[Genotoxic and Mutagenic Properties of Synthetic Betulinic and Betulonic Acids].

Synthesis of betulinic acid was performed from the birch bark extract (Betula pendula). Betulonic acid was intermediate of the synthesis. Both acids were isolated with purity 95%. Genotoxicity and mutagenicity of obtained compounds were analyzed by Ames test and SOS chromotest, none of these properties have been detected.

[Isolation of pomolic acid from Chamaenerion angustifolium and evaluation of its genotoxicity by microbiological tests].

Fireweed (Chamaenerion angustifolium) lipophilic constituents were investigated by GC-MS analysis. 28 aliphatic and 6 triterpenic acids were found out at first time. Pomolic acid genotoxicity and mutagenicity were analyzed by Ames test and SOS chromotest. Genotoxic and mutagenic properties of pomolic acid were not detected.

Inhibitory effect of ursolic acid derivatives on recombinant human aldose reductase.

Aldose reductase (AR) is the first enzyme in the polyol pathway. AR has been reported to play an important role in the pathogenesis of diabetic complications. Ursolic acid and fourteen synthetic derivatives with ursane skeleton were tested for recombinant human aldose reductase (rhAR) inhibitory activity for development of diabetic complications. Among them, N-(3beta-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid (XV) showed most potent rhAR inhibitory activity in vitro. Inhibition mode of N-(3beta-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid (XV) was tested uncompetitively by kinetic analysis using the Lineweaver-Burk plots. Ursolic acid derivative N-(3beta-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid is able to inhibit rhAR uncompetitively and could be offered as a lead compound for AR inhibition.

[Bioconversion of beta-sitosterol and its complex esters by Rhodococcus actinobacteria].

The ability of pure cultures of Rhodococcus actinobacteria from the Ural specialized collection of alkanotrophic microorganisms (World Federation for Culture Collections accession number 768; http://www.ecology.psu.ru/iegmcol) to convert beta-sitosterol (BSS) and its 3beta-acylated derivatives was studied. Rhodococcus strains with pronounced cholesterol oxidase activity, capable of converting BSS to stigmat-4-ene-3-one in the reaction of cooxidation with n-hexadecane, were selected. The dependence of the activity of cholesterol oxidase of rhodococci on the length of the acyl group in BSS esters was studied. Conditions under which Rhodococcus cells convert BSS to 17beta-hydroxyandrost-4-ene-3-one (testosterone), commonly used in pharmacology, were determined.

A prototype prophylactic anti-influenza preparation in aerosol form on the basis of Abies sibirica polyprenols.

This research investigates a promising antiviral compound based on polyprenols from Siberian silver fir (Abies sibirica). The physico-chemical characteristics of a preparation developed in aerosol form and an estimation of its protective efficacy against aerosol challenge of laboratory animals are presented. It is shown that (1) by using a simple ultrasonic disperser one can obtain aerosol of three formulations studied with about 70% of its mass accumulated in the size range below 1.8 microm; (2) 40-100% of aerosol particles contain preparation for different formulations; (3) after delivering under specified schedules, the preparations as developed can protect up to 100% of mice against 5 LD(50) of influenza A/Aichi/2/68 (H3N2) virus aerosol infection. Animals inhaled twice the preparation doses (which were 100 times lower than injection ones of the same efficacy) and did not exceed 10 microg/mouse. It was shown that the mode of action of this immunomodulating preparation was nonspecific stimulation of immune cells' various activities.

[Mechanisms of mice resistance to influenza virus A/AICHI/2/68 after preventive injection with polyprenols ]. / Mekhanizmy rezistentnosti myshei k virusu grippa A/AIChI/2/68 pri profilakticheskom vvedenii poliprenolov.

Preventive effect in influenza can be attained by intramuscular injections of fir (Abies) polyprenols. One of 5 tested polyprenol preparations (No. 1), injected 2 days before aerogenic infection with influenza virus, reliably protected mice from disease. Mice pretreated with polyprenol preparations or Hanks' solution did not differ by accumulation of interferon in the lungs One day after aerogenic infection. Three days after injection of polyprenol preparation No. 1 the weights of the spleen and thymus significantly decreased. One day after injection cell count in the bronchoalveolar tract of mice was almost 2-fold higher than in the control at the expense of lymphocytes and macrophages. After 3 days the relative and absolute counts of macrophages decreased and those of lymphocytes decreased significantly. Three days after injection macrophages were 2-fold more active in absorption of zymosan granules. Preparation No. 1 affected the production of superoxide anion radicals, whose production by all macrophages in the bronchoalveolar tract of mice was significantly higher on day 1 postinjection than on day 3 and higher than on days 1 and 3 after injection of preparation No. 2.

Effect of intramuscularly injected polyprenols on influenza virus infection in mice.

This study demonstrates the possibility of achieving a prophylactic effect by intramuscular injection of Abies sibirica polyprenols for the control of influenza virus infection in mice. One of the five polyprenol preparations tested, preparation N1, which had the lowest hydrophilic-lipophilic balance (8.6), produced a significant protective effect when injected in a dose of 2000 microg/mouse 2 days before aerosol infection of mice with influenza virus. A moderate protective effect was also observed using a second preparation, designated N2. One day after aerosol infection, animals pre-treated with 2000 microg doses of the polyprenol preparations or Hanks' solution showed no difference in the level of interferon accumulation in the lungs. Three days after injection of preparation N2 and N1, a significant decrease in spleen and thymus weights was, observed in the mice. One day after injection of these preparations, the number of lymphocytes in the bronchoalveolar tract of the mice exceeded almost twice that seen in mice treated with placebo. After 3 days, relative and absolute numbers of macrophages decreased, whereas those of lymphocytes increased significantly. Three days after the administration of preparations N1 and N2, macrophages became approximately twice as active in absorbing zymozan granules. Preparation N1 affected the system of superoxide radical anion production to a greater extent than preparation N2. The production of radical anions by the macrophages of the bronchoalveolar tract in the mice, 1 day after intramuscular injection of preparation N1, was significantly higher than that seen on day 3 and that induced by preparation N2 1 and 3 days after injection. These data indicate that emulsions of polyprenols that have relatively low hydrophilic-lipophilic balance, inhibit influenza virus infection in mice through a modulation of the host immune response.