Monooxygenase System and NO Metabolism in Liver Microsomes of Rats with Toxic Hepatitis and the Effect of Sesquiterpene Lactones.

We analyzed changes in activities of enzymes of phases I and II of xenobiotic biotransformation and parameters of NO metabolism in liver microsomes of rats with toxic CCl4-induced hepatitis after a 14-day course of sesquiterpene lactones from Artemisia leucodes (10 mg/kg). It was found that toxic hepatitis was associated with significant inhibition of NADPH-cytochrome c-reductase, benzo(a)pyrene hydroxylase, and NADPH-diaphorase, reduced cytochrome P-450 content, and enhanced induction of nitrate/nitrite reductase with accumulation of NO metabolites in the liver. Administration of sesquiterpene lactones stimulated activity of the studied components of the cytochrome P-450 system and promoted recovery of the NOergic system components; the effects were most pronounced in 7 and 14 days after treatment.

[STEROIDAL GENINS AND GLYCOSIDES OF SPIROSTAN AND FUROSTAN SERIES AS ANTHELMINTHIC AGENTS].

It was established that steroidal genins and their glycosides of the spirostan series and (especially) furostan series show anticestodal activity against Hymeiolepis nana species. Search for anthelminthic agents in the indicated series of compounds is a promising direction of research.

[EXPERIMENTAL ASSESSMENT OF THE IMMUNOTROPIC EFFECTS OF ARABINOGALACTAN AND PECTINACEOUS POLYSACCHARIDES ISOLATED FROM FERULA KUCHISTANICA.]

It is established that arabinogalactan and pectinaceous polysaccharides isolated from Ferula kuchistanica are capable of stimulating a primary immune response in mice by increasing the number of antibody-producing cells in the spleen in response to immunization with sheep red blood cells in both intact animals (on average by 51.0%; p < 0.005) and those with secondary immunodeficiency caused by irradiation (on average by 164.4%; p < 0.005). The treatment with compounds studied also significantly increased the functional condition of cells of the mononuclear phagocyte system (on average by 27.0%; p < 0.005).

[Stress-protective properties of phytoecdysteroids].

Introduction of phytoecdysteroids (ecdysterone, turkesterone and ñyasterone) to rats subjected to prolonged immobilization stress significantly decreased involution of the thymus and spleen, contributed to normalization of increased mass of adrenal glands, and restored their content of ascorbic acid and cholesterol. In the liver of stressed animals, phytoecdysteroids prevented sharp decrease in the glycogen concentration, showed a clear trend toward normalization of the ratio of lactic and pyruvic acids, maintained homeostasis of macroergic phosphorus compounds, and increased the activity of antioxidant enzymes that inhibit lipid peroxidation. With respect to the stress-protective activity, the studied phytoecdysteroids are in some cases superior to eleutherococcus extract.

[Estimation of the hypoglycemic effect of phytoecdysteroids].

A series of phytoecodysteroids, including alpha-ecdysone, 2-deoxy-alpha-ecdysone, and 2-deoxyecdysterone isolated from Silene praemixta, integristerone A and ecdysterone isolated from Rhaponticum carthamoides and 22-acetylcyasterone and turkesterone isolated from Ajuga turkestanica, exhibit a pronounced hypoglycemic effect in experiments on intact male rats. The most active compounds--ecdysteron and turkesterone--also produce an expressed hypoglycemic effect in animals with model hyperglycemia induced by the administration of glucose, adrenalin and alloxan. Phytoecdysteroids are substances possessing protein-anabolic activity and are somewhat similar to steranobols in this aspect. Phytoecdysteroids exhibit unidirectional effect and are well comparable with steranabol actionon the carbohydrate metabolism.

[Pharmacological effects of Abies polyprenols and carsil on alcohol-induced hepatitis].

The introduction of polyprenols isolated from fir (Abies) tree in male rats weighing 170 - 180 g with alcohol-induced hepatitis favored reduction in hepatocyte cytolysis and cholestasis and led to an improvement of the protein- and glycogen-synthesizing function of liver. A clear tendency to normalization of the maintenance of total lipids, triglycerides and phospholipids and the inhibition of lipid peroxidization processes in the damaged organ was observed. The introduction of Abies polyprenols also improved the process of bile secretion and its chemical composition.

[The efficacy of ecdystene versus metronidazole in the treatment of lambliasis].

Ecdisten, the drug designed on the basis of the phytoecdisteroid ecdisterone isolated from Rhaponticum carthamoides, was used in the treatment of first diagnosed (primary) and persistent (resistant to traditional lambliacides) lambliasis. A control group received metronidazole. Daily parasitological monitoring of lamblia elimination while treating with ecdisten in a daily dose of 20 mg for 10 days indicated the absence of lamblia in 70% of the patients with primary lambliasis on days 3 to 5; in the remaining 30%, parasitic elimination was accomplished on days 6-7 of treatment. In the patients with persistent lambliasis, the parasites were eliminated in 43.2% of cases on days 4-5 and in 56.6% on days 6-10. Metronidazole just on the second day of therapy caused parasitic elimination in 28.6% of the patients. All the patients were freed from lamblia within 5 days. Improvement occurred more rapidly with ecdisten treatment; immunological normalization was seen when ecdisten was used. Seven-ten-day course of ecdisten is sufficient for the treatment of primary lambliasis; when persistent lambliasis is treated, its course should be prolonged. If required, the course may be repeated, by increasing the daily dose.

[Effects of phytoecdysteroids and bemithyl on functional, metabolic, and immunobiological parameters of working capacity in experimental animals].

Influence of phytoecdysteroids (isolated from Ajuga turkestanica) and bemithyl on the duration of swimming of laboratory animals (mice, rats) under various experimental conditions was studied. Turkesteron and cyasteron increased duration of dynamic work carried out by animals, decreased fatigue, and accelerated recovery processes to a greater extent that did bemithyl. The positive influence of phytoecdysteroids on the working capacity is based on the activation of metabolic processes in skeletal muscles, directed to support the homeostasis of energy production. Phytoecdysteroids also accelerate recovery of immune reactions which are decreased due to the exhausting physical work.

Molecular modelling and QSAR analysis of the estrogenic activity of terpenoids isolated from Ferula plants.

The relationship between chemical structure and estrogenic activity in a series of terpenoid esters with aromatic and aliphatic acid substituents isolated from Ferula plants, was studied. The fragments of the terpenoid structure that are potentially responsible for estrogenic activity were revealed. A quantitative structure-estrogenic activity study has been carried out using the QSAR approach with use of data derived from quantum-chemical calculations as well as data generated from three-dimensional structures of terpenoids. A number of molecular descriptors was obtained from the density functional theory (DFT) at the B3LYP/6-31G(d, p) level of calculation. Comparative analysis of the quantum-chemical computational data was also performed to confirm hypothesis concerning importance of the distance between the oxygen of alcohol hydroxyl group and the functional group in the para-position of the benzene ring (the hydroxyl or methoxy group). Use of the Genetic Algorithm in the QSAR analysis allowed the structural and physicochemical parameters of the terpenoids responsible for estrogenic activity to be determined. A significant QSAR model was obtained with an r(2) value of 0.892. The resulting model showed a reliable dependence of estrogenic activity of the terpenoids on such parameters as molecular shape, number of phenolic groups, surface polarity and the energy of the highest occupied molecular orbital.

[Experimental and clinical evaluation of the efficacy of ecdysten in the treatment of hepatitis]. / éksperimental'no-klinicheskaia otsenka effectivnosti primeneniia ékdistena pri lechenii gepatita.

The properties of ecdysten, an exdysterone-based preparation, were studied under experimental (of heliotrine induced hepatitis model in rats) and clinical (chronic viral hepatitis B) conditions. A 2-week treatment with ecdysten in a daily dose of 5 mg/kg (p.o.) significantly improved the state of rat liver, as manifested by normalization of the enzymatic activity of blood serum, stimulation of the protein and glycogen synthesis, inhibition of lipid peroxidation, and activation of all chains of microsomal oxidation of hepatocytes. The inclusion of ecdysten into a complex therapy scheme for patients with chronic viral hepatitis B (5-mg tablets twice per day over a period of 30 days) substantially improved the clinical and biochemical indices of the functional state of liver, positively influenced the humoral and cell immunity and the resistance factors, and normalized the course of autoimmune processes accompanying the liver pathology.

[Cardiotropic activity of total bufadienolides from the poison of Central Asian toad Bufo viridis]. / Kardiotropnaia aktivnost' summy bufadienolidov iz iada sredneaziatskoi zhaby Bufo viridis.

The sum of bufadienolides (bacagin) isolated from the poison of Bufo viridis toad occurring in Central Asia produces a selective strophanthin-K-like action upon the heart function, increasing myocardial contractility, retarding cardiac rhythm, and positively influencing the parameters of myocardial metabolism. The mechanism of realization of the positive ionotropic effect of bacagin is probably related to the ability of increasing the basal level of cytosol calcium at the expense of inhibiting the activity of Na+/K(+)-ATPase and, to some extent, Ca(2+)-ATPase in endoplasmic reticulum.

[Ecdysten in the treatment of giardiasis]. / Ekdisten v lechenii liamblioza.

The drug ecdisten as tablets is the natural compound ecdisteron was extracted from Rhaponticum carthamoides (Willd.) Jljin. Ecdisten was tested in the treatment of 32 and 3 patients with persistent and acute giardiasis, respectively. A ten-day course of ecdisten, 5 mg 3 or 4 times a day, resulted in a clinical and parasitological recovery in 22 (68.7%) and 3 patients, respectively. After the reuse of a ecdisten course in 4 patients with persistent giardiasis wherein its initial dose was increased, recovery was achieved in 3 cases, the efficacy of the agent was 78.1%. Ecdisten should be used to treat giardiasis, in its chronic pattern or resistance to conventional giardicial agents.

[Experimental study of pharmacotherapeutic effect of phytoecdisteroids and nerobol in toxic liver damage]. / Farmakoterapevticheskii éffekt fitoékdisteroidov i nerobola pri toksicheskom porazhenii pochek v éksperimente.

Phytoecdysteroids ecdysteron and turkesteron isolated from Ajuga turkestanica (Rgl.) Brig. decrease the manifestations of uremic intoxication in rats with experimental renal pathology induced by a nephrotoxic mixture (containing uranyl acetate and glycerol). Injected in a dose of 5 mg/kg, the drugs restore glomerular filtration level, favor the disappearance of the albuminuria and normalize urinary sediments. The nephroprotector effect of the phytoecdysteroids studied resembles the action of a steroidal anabolic drug nerobol.

[The results of experimental study of phytoecdysteroids as erythropoiesis stimulators in laboratory animals]. / Rezul'taty eksperimental'nogo izucheniia fitoékdisteroidov v kachestve stimuliatorov eritropoéza u laboratornykh zhivotnykh.

Phytoecdysteroids alpha-ecdysone, 2-desoxyecdysterone, ecdysterone, sileneoside A, and turkesterone isolated from Rhaponticum carthamoides (Willd.) IIjin, Silene brahuica Boiss and Ajuga turkestanica (Rgl.) Repeated administration of brig increased the content of erythrocytes and hemoglobin in the blood of intact rats. The most active of them--ecdysterone, sileneoside A, and, particularly turkesterone, cause also a marked effect on red blood regeneration in hemotoxic phenylhydrazine anemia. In its capacity for simulating erythropoiesis turkesterone resembles the well-known steroidal anabolic drug nerobol.

[Comparative study of the effect of cycloartane and cardiac glycosides on various parameters of myocardial metabolism in animals]. / Sravnitel'noe izuchenie vliianiia tsikloartanovykh i serdechnykh glikozidov na nekotorye pokazateli metabolizma miokarda u zhivotnykh.

Administration of cycloartane (askendoside D-10 mg/kg, cyclosiversioside F-25 mg/kg) and heart glycosides (strophanthin K-0.36 mg/kg, celanide-1 mg/kg) for 3-10 days is found to exert unidirectional effect on the indices of carbon, lipid and adenine nucleotide metabolism in animal myocardium under study. Glycogen and ATP content increases under parallel decrease of lactate and nonesterified fatty acid content. Differences in the effect of cycloorthane and heart glycosides and especially on the indices of myocardial carbon metabolism were registered under more prolonged administration. Administration of heart glycosides in contrast to cycloorthane ones promotes a decrease of glycogen level and redox potential and increase of lactate content.

[The effect of proanthocyanidins from Alhagi pseudoalhagi (M. B.) Desv on the course of experimental myocardial infarct]. / Vliianie proantotsianidinov iz iantaka lozhnogo na techenie éksperimental'nogo infarkta miokarda.

Intravenous proantocyanidin isolated from Alhagi pseudoalhagi (M. B.) Desv, 5-10 mg/kg, has no effects on the general hemodynamics and cardiac contractility of intact rats and rabbits. The agent given to animals with experimental myocardial infarction reduces serum creatinine phosphate levels and lipid peroxidation both in the myocardium and serum, as estimated by the amount of malonic dialdehyde and dienic conjugates), normalizes free fat acid content and cardiac phospholipid spectrum. At the same time the size of a myocardial necrotic zone became diminished.

[Effect of phytoecdysteroids and nerobol on parameters of carbohydrate and lipid metabolism and phospholipid spectrum of liver mitochondrial membrane in experimental diabetes mellitus of rats]. / Vliianie fitoékdisteroidov i nerobola na pokazateli uglevodnogo i lipidnogo obmenov i fosfolipidnyi spektr membran mitokhondrii pecheni krys pri éksperimental'nom sakharnom diabete.

Phytoecdysteroids: ecdysterone and turkesterone, introduced orally to male rats with the body mass 180-120 g in a dose of 5 mg/l kg of mass and nerobol in a dose of 10 mg per 1 kg of the mass for 15 days against a background of the developed alloxan diabetes cause a considerable decrease in the content of free fatty acids of the blood serum, sharply increased after the subcutaneous injection of alloxan to the animals (150 mg per 1 kg of the mass). The content of glycogen, malonic dialdehyde, pyruvic acid and calcium transporting function of the liver mitochondria are also normalized. These changes are closely interrelated (and may be mutually conditioned) with the preparation-induced reduction of phospholipid spectrum of the liver mitochondrial membranes pathologically changed owing to insulin insufficiency. In this case phytoecdysteroids in the first turn normalize the fractions of phospholipids which play the structural role in the mitochondrial membranes, and nerobol normalizes the level of minor and monoacylic phospholipids.

[Effect of salvipholin on the carbohydrate and lipid metabolism in the rat liver in alloxan diabetes]. / Vliianie sal'vifolina na uglevodnyi i lipidnyi obmen v pecheni krys v usloviiakh alloksanovogo diabeta.

Peroral administration of salvipholin in a dose of 50 mg/kg to intact male rats (the body weight 180-220 g) had a positive effect on the carbohydrate-lipid metabolism in the liver and blood serum of animals. Administration of the same dose to rats with alloxan diabetes induced a significant decrease in the content of glucose, free fat acids, triglycerides and lysophospholipids of the liver and blood serum. The level of these components has sharply increased after subcutaneous alloxan administration in a dose of 150 mg/kg, the content of glycogen and pyruvic acid being normalized and insulin deficiency removed. These changes are closely related to salvipholin-promoted restoration of phospholipid spectra of the blood serum and liver of experimental animals disturbed under conditions of insulin deficiency. The possible mechanism of the salvipholin action is analyzed.

[An experimental study of the hepatoprotective properties of phytoecdysteroids and nerobol in carbon tetrachloride-induced liver lesion]. / Eksperimental'noe izuchenie gepatoprotektornykh svoistv fitoékdisteroidov i nerobola pri porazhenii pecheni chetyrekhkhloristym uglerodom.

The phytoecdisteroids ecdisterone, turkesterone and cyasterone were administered in a dose of 5 mg/kg per os to rats with hepatitis induced by subcutaneous injections of CCl4. Similarly to the anabolic drug nerobol (10 mg/kg), the above agents not only interfere with the manifestation of the hepatic action of CCl4 (in this case the effect of the phytoecdisteroids is more remarkable) but also favour a more rapid normalization, as compared to the control, of functional and metabolic disorders in the liver. The phytoecdisteroids and nerobol noticeably stimulate the recovery of bile secretion, the synthesis of bilirubin and bile acids, cholesterol excretion.

[Hypoglycemic activity of bicyclic diterpenoids of the clerodane series as compared to adebit and maninil]. / Izuchenie gipoglikemicheskoi aktivnosti bitsiklicheskikh diterpenoidov klerodanovogo riada v sravnenii s adebitom i maninilom.

Biocyclic diterpenoids--salvin, salvicin and salvifolin, administered per os to rats at a dose of 50 mg/kg show marked hypoglycemic activity in intact animals as well as in animals with experimental hyperglycemia developing against a background of GTT (3000 mg/kg intraperitoneally) or alloxan (150 mg/kg subcutaneously). They are superior to adebit but inferior to maninil. Prophylactic and therapeutic administration of these compounds ensure the preservation of islet beta-cells in animals with alloxan diabetes.