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Herbal products toxicology and clinical pharmacology

Phytotherapy for the correction of excess body weight is widely used. However, a comprehensive study of herbal preparations on the organism of model animals has been carried out only for a few plant species. Supplementing the diet of rats with closely related sage species (Salvia officinalis L. and S. sclarea L.) against the background of high-fat hypercaloric diet triggered multidirectional changes in their metabolism. The addition of crushed dry shoots of S. officinalis to the diet of animals led to a sharp increase in their body weight (up to 130.8% of the initial one in 30 days of the experiment). The body weight of the rats treated with S. sclarea for 30 days increased only up to 103.8% of their initial weight and was lower than in the control group. Addition of S. officinalis caused an increase in daily weight gain up to 253.1% of the control group, and S. sclarea – its decrease to 27.8% of the daily weight gain in the control group. In the S. officinalis group, the relative weight of the brain, spleen, and thymus decreased, while in the S. sclarea group, the relative weight of the thymus decreased and that of the colon increased. Under the influence of S. officinalis, the concentration of urea, total bilirubin, and triglycerides in the blood plasma of male rats decreased and the concentration of total protein and the activity of alkaline phosphatase increased. While consuming S. sclarea shoots, there was an increase of alkaline phosphatase activity in the rats’ blood, but atherogenic index (23.1% of the level of the control group) sharply dropped due to an increase in the concentration of high-density lipoprotein cholesterol (286.9% of the control) and a decrease in the concentration of low-density lipoprotein cholesterol (67.7% of control). In rats feeding on S. sclarea shoots, we observed a decrease in the concentration of triglycerides in the blood (39.9% of the control), a decrease in the activity of gamma-glutamyl transferase (62.8%), and an increase in the Ca/P ratio (132.5% of the control group). No significant changes were observed in CBC and WBC differential of male rats when eating S. officinalis and S. sclarea shoots. According to the results of the open field test, the physical and orientational activity of male rats under the influence of S. officinalis significantly decreased by the end of the experiment. Emotional status of rats, on the contrary, decreased when they ate dry crushed shoots of S. sclarea in the composition of the food. Thus, excess body weight of rats in the conditions of hypercaloric diet led to more pronounced deviations from the norm while consuming dry crushed shoots of S. officinalis. The addition of S. sclarea dry crushed shoots to the animals’ diet normalized the body weight in comparison with the control group, reduced the negative manifestations of obesity at the biochemical and organismal levels. In this regard, the substances that contains S. sclarea should be carefully studied for anti-atherosclerotic activity, and tea supplemented with S. sclarea shoots can be recommended as a corrective supplement in the diet of overweight people.

Effect of Salvia officinalis and S. sclarea on rats with a high-fat hypercaloric diet

The pharmacological effects of medicinal plants play a primary role in the mild correction of body weight in humans and animals, reducing the accumulation of fat in their bodies during a state of obesity. Origanum vulgare L. and Scutellaria baicalensis Georgi are widely used as food additives and medicinal plants, but their comprehensive physiological evaluation in model animals in a state of obesity has not been carried out. In a 30-day laboratory experiment on male rats which had developed obesity through a hypercaloric diet, the effects of adding the dry crushed grass O. vulgare or dry crushed roots of S. baicalensis to their feed was evaluated. During the experiment, the rats fed with O. vulgare increased in body weight to only 105.5% of their initial weight, while the body weight of the control group increased to 111.5%, and that of animals fed on S. baicalensis increased to 124.0% of their initial body weight. The average daily increase in the rats’ body weight when O. vulgare was added to their diet decreased to 205 mg/day, and when S. baicalensis was added, on the contrary, it increased to 1417 mg/day, compared to 700 mg/day among the control group. Under the influence of O. vulgare, the lipid metabolism of the rats normalized: the atherogenic index decreased to 33.7%, compared with the values of the control group, due to an increase in the concentration of high-density lipoproteins from cholesterol. The concentration of triglycerides decreased, and the concentration of glucose decreased. The roots of S. baicalensis being added into the diet of rats increased the activity of alkaline phosphatase and decreased the concentration of urea. The atherogenic index also decreased (by up to 35.5% in the control group) and the concentration of high-density lipoprotein cholesterol increased, while the concentrations of triglycerides and glucose decreased. The physical activity of the rats showed a slight tendency to decrease when both O. vulgare and S. baicalensis were added to their diet. Both plant species contributed to a decrease in the emotional status of animals, which was most pronounced when the O. vulgare grass was added to the feed. The results of the study demonstrate the potential of the use of O. vulgare and S. baicalensis as herbal supplementations for the correction of hyperlipidemia and type-2 diabetes mellitus in overweight patients.

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Effects of Origanum vulgare and Scutellaria baicalensis on the Physiological Activity and Biochemical Parameters of the Blood in Rats on a High-Fat Diet

Dose-dependent changes in protein metabolism in the blood and hematological parameters of pregnant rats under the effect of vanadium citrate are presented in the article. The animals were divided into five groups: group I – non-pregnant females, II – pregnant females consuming pure water without additives, III, IV, V – females which during the mating and pregnancy period received the solution of vanadium citrate at concentrations of 0.03, 0.125 and 0.50 μg V/mL water. The research findings show that in pregnant animals of group II, the level of urea and alkaline phosphatase activity increased, meanwhile aspartate aminotransferase activity decreased, as compared to the non-pregnant females of group І. The levels of total protein and albumin decreased; however, the content of β-globulins increased in the pregnant animals of group II, as compared with that in group I. Also, in the rats of group II, there was a decrease in hemolysis time, total content of erythrocytes and hemoglobin, the content of old and mature erythrocytes, while the content of young erythrocytes increased, as compared to group I. The platelet content and thrombocrit in rats of group II increased in comparison with group I. The content of leukocytes and lymphocytes in pregnant animals of group II decreased, while the content of granulocytes increased, in contrast to non-pregnant rats. Under the effect of vanadium citrate at concentrations of 0.03–0.50 μg V/mL, there was a significant increase in the maximum number of prohemolized erythrocytes, the time of maximum hemolysis was delayed by 0.4–0.6 min, as compared with the pregnant rats of group II. This did not affect the time of total hemolysis in rats of groups III and V, as compared with the pregnant animals in group II. Under the effect of vanadium citrate, an increase in the content of young erythrocytes was observed, as compared with group II. The hemoglobin content decreased at the concentration of 0.125 μg V/mL, while at the concentration of 0.50 μg V/mL it increased, as compared to the pregnant animals of group II. Also, under the effect of vanadium citrate there was a decrease in the mean hemoglobin concentration in the erythrocyte. In pregnant animals fed with vanadium citrate solutions, the platelet content and thrombocrit, the relative width of platelet distribution by volume decreased, as compared with the pregnant rats of group II. The content of leukocytes, lymphocytes and granulocytes under the effect of vanadium citrate increased, as compared with the pregnant animals in group II. Under the effect of vanadium citrate at the concentration of 0.03 μg V/mL, the level of albumin, creatinine and aspartate aminotransferase activity increased in blood plasma in comparison with group II. Meanwhile, at the concentration of 0.125 μg V/mL, the relative content of γ-globulins and aspartate aminotransferase activity increased, alkaline phosphatase activity and urea level decreased in comparison with group II. However at the concentration of 0.50 μg V/mL, the relative α- and γ-globulins content and aspartate aminotransferase activity increased, at the same time, the relative β-globulins content and urea level decreased in comparison with group II. Therefore, vanadium citrate normalizes the indicators of protein metabolism during pregnancy, thus it can be considered as a potential dietary drug for the pregnant.

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Hematological parameters and protein metabolism in the blood of pregnant rats under the effect of vanadium citrate

SUMMARY Research background Rhodiola rosea (golden root) and Punica granatum (pomegranate), as well as a number of other species of medicinal plants, exert an array of biological effects: adaptogenic, antioxidant and anti-inflammatory. However, there are not enough contemporary studies of their influence on metabolic processes, especially in cases of imbalanced diet. Lipid dysregulation is the main reason for many diseases, including obesity, cardiovascular disorders, non-alcoholic fatty liver disease, hypertension, atherosclerosis and insulin resistance. Recently, a growing amount of evidence has suggested the positive effects of certain natural nutrients on lipid metabolism. The work aims to define the general effect of golden root rhizome and pomegranate peel on physiological activity and metabolic processes in model animals fed with excessively fat diet. This study is relevant for the development of drugs and food additives for treatment and prophylaxis of metabolism disorders. Experimental approach In a 30-day experiment, we determined the effect of golden root (Rhodiola rosea L.) rhizome and pomegranate (Punica granatum L.) peel on the physiological activity and metabolic processes of 24 laboratory rats consuming a high-fat diet. The physical activity was evaluated according to the mass gain of animals and change in the relative mass of the internal organs, and also the functional conditions of the central nervous system, as demonstrated by the indicators of the locomotor activity and emotional status, determined in the open field test. The influence on the metabolic processes was revealed by biochemical and clinical blood analyses. Results and conclusions Body mass of rats fed with golden root (R. rosea) reached 125.8 % of the initial body mass; when fed on pomegranate (P. granatum), it reached 123.9 %; and the control group reached only 111.5 % of the initial body mass. The rhizomes of R. rosea in the diet of male rats during the month of the experiment did not cause significant changes in the relative organ mass, and the pomegranate peel fruits led to a decrease in the thymus relative mass, as well as liver and brain. R. rosea rhizomes in the rats' diet led to an increase in the activity of alkaline phosphatase, and also to a decrease in the concentration of urea and urea nitrogen. Diet supplemented with R. rosea also contributed to a strong decrease in plasma concentrations of bilirubin and triglycerides (up to 57.0 % compared with the concentration in the control group). The rhizomes of R. rosea contributed to an unreliable decrease in the atherogenicity index. The pomegranate peel also greatly increased alkaline phosphatase activity and reduced plasma triglyceride concentrations. In addition, in rats consuming the peel of P. granatum, blood glucose concentration decreased. Under the influence of P. granatum, a strong increase in the atherogenic index of plasma (up to 518.6 % of the control) was observed because of a decrease in the concentration of high-density lipoproteins (up to 57.1 %) and a simultaneous elevation of the concentration of low-density lipoproteins (up to 158.3 % of the control). Open field test between groups remained without significant changes. Novelty and scientific contribution The results indicate that the rhizome of R. rosea and peel of P. granatum are safe as food additives to high-fat diet and did not cause pathological changes and side effects, and at the same time significantly influence the metabolic processes (lipid and carbohydrate). Our study theoretically substantiates the use of R. rosea rhizome and P. granatum peel for the production of nutraceutical and pharmacological products for the correction of metabolic disorders of people and animals. Doses and periods of their application require further research.

https://doi.org/10.17113/ftb.61.02.23.7913

Effect of Rhodiola rosea Rhizome and Punica granatum Fruit Peel on the Metabolic Processes and Physiological Activity of Rats Fed with Excessively Fat Diet

Plant food additives are becoming more and more popular and broadly applied products, though the information on risks they poses to the organism is limited and contradictive. Obesity and overeating are some of the commonest health issues around the world, and people are increasingly consuming workability-enhancing preparations as a simple and fast method of weight control. The plant-based preparations are considered less harmful than the synthetic chemical ones. Lavandula angustifolia Mill., Melissa officinalis L. and Vitex angus-castus L. are broadly used as food additives and medicinal plants, despite the fact that their complex physiological assessment on model animals in the conditions of obesity has not yet been performed. We carried out a 30-day experiment on white male rats. All the animals were given high-fat diet, and the experimental animals, in addition to this diet, received 5% crumbled dry herbs of L. angustifolia, M. officinalis or V. angus-castus. Taking into account the overall amount of consumed food, the mean daily gain in body weight; at the end of the experiment, we determined the index of the weight of the internal organs, biochemical and morphological blood parameters. At the beginning and the end of the experiment, the rats were examined for motor and orienting activities, and emotional status. Rats on high-fat diet gained up to 112% body weight by the end of the experiment, while rats that had received V. angus-castus gained up to 119%, M. officinalis – 135%, L. angustifolia – 139%, compared with the initial body weight. Addition of medicinal plants to the diet led to increase in average daily weight increment, significantly and reliably after consuming lavender and lemon balm, less significantly and unreliably after eating Vitex. L. angustifolia and M. officinalis reduced the relative brain weight, and ingestion of L. angustifolia and M. officinalis caused notable decrease in the relative mass of the thymus (down to 58% and 47% of the relative weight of thymus in animals of the control group respectively). Also, these plants decreased the motor and orienting activities of the rats by the end of the experiment. As for the biochemical parameters of blood, the activity of alkaline phosphatase significantly increased to 406% following consumption of Melissa, to 350% after consuming lavender, and to 406% after Vitex, compared to the control group. Furthermore, all the groups were observed to have increased AST and ALT activities. Intake of lavender led to increases in cholesterol (to 125%) and LDL cholesterol (to 228%), whereas the groups that consumed lemon balm were observed to have decreases in urea nitrogen (to 79%), totalbilirubin (to 63%) and triglycerides (to 63%). Addition of Vitex led to increase in the index of aterogenecity against the background of notable fall in HDL cholesterol (to 52% of the control group). The medicinal plants also contributed to the normalization of the glucose level. Morphological analysis of blood revealed no significant changes, except heightened content of monocytes in blood, which is characteristic of all groups, including the control. Effects of L. angustifolia, M. officinalis and V. angus-castus on the organism of rats on excessive-fat diet require additional histological, histochemical and immunological surveys.

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M. A. Lieshchova

Papers

Influence of Lavandula angustifolia, Melissa officinalis and Vitex angus-castus on the organism of rats fed with excessive fat-containing diet