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Vol 23, No 11 (2020)


Field restharrow (Ononis arvensis L.) - promising source of substances with different biological activity

Luzhanin V.G., Ponkratova A.O., Whaley A.K., Grishukova E.A., Yakovlev G.P.


Field restharrow (Ononis arvensis L.) is a perennial herb from the legume family, represented in Russia by two subspecies: O. arvensis subsp. arvensis and O. arvensis subsp. spinescens. The geographic area in which the plant can be found covers most of the European territory of Russia, Ukraine, Belarus, Moldova, the Caucasus and Transcaucasia, as well as the Baltic States, where it reaches the shores of the Gulf of Finland. This review includes the plants botanical description, secondary metabolite composition, as well as the description of the biological and pharmacological activity of O. arvensis. Polyphenolic compounds can be distinguished as the main secondary metabolites of O. arvensis, among which the representative groups are isoflavones (formononetin, pseudobaptigenin, calicoside, their glycosides and derivatives), dihydroisoflavonoids (sativanone and onogenin, their glycosides and derivatives), pterocarpans (medicarpine and maakiain, their glycosides and derivatives), phenol carboxylic acid (caffeic, chlorogenic, ferulic, etc.). Among other polyphenolic compounds, flavonols, flavones, flavan-3-ols, dihydrochalcones, hydrolyzable tannins, stilbenoids and flavanones have also been found in field restharrow. In folk medicine, Ononis arvensis has found application in the treatment of hemorrhoids, articular rheumatism, diseases of the liver, bladder and kidneys, skin diseases (dermatoses, eczema), as well as a diaphoretic, hemostatic and diuretic agent. There is reliable data on the choleretic, analgesic and antihypoxic effects of O. arvensis aqueous-alcoholic extracts, as well as their effect on the motor function of the gastrointestinal tract. Extracts from the perennial part of fieldrestharrow showed antibacterial activity against Escherichia coli, Candida albicans, Staphylococcus aureus, Pseudomonas aeruqinosa and Salmonella typhimurium. Thus, a wide variety of biologically active substances, causing a multidirectional pharmacological effect in this plant, makes O. arvensis a promising plant from which individual compounds can be isolated - that in the future could become potential pharmaceutical substances.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(11):3-9
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Comparative analysis of multivitamins for children

Bochanova E.N., Gackich I.V., Potupchik T.V., Veselova O.F., Nozdrachev K.G.


Purpose of this study was to study the composition and structure of sales of multivitamin complexes for children in Krasnoyarsk in 2019, to identify the optimal multivitamin complex for children aged 7 years. Material and methods. The study was conducted on the basis of pharmacy N.140 of JSC «GubernskieApteki», where instructions for the use of multivitamin complexes for children of various manufacturers were studied.The assessment of compliance of the composition of multivitamin complexes with the norms of physiological needs, according to the methodological recommendations of Methodical recommendation MR was carried out «Norms of physiological needs in energy and food substances for various groups of the population of the Russian Federation». The results of the study showed that in most multivitamin complexes for children, produced both as a drug and a dietary Supplement, the content of vitamins differs from the recommended daily dose of their consumption. Conclusion. The leaders of sales are multivitamin complexes «Vitamishki» and «Complivit», which are characterized by the lowest price per package, but the highest cost of a 1-month course of administration («Vitamishki»), while they do not correspond in composition to the physiological needs of vitamins in children in all age categories. Multivitamin complexes of the «Multi-tabs»series are preferred for children aged 7 years in terms of price / guality.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(11):10-15
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The plants water-soluble pectin isolated from genus Saussurea DC. Enhance functional activity of antigen-presenting cells

Ligacheva A.A., Rechetov Y.E., Avdeeva E.Y., Danilets M.G., Trofimova E.S., Sherstoboev E.Y., Belousov M.V.


Relevance. Pectins are macromolecules containing fragments of linear and branched polysaccharides. Their immuno-modulating properties, possible mechanisms of immunostimulating and anti-inflammatory action, depending on the structure, have been actively studied recently. Purpose of the study. Determination of the relationship between the composition of pectin substances (PS) isolated from plants of the genus Saussurea (DC.) and the ability to activate antigen-presenting cells. Material and methods. PS was obtained by dialysis against water from a previously purified aerial part of the S. controversa DC. (SC), S. salicifolia L. (SS) and leaves with petiolesof the S. frolovii Ledeb. (SF). Protein was quantified by the Lowry method. The content of uronic acids was determined in the reaction of carbohydrate oxidation products with 3,5-dimethylphenol. Molecular weight characteristics - by high-performance exclusion chromatography. Monosaccharide composition - by gas chromatography after complete acid hydrolysis of PS. NO-stimulating properties of PS were studied in a model of mature murine peritoneal macrophages using the Grace reagent. To determine the endotoxin impurity, the antibiotic polymyxin B was used. Cell proliferation was studied in the MTT test. Results. The isolated PSs are arabinogalactouronans. The content of uronic acids is 94-96%. The major component of PV SS and SF is galactose, PS SC is arabinose. Minor residues are represented by rhamnose, xylose, mannose (except for Sc), and glucose (except for SC and SF). All samples have a protein impurity of 2,5-13%. Pectin substances SF, SC, and SS increase nitrite production by macrophages by 2-10 timesdepending on the concentration of substances and plant species. PS SF and SC at all doses, and PS SS at 2 pg/ml did not affect cell proliferation. Pectin substances SS in high doses reduced it by 1,2 times. The NO-stimulating properties of PS SC and SF are due to the significant endotoxin impurity. PS SS have an insignificant content and have the greatest effect on the functional activity of macrophages. Conclusion. Pectin substances from plants of the genus Saussurea, containing in varying degrees a concomitant admixture of protein and endotoxin, exhibit NO-stimulating activity, which depends on the plant species and the structure of the macromolecule.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(11):16-21
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Searching for selective inhibitors of matrix metalloproteinase type 2 in a series of benzoylamino (phenylsulfonyl)-substituted cyclic amino acid derivatives

Grigorkevich O.S., Mokrov G.V., Zolotov N.N., Barchukov V.V., Kryzhanovskii S.A., Gudasheva T.A.


Relevance. Matrix metalloproteinases type 2 and 9 (MMP-2, MMP-9) initiate collagen degradation of the extracellular myocardial matrix in acute infarction which is accompanied by their release into the systemic circulation. MMP inhibitors are known to reduce post-infarction remodeling of the left ventricle of the heart. Effective cardiotropic drugs can be created based on them. Aim. Searching for selective matrix metalloproteinase type 2 inhibitors among benzoylamino(phenylsulfonyl)-substituted cyclic amino acid derivatives. Material and methods. Potential inhibitors were designed and synthesized earlier in the Zakusov Institute of Pharmacology. Inhibition constants were determined fluorimetrically using a substrate Mca-Lys-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-Nhh and recombinant, active human MMP-2 and MMP-9. Effect of the most active inhibitors on the level of MMP-2 in the rat blood plasma with acute myocardial infarction (AMI) was determined in outbred male rats. AMI was reproduced by ligation of the coronary artery. The level of MMP-2 was determined by enzyme immunoassay. Results. It was shown that l-{4-[(4-chlorobenzoyl)amino]phenyl}sulfonyl-L-proline (code AL-828) and l-{4-[(2-chlorobenzoyl)-amino]phenyl}sulfonyl-L-proline (code ML-269) are selective MMP-2 inhibitors with inhibition constants 45±8,5 pM and 82,5±17,2 pM, respectively. Compounds AL-828 and ML-269 reduce the level of MMP-2 in the blood plasma of rats with AMI in the doses of 30 mg/kg/day per os by 9% and 19% with p=0.08 and p=0.007, respectively, and, at least, are not inferior in their activity to the comparison drug doxycycline (40 mg/kg/day). Conclusion. Selective inhibitors of MMP-2, compounds ML-269 and AL-828, which can become the basis for the creation of cardioprotective drugs that prevent pathological post-infarction remodeling of the left ventricle of the heart were revealed.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(11):22-27
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Influence of the Rhaponticum uniflorum dry extract on the behavior of white rats in positive supported tests

Razuvaeva Y.G., Markova K.V., Toropova A.A., Olennikov D.N.


The purpose: of the study was to evaluate the Rhaponticum uniflorum L. DC. dry extract on the white rats behavior in positive supported tests. Material and methods: The studies were carried out on white Wistar rats. The R. uniflorum dry extract in the doses 50,100 and 200 mg/kg was administered {per os) to animals experimental groups. The amount of food ingested by the animals was measured in the hyponeophagia test. The food-procuring conditioned reflex was formed in a T-shaped labyrinth. Results. It was found that 63-88% of the animals ate food under unfamiliar conditions in the experimental groups, while in the control group only 38%. The food-procuring conditioned reflex was formed in 29 and 38% of animals treated with R. uniflorum at doses of 100 and 200 mg/kg, whereas in the control group, no animal reached the learning criterion. Against the background of the introduction of the R. uniflorum at a dose of 50 mg/kg, food-procuring conditioned reflex developed in 71% of the animals of the first experimental group. Conclusions. The R. uniflorum dry extract has an anxiolytic-like effect, promoting the adaptation of animals to unfamiliar conditions and increasing the amount of food in the hyponeophagia test, as well as faster development of the food-procuring conditioned reflexe in the T-shaped labyrinth.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(11):28-33
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Patterns of hair mineral and trace element contents in children with Down’s syndrome and mental retardation

Grabeklis A.R., Skalnaya A.A., Mazaletskaya A.L., Ajsuvakova O.P.


Relevance. Down's syndrome is a genetic disorder caused by trisomy of chromosome 21. It manifests itself in a wide range of symptoms, including neuropsychiatric disorders, which may be partly due to disturbed metabolism of essential metals in the body. Objective. To study the content of essential minerals and trace elements in hair of children with Down's syndrome and mental retardation in order to find possible common patterns. Material and methods. The study involved 109 children with mental retardation, 75 children with Down's syndrome, and 107 healthy children aged 1 to 7 years (3.28 ± 1.88 years).Co, Cr, Cu, Fe, I, Li, Mn, Se, V, Zn, Ca, K, Mg, Na, Pw as guantitatively determined in hair by inductively coupled plasma mass spectrometry (ICP-MS). Results. The content of cobalt, copper, iron, selenium and vanadium in hair of children with mental retardation and Down's syndrome was lower than in control group by 12% and 11%, 8% and 11%, 18% and 16%, 36% and 15%, 47% and 34%, respectively. At the same time, the level of chromium, lithium, manganese, and zinc as compared to the control group was lower only in children with mental retardation, by 21%, 22%, 11% and 27%, respectively. In children with Down's syndrome the iodine level exceeded the control values by 54%, though in children with mental retardation such differences were not revealed. The phosphorus content in children with mental retardation and Down's syndrome was lower and higher than the control values by 8% and 24%, respectively. The magnesium content in the hair of children with mental retardation was lower than that in healthy subjects and children with Down's syndrome by 18% and 13%, respectively.Allthementioneddifferenceswerestatisticallysignificant (p < 0.05). Conclusion. There are a number of common patterns in altered metabolism of essential minerals and trace elements in children with Down's syndrome and mental retardation. Despite the undoubtedly genetic cause of pathological changes in Down's disease, these al terations can partially cause neuropsychiatric disorders observed in Down's syndrome patients.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(11):34-39
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Traits of growth of various species of medicinal plants of the genus Aloe in greenhouse and the accumulation of phenolic compounds in them

Zagoskina N.V., Lapshin P.V., Nazarenko L.V., Sazhina N.N.


The growth of ten species of the genus Aloe (A. variegata, A. isaloensis, A. dorotheae, A. striata, A. immaculata, A. congolensis, A. deltoideodonta, A. vera, A. arborescens, and A. pluridens) grown in greenhouses, as well as morphometric parameters and the total content of phenolic compounds in their leaves, were studied. The investigated species are characterized by significant differences in the height of plants and the square of their leaves. A. arborescens and A. vera were the tallest plants, while A.immaculata was the lowest. With the ontogenetic development, the leaf area in all species increased and in the adult state was 1.5 - 3 times higher than that in young ones. A. vera had the highest scores, and the smallest ones are in A. isaloensis. Determination of the total content of phenolic compounds showed a higher level in leaves aged 1.5 year compared to the earlier stages of their ontogenesis (6 months), which is most expressed in A. congolensis. The lowest content of these secondary metabolites was observed in A. variegata, A. immaculata, A. striata. A. arborescens, A. pluridens, A. vera and A. dorotheae it was 2-3 times higher. The highest total content of phenolic compounds is typical for A. deltoideodonta (independently of leaf age), A. isaloensis and A. congolensis. All this indicates significant differences in the accumulation of phenolic compounds in the leaves of various Aloe species and the dependence of this process on the ontogenetic phase of their development.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(11):40-46
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Effects of cultural conditions on IAA-productivity of endophytic bacterial strain Klebsiella RE3 isolated from roots of Camellia (Camellia sp)

Nguyen Van Zhang -., Vu Thi Ngoc Diep -., Pham Khanh Huyen -., Kalashnikova E.A., Kirakosyan R.N.


Relevance. Camellia (in Vietnam, the camellia is called tea with yellow flowers) is not only used as ordinary tea, but also as a medicinal one. Camellia helps prevent tumors, diabetes, reduce cholesterol. Nowadays, research projects with a camellia in Vietnam have mainly focused on the studying of morphological and biological characteristics and selection of camellia. Scientific research in connection with the endophytic microorganisms of camellia was limited. Objective. The purpose of these studies was to assess the effect of cultural conditions and various carbon and nitrogen sources on the IAA producing activity of the strain Klebsiella RE3. Material and methods. The strain Klebsiella RE3 was isolated from the roots of tea shrubs (Camellia sp.) Growing in the gardens of TD-GOLDEN TEAVIET (Tra Hoa vang Tam Däo), located in Quan Ngoai village, Tam Quan municipality, Tam Dao district (Tam Däo), Vinh Phuc Province, Vietnam. Results. The research results showed that strain RE3 synthesizes the maximum IAA after 72 hours of cultivation at pH 7 (13.95 pg / ml), temperature (14.28 pg / ml). Conclusion. Of all the tested carbon and nitrogen sources, D-sorbitol and NH4NO3 are the best carbon and nitrogen sources for strain RE3 with IAA production of 12.9 pg / ml and 11.35 pg / ml, respectively.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(11):47-54
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