Verkhovodova Y. Pharmacological evaluation of the effectiveness of extracts of Common Sage for the prevention and treatment of dysbiotic disorders associated with the use of antibacterial agents.

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0421U101977

Applicant for

Specialization

  • 14.03.05 - Фармакологія

11-05-2021

Specialized Academic Board

Д 64.605.03

National University of Pharmacy

Essay

In the dissertation of Verkhovodova Yu.V. the results of the pharmacological study of the effect of probiotics for the prevention and correction of intestinal dysbiosis were evaluated. The pharmacological properties of S. officinalis extracts in the aspect of possible further preclinical research and development on its basis of the leader compound for prevention and correction of antibiotic-associated dysbioses are given. The results of studies of different dosages and the effects associated with them, identifying the effective dose 50 mg/kg. Extracts of S. officinalis were investigated in the study (№1 – S. officinalis decoction, №2 – 50% S. officinalis leaf extract, №3 – 96% S. officinalis leaf extract, №4 – lysine complex, №5 – arginine complex, №6 – polysaccharide complex, №7 – purified complex, №8 – saponin complex, №9 – phenolic complex, №10 – flavonoid complex, №11 – hydroxylcinnamic complex). In the study of acute toxicity, it was found that all extracts belong to class V, almost non-toxic substances, which indicates the safety of the studied compounds. When studying the antimicrobial activity of the extracts, it was found that in most cases the extracts had an antimicrobial effect at the level of weakly active or active substances. The antimicrobial activity of the studied extracts is due to the presence in their composition of alpha and beta thujone, cineole, rosemary acid, phenolic and polyphenolic compounds. Extracts № 4 (complex of phenolic compounds with L-lysine), № 9 (phenolic complex), №10 (flavonoid complex), №11 (hydroxycinnamic complex) had the greatest antimicrobial effect, among them extract № 4 had the most powerful action. As a result of studying the effect of S. officinalis extracts on vascular permeability, it was found that phytoextracts showed a pronounced capillary-strengthening activity. Phytoextract №4 was slightly more active than extract №2. The most pronounced vasostrengthtening effect of phytocomplex was shown during increased vascular permeability caused by injection of formalin, carrageenan, histamine and protein. Staining of these papules was slowed by 2.0, 1.8, 1.7 and 1.7 times, respectively, compared with the control group. A study of the diuretic activity of S. officinalis extracts showed that all extracts, except the extract №7 (purified complex) have an antidiuretic effect at the level of adiurecrine. The extract № 4 (lysine complex) and 5 (arginine complex) have the most pronounced antidiuretic effect. This effect is due to the action of phenolic compounds – hydroxycinnamic acids, which predominate quantitatively on prostaglandins (antiprostaglandin effect). The identified characteristics of the extracts must be taken into account in the prospect of use in the presence of concomitant pathology, namely the need for dose adjustment or use in case of diabetes insipidus. Since most extracts showed an effect at a dose of 50 mg/kg, it was chosen conditionally therapeutic. As a result of the study, it was found that the studied extracts have the ability to stabilize cell membranes at the level of vitamin E in phytoextract №2 and exceed this activity in extract №4. The membrane stabilizing activity of extract №2 and extract №4 was 25% and 31.5%, respectively. As a result of research of the antiexudative activity of extracts of S. officinalis it is established that 9 of 11 extracts have the antiexudative effect. Extract № 5 and 6, which contain, respectively, L-arginine and polysaccharides have no antiexudative activity. During the entire study period of inflammation (4 hours) antiexudative effect was found in extracts № 1 (S. officinalis decoction), № 2 (50% S. officinalis extract), № 4 (lysine complex), № 11 (hydroxycinnamic complex). Extracts that reduced inflammation during 1-2 hours of the experiment were extracts № 7 (purified complex), № 8 (saponin complex), № 9 (phenolic complex), № 10 (flavonoid complex). Extract № 3 (96% S. officinalis extract) reduced inflammation during 3-4 hours of the experiment. It was found that the treatment of animals with the studied extracts of S. officinalis №2 and №4 at doses of 50 mg/kg on the background of experimental colitis led to the normalization of hematological parameters of peripheral blood in rats. The №4 extract more actively suppressed inflammatory processes in the mucous membrane of the large intestine, had a positive effect on the hematological parameters of the peripheral blood of rats, exceeding the effect of the comparison drug – rifaximin. Due to the effectiveness of the phytoextract №4 was more active in relation to the extract №2. A morphological study of the wall of the small and large intestine of rats was performed with intragastric application of extracts of S. officinalis in infectious colitis. The effect of extracts №2 and №4 at a dose of 50 mg/kg was studied.

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