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Vol 24, No 6 (2021)


Growth factor of vessel endothelium in new coronaviral disease - 2019 (COVID-19) complicated with pneumoni

Murkamilov I.T., Sabirov I.S., Fomin V.V., Kudaibergenova I.O., Murkamilova Z.A., Yusupov F.A.


Theaimofthestudyistostudythevascularendothelialgrowthfactorinthenewcoronavirus disease -2019 (COVID-19). Material and methods.The object of the study is patients (36 men and 28 women, mean age 48.9 ± 15.3 years) with laboratory and clinical and epidemiologically confirmed diagnosis of COVID-19, complicated by pneumonia. The indicators of peripheral and biochemical blood were analyzed. Serum levels of vascular endothelial growth factor (VEGF) concentration were assessed by quantitative enzyme-linked immunosorbent assay. The patients were divided into 2 groups depending on gender (men, n = 36 (56.25%); women, n = 28 (43.75%) and the degree of blood oxygen saturation (group A, n = 26 (40.62%) Sa02 level below 90%; group B, n = 38 (59.38%) Sa02 level above 90%). Results. In the subgroup of men with COVID-19 complicated by pneumonia, significantly low levels of hemoglobin (Hb) oxygen saturation, lymphocyte counts, as well as high levels of leukocytes and blood creatinine were detected.The content of Hb and the average concentration of Hb in erythrocytes (MHC) were significantly lower among women with COVID-19 complicated by pneumonia. In a subgroup of men, there was a significant increase in VEGF concentration. A close relationship was recorded between concentration of VEGFandSat02(r=-0.341,p = 0.019),averageHbcontentinerythrocyte(MCH)(r=-0.201,p = 0.045),relativenumberoflym-phocytes (r = -0.362, p = 0.018), distribution width erythrocytes (r = 0.381, p = 0.010), the number of platelets (r = 0.503, p = 0.007), erythrocyte sedimentation rate(ESR) (r= 0.555, p = 0.001), as well as with the concentration of C-reactive protein (CRP) (r = 0.394, p = 0.005). Conclusion. The VEGF concentration correlates with the indices of Hb oxygen saturation, the number of platelets, the relative number of lymphocytes, the width of distribution of erythrocytes, ESR, MCH, as well asthe level of CRP in the blood. The predictor ofthe severity of COVID-19 in men was the level of oxygen saturation, the number of leukocytes, the relative number of lymphocytes and blood creatinine, and in females - additionally also the level of Hb and the MCHS indicator.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(6):3-10
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Modern trends in the development of pharmaceutical technology in the production of extraction drugs (review)

Dzhavakhyan M.A., Pavelieva O.K.


Various extraction methods with the use of ethanol, ethers and acids are extensively employing in industry. Their use is associated with multi-stage utilization, the need to detect and remove the residual toxic solvents from the target product. Currently, the search for new extractants that meet the principles of "green chemistry", such as the use of renewable plant resources and alternative solvents, is relevant. Deep eutectic solvents (DES) are of interest for modern pharmaceutical technology as an alternative to traditional organic extractants. They are characterized by the formation of strong hydrogen bonds and, due to their extremely low vapor pressure, are widely used in polymer chemistry and synthetic organic chemistry. The prospects for their use are due to their low toxicity, biodegradability, the possibility of selective extraction of a specific substance and renewal of the extractant. In numerous works of foreign scientists, the results of studying the effect of DES on the yield of various groups of biologically active substances (BAS) from both dried and fresh plants are described. The extraction processes with deep eutectic solvents are based on the replacement of solvent molecules with biologically active substances with the cleavage of old hydrogen bonds and the formation of new ones. DES performed well both for the extraction of groups of compounds and for the selective extraction of individual biologically active molecules. At the same time, the use of DES is characterized by the complexity of the choice of the initial substances, the need to select their ratio, and the aggregation instability of some systems. This review presents data on the DES fabrication technology. The most common components, melting points of ready-made mixtures and information on their stability are noted. We analyzed the data on the toxicity of the resulting mixtures and their possible biological activity, since many components are primary metabolites. This review summarizes the existing data on the toxicity and extraction capacity of eutectic solvents over the past 20 years.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(6):11-19
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Scientific basis for rational use of the bark Quercus robur in pharmaceutical practice

Ryabov N.A., Ryzhov V.M., Kurkin V.A.


Introduction. Quercus robur L. is a woody plant of the Beech family Fagaceae, growing in the European part of Russia. The official raw material of Quercus roburL\\stbe bark ofyoung branches, but it isalso advisable to study the perennial bark ofthe stem parts in order to discover important biologically active compounds. Currently, the issue of complex processing of perennial stem parts of Quercus roburbark has not been resolved, therefore perennial oak bark is practically not used in wood processing. Purpose of the study. Comparative phytochemical analysis of the aboveground organs of Quercus robur - the bark of perennial stem parts of industrial raw materials obtained as waste ofthe wood processing industry and pharmacopoeial raw materials of Quercus robur. Material and methods. The objects of the study were samples of the bark Quercus robur L.: pharmacopoeial bark (Kras-nogorskleksredstvaJSC, Krasnogorsk) and perennial stem bark obtained as production waste from the wood processing company 000 «DUO». Also, the objects of the study were alcohol extracts at various concentrations of ethyl alcohol (50,60,70,80%), as well as on chloroform ofthe chemically pure grade in a ratio of 1:5 (raw material-extractant) based on the pharmacopoeial bark of Quercus robur L. and perennial bark. As methods for analyzing the extracts, chromatography in a thin layer of sorbent was used; the analysis was carried out on PTSKh-AF-A-UV plates ofthe "Sorbfil" brand. Chromatography was carried out ascending in a solvent system chloro-form-ethanol-water (26:16:3). The detection of spots of substances was carried out by viewing chromatograms in lamps with UV light with wavelengths of 254 nm and 366 nm. In addition, the chromatograms were processed with the phosphoric tungstic acid (FVA) reagent, followed by heating to 100 ° С for the development of flavonoids and other compounds.A spectrophotometric study was carried out to quantify the content of the sum of tannins and flavonoids in raw materials based on the bark of an Quercus robur. Forthese purposes, we used the method of direct and differential spectrophotometry on a spectrophotometer - "SF-2000" (Russia) in cuvettes with a layerthickness of 10 mm. 95% ethyl alcohol was used asa solvent. The reference solution is95% ethyl alcohol. Results. Comparative spectrophotometric, titrimetric and chromatographic studies of alcohol extracts of concentrations of 50,60,70, 80%, as well as chloroform extracts of Quercus robur bark samples: pharmacopoeial raw materials and perennial oak bark have been carried out. It was found that 60% alcoholic extract from pharmacopoeial bark and perennial bark are distinguished by a relatively high content of flavonoids. In particular, the content of flavonoids in terms of cynaroside in oak bark (pharmacopoeial raw material) for 60% alcohol is 1.69%, in perennial bark - 1.18%. The content of tannins in oak bark samples was determined by titrimetric method of analysis: in pharmacopoeial bark6.40%, in perennial bark-8.90%; spectrophotometric method: in the pharmacopoeial cortex-1.70%, in the perennial cortex -15.20%. Chromatographic analysis of the studied samples of the Quercus robur bark extracts in comparison with the standards revealed the presence of the flavonoid quercetin (Rf ~ 0.82) and theflavonol glycoside rutin (Rf ~ 0.2) in both samples. Conclusion. The expediency of using non-pharmacopoeial raw materials - perennial oak bark, which is today a waste of the wood processing industry, is shown in the framework of solving urgent problems of nature management, ecology and waste-free production, as well as using raw materials as an affordable and inexpensive source of valuable phenolic BAS.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(6):20-28
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Pharmacognostic research aboveground part of Momordica harantia

Sampiev A.M., Shevchenko A.I., Nikiforova E.B., Morozov A.I.


Relevance. Features of the anatomical structure of plant raw materials are diagnostic features used for its identification. The aim of this study was a pharmacognostic study of the aboveground part of the harantium momordica. Material and methods. Preparation of plant material for microscopic examination and analysis of micro-preparations was carried out using pharmacopoeia techniques. The prepared micro-preparations were studied using a microscope ofthe LW 200 T series. The content of phenolic compounds was determined by capillary electrophoresis. Results. Asa result of the conducted studies, the features ofthe anatomical structure ofthe leaves, flowers and fruits of momordica were revealed.The electrophoretic study confirmed the presence of phenolic compounds in the studied raw materials, represented by flavonoids and phenol-carboxylicacids. Conclusion. Pharmacognostic analysis of the aboveground part ofthe harantium momordica revealed anatomical and diagnostic signs and numerical indicatorsthat can be used asthebasisforregulatory documentation for medicinal rawmaterials.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(6):29-35
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Validation of the methodology of quantitative determination of flavonoids in the herbae of Cirsium arvense (L.)

Shamsutdinova S.R., Pupykina K.A., Krasyuk E.V., Startseva L.V.


Relevance. One ofthe main groups of active substances ofthe Cirsium arvense L. are flavonoids, among which apigenin predominates. An urgent problem is the study of new types of medicinal plant raw materials and their introduction into medical practice, which requires research on the developmentof methodsforthe quantitative determination of the main group of BASand validation ofthe method. The purpose ofthe work. Validation evaluation ofthe method of quantitative determination of flavonoids in the herba ofthe Cirsium arvense L. Material and methods. The object ofthe study is samples ofthe herba ofthe Cirsium arvense L. The quantitative determination of flavonoids was carried out by differential spectrophotometry with the selection of optimal extraction conditions, and the method was validated. Results. A method for the quantitative determination ofthe amount of flavonoids in terms of apigenin (Amax = 388 ± 2 nm) was developed. The optimal parameters of extraction of flavonoids were determined: the extractant-ethyl alcohol 40%, the ratio of raw materials and extractant 1: 30, the degree of grinding - 2 mm, the extraction time-30 minutes, three-time extraction, the complexing agent-1 ml of 2% aluminum chloride solution, the reaction develops within 45 minutes and the complex remains stable for 1 hour. The content ofthe sum of flavonoids in terms of apigenin is 2.78 ±0.09%. Validation ofthe method wascarried out according to thefol-lowing parameters: linearity, correctness and precision. It was found that within the limits ofthe measured concentrations (optical density 0.241-0.389), the dependence of the apigenin content on the theoretical content of flavonoids in the herba ofthe Cirsium arvense L. is linear. The correctness ofthe method was established by measuring the quantitative content ofthe sum of flavonoids in solutions with a known concentration of apigenin and it was found that the values lie within the confidence intervals ofthe corresponding average results. Precision wasstudied by the indicators-repeatability (convergence); intra-laboratory and inter-laboratory reproducibility, while it was found that the relative error of the average result did not exceed 10%. Conclusions. The linear nature, correctness and precision ofthe developed methodology for the quantitative determination of flavonoids in the herba ofthe Cirsium arvense L. in terms of apigenin and the possibility of its further use for the standardization ofthe studied raw materials are justified.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(6):36-41
pages 36-41 views

Synthesis and assessment of analgesic activity of a new 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidin-4-olate sodium

Kuvaeva E.V., Kolesnik D.A., Levshukova P.O., Ivkin D.Y., Yakovlev I.P.


Aim. 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidine-4-sodium olate synthesis (test compound, target compound) and its acute toxicity, analgesic activity in silico and in vivo evaluation. Material and methods. The target compound was obtained by the interaction of 5-butyl-6-hydroxy-2,3-diphenylpyrimidin-4 (3H) -OH radicals and an sodium hydroxide aqueous solution equimolar amount. The structure was proved by NMR 1H and 13C spectroscopy. The test compound acute toxicity prediction was carried out using the GUSAR software. Acute toxicity in vivo was determined in white outbred male mice. Biological activity computer screening was performed using the PASS program located on a web service freely accessible via the Internet. For the analgesic activity experimental assessment, two models were used: tail-flicking ofthe tail from heat radiation and acetic acid cramps. Results. Sodium 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidine-4-olate was synthesized in quantitative yield. The structure is proved using 1H and 13C NMR spectroscopy. The acute toxicity predicted and experimental data allow to classify the compound under study as moderately hazardous. During the biological activity screening with the PASS program help, data on the alleged analgesic effect we re obtained. The analgesic activity study in vivo showed that the target compound hasa pronounced effect. Conclusion. A new compound, 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidine-4-sodium olate, was synthesized. Its structure has been proven using modern physicochemical analysis methods. The computer modelling results made it possible to determine the toxicity class and potential biological activity. With the experimental pharmacological studies help, it was proved that the studied compound has a toxicity low level and shows pronounced analgesic activity.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(6):42-46
pages 42-46 views

Effect of hardy retardant on quality indices of raw materials, Mentha piperita, Dracocephalum moldavica and Chamomilla recutita

Tropina N.S., Sidelnikov N.I., Bykova O.A.


Relevance. The technology of growing essential oil crops provides for maximum yield in combination with a high content of essential oil and its main components. The greatest increase in the content of essential oil with simultaneous increase in the synthesis of active substances is observed when chemical retardants are used in the before harvesting period. In last years, natural Hardy retardant, whose active substancesare orthodiphenolsand epibrassinolide,hasbeen tested on medicinal and etheroil cultures. The purpose ofthis workisto assessthe effect of Hardy's retardant on the content ofthe main componentsof essential oil Mentha piperita, Chamomilla recutita and essential oil raw materials of Dracocephalum moldavica. Material and Methods. Research was conducted in the North Caucasus branch ofVILAR in the conditions ofthe Western Caucasus in the period 2018-2020. Hardy treatment was carried out in the start of budding phase at a flow rate of 0.2 l/ha, working solution flow rate of 300 l/ha. Control plots were sprayed with water. Harvesting of raw materials was carried out 10 days aftertreatment. Results. It was revealed that the use of Hardy's retardant in the pre-harvest period activates the process of accumulation of secondary metabolites in essential oil. Treatment of Mentha piperita by Hardy contributes to a 5% increase in menthol content, menthol acetate by 2 timesand a 54.4% decrease in the level of the toxic component of neomentol. In Chamomilla recutita essential oil, an increase of 1.3 timesoverthe control of basic components such asA-bisabolol, hamazulene by 22% and bisabolol of Aoxide by 18% was noted. Under the influence of retardant in the essential oil raw material ofthe Dracocephalum moldavica, the content of rosemary acid increases by 27% and glucose rosemary by 30%. Conclusion. The obtained data suggest that Hardy retardant treatment of essential oil cultures in the before harvest period improves the quality raw material of essential oil and essential oil by increasing the content ofthe main most significant components, which indirectly affects the improvement of the chemical composition.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(6):47-51
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Cultivation parameters and phytochemical screening of plants Marsilea hirsuta R. BR. under in vitro conditions

Sarkisova M.V., Cherednichenko M.Y.


Actuality. To preserve natural populations of Marsilea hirsuta it is possible to propose the use of clonal micropropagation, taking into account physiological and biochemical characteristics of aseptic plants. Aim. Selection of optimal conditions for in vitro cultivation of M. hirsuta plants and primary phytochemical screening of plant extracts. Material and methods. Isolated explants of M. hirsuta aseptic plants were cultivated on nutrient media with various mineral composition, acidity and consistence. Primary phytochemical screening extracts wascarried out according to standard methods. Results. The use of 2-nodal cuttings led to the formation of maximum amount of micro-shoots (7). A decrease in acidity to pH 4 has no significant effect on the efficiency of adventive shoots formation, their morphology and height. At pH 6 or 7, weakened plants with pale green leaves and a poorly developed root system are formed. On the 3rd day on a liquid medium, the plants develop better than on a solid one; by the 7th day, the indicators on both media variants are equalized, after the 10th day, growth on a liquid medium slows down. Primary phytochemical screening of plant extracts showed the presence of components such as tannins and phenolic compounds, flavonoids, alkaloids and proteins. Conclusion. The optimal cutting size is 2 nodes. To obtain the maximum number of nodes and shoot length for the minimum cultivation time, it is recommended to grow M. hirsuta on a liquid nutrient medium (pH 4...5) with a transplant every 10 days. Primary phytochemical analysis showed the presence of some valuable compounds.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(6):52-56
pages 52-56 views

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