Vol 27, No 2 (2024)

Introduction. Diabetes mellitus and its complications remain one of the leading global diseases. Although there has been significant progress in diabetic peripheral neuropathy (DPN) diagnostics and treatment, the search for the molecular basis of its pathogenesis remains relevant. This search will enable targeted action on specific molecules and increase treatment effectiveness. Aim of the study. The aim of the present study was to analyse the mRNA levels of nuclear factor kappa-bi (NF-kB), apoptosis-inducing factor (AIF) and fibroblast growth factor 21 (FGF21), as well as changes in clinical and biochemical parameters in DPN patients undergoing inpatient treatment.

Material and methods. DPN patients (n=45) undergoing inpatient treatment were included in the study. Clinical and biochemical parameters were analysed on admission and before discharge. Transcript levels of the AIF and NF-kB genes were determined by real-time reverse transcription-polymerase chain reaction. FGF21 levels were determined by enzyme-linked immunosorbent assay.

Results. On admission to the hospital, the patients showed the main clinical signs of DPN. After treatment, there was a change in blood biochemical parameters towards control values (p<0.05). At the same time, there was a decrease in the mRNA level of the factors NF-kB (p=0.021) and AIF (p=0.015) in the patients' blood cells. There was an increase in FGF21 levels. Correlations were found between clinical and biochemical parameters, transcript levels of NF-kB and AIF factors and FGF21 levels.

Conclusion. The conducted studies testify about the positive influence of the therapy carried out in the hospital conditions on inflammatory and apoptotic processes, which is evidenced by the decrease in the mRNA level of the NF-κB and AIF factors genes, as well as by the increase in the concentration of FGF21, which is apparently associated with the decrease in the oxidative stress intensity.

The purpose of the study is to study the metabolic profile of the cannabimimetic 4F-MDMB-BICA in the urine of consumers and to identify markers of 4F-MDMB-BICA use using gas chromatography with a mass spectrometric detector (GC-MS) and liquid chromatography with tandem mass spectrometry (LC-MS/ MS) in the urine of consumers of psychoactive substances, for chemical-toxicological and forensic chemical analysis.

Material and methods. The study of urine samples of 4F-MDMB-BICA cannabimimetic users using enzymatic hydrolysis in combination with solid-phase extraction and gas chromatography with mass spectrometric detection showed that the 4F-MDMB-BICA marker and, in some cases, its nor-metabolite are detected in the urine of consumers. The 4F-MDMB-BICA nor-metabolite is a common biotransformation product for the cannabimimetics 4F-MDMB-BICA and 5F-MDMB-PICA, resulting from the hydrolysis of the ester bond and N-dealkylation of the heterocyclic core.

Results. 35 compounds were identified by liquid chromatography with tandem mass spectrometry, including the original parent 4F-MDMB-BICA, 31 metabolites of biotransformation phases I and II, and 3 metabolite artifacts; it was found that the latter are the product of intramolecular cyclization of 4F-MDMB-BICA metabolites. 16 previously undescribed compounds, including 15 metabolites and one artifact were identified. The putative structures, mass spectra and some characteristics of the identified compounds are given, including retention time, MRM transitions, and relative peak area of the substance.

Conclusion. From the presented data, it can be seen that the main pathways of 4F-MDMB-BICA metabolism in the human body are hydrolysis of the ester group, hydroxylation of alkyl radicals and the heterocyclic core, oxidative defluorination, and N-dealkylation. The hydrolysis products of the ester bond and hydroxyl derivatives are subsequently conjugated with glucuronic acid.

Introduction. Alzheimer's disease is one of the most common forms of dementia, the pathogenesis of which is based on the accumulation of β–amyloid plaques in brain structures and the development of cholinergic deficiency.

The aim of the study was to evaluate the effect of chalcone analogues on the change in acetylcholinesterase activity and the process of β-amyloid aggregation in vitro.

Material and methods. The tested compounds were six bis-substituted chalcone analogues, which were dissolved in dimethylsulfoxide during the analysis to obtain double dilutions. The effect of the studied substances on the activity of acetylcholinesterase was evaluated by the modified Ellman method. The change in the aggregation process of β-amyloid particles was determined in reaction with congo red after 3, 6 and 9 days of incubation. Based on the obtained results of the «% inhibition- concentration» relationships, the IC₅₀ index was calculated, which was expressed in mmol/ml.

Results. In the course of the study, it was shown that the analyzed chalcone analogues inhibit the aggregation of β-amyloid particles starting from the 6^th day of incubation with a maximum on the 9^th day. At the same time, the compounds that showed the highest level of activity were trimethoxy-substituted substances under the codes AZBAX4 and AZBAX6, whose IC₅₀ on the 9^th day of the study was 21.4±0.928 mmol/ml and 32.4±0.456 mmol/ml, respectively. Also, a high level of anticholinesterase properties was established for these compounds with IC₅₀ of 35.9±0.991mmol/ml and 25.1±0.261 mmol/ml, respectively. The rest of the tested compounds showed a lower level of activity.

Conclusion. The study showed that chalcone analogues under the codes AZBAX4 and AZBAX6 inhibit the activity of acetylcholinesterase and the process of aggregation of β-amyloid in vitro, which makes these compounds promising for further study in order to develop medicines for the pathogenetic treatment of Alzheimer's disease.

Introduction. The object of increased attention of researchers is calamus (Acorus calamus L.), for the components of which a wide range of pharmacological activities have been identified – immunomodulatory, anti-inflammatory, analgesic, antioxidant, neuroprotective, hypolipidemic, antitumor. According to previous studies, it was found that α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronan, isolated from the rhizomes of Acorus calamus L., has antimetastatic, antiblastoma, and immunomodulatory properties. The substance can also reduce the toxic effect on the hematopoietic system and increase the effectiveness of chemotherapy. Based on it, a finished dosage form was obtained - a solution for intravenous administration of 10 mg/ml, which requires the development of valid quality control methods for inclusion in the draft regulatory document on the quality and registration of a new drug. The aim of the study was to determine the metrological characteristics of the chromatographic technique for the quantitative determination of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronan in the finished dosage form.

Material and methods. The object of the study was the finished dosage form - a solution for intravenous administration of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronan Acorus calamus L. 10 mg/ml, produced on the basis of the educational establishment of the Technology Implementation Center of the Federal State Budgetary Educational Institution of Higher Education of the Siberian State Medical University of the Ministry of Health Russia. Quantitative determination was carried out using a Dionex Ultimate 3000 liquid chromatograph (Thermo, Germany) with a refractometric detector RI-101. Validation assessment was carried out according to the following indicators: linearity, accuracy, precision under repeatability conditions.

Results. Linear regression analysis of the obtained results using the least squares method showed that the technique is linear in the concentration range of 80–120%. When determining the accuracy, the openability for concentrations of 80, 100 and 120% varied in the range of 99.68–101.96%. The values of the relative standard deviation did not exceed the permissible values when assessing precision 0.82–4.51%.

Conclusions. The methodology is valid for the studied indicators and can be recommended for inclusion in the draft regulatory document on quality.

The biographical sketch is dedicated to Serafima Alexandrovna Vichkanova (1924–2017), Doctor of Biological Sciences, Professor, Honored Scientist of the Russian Federation, who worked in the laboratory of antimicrobial and antiviral agents at the All–Russian Research Institute of Medicinal and Aromatic Plants (Moscow). The main life stages, the scientific directions being developed and the contribution to the formation and development of the field of studying the antimicrobial properties of plants and substances from them in order to create new effective chemotherapeutic agents for the treatment of viral, bacterial, fungal and other infections, as well as a list of the main scientific works are presented in the article.