selecting medicines subject to the MEA. For 34 indications (58.6%), no final decision on conducting an MEA had been recorded as of July 2026. The findings provide the first systematic data on the implementation of the Ukrainian MEA framework and may contribute to the further optimization of negotiation procedures, policy development, and improved patient access to innovative medicines
