УДК: 615.8:614
The monograph presents the results of experimental and clinical- physiological studies of the influence of the Ukrainian phytocomposition “Balm Truskavets’” on the neuro-endocrine-immune complex, metabolism and physical performance with the aim of sanogenetic justification of its use to increase the effectiveness of rehabilitation of patients with maladaptation.
In an experiment on rats of both sexes, the authors found modulating effects of phytocomposition on post-stress changes in neuroendocrine- immune complex, metabolome, electrocardiogram (ECG), and gastric mucosa. First of all, it was confirmed that acute water- immersion and restraint stress (WIRS) causes in control animals an increase in sympathetic tone, blood levels of catecholamines and corticosterone, combined with a decrease in vagal tone and serum testosterone levels. Such a neuro-endocrine reaction is accompanied by damage to the myocardium and gastric mucosa, an increase in the percentage of macrophages, fibroblasts and Hassal’s corpuscles in the thymus, entropy in the spleen, theophylline-resistant T-lymphocytes, natural killer cells and polymorphonuclear neutrophils in the blood, as well as the activity of serum alanine transaminase and creatine phosphokinase. Instead, the mass of the spleen and the percentage of lymphoblasts in it, theophylline-sensitive T-lymphocytes and eosinophils in the blood, the content of malondialdehyde and cholesterol in the serum, as well as the catalase activity of serum and erythrocytes, decrease. Preventive use of phytocomposition, first of all, to one degree or another minimizes adverse post-stress deviations from the norm of most of the listed parameters, and even completely prevents deviations of 5 parameters. Secondly, it initiates an increase in the level of PTH and the activity of serum acid phosphatase, the percentage of reticulocytes in the spleen and the intensity of phagocytosis of blood neutrophils, but at the same time a decrease in their bactericidal activity, as well as the percentage of monocytes and B-lymphocytes in the blood. Thirdly, it potentiates the post-stress increase in sympathetic tone and damage to the gastric mucosa, as well as natural killers, on the one hand, and the decrease in vagal tone, the level of testosterone and malondialdehyde in the serum, as
well as the mass of the spleen – on the other hand. Fourthly, it reverses the catalase activity of erythrocytes and the entropy of the splenocytogram. Thus, phytocomposition has a generally favorable adaptogenic effect on the post-stress state of the neuro-endocrine-immune complex, ECG and metabolome. However, there are certain adverse effects as the so-called adaptation fee.
The authors found that the severity of damage to gastric mucosa significantly correlates with changes in ECG parameters, in particular, depression of the T wave and S-T joint, which indicate myocardial dystrophy. Further, it was found that such a connection is caused by the damaging effect on both targets of increasing the level of parathyroid hormone, as well as the production of aldosterone and catecholamines by enlarged adrenal glands. In addition, an increase in the level of corticosterone and sympathetic tone with a simultaneous decrease in vagal tone as well as serum calcitonin and testosterone cause damage only to the gastric mucosa, but not to the myocardium. Such a constellation of neuro-endocrine reactions to stressors (cold, immobilization, hunger, etc.) determines the severity of damage to the gastric mucosa and myocardium by 73%. Thus, the condition of the gastric mucosa and myocardium as essential targets of stressors is determined by the damaging and protective effects of adaptive hormones and the autonomic nervous system.
Next, metabolic and immune accompaniments of ECG and damage to gastric mucosa parameters were analyzed. It was found that Serum levels of Phosphates, Сatalase and α-LP Cholesterol as well as erythrocyte level of Potassium (as marker of Kalihistia) and Na,K-ATPase activity of the shadows of erythrocytes (as marker of membranes of myocardiocytes) are positively correlated with ECG markers of damage to myocardium such as T wave amplitude and ST junction, and negatively correlated with visual markers of damage to the gastric mucosa, i.e. reflect intactness (normality) of both targets of stressors – myocardium and gastric mucosa. Erythrocyte level of Sodium and serum levels of Potassium and Alkaline Phosphatase reflect the intactness of the gastric mucosa only. While serum level of Calcium reflects damage to the gastric mucosa. Taken together, the listed metabolic factors determine the morpho-functional state of the gastric mucosa and myocardium by 72% (R=0.851). Damage to the gastric mucosa and myocardium is more severe, the lower the bactericidal
activity of blood neutrophils, and the greater the mass of the thymus. The spleen mass and the content of fibroblasts in the thymus are negatively correlated only with the severity of damage to the gastric mucosa, while the percentages of reticulocytes and lymphoblasts in the spleen are positively correlated with it. Finally, the higher the percentage of macrophages in the thymus, the deeper the damage to the myocardium. The canonical correlation between the listed immune parameters and markers of the two targets of stressors is very strong (R=0.809). Thus, WIRS causes changes in the neuro-endocrine-immune complex, which lead to changes in the metabolome and damage to the gastric mucosa and myocardium.
The next goal was a detailed analysis of sexual dimorphism in these parameters in baseline and post stress situations. By the method of discriminant analysis was selected 23 variables (4 endocrines, 6 immune, 9 metabolic as well as 4 markers of damage in gastric mucosa and myocardium) whose constellation is characteristic for each group. The distance between the centroids of the major discriminant root of intact females and males as a measure of sexual dimorphism is 16.2 units. Acute stress increases it in control rats to 23.4 units, and in pretreated by phytoadaptogen – up to 29.4 units. Acute stress increases the severity of sexual dimorphism also in relation to variables, information about which is condensed in the minor root – from 0.99 to 2.29 units, while preventive use of phytoadaptogen limits it to 1.63 units. Thus, in intact rats, significant sex differences were found for a number of endocrine, immune, and metabolic variables, which increase under the influence of acute stress per se, and to an even greater extent against the background of preventive use of a phytoadaptogen.
In a separate experiment, the ability of phytocomposition to prevent the adverse actotropic effect of Naftussya bioactive water was investigated. It was found that the weekly use of Naftyssya bioactive water reduces the duration of swimming of rats to exhaustion by 30% compared to the daily water control. Addition of phytoadaptogen to Naftyssya softens its negative actotropic effect by up to -9%, and adding Balsam to daily water prolongs the maximum duration of swimming compared to the control by 11%. A positive correlation of the swimming test with 17-KS excretion and water diuresis was revealed, but a negative correlation with mineralocorticoid activity, spontaneous diuresis and
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neutrophils phagocytosis. Thus, phytoadaptogen reverses the adverse effects of Naftussya bioactive water on dynamic muscle performance in healthy rats by mitigating the decrease in the excretion of 17-ketosteroids and increased mineralocorticoid activity.
At the preparatory stage of clinical and physiological studies, the authors supplemented previously known data on the close relationship between the parameters of gas discharge visualization (GDV, electrophotonic) and neuroendocrine-immune complex with their own data on the relationship of EEG parameters with the energy and asymmetry of virtual Chakras, reconstructed on the basis of GDV parameters. It was found that the coefficients of canonical correlation between the EEG parameters and virtual Chakras Energy are in the interval 0,415÷0,564 and 0,358÷0,528 when registering without a filter and with a filter, respectively. Additional inclusion of HRV and endocrine parameters increases the strength of the canonical correlation to 0,768 and 0,772, respectively. The coefficients of canonical correlation between the EEG parameters and individual virtual Chakras Asymmetry are in the interval 0,284÷0,634 and 0,152÷0,458 when registering without a filter and with a filter, respectively. Integral coefficient of the canonical correlation is 0,820. The above data, taken together with the previous ones, state that between parameters of neuroendocrine-immune complex and GDV in general and virtual Chakras in particular, exist strong canonical correlation suggesting suitability of the latter method.
The purpose of next study was relationships between levels of major adaptation hormones and EEG&HRV parameters at human with maladaptation. Using the method of canonical correlation analysis, it was found that the level of triiodothyronine is determined by the constellation of 17 EEGs and 4 HRVs parameters by 87,5%. The rate of determination of the cortisol level by 14 EEGs and 3 HRVs parameters is 83,7%, and aldosterone by the other 14 EEGs and 3 HRVs parameters is 80,0%. Neuromodulation of testosterone and calcitonin levels is characterized by sexual dimorphism. With the same coefficients of determination (92,4%), the regression model for testosteroneemia in women included 15 EEGs parameters and no HRV parameters, instead testosteroneemia in men is modulated by other 11 EEGs parameters and one HRV parameter. The level of calcitonin in women is determined by 86,2% by the constellation of 9 EEGs and 2 HRVs parameters, while in men by 83,5% by the other 5 EEGs and 4 HRVs parameters. Thus, levels of the main adaptation hormones are accompanied by specific patterns of EEG and HRV parameters.
At the next stage, the immediate effects of a single use of the phytocomposition “Balm Truskavets’” on HRV, EEG and GDV parameters at 12 women and 62 men with dysfunction of neuro-endocrine-immune complex were investigated. Discriminant analysis revealed 26 EEG, 6 HRV and 7 GDV parameters characteristic of the baseline state and after consumption of phytocomposition or tap water. The use of balm causes the normalizing decrease of increased sympathotonic markers and the increase of decreased vagotonic markers. Physiologically favorable vegetotropic effects of the balm are accompanied by a further increase in the initially increased activity of β-rhythm-generating cortical and subcortical structures as well as activation of θ-rhythm-generating and inhibition of α- and δ-rhythm-generating nuclei whose initial activity was within normal limits. Neurotropic effects are accompanied by a decrease in fractality and entropy and an increase in the area of gas discharge image, as well as the energy of the first, fourth, fifth and seventh virtual Chakras. Thus, Ukrainian phytocomposition “Balm Truskavets’” causes favorable immediate neurotropic and biophysic changes at patients with dysfunction of neuro-endocrine-immune complex.
This provided the basis for studying long-term (9-day course) effects on parameters of neuro-endocrine-immune complex and biophotonics at 16 women and 24 men with maladaptation. A noticeable effect of the phytocomposition on 38 parameters was revealed, grouped into 6 clusters, of which 4 are enhancing and 2 are reducing. In particular, the reduced levels of the adaptation index and phagocytosis parameters increase significantly, instead, the increased levels of the strain index, testosterone, triiodothyronine, LF band HRV as well as two biophotonics parameters decrease, that is, there is a normalizing/beneficial effect. At the same time, normal levels of HRV-markers of vagal tone decrease, and cortisol and circulating catecholamines as well as the activity of β- and α-rhythm generating neurons increase, but within the normal range. Finally, there is a further increase in the upper limit levels of activity of δ-rhythm generating neurons. Thus, Ukrainian phytocomposition “Balm Truskavets’” exerts classical adaptogenic effects on parameters of neuroendocrine-immune complex as well as biophotonics and acupuncture in humans with maladaptation.
The discovery of the adaptogenic properties of the phytocomposition provided the basis for studying its ability to increase the effectiveness of rehabilitation at the Truskavets’ spa for patients with maladaptation. In the first study, it has been found that at patients with post-radiation encephalopathy standard balneotherapy increases the decreased level of T-helper lymphocytes, but further decreases the level of B-lymphocytes, glomerular filtration rate and PWC150, in combination with increased normal levels of blood creatinine and urea, as well as decreased levels of diastolic blood pressure and heart rate. This is accompanied by a further increase in the sympathetic tone and the leveling of the increased of ULF band HRV as marker of level of catecholamines and glucocorticoids. Additional use of phytocomposition limits the adverse effects of standard balneotherapy by modulating EEG and HRV parameters. Thus, phytocomposition «Balm Truskavets’» limits the adverse effects of standard balneotherapy at the Truskavets’ spa in patients with post- radiation encephalopathy.
The effect of standard balneotherapeutic complex of the Truskavets’ Spa on the physical performance of both rats and resort patients is ambiguous. Therefore, the search for means of correcting its adverse or neutral actotropic effects remains relevant. The results of the experiment on rats provided the basis for clinical testing of the effectiveness of the phytocomposition. At the preparatory stage, the relationships between PWC and the parameters of neuro-endocrine regulation as well as sexual differences in such relationships were investigated. The object of observation were 30 women and 30 men with maladaptation. For estimation of PWC a two-stage bicycle ergometry used. Parameters of EEG, HRV and adaptation hormones levels registered twice with an interval of 4 or 7 days. It was found that PWC levels in men are generally downregulated by cortisol, triiodothyronine, sympathetic tone, and θ-rhythm generating neurons, but upregulated by testosterone, calcitonin, vagal tone, and related α-rhythm generating neurons. In women, PWC levels are borderline downregulated by cortisol and aldosterone, but significantly upregulated by circulating catecholamines and β-rhythm generating neurons. The object of last observation were 40 women with chronic cholecystitis in remission phase, who came for rehabilitation at the Truskavets’ Spa. Registered PWC150, adaptation hormones levels, parameters of HRV, EEG, immunity, metabolism as well as GDV. Members of the control group received for two weeks standard balneotherapy: drinking of Naftussya bioactive water, application of Ozokerite, baths with mineral water. Members of the main group additionally received a phytoadaptogen. The analysis of individual changes revealed that normal levels of PWC in control group fell to the lower zone of the norm. Phytoadaptogen prevents PWC decrease. This is accompanied by the prevention of both a decrease in power spectral density (PSD) T4-θ EEG and VLF band HRV, leukocytes level as well as area and symmetry of GDV, as well as an increase in vagal tone and entropy of HRV as well as a rightward shift in the symmetry of the virtual first Chakra of GDV. In addition, phytoadaptogen reverses balneotherapy-induced moderate decrease in the frequency of α-rhythm, PSD O1-β, sympathetic tone, serum levels of catecholamines, testosterone and IgG, activity of Na,K-ATPase of erythrocyte shadows as well as Energy of the first, third and fourth virtual Chakras. Phytoadaptogen potentiates the reduction of PSD P4- β, IgM and cholesterol as well as initiates the reduction of δ-rhythm variability, PSD of α-rhythm in C3, C4, P4 and Fp2 loci, entropy in F4 locus as well as serum potassium while increasing in serum cortisol and calcitonin, blood B-lymphocytes levels as well as PSD Fp2-δ. Thus, the phytoadaptogen «Balm Truskavets’» prevents the adverse effect of the standard balneotherapeutic complex of the Truskavets’ Spa on PWC by, apparently, its neuro-endocrine effects.