Effect of Filipendula extract on the rhythmic organization of the daily dynamics of body temperature and behavioral activity in rats

Human interaction with environmental factors is considered in close connection with its repetitive endogenous processes which are based on biological rhythms. However, many factors of modern life contribute to the change in the temporary organization of life processes, leading to the development of desynchronosis. As a result of all this, the chronophysiological problem of human adaptation is actualized. It is known that timely diagnosis and correction of desynchronosis improves not only the performance of a person, but also his health. Desynchronosis is a "modern disease", and the problem of its correction deserves special attention. Lithium compounds play an important role in the synchronization mechanisms of circadian rhythms. It was found that the cation extends the periods of circadian rhythms, increases their amplitude, and also delays daily rhythm phases of the pulse activity of pacemaker neurons of suprachiasmatic nuclei (SCN), which are the main pacemakers in humans and mammals. All this leads to a slowdown in the "biological clock". The most promising is the search and expansion of drugs with a natural complex of macro- and microelements in the form of water and alcohol extracts from plant raw material accumulating lithium which has chronobiological activity. We established a high content of lithium in the representative of the family Rosaceae - Filipendula ulmaria L. (Max.). The content of the bioelement was about 19.9 mg/kg of the raw material, which in comparison with other plants indicated a very high concentration of the element in the raw material. After obtaining the dry extract of F. ulmaria, we found that the content of lithium was 90 mg/kg. The content of lithium in the extract of another type - F. vulgaris - was 22.9 mg/kg. Therefore, the aim of this research was to identify a specific chronobiological activity of lithium in lithium-containing extracts of two species - F. ulmaria and F. vulgaris. During the winter and summer solstices, we studied the influence of plant extracts on the rhythmic organization of the daily dynamics of body temperature and behavioral activity of rats. To obtain extracts of the plant, we collected F. ulmaria and F. vulgaris during the flowering phase in their natural habitat in the ecologically clean Kozhevnikovsky district of Tomsk region. The plants were dried at room temperature and stored until extract preparation. We applied the method of multiple percolations to get plant extracts. At the same time, we used crushed grass of these plants with a particle size of 3-5 mm and a moisture content of 13-15%. 20% ethyl alcohol was used as a solvent. The ratio of the raw material and extragent was 1:2, at each stage; the extraction was carried out after 24 hours. The resulting extracts were combined and released from mechanical inclusions. Then, the liquid extract was dried at a temperature of no more than 30-40 °C and dispersed. Animals were kept in natural light (natural seasonal desynchronosis develops in the conditions of solstices), at comfortable temperature of 22°C and with free access to food and water (standard diet). The open field method was used to determine the behavioral activity of rats. The body temperature was estimated by measuring rectal temperature. Primary chronograms were obtained for each animal for three consecutive days, measuring the abovementioned parameters every 4 hours. Statistical processing of chronobiological data was conducted by methods of one-way ANOVA and cosinor-analysis. After completion of the experiment, we determined lithium concentration in rat organs using the method of flame photometry. The statistical significance of the differences between the samples was established using the nonparametric Mann-Whitney U-test, and the statistical processing of chronobiological data was performed using the methods of variance analysis and cosinor-analysis. All procedures with animals were carried out in compliance with international rules and standards for treating laboratory animals that do not contradict the International Guiding Principles for Biomedical Research Involving Animals (Geneva, Switzerland; 1985). Our studies showed that both lithium-containing plant extracts had a rhythm-modulating action. However, these properties were more pronounced in F. ulmaria extract with high lithium content. During the winter and summer solstices, it accelerated the restructuring of behavioral activity and body temperature rhythms of rats in the free running state (See Table 1), and in summer the extract facilitated internal synchronization between rhythms (See Table 2). The rhythmic and modulating effect of the extract was directed to both behavioral and the temperature rhythms of two different, but interrelated oscillators in the animal body. It manifested itself in the accelerated restructuring of behavioral and temperature rhythms to the free running mode (See Table 1 and 2), characteristic of the winter and summer solstices. In addition, under the influence of F. ulmaria extract, the content of lithium in the organs of rats significantly increased in comparison with the intact group of animals, and under the influence of F. vulgaris it did not change (See Table 3). It is probable that the increase in the content of the cation in the organism of rats under the influence of F. ulmaria extract explains its expressed rhythm-modulating effects, as the rhythm-modulating properties of other inorganic and organic components of F. ulmaria extract (flavonoids, catechins, coumarins, tannins, cations of other metals and anions) are currently not known. We can assume the presence of similar properties in the above-mentioned biologically active substances, as F. vulgaris extract, without changing lithium content in the bodies of animals (See Table 2), demonstrated some rhythm-modulating activity in relation to the rhythm of behavioral activity (See Table 2). However, given the nature of this effect, it must have been a consequence of delaying the rhythms by the external cycle of the extract forced administration as a stress cycle. Thus, during the winter and summer solstices, F. ulmaria extract, increasing lithium content in the body of rats and accelerating the restructuring of behavioral activity and body temperature rhythms to the mode of endogenous oscillators, smoothed seasonal desynchronosis in the rhythm of animals. The paper contains 3 Tables and 27 References.

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