ScienceRise: Pharmaceutical Science

Impact of the natural oligoribonucleotides in complexes with D-mannitol on tumor growth and expression of immune cell markers in a mouse melanoma В16 model

2025-04-11T17:54:45+03:00

Cancer remains a leading cause of mortality worldwide, with chronic inflammation playing a critical role in tumour initiation and progression. Natural oligoribonucleotides in complexes with D-mannitol (ORN-D-M), derived from yeast RNA, have demonstrated anti-inflammatory and immunomodulatory effects in various disease models. Previous studies have shown their cytotoxicity against the B16 mouse melanoma cell line in vitro. This study aimed to evaluate the antitumor properties of ORN-D-M in a B16 mouse melanoma model.

Materials and methods. The B16 melanoma model was established by transplantation of B16 cells into C57BL/6 mice. ORN-D-M was administered at varying doses via different routes (subcutaneous, oral, intraperitoneal), under prophylactic and therapeutic regimens, and simultaneously with transplantation of malignant cells. Tumour growth dynamics, survival, and gene expression of immune cell markers in peripheral blood (Cd3, Cd247, Cd4, Cd8, Cd68) using RT-qPCR were assessed.

Results. It was shown that simultaneous administration of ORN-D-M with tumour cell transplantation dose-dependently inhibited tumour formation and improved survival. However, neither therapeutic nor prophylactic administration after tumour transplantation showed significant effects. Additionally, ORN-D-M did not affect the mRNA expression of immune cell markers during the late stage of B16 melanoma.

Conclusion. ORN-D-M exhibits a dose-dependent cytotoxic effect when administered simultaneously with tumour cells but lacks efficacy in therapeutic or prophylactic regimens. Future studies should focus on optimizing targeted delivery systems to enhance drug stability and effectiveness in cancer therapy

Development of the composition and technology of preparation of a suspension with adapalene for the treatment of acne taking into account the biopharmaceutical factors

2025-01-20T19:39:43+02:00

The aim of the research is the development of the suspension with adapalene for use in the symptomatic block of complex acne therapy composition and technology of preparation.

Materials and methods. The objects of the study were suspension samples, which included active pharmaceutical ingredients (adapalene, hyaluronic acid, liquid aloe extract and zinc oxide), and purified water.

Results. Hyaluronic acid was determined as the optimal stabilizer and its concentration was selected using the resuspension method, at which the suspension is a stable system. It was established that the samples, which include adapalene, zinc oxide, liquid aloe extract, hyaluronic acid and purified water, have satisfactory physical and chemical properties.

Conducted rheological studies showed that due to the potentiation of associative thickening, optimal rheological indicators of the suspension, which affect both the extrusion and consumption properties of the developed suspension, were obtained.

The quantitative content of adapalene in the developed suspension was confirmed by the method of alkalimetry. The completeness and speed of release of adapalene from the suspension was confirmed by the method of dialysis through a semipermeable membrane.

Conclusions. An extemporaneous suspension, based on adapalene, zinc oxide and liquid aloe extract, with the addition of a stabilizer – hyaluronic acid, was developed. The proposed suspension has satisfying consumer, physical and chemical properties, and meets the quality requirements established for suspensions

Synthesis and biological activity of 2-arylidene-5,6-dihydroimidazo[2,1-b]thiazoles and 6,7-dihydro-5h-[1,3]thiazolo[3,2-a]pyrimidines

2025-04-09T16:05:33+03:00

The aim. The present study is devoted to searching for potential biologically active agents among functionalized imidazo[2,1-b]thiazoles and thiazolo[3,2-a]pyrimidines.

Materials and methods. The interaction of preparatively available 5,6-dihydroimidazo[2,1-b]thiazolone and 6,7-dihydro-2H-thiazolo[3,2-a]pyrimidinone with several substituted benzaldehydes in boiling acetic acid in the presence of anhydrous sodium acetate leads to new 2-arylidene-substituted 5,6-dihydroimidazo[2,1-b]thiazoles and 6,7-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidines as potential pharmacological agents. Their antimicrobial activity was studied using the micromethod of two-fold serial dilutions in a liquid nutrient medium. The antioxidant activity of the synthesized compounds was evaluated using a DPPH assay.

Results. A library of 2-arylidene-5,6-dihydroimidazo[2,1-b]thiazolone and 6,7-dihydro-2H-thiazolo[3,2-a]pyrimidinone was synthesized by condensation of 5,6-dihydroimidazo[2,1-b]thiazoles and 6,7-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidines with series of aromatic aldehydes. Pharmacological in vitro screening results revealed that synthesized compounds possess moderate antimicrobial activity with MBC and MFC values of 31.25-62.5 mg/mL. While studying the antioxidant activity, it was found that all derivatives effectively inhibited DPPH radicals with an inhibition rate of 42.3-94.4 %. The best antiradical effect was observed for the molecule's derivatives containing 3-methoxy-4-hydroxy- or 2-hydroxyphenylmethylidene fragments.

Conclusions. It was found that the Knevenagel condensation of 5,6-dihydroimidazo[2,1-b]thiazolone and 6,7-dihydro-2H-thiazolo[3,2-a]pyrimidinone with aromatic aldehydes is a convenient approach for structure modification and optimization using pharmacophore fragments for these types of heterocycle. The synthesized arylidene derivatives are characterized by moderate antimicrobial and good antioxidant activity in vitro models

Study of the component composition of essential oils of pentaphylloides Fruticosa (L.) О. Schwarz (Dasiphora fruticosa (L.) Rybd.) raw materials

2025-04-11T17:03:36+03:00

Pentaphylloides fruticosa (L.) О. Schwarz (Dasiphora fruticosa (L.) Rybd.) is one of the most common species in Eurasia. There are about 150 known varieties of Pentaphylloides fruticosa, which are used as an ornamental plant. The content of tannins, polyphenols, flavonoids, and macro- and microelements was detected and determined in the above-ground part of some varieties of Pentaphylloides fruticosa. Studies on the content and composition of essential oils have not been conducted.

The aim. The aim of the work was to study the quantitative composition and identification of components of essential oil from raw materials Pentaphylloides fruticosa.

Materials and methods. Hydrodistillates obtained from dried raw materials of Pentaphylloides fruticosa, collected from different growing sites in Ivano-Frankivsk and Vinnytsia regions (Ukraine), were analyzed by gas chromatography-mass spectrometry.

Research results. Up to 91 essential oil components were identified and quantified in the studied raw materials. The content of essential oils was from 0.52 to 3.11 mL/kg, depending on the type of raw material. The predominant essential oil compounds in the raw material of Pentaphylloides fruticosa were linalool, geraniol, (E)-β-damascenone, (E)-geranylacetone, (E)-β-ionone, L-β-elemene, germacrene D, hexahydrofarnesyl acetone, phytol, benzyl benzoate. The largest amount of essential oil components was found in shoots with yellow flowers of Pentaphylloides fruticosa. The results of the study revealed strong positive correlation links (> 0.9) between such pairs of compounds as L-carvone and hexahydrofarnesyl acetone, benzyl benzoate and 1,2-diphenoxyethane; L-β-pinene and α-muurolene, L-β-pinene and hexahydrofarnesyl acetone; L-bornyl acetate and L-β-elemene, L-bornyl acetate and benzyl benzoate, L-bornyl and 1,2-diphenoxyethane, D-limonene and eucalyptol, L-β-pinene and L-carvone.

Conclusions. In connection with the obtained research results and the identification of such compounds as linalool, geraniol, (E)-β-damascenone, (E)-geranylacetone, (E)-β-ionone, germacrene D, phytol, benzyl benzoate, it is advisable to further study the species Pentaphylloides fruticosa, its pharmacological activity and possibilities for further application in medicine

HTA in Germany: basics in practice and education

2025-04-15T14:00:21+03:00

The aim. The aim of the investigation was to elucidate the HTA system's development process and its educational component by studying the basic functions and options of services that are responsible for its functioning in Germany.

Material and methods. Official sites of government and non-government non-profit organizations and government publications in specialized open sources have been used. Research methods include mostly descriptive approaches and methods for collecting data: observation, generalization data, graphics and methods for analyzing data: qualitative content analysis.

Results. The creation of the HTA system in Germany has been ongoing since 1994. State institutions responsible for HTA have changed, and their areas of responsibility and control have been reformatted. Today, 5 institutions/organizations that ensure the effective functioning of the HTA in Germany are presented. A basic training program aimed at training executors (reporters) and decision-makers is presented. A grid of 7 basic competencies in HTA education in Germany is presented. The program is presented in 10 modules, which are grouped by the authors into three cycles: Fundamental (Modules 1-6), Methodological (M. 7-9) and final cycles (M. 10).

Conclusions. To build or improve the HTA system, attention should be paid to the periodicity of updating information, which will contribute to a more accurate identification (satisfaction) of the needs of the country's HTA, both from the standpoint of implementation and ensuring applied functioning, and for the educational component of the HTA process. Constant review and assessment of the need/basic scope of the national HTA and stakeholders. The best way to do this is to study existing models and mechanisms of HTA in countries with the most developed and advanced healthcare systems

Synthesis of new 4,4'-(1H-1,2,3-triazole)-bis(1H-pyrazol-5-ols) and prospects for their study as potential antitumor agents

2025-04-16T18:51:26+03:00

The aim of our work is to develop an efficient synthesis of a series of novel 4,4'-(1H-1,2,3-triazol)bis(1H-pyrazol-5-ols), synthesize the target substances, and perform molecular docking focusing on the interaction of the synthesized compounds with the active sites of known cytostatics targeting various stages of oncogenesis.

Materials and methods. The structure and purity of the obtained substances were confirmed by ¹H NMR spectroscopy, ¹³C NMR spectroscopy and LC/MS. Docking studies were performed for the substances synthesized using Autodock 4.2 software.

Results and discussion. A series of novel 4,4'-(1H-1,2,3-triazol)bis(1H-pyrazol-5-ols) were synthesized via a tandem Knoevenagel–Michael reaction from two equivalents of 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one with various 1,2,3-triazole aldehydes catalyzed by ammonium acetate in ethanol in high yields. As a result of the analysis of the array of docking computations and a detailed analysis of the geometric arrangement in the active sites of tumour targets (C-abl kinase, deoxycytidine kinase (dCK), CSF1 receptor, EGFRK receptor, FOLR2 receptor, it was found that the synthesized derivatives may have antitumor effects through the mechanism of inhibition of the EGFRK receptor.

Conclusions. According to the molecular docking data, the newly synthesized derivatives 4,4'-((1H-1,2,3-triazol-4-yl)methylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) may have an antitumor effect through the mechanism of EGFRK receptor inhibition

Polysaccharide profile, acute toxicity and bile secretion effects of the choleretic herbal preparation 'Safroart herbal tea'

2025-04-23T13:59:57+03:00

The aim. The aim of this study was to determine the polysaccharide composition of the choleretic collection "Safroart herbal tea", focusing on the identification of key carbohydrate fractions and their monosaccharide composition, as well as to evaluate its acute toxicity and choleretic activity. This investigation contributes to understanding the biochemical and pharmacological properties underlying the plant's therapeutic effects.

Materials and methods. The herbal collection was subjected to sequential extraction to isolate its polysaccharides, which were fractionated into water-soluble polysaccharides (WSPS), pectin substances (PS), and hemicelluloses (HMC). These fractions were analyzed using paper chromatography, gas chromatography (GC), and infrared (IR) spectroscopy. For pharmacological evaluation, acute toxicity was assessed in mice using a single-dose administration protocol, and the choleretic effect was studied in rats by measuring bile secretion over a 4-hour period following administration of a 10 % aqueous infusion.

Results. Alcohol-soluble sugars, including sucrose and fructose, were identified. WSPS were primarily composed of glucose, galactose, and arabinose, while PS and HMC contained rhamnose, arabinose, and xylose. IR spectroscopy confirmed the structural features of the fractions. The herbal collection was classified as practically non-toxic (LD₅₀ > 4000 mg/kg). In vivo studies revealed a 27.4 % increase in bile secretion in treated rats compared to controls, confirming a significant choleretic effect.

Conclusions.‘Safroart herbal tea’ contains a complex mixture of polysaccharides with distinct monosaccharide profiles and demonstrates both safety and choleretic efficacy in experimental models. These findings support its potential use as a natural hepatobiliary remedy and contribute to the phytochemical and pharmacological understanding of its therapeutic action

Development of technology for obtaining dry extract «Helminth ART» and the study of its anthelminthic activity

2025-04-25T15:14:04+03:00

The aim. This research work is devoted to the development of an optimal method for obtaining anthelmintic dry extract "Helmint-ART" from raw materials of plants growing in Uzbekistan: aerial (aboveground) part of wormwood, pumpkin seeds, tansy flowers, garlic bulbs and to study the acute toxicity and anthelmintic activity.

Materials and methods. Two different methods for obtaining dry extract (DE) "Helmint-ART" from plant raw materials: the aerial part of wormwood, pumpkin seeds, tansy flowers and garlic bulbs were used. The first method: prepare an extract of plants raw materials and then prepare DE substance from them. The second method: a separate DE was obtained from each selected object and then mixed in a certain ratio. Quantitative indicators of biologically active substances were determined with high-performance liquid chromatography. The study of anthelmintic effect of the DE "Helmint-ART" was carried out on intestinal parasitosis experimental models in mice: hymenolepidosis (causative agent Hymenolepis nana) and aspiculurosis (causative agent Aspiculuris tetraptera).

Results. It was found that the second method for obtaining DE named "Helminth-ART" was optimal.

Determination the "acute" toxicity showed that DE "Helminth-ART" at a dose 3000 mg/kg do not cause changes in animal’s behavior and their death. Anti-cestode activity of DE "Helmint-ART" was 74.9 % and was slightly higher (statistically unreliable) than that of comparison drug Fenasal (71.2 %) and significantly exceeded that of the infusions of common tansy flowers (50.2 %), pumpkin seeds (56.8 %). Anti-nematodosis activity (90.2 %) of DE "Helminth-ART" significantly exceeded the activity of infusions of tansy flowers (68.6 %), pumpkin seeds (76.9 %), Pyrantel (80.1 %).

Conclusions. The optimal method of the technology of the DE "Gelmint-ART" was determined based on a comparison of two methods. The second method is optimal in terms of economy of extractants, high proportion of the DE released, their quality indicators, content of the biologically active substance luteolin.

The pronounced DE "Helmint-ART" anthelmintic effect and acceptable acute toxicity were established

Determination of amino acids content of the Mahonia aquifolium by GC/MS

2025-04-25T22:23:58+03:00

Medicinal plants are unique sources of healing compounds that are used both for the prevention and treatment of various diseases of the human body. In this regard, one of the oldest medicinal plant families - Berberidaceae, is of great interest. The genus Mahonia Nuttall is the second largest genus in the Berberidaceae family and contains nearly 70 species which are used in traditional medicine. Mahonia aquifolium (Pursh) Nutt. (M. aquifolium) is one of the most abundant and cultivated medicinal plants of the genus Mahonia. There is insufficient information in the literature on the biologically active substances of Mahonia aquifolium. The studies of the Mahonia species have focused on alkaloids, such as berberine, jatrorrhizine, and palmatine, which are the main constituents of compounds. The Mahonia aquifolium, as an insufficiently studied plant, is a promising object of study, including amino acid composition.

The aim. The aim of our study was to identify and determine the quantitative content of amino acids using the GC/MS method in Mahonia aquifolium fruits, flowers, and leaves.

Materials and methods. The determination of amino acids composition of Mahonia aquifolium was conducted using Agilent Technologies 6890 chromatograph with mass spectrometric detector 5973 (Agilent Technologies, USA).

Results. The results of the study revealed that the raw material of Mahonia aquifolium contains more bound and less free amino acids. Bound L-leucine was present in all the analyzed samples in the greatest amount (30.885 mg/g in the flowers, 37.765 mg/g in the leaves, and 29.053 mg/g in the fruits). L-proline was among the free amino acids with a high content in flowers (73.304 mg/g) and leaves (32.031 mg/g) of Mahonia aquifolium. In addition, a high content of glycine in free form was found in the fruits (12.212 mg/g) of the study plant.

Conclusions. Using the GC/MS method determined, the amino acids in the herb of Mahonia aquifolium. High L-proline, L-leucine, and L-aspartic acid concentrations predominate among free and bound amino acids in all the analyzed samples. These amino acids are considered distinguishing markers of the Mahonia aquifolium. This research contributes to using this plant's raw material for new remedies that may be possible in the future

Problems of classification, safety assessment and risk management of medical devices with biologically active substances

2025-04-27T14:06:52+03:00

The aim of the work was to investigate scientific and technical approaches for ensuring biological safety and classifying medical devices containing biologically active substances in the context of new international standards and regulatory requirements.

Materials and methods. The study includes an analysis of the current regulatory landscape, including Regulation (EU) 2017/745, international standards ISO 10993, and guidance documents from the Medical Device Coordination Group (MDCG). Classification specificities of medical devices containing biologically active substances were examined, taking into account their mechanism of action. Approaches to biocompatibility assessment and systemic risk analysis were reviewed using the Weight of Evidence (WoE) concept.

Results. Key differences between the classification of medical devices under Directive 93/42/EEC and Regulation (EU) 2017/745 were analysed. The study identified specific aspects of biocompatibility assessment for medical devices containing biologically active substances, as well as challenges related to the standardisation of their physicochemical characteristics. Examples were provided to distinguish between medicinal products and medical devices based on their mechanism of action. The implementation of modern methods for assessing medical devices' safety and regulatory status was also examined.

Conclusions. The new regulatory requirements, in particular the provisions of Regulation (EU) 2017/745, significantly impact the classification and biological safety assessment of medical devices containing biologically active substances. An adaptation of the biocompatibility assessment methods was proposed, considering modern trends and the "Weight of Evidence" approach. The study highlights the need to update Ukraine's national regulatory framework to align with European standards and to introduce clearer methodological approaches to differentiate between medicinal products and medical devices

Combined methanolic extracts of selected medicinal plants in southern Philippines as a potential therapeutic tool for diabetes and obesity

2025-04-29T17:37:02+03:00

Type 2 Diabetes (T2D) is a significant public health problem with an increasing number of cases over the years. With this, the search for cheaper and natural alternatives also continues. Oxidative stress, obesity, and advanced glycation end products (AGEs) formation contribute to T2D pathogenesis.

The aim. This study employs a range of functional assays to assess the antidiabetic, antioxidant, anti-obesity, and antiglycation activities of air-dried leaf methanolic extracts from the combined extract (CoM) of Clitoria ternatea, Ficus septica, Heliotropium indicum, and Celosia ignea. Additionally, quantitative screening was conducted to determine the presence of key bioactive secondary metabolites, particularly flavonoids and phenolic compounds.

Materials and methods. Glucose adsorption and glucose diffusion were utilized to measure the antihyperglycemic effects; BSA protein-methylglyoxal and BSA-glucose reactions were used as models for the glycation studies; the pancreatic lipase enzyme inhibition was employed to assess the sample extracts’ potential lipid-lowering effects; and quantitative phytochemical screening for total phenolic compounds and total flavonoid contents was conducted for initial characterization of phytoconstituents presents.

Results. This study reported the glucose adsorption capacities of CoM at various concentrations (25, 50, 100 ppm) indicative of its potential antihyperglycemic effects. An in vitro glucose diffusion assay, on the other hand, showed a negative result (1.82±0.06 at 100-ppm) relative to the control. The CoM also exhibited antioxidant capacities via iron-reducing assay and H₂O₂ scavenging activity (57.86±8.28 % at 25-ppm). PPL inhibition was evaluated to indicate potential antiobesity and this study reported that CoM (75-ppm) inhibited 52.13±7.16 % enzyme activity. Antiglycation tests revealed that CoM extracts are potential inhibitors of AGEs formation as it (100-ppm) inhibited 72.23±2.71 % of the glycation (BSA-glucose model) and 55.46±13.43 % (BSA-MGO model). Phytochemical screening results support the presented properties with TPC and TFC of 11.29±2.10 GAE mg/ g sample and 5.83±0.03 QE mg/ g sample, respectively.

Conclusion. Overall, the combined methanolic plant extracts, CoM, may be utilized as a treatment strategy for oxidative stress-driven metabolic disorders such as diabetes and obesity. While this provides promising results, further investigation must still be done on the bioactive compounds of the sample