STUDY OF PSYCHOMODULATING PROPERTIES OF ASTRAGALUS VULPINUS WILLD EXTRACT AGAINST THE BACKGROUND OF INFORMATIONAL OVERLOAD

Одной из главных задач современной фармакологии является разработка новых способов коррекции различных стресс-индуцированных состояний. Существенную роль в решении данной проблемы могут сыграть средства растительного происхождения. Интерес представляет Астрагал лисий (Astragalus vulpinus Willd) – растение крупного рода Астрагал семейства Бобовые, произрастающий в Астраханской области. Цель исследования – изучение влияния экстракта травы Астрагала лисьего на психоэмоциональное состояние животных в условиях информационного стресса (ИС). Материалы и методы. Эксперимент был выполнен на нелинейных крысах-самцах. Все манипуляции с животными проводили согласно правилам и принципам работы с лабораторными животными. Животные были разделены на группы: 1-я группа – контрольные крысы; 2-я группа – животные, подвергавшиеся воздействию ИС в течение 20 дней; 3-я группа – животные, получавшие на протяжении 14 дней внутрижелудочно жидкий экстракт Астрагала лисьего в дозе 50 мг/кг/ сут и подвергавшиеся воздействию ИС; 4-я группа – животные, получавшие препарат сравнения – фенибут в дозе 25 мг/кг в течение 14 дней на фоне ИС. Модель ИС представляла собой многоальтернативный лабиринт, в котором формировали пищедобывательные навыки. Психоэмоциональное состояние крыс изучали в «Суок-тесте» (СТ), который представляет собой комплекс нескольких классических поведенческих моделей. Результаты и обсуждение. Изучение поведения лабораторных животных в СТ в условиях информационной нагрузки показало формирование состояния повышенной тревожности, что проявлялось снижением двигательной и исследовательской активности белых крыс. Установлено, что экстракт Астрагала лисьего проявляет анксиолитическое и антидепрессивное действие, устраняя проявления тревожно-депрессивного состояния, развивающиеся в условиях информационного стресса. Заключение. Оценивая влияние экстракта Астрагала лисьего по сравнению с активностью фенибута, можно сделать вывод о том, что исследуемые средства устраняют изменения психоэмоционального состояния тревожно-депрессивного характера, демонстрируя практически сопоставимое анксиолитическое и антидепрессивное действие. Ключевые слова: информационный стресс, Астрагал лисий, экстракт, поведение, Суок-тест, тревожно-депрессивные нарушения, анксиолитическое действие, антидепрессивное действие

The tempo of modern living presupposes an intensive flow of information; a person is in a constant field of transmission and receiving various information (Internet, television programs, social networks, radio, newspapers, a constant increase in professional knowledge, etc.).A large daily flow of information often leads to informational overload, the so-called information stress [6,7,8].DOI: 10.19163/2307-9266-2018-6-3-255-268 Nowadays, a special attention is paid to the study of factors causing stress, the mechanisms of the development of stress reactions and methods for their correction [9].In spite of the fact that modern psychopharmacological drugs help to cope with increased anxiety and depressive disorders, with emotional stress disturbances in stress, one should also bear in mind their negative consequences for the organism, which are manifested by serious undesirable side reactions.
Therefore, the search for ways to correct these disorders arising in functional disorders of the central nervous system, continues to be one of the most important tasks of modern pharmacology.Herbal medicinal products, having a multi-profile effect, can play a significant role in solving this problem [10,11,12,13,14,15,16].The plants of the Astragalus genus of the Legume family (Fabaceae) are of great interest as new promising plant sources of biologically active substances.Biologically active compounds (flavonoids, alkaloids, coumarins, triterpene saponins, tannins, nitrogen-containing compounds, including non-protein amino acids, organic acids, polysaccharides, phenolic acids and their esters, glycyrrhizic acid salts, various vitamins, such as C, PP, E, mineral components, essential oils, mucus, gums, etc.) of the Astragalus genus [17,18,19,20,21,22] have a wide range of effects on various functional systems of the body.The results of numerous studies show that an Astragalus membranaceus (Fish.)Bunge extract, Astragalus glycyphyllos and Astragalus onobrychis L. extracts exhibit antihypoxic, anxiolytic, membrane-stabilizing, nootropic, antioxidant, antistress, immunomodulatory, immunostimulating and antimicrobial actions [23,24,25,26,27,28,29,30]. Nowadays, there are literature data on the study of the physiological activity of various representatives of the Astragalus genus.It has been proved that Astragalus glycyphyllos L. shows antimicrobial activity against gram-positive bacteria of Streptococcus pyogenes.It has been experimentally revealed that the dry extract of Astragalus membranaceus has a pronounced immunomodulating effect, which manifests itself in the increasing activity of humoral, cellular and macrophage immunity units in experimental immunosuppression.In addition, it has been shown that the phyto-drug in question stimulates the animals' orientation and research activity, having also nootropic and anxiolytic effect.The study of the properties of an aqueous extract of Astragalus galactites showed that the infusion of this plant has an antioxidant activity, the ability to protect the biological substrate from peroxide damage and regulate the activity of oxidase enzymes in blood plasma.It should be emphasized that species of this genus possess GABA-ergic activity.The protective effect of the extract and decoction of Astragalus Mongolian on convulsions caused by corazole, bicuculline and thiosemicarbazide [31,32,33,34,35] gives evidence of the participation of the GABAergic system in manifestations of its activity.A special interest as a promising source of biologically active compounds is represented by Astragalus vulpinus Willd, a plant of a large Astragalus genus of the legume family (Fabaceae), growing on the territory in the Astrakhan Region.
THE AIM of the study is the impact assessment of the Astragalus vulpinus Willd extract on the behavioral activity of laboratory animals against the background of informational overload (IО).
MATERIALS AND METHODS.The experiment was performed on nonlinear male rats (aged 6-8 mths), obtained from the vivarium of the technopark laboratory at FSBI "Astrakhan State Medical University", Ministry of Health of Russia.The organization of the investigation with the use of laboratory animals kept under standard conditions in the vivarium of FSBI "Astrakhan State Medical University", Ministry of Health of Russia, was carried out according to the rules adopted by the "International Convention for the Protection of Vertebrates used for Experimental and Scientific Purposes" (Strasbourg, 1986), the requirements of the Directive of the European Parliament and of the Council of the European Union for the protection of animals used for scientific purposes (2010/63 / EU), Order of the Ministry of Health of the Russian Federation No. 199n dated 01.04.2016 "On the approval of the Rules of Laboratory Practice" and the protocol of the Ethical Committee of the Federal State Educational Establishment "Astrakhan State Medical University" of the Ministry of Health of Russia No. 8 dated November 24, 2015.
Experimental groups.All the animals were synchronized by food with free access to water.The animals were divided into groups (n=10): Group 1 -the control rats which received intragastrically distilled water in the equivalent volume for 14 days; Group 2 -the animals exposed to IО for 20 days; Group 3 -the animals treated with intragastric liquid extract of Astragalus vulpinus Willd in the dose of 50 mg / kg /a day (this dose of extract corresponds to anhydrous substance and is calculated taking into account its residual moisture content) for 14 days and exposed to IО; Group 4 -the animals treated with the comparative drug of Phenibut in the dose of 25 mg / kg for 14 days against the background of informational overload (the substance was provided by Volgograd State Medical University of the Ministry of Health of the Russian Federation).The choice of the comparative drug is due to the data presented in the scientific literature proving that the plants of the Astragalus genus have a GA-BA-ergic activity underlying the antistress effect.
Object of study.The herb of Astragalus vulpinus Willd was collected during the period of active flowering in the Volga region of Astrakhan (Tatarskaya Bashmakivka village, "Baer" hillocks) and air-shadow shrouded.Biologically active compounds from the dried and ground raw material were extracted with a 60% solution of ethyl alcohol.The alcohol from the water-ethanol extract was distilled on a rotary evaporator Hei-VAP Value G3 (Germany).
Experimental model.In order to model informational overload, a multi-alternative labyrinth was used; there the formation of food-producing skills was formed [36].Prior to stressing, food deprivation was performed

Фармакология и клиническая фармакология Pharmacology and clinical pharmacology
for 23 hours.To complicate the task set before the rats, the structure of the labyrinth was changed every day.The evaluation of the psychomodulatory activity of the Astragalus vulpinus Willd extract was carried out on the basis of the results of studying the behavioral characteristics of the animals in Suok-test, a behavioral anxiety model recommended in modern psychopharmacology for screening medicines, including promising phyto-drugs [37].
Statistical processing of results.For statistical processing of the results obtained, Microsoft Office Excel 2007 and BIOSTAT 2008 Professional 5.8.4.3.with the definition of Student's t-test with the Bonferroni correction were used.The results were significant for p <0.05.
RESULTS AND DISCUSSION.The assessment of the behavior of stressed animals in the ST against the background of informational overload showed the formation of a state of increased anxiety, which was manifested by a decrease in motor and research activities in the two test compartments -both light and dark.So, in the light test compartment, the number of visited segments decreased by 58% (p<0.001) (Fig. 1), the number of research "peeping down" decreased by 27% (p<0.05) (Fig. 2).In addition, the duration of the animals exposed to the informational overload in the bright alley of the test, decreased by 32% (p<0.05), and the time of the latent period (LP) of their exit from the center, in contrast, increased by 70% compared with the intact individuals (p<0.01) (Fig. 3).In contrast to the control animals, in the group of the stressed rats in the light section of the "Suok-test" there was an increase in the frequency of "slipping" of the hind legs 12 times (p <0.001); an increase in the frequency of the number of short-term grooming acts was 2 times (p <0.01); an increase in the frequency of the number of fecal boluses was 9 times (p<0.001)(Fig. 4).In the dark compartment of the test, there was a decrease in the number of visited segments by 52% (p<0.001) (Fig. 1), the number of "peepings down" was decreased by 24% (p>0.05) and the number of directed head movements was decreased by 47% (p<0.05) in relation to the group of control individuals (Fig. 2).It should be noted that, in contrast to the control animals, in stressed rats in the dark compartment, the increase in "slipping" of the hind legs was 61% (p<0.01), the num-ber of acts of short-term grooming and fecal boluses was 2 times on average, and freezing was also detected there (Fig. 4).

Fig. 4 -Impact of Astragalus Willd extract on the anxiety level of animals in Suok-test against the background of informational overload
The assessment of complex ethological parameters in the light and dark compartments of the test showed that against the background of the IO, the average speed, the average distance between the stops and the average speed of movements compared to the control group, significantly decreased (Fig. 5).The administration of Astragalus vulpinus Willd to the animals, alongside with the elimination of the increased anxiety phenomena, led to the activation of research and locomotor behavior, which was confirmed by a statistically significant increase in the number of visited segments and stops in the compartment (Fig. 1), the number of "peeks down" (Fig. 2), transitions through the Central test area in both light and dark compartments.In addition, the administration of Astragalus vulpinus Willd extract to the animals exposed to the excessive informational load, led to the increase in the residence time in the light half of ST by 90% (p<0.01) and a decrease in the time of LP exit from the center by 51% relative to the indicators in the stressed individuals (p<0.001) (Fig. 3).It should be noted that in the light compartment of ST, the following indices influenced by the studied extract, decreased: the frequency of "slipping" of the hind legs by 76% (p<0.01),short-term grooming acts by 89% (p<0.001),fecal boluses by 50% (p<0.01) in comparison with the stressed rats.When analyzing behavioral indices of the animals against the background of the Astragal extract administration in the dark alley in ST, we registered a decrease in the number of "slips" of hind legs by 48% (p<0.01), the frequency of short-term grooming by 78% (p<0.001), a number of bolus acts by 40% (p<0.001), as well as shorter fade times (freezing) (Fig. 4).The admin-istration of Astragalus vulpinus Willd to the stressed animals led to the increase in complex ethological parameters (average speed, average distance between stops and average speed of movements) in both alleys of the test -light and dark (Fig. 5).Assessing the effect of Astragalus vulpinus Willd extract compared with the activity of Phenibutum, it can be concluded that the administration of the herbal medicinal products under study leads to the elimination of anxiety and depressive changes in the psycho-emotional state of animals, showing almost comparable anxiolytic and antidepressant effect.

Фармакология и клиническая фармакология Pharmacology and clinical pharmacology
CONCLUSION.Thus, the study of the behavior of rats in "Suok-test" against the background of informational overload showed the formation of a state of increased anxiety, which was confirmed by a decrease in motor and research activities of laboratory animals.Complex assessment of the behavior parameters of animals in Suok-test showed that the administration of Astragalus vulpinus Willd extract in against the background of informational overload has a corrective effect on the psychoemotional status, which manifested itself in the activation of the orienting-research component of behavior, as well as in the elimination of anxiety-depressive disorders in the behavior of white rats, hereby determining the necessity for further in-depth studies of the spectrum and mechanisms of pharmacological activity.Pharmacy & Pharmacology V. 6 N 3, 2018