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Vol 25, No 12 (2022)

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Articles

Chemometric approach to investigation of the role of adipose tissue as a target for toxic metal effects

Skalny A.V., Nikolenko V.N., Fatkhudinov T.K., Chang J., Morozova G.D., Zolotenkova G.V., Huang S., Tinkov A.A.

Abstract

The objective of the present study was to assess toxic metal content in human adipose tissue and evaluate patterns of toxic and essential trace element accumulation in adipose tissue compared to liver.

Material and methods. The samples of right-sided pararenal adipose tissue and right lobe of the liver were obtained from autopsy of 28 patients aged from 33 to 63 years old who died from complications of cardiovascular diseases.

Results. Assessment of toxic and essential element levels was performed using inductively-coupled plasma mass spectrometry. The obtained data demonstrate comparable levels of toxic metals in adipose tissue and liver. Specifically, no significant group difference in aluminium and arsenic content was observed between liver and adipose tissue. Lead and tin content in adipose tissue was 23% and 46% lower than that in liver, respectively. At the same time, the levels of cadmium and mercury in liver exceeded the respective values in adipose tissue by a factor of 2.6 and 4.5. In view of manyfold differences in total protein levels in adipose tissue and liver, toxic metal accumulation in adipocyte cytoplasm far exceeds that in hepatocytes.

Conclusion. Therefore, the obtained data demonstrate that adipose tissue may be considered as a target for toxic metal effects, thus underlying the epidemiological association between toxic metal exposure and obesity prevalence.

Problems of Biological Medical and Pharmaceutical Chemistry. 2022;25(12):3-9
pages 3-9 views

Modeling and dynamics of endogenous and exogenous oxidative stress in vitro

Abalenikhina Y.V., Pravkin S.K., Shchulkin A.V., Rokunov E.D., Nemtinov D.S., Vasilyeva E.P., Yakusheva E.N.

Abstract

Relevance. The effect of pro-oxidants on the cell can cause different effects depending on the dose and duration of exposure, therefore, adequate experimental models of oxidative stress (OS) in vitro are needed to study these processes.

The aim of the study was to study the dynamics of OS development in endogenous and exogenous in vitro models.

Material and methods. The study was carried out on a line of Caco-2 cells. Hydrogen peroxide (H2O2) and DL-butyonine sulfoximine (BSO) were added to cells at concentrations of 0.1–100 μM s and 1–500 microns, respectively, at the confluence of 3, 24 and 72 hours. At the end of the exposure, the percentage of viable cells was determined (MTT test), the level of reactive oxygen species (MitoTracker Red CM-H2 XRos), the amount of Nrf2 and glutathione peroxidase (ELISA), the concentration of carbonyl derivatives of proteins (photometric method.)

Results. H2O2 at concentrations of 5–50 μM and BSO – 10; 50; 100 μM cause an increase in the level of carbonyl derivatives of proteins, the level of transcription factor Nrf2 and antioxidant enzyme – glutathione peroxidase at exposure time of 24 and 72 hours. The concentration of H2O2 100 μM and BSO 500 μM are toxic to the Caco-2 cell line. The incubation period of 3 hours does not cause the development of OS.

Conclusion. Hydrogen peroxide at concentrations of 5-50 μM, BSO – 10; 50; 100 μM and exposure time of 24 and 72 hours cause the development of compensated oxidative stress (eustress), and H2O2 at concentrations of 100 μM and BSO – 500 μM are toxic to cells of the Caco-2 line.

Problems of Biological Medical and Pharmaceutical Chemistry. 2022;25(12):10-17
pages 10-17 views

Pharmaceuticals based on Ziziphus Jujuba compounds in gastrointestinal illness treatments: the prospects of application

Semkina O.A., Asaturov Y.V., Borisenko E.V.

Abstract

Currently, plant-derived medicines have a long history of use for the prevention and therapy of human disease, and to the treatment of gastrointestinal illness disorder in particular. With that, one of the topical problem of pharmacy is to research phytochemical composition of plants, innovation technologies of manufacturing plant - based extracts in order to create new biologically active compositions for the pharmaceutical industry use. This paper is concerned with gathering the current knowledge related to the medicinal characteristics the fruit of Z. Jujuba Mill. Specifically, its phytochemical contents and pharmacological activities in the treatment of gastrointestinal illness disorder.

Particular attention has been given to the sum of the main phytochemicals, including flavonoids, saponins, glycosides, polysaccharides and triterpenic acids, which are responsible for the reported pharmacological properties of Zizyphi Fructus, including anti-inflammatory, antioxidant, antiucleric, hepatoprotective and gastrointestinal activities.

Authors was led to the conclusion that the sum of the knowledge on the Zizyphi Fructus based pharmaceuticals for gastrointestinal illness disorders is not far enough advanced and requires more in-depth study.

Russian and foreign sources of literature placed in the public domain were analyzed; the following electronic databases were used: PubMed, elibrary, CyberLeninka and the Google-academy search engine.

Problems of Biological Medical and Pharmaceutical Chemistry. 2022;25(12):18-24
pages 18-24 views

Statistical analysis of metrological characteristics: a method of diosmin quantitation

Voronin A.V., Karpov A.V.

Abstract

The aim of the work was a statistical analysis of the metrological characteristics of the method of diosmin quantitation by UV spectrophotometry in medicinal formulations.

Material and methods. Medicinal formulations with diosmin were used as reference materials. The quantitation of diosmin was done by UV spectrophotometry at wavelengths of 268 nm and 370 nm. Statistical processing of quantitation data was carried out by variational statistics, correlation analysis.

Results. The values of specific absorption indices for diosmin in sodium hydroxide solution 0.02 mol/L at wavelengths of 268 nm and 370 nm were determined, they amounted to 463.0±24.6 and 259.0±9.9. The methods of spectrophotometric quantitation of diosmin in medicinal formulations at wavelengths of 268 nm and 370 nm do not statistically significantly differ in reproducibility. The pharmacopoeial algorithm using the t-test for analytical data by UV spectrophotometry of diosmin shows the failure of a systematic error. Relative errors of the average diosmin concentration and systematic errors at analysis on wavelengths of 268 nm and 370 nm differ statistically significantly. The analysis of the correlation dependencies "relative error of the average value – analytical wavelength" and "systematic error – analytical wavelength" shows a relationship between these parameters. With an increase of the systematic error of diosmin quantitation a nonlinear and insignificant fluctuation in relative error of the average diosmin concentration was observed.

Conclusion. Comparison of the average values of the diosmin concentration to medicinal formulation at two analytical wavelengths is not a sufficient statistical test to verify the correctness of analytical method, since subsequent statistical analysis shows a significant difference between systematic errors and relative error of the average diosmin concentration.

Problems of Biological Medical and Pharmaceutical Chemistry. 2022;25(12):25-31
pages 25-31 views

Theoretical substantiation of the physico-chemical interaction of the active components of the dry extract of ginko biloba leaves and chitosan by the quantum-chemical calculation method

Kovtun E.V., Pogrebnyak A.V., Stepanova E.F., Pogrebnyak L.V.

Abstract

Relevance. One of the main tasks arising in the design of dosage forms is the choice of the optimal combination of excipients and active ingredient. At the same time, the quantum-chemical prediction of the physicochemical properties of organic molecules of small and medium size is a promising direction.

The purpose of the study is the theoretical substantiation of the physicochemical interaction of the active components of the dry extract of ginkgo biloba leaves and the gel–forming agent chitosan by a quantum chemical calculation method.

Material and method. The interaction of a number of molecules included in the chitosan hydrogel was evaluated using quantum chemical calculations using the semiempirical PM7 molecular orbitals method. The initial geometry was generated using the HyperChem 8 molecular modeling program.

Results. The geometrical and electronic structure of molecules are presented in two approximations: taking into account hydration (the dielectric permittivity of the medium EPS=78.4 is given, the calculation of hydration using the A. Klamt COSMO and COSMO-RS solution models) and without taking into account hydration (in a model vacuum). Molecular descriptors used to evaluate the ability of hydrogel molecules to interact with chitosan have been calculated.

Conclusions. The theoretical prediction proves the feasibility of combining rutin, quercetin and gingcolide in a mild dosage form with the use of chitosan as a gel-forming agent.

Problems of Biological Medical and Pharmaceutical Chemistry. 2022;25(12):32-36
pages 32-36 views

A new method of tincture preparation in the base of saposhnikovia divaricata roots – the source of chromones, its standatization and determination of antiradical activity

Rabdanova N.P., Urbagarova B.M., Taraskin V.V., Tykheev Z.A.

Abstract

Relevance. Saposhnikovia divaricata (Turcz.) Schischk. is a rich source of chromones. Dry and liquid extracts, preparations of individual substances, as well as cosmetics for problem skin are produced from the roots of S. divaricata. However, there are no data of the tincture preparation in the base of on the S. divaricata despite their ease of administration.

The aim of the work is to develop a new method of tincture preparation in the base of S. divaricata roots, its standardization and determination of antiradical activity.

Material and methods. To obtain the tincture, we used the raw material S. divaricata roots produced by the "Daurskaya zagotovitel'naya kompaniya" in 2019. The choice of the optimal method for the tincture preparation was carried out using various periodic and intensive extraction methods. Ethyl alcohol was used as an extractant in the concentration range from 40 to 70%. For maximum extraction of chromones, the degree of grinding of raw materials was selected. Determination of the quantitative content of chromones was carried out by HPLC-UV using solutions of standard samples of prim-O-glucosylcymifugin, cymifugin and 4'-O-β-D-glucosyl-5-O-methylvissaminol. The antiradical activity of the tincture was evaluated using the DPPH test.

Results. The optimal conditions for the tincture preparation from the roots of S. divaricata splayed by the output of active substances - prim-O-glucosylcymifugin, cymifugin and 4'-O-β-D-glucosyl-5-O-methylvissaminol were selected. The optimal extraction parameters have been established: extractant (50% ethyl alcohol), degree of grinding (raw material, passing through a sieve with a diameter of 0.5 mm).

Conclusions. A method of tincture preparation in the base of S. divaricate roots has been developed, and the optimal conditions for its production have been selected. Extraction on the Soxhlet apparatus makes it possible to isolate twice as many chromones as compared to other extraction and circulation methods for tincture preparation. The best extractant of 50% ethyl alcohol. The optimal size of root grinding is 0.5 mm. The antiradical activity of the tincture was determined by the DPPH test.

Problems of Biological Medical and Pharmaceutical Chemistry. 2022;25(12):37-43
pages 37-43 views

Identification of phenolic compounds and development of a method for quantitative determination of the amount of phenolcarboxylic acids in the herb of Phacelia Tanacetifolia benth.

Sheykhmagomedova P.A., Popova O.I.

Abstract

Relevance. Modern requirements to the quality of medicinal herbal raw materials (herbs) include the assessment of the content of active substances. Development of the method of quantitative determination of the amount of active substances is one of the stages of standardization of a new type of herbal plants.

The aim of the study is to identify phenolic compounds and to develop a method of quantitative determination of the sum of phenolcarboxylic acids as a dominant group of biologically active substances in the herb of phacelia tanacetifolia.

Material and methods. The object of research was a herb of phacelia tanacetifolia, grown in territory of Republic Dagestan in vicinities of Kaspiysk. The herb was collected during flowering in April, 2022 and dried by air-shadowing method. Phenolic compounds were studied by thin-layer chromatography on chromatographic plates "Sorbfil PTSH-P-A" (Russia, 10*15). Identification was performed in the presence of standard samples. The plates were viewed in UV light before and after treatment with 2% alcohol solution of aluminum chloride. The sum of phenolcarboxylic acids was determined by direct spectrophotometry.

Results. Phenolcarboxylic acids (chlorogenic and caffeic acids) and flavonoids (rutin and quercetin) were identified in phacelia herb. In the course of the study the optimum conditions of extraction under which the maximum yield of the sum of phenolcarboxylic acids is observed were established. The obtained spectrum of alcoholic extraction from phacelia herb had maximum absorption at wave length 330 nm that corresponds to the absorption maximum of standard sample of chlorogenic acid.

Conclusions. The presence of phenolcarboxylic acids (chlorogenic and caffeic acids) and flavonoids (rutin and quercetin) in phacelia herb has been established by the thin-layer chromatography method. The methods of quantitative determination of the sum of phenolcarboxylic acids in 70% alcohol extract of the herb of phacelia tanacetifolia recalculated to chlorogenic acid have been developed.

Problems of Biological Medical and Pharmaceutical Chemistry. 2022;25(12):44-50
pages 44-50 views

Studying the chemical composition of the essential oil of the aboveground part of Artemisia Marschalliana spreng. natural populations of Dagestan

Vagabova F.A., Aliev A.M.

Abstract

The purpose of the study is to assess the variability of the content of the main components of the essential oil (EO) of the aerial part of Artemisia marschalliana Spreng. samples from the place of plant growth in order to search for source plants with a high yield of essential oil containing the most valuable components in terms of pharmacological activity.

Material and methods. The aerial part of A. marschalliana was collected in different natural Dagestan populations during the flowering phase in 2014. The essential oil was obtained by hydrodistillation (Clevenger method) for 4 hours from dry raw materials prepared by conventional methods.

Results. The EO yield varied from 0.19% to 0.46% in terms of air-dry raw material. As a result of chromato-mass spectrometry, a different number of components (41–51) was isolated from the EO samples, which amounted to 96,67%; 96,54%; 97,82% of identified compounds from samples, respectively. The main common components of the EO of all populations are isomers of α-, β-pinenes, limonene, trans-caryophyllene, spatulenol. In terms of quantity and qualitative composition of the main oil compounds, samples of A. marschalliana collected in the vicinity of the villages of Tsudahar (1100 m a.s.l.) and Charoda (1490 m a.s.l.) correspond to each other. The EO sample (Botlikh population) is very different from the samples of the other two populations, which makes it possible to judge the presence of two chemotypes of A. marschalliana in the flora of Dagestan.

Conclusions. For the first time, data are presented on the study of the composition of the essential oil from the aerial parts of wild Dagestan samples of A. marschalliana. Comparison of the results on the yield and component composition of the EO of the studied samples revealed a difference in the final yield of EO, similarity and difference in the composition of essential oils, which may be due to various abiotic factors of the growing environment and conditions, time of collection. The results obtained make it possible to characterize the EO of A. marschalliana as a source of valuable components, and the plant itself as a promising medicinal raw material.

Problems of Biological Medical and Pharmaceutical Chemistry. 2022;25(12):51-59
pages 51-59 views

The assessment of ROM and RMM combined chemotherapy outcome on an experimental leprosy in mice footpad

Solomka V.S., Verbenko D.A., Nikonorov A.A., Karamova A.E.

Abstract

Relevance. The leprosy standard combined therapy recommended by the World Health Organization includes: dapsone, rifampicin and clofazimine. In the Russian Federation however only two of them are registered, making full-fledged leprosy patients therapy impossible. Alternative leprosy treatment regimens with various combinations of rifampicin and fluoroquinolones have been proposed, eg. rifampicin, ofloxacin and minocycline (ROM) or rifampicin, moxifloxacin, and minocycline (RMM), but the assessment of their effectiveness is ambiguous.

The purpose of study is the assessment of ROM and RMM combination leprosy drug therapy outcomes on an experimental disease model - in the paw pads of mice.

Material and methods. the experiment was performed on 50 BALB/cNude mice. Infectious material was obtained from a patient of the Sergiev Posad Branch of the Federal State Budgetary Institution "GNTSDK" of the Ministry of Health of the Russian Federation diagnosed with "Lepromatous leprosy" (A.30.5 according to ICD10). The reproduction of the experimental model of the disease was carried out according to the Shepard model at mouse paw pads. The presence of M. leprae was assessed by real-time PCR using the multicopy species-specific region of the M. leprae genome RLEP. The experiment included the stages of an experimental leprosy reproduction in mice paw pads and subsequent treatment using ROM and RMM combination chemotherapy regimens.

Results. The obtained results demonstrate the high efficacy for both ROM and RMM combination chemotherapy regimens for the treatment of experimental leprosy in mice.

Conclusions. The obtained results of high efficiency of experimental leprosy chemotherapy with ROM or RMM regimens paw the way to recommend conducting clinical trials of these regimens in leprosy patients.

Problems of Biological Medical and Pharmaceutical Chemistry. 2022;25(12):61-64
pages 61-64 views

Retraction (revocation) of a scientific article

Problems of Biological Medical and Pharmaceutical Chemistry. 2022;25(12):65-67
pages 65-67 views

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