In the pharmacotherapy of the respiratory system diseases, phytotherapy attracts attention due to the high preventive and therapeutic potential of biologically active substances of medicinal plants. At the same time, verification of the effectiveness and safety of herbal drugs is necessary. That is why scientific research of folk medicine plants including common verbena (Verbena officinalis L.) of the Verbenaceae family has been carried out. The aim of the work is the analysis of verified data on the chemical composition of the herb verbena, the results of pharmacological and toxicological studies directed at determining the effectiveness and safety in the treatment of infectious and inflammatory diseases of the respiratory tract. The search for verified data using Internet resources, comparative analysis, systematization and generalization of data were carried out. The main secondary metabolites that determine the profile of verbena herb biological activity are iridoid glycosides (verbenalin, aucubine and gastatoside), as well as phenylpropanoid glycosides (verbascoside, isoverbascoside and eukovoside). Thus, the antibacterial and antifungal activity of certain verbena extracts against clinically significant strains of bacteria and fungi has been proven. The anti-inflammatory effect of various extracts of the Verbena herb was established on carrageenan-induced and formalin-induced edema models. The antioxidant effect of certain verbena herb fractions has been proven by in vitro methods. It is important at presence of diseases for which oxidative stress is an important pathogenetic factor. The results of clinical studies have confirmed the anti-inflammatory and antibacterial activity of the vervaine herb decoction applied topically in the case of chronic gingivitis. The expediency of verbascoside use for increasing the barrier functions of the oral mucosa, promoting epithelization, reducing pain and other signs of inflammation in oral mucositis against the background of tumour chemotherapy has been substantiated. Toxicological studies have shown that different verbena herb extracts belong to the class of low-toxic or practically non-toxic substances when taken orally. Thus, the antimicrobial, anti-inflammatory and antioxidant effects of verbena, as well as its high level of safety, substantiate the prospects for the use of this medicinal plant in the treatment of the respiratory system diseases.

У системі підготовки майбутніх спеціалістів фармації фармакологія займає перехідну позицію між базовими фундаментальними (біологія, фізіологія з основами анатомії людини, патофізіологія, біологічна хімія, мікробіологія з основами імунології) та спеціальними профільними предметами (фармакотерапія, клінічна фармація, фармацевтична опіка). Цілком обґрунтовано фармакологія вважається інтегральною дисципліною, що формує професійне мислення як провізорів (фармацевтів), так і лікарів. Тому не викликає сумнівів важливість постійного вдосконалення методик викладання фармакології в закладах вищої медичної та фармацевтичної освіти, а також визначення успішності засвоєння матеріалу дисципліни як універсального індикатора ефективності навчання. Мета дослідження – оцінити успішність вивчення фармакології майбутніми спеціалістами фармації (вітчизняними та іноземними здобувачами вищої освіти) за результатами аналізу підсумкових оцінок, балів за письмовий курсовий іспит і відсотків правильних відповідей з дисципліни на ліцензійному тестовому іспиті КРОК-1 «Фармація», а також розробити процесну модель діяльності з підвищення якості підготовки з фармакології. Встановлено, що в цілому вітчизняні здобувачі вищої фармацевтичної освіти докладають найбільших зусиль до складання іспиту КРОК-1, що визначено за кращими результатами іспиту КРОК-1 порівняно з поточним рейтингом і курсовим іспитом. Іноземні здобувачі вищої фармацевтичної освіти мають нижчу поточну успішність і гірше, ніж вітчизняні, складають ліцензійний іспит КРОК-1. Кореляційний аналіз показав статистично значущі взаємозв’язки між поточним рейтингом, курсовим іспитом і відсотком правильних відповідей тесту КРОК-1 з фармакології. Проте у вітчизняних здобувачів вищої освіти зв’язки між поточним рейтингом і результатом іспиту КРОК-1 й результатами курсового та ліцензійного іспитів сильніші, ніж в іноземних, що може свідчити про більшу увагу до фундаментальних знань у процесі підготовки та складанні іспиту КРОК-1. Запропоновано процесну модель діяльності з покращання успішності вивчення фармакології та підвищення фармакологічної компетентності майбутніх фармацевтів відповідно до стандартів ISO 9001:2015.

The interest in herbal products capable of normalizing carbohydrate and lipid metabolism thus counteracting the “diseases of civilization” grows steadily. Biological activity of these preparations is often mediated by phenolic compounds. In this aspect, the raw material of European mountain ash (Sorbus aucuparia L.) has significant prospects, and its fruit are used in traditional medicine in diabetes.Aim. To obtain alcohol and ethyl acetate-alcohol extracts from European mountain ash leaves, study their phenolic composition by the HPLC method, determine the effect of the extracts on glucose metabolism in intact rats, as well as evaluate the effect of the most effective extract on lipid metabolism, uric acid metabolism, and the excretory renal function.Materials and methods. The alcohol soft extract (ASE, extractant – 50 % ethanol) and the ethyl acetate-alcohol soft extract (EAASE, extractant – a mixture of ethyl acetate and 96 % ethanol (8:2) after preliminary extraction of the raw material with chloroform) were obtained from leaves of European mountain ash. Using HPLC (Shimadzu LC20 Prominence chromatograph) the phenolic composition of the extracts was studied. The effect of the extracts (100, 250, 500 mg/kg intragastrically after single administration) on glycemia was determined in intact normoglycemic rats compared to the infusion of bilberry shoots (Vaccinium myrtillus L.) at a dose of 10 ml/kg (1:10). The effect of the extract, which showed the ability to reduce glycemia (ASE at a dose of 500 mg/kg for 6 days), on the content of glucose, uric acid, urea, creatinine, triglycerides and total cholesterol in the blood and on the excretory renal function under the conditions of water diuresis was also studied.Results. Chlorogenic acid, quercitrin (predominant in EAASE; 11.61 mg/g) and rutin (predominant in ASE; 3.57 mg/g), and in small amounts gallic, neochlorogenic and caffeic acids, catechin and hyperoside were identified in the extracts by HPLC. ASE after single administration at a dose of 250 and 500 mg/kg exerted a statistically significant hypoglycemic effect in normoglycemic rats, exceeding the effect of the infusion of bilberry shoots (10 ml/kg). The effect was also present after administration for 6 days at a dose of 500 mg/kg, which was characterized by the high level of safety, since it caused neither changes in the given indicators of lipid, nitrogen, purine metabolism, nor the shifts of indicators of the excretory renal function.Conclusions. The data obtained substantiate the expediency of further studies of the extracts from European mountain ash leaves for the development of new drugs or dietary supplements.

There is an increasing interest in the use of herbal preparations as part of the combined therapy, including cases of hyperuricemia and gout. Preparations of goutweed (Aegopodium podagraria L.) aerial part are characterized by organoprotective and favorable metabolic effects, including the effect on the uric acid metabolism largely related to hydroxycinnamic acids. Allopurinol continues to be the most widely used hypouricemic drug.Aim. To characterize the renal, metabolic, and psychotropic effects of goutweed tincture combined with allopurinol in rats under the conditions of the excessive intake of purine derivatives and proteins.Materials and methods. The experiments were performed on the background of the excessive intake of purine derivatives and proteins in rats (10-day administration of the yeast extract in the dose of 10 g/kg with addition of molybdenum in the amount of 0.3 mg per animal and i/p injection of inosine in the dose of 50 mg/150 g). Goutweed tincture (1 ml/kg), allopurinol (50 mg/kg) and their combination were administered intragastrically during the whole period of the studies. The state of the excretory renal function, biochemical parameters of the blood plasma, the activity of xanthine oxidase (CSR) and the content of uric acid in the liver and kidneys, as well as the state of the CNS in the combined open field and an elevated plus maze tests were studied. Results. The renal injury on the background of excessive purine derivatives and proteins was verified by the criteria of hyperfiltration with increased water reabsorption and reduced ability of the kidney to excrete water load, a decrease in urea clearance and an increase of proteinuria. The level of urea and nitrogen of amino groups of the low-molecular compounds in the blood plasma increased in the absence of changes in creatininemia and uricemia (with a marked increase of renal excretion of uric acid on the background of the liver xanthine oxidase increased activity). Under the conditions of the excessive intake of purine derivatives and proteins goutweed tincture provided effective excretion of potassium, normalized the total protein content in the blood, as well as urea clearance without affecting other parameters and not leading to toxic effects. It also did not change the uric acid content and the xanthine oxidase activity of the liver and kidneys. On the background of allopurinol, the severity of the kidney damage increased with the threefold increase in the relative kidney weight, hyperazotemia, an abrupt decrease in GFR and urea clearance, reabsorption decrease, a tendency to increase in natriemia and, especially kalemia, a significant increase of proteinuria, as well as an increase in the total protein content in the blood. Goutweed tincture did not enhance the toxicity of allopurinol and did not prevent xanthine oxidase inhibition. It exerted the marked antiproteinuric effect, maintained sodium reabsorption, leading to the decrease in its excretion, reduced natriemia on the background of normokalemia. The tincture reduced the anxiety of animals in the elevated plus maze test, this effect was evident when the tincture was combined with allopurinol; in this case the intensity of vegetative and emotional signs in the open field test was also reduced. Conclusions. Goutweed tincture does not enhance the toxicity of allopurinol under the conditions of the excessive intake of purine derivatives and proteins.

Topicality. Combined use of herbal originated substances with the conventional drugs is a promising area of therapy improvement. The tincture and the extract obtained from goutweed (Aegopodium podagraria L.) are able to normalizecarbohydrate and lipid metabolism, the tincture partially increases the efficacy of metformin in the experiment. The aim of this study was to evaluate the influence of goutweed tincture and the extract as well as their combinationswith metformin on the histological structure of the internal organs of rats with lipid metabolism disorders.Materials and methods. Combined use of atherogenic diet and protamine sulfate administration was applied.Results and discussion. In the untreated group the histological examination allowed identifying the changes in kidneys (granular dystrophy of tubular epithelium, focal perivascular lymphocytic infiltration, focal sclerosis of the arterial walls); heart (granular dystrophy of cardiomyocytes, perivascular sclerotic with limited lymphohistiocytic infiltration and foci of ischemic changes in myocardium); liver (expressed granular dystrophy of hepatocytes, widening of space of Disse, signs of compensatory hypertrophy); while there were no changes in aorta. Metformin (50 mg/kg intragastrically) failed to demonstrate a normalizing influence on the liver structure, and necrobiosis and vacuolar dystrophy of hepatocytes were evident, it did not influence significantly of the kidney structure, and exerted a protective effect on the structure of the blood vessels of the heart, still not eliminating ischemic changes. Goutweed extract (1 g/kg intragastrically) and the tincture (1 ml/kg intragastrically) counteracted the changes in the structure of the kidney vessels and myocardium, including ischemic changes, while the liver histopathological changes were similar to those in metformin group. After combined administration of goutweed tincture and metformin as well as the extract and metformin at doses stated above the protective activity in regard to the heart structure was maintained, against the background of metformin with the tincture such activity in regard to the kidney structure was also evident; the toxicity of the investigated drugs was not enhanced, and there was no increase in the severity of the liver changes.Conclusions. Further ivestigation of goutweed preparations with metformin is expedient.

The tincture and the extract of the aerial part of goutweed (Aegopodium podagraria L.) are characterized with a favorable effect on the lipid and uric acid metabolism, as well as with the antidiabetic activity. The tincture is capable of increasing metformin efficacy in the experiment. Taking into account the role of uric acid metabolism disorders in the pathogenesis of “diseases of civilization” it is expedient to assess the possibility of correcting these disorders by goutweed preparations combined with metformin.Aim. To determine the effect of goutweed tincture and the extract, as well as their combinations with metformin on the uric acid metabolism in rats with the primary disorder of the lipid metabolism.Materials and methods. The model presupposed administration of protamine sulfate to rats against the background of the atherogenic diet was used. The tincture and the extract of goutweed (1 g/kg and 1 ml/kg intragastrically, respectively), metformin (50 mg/kg intragastrically) and their combinations were administered during the whole period of the model simulation. The xanthine oxidase (XO) activity in the liver and kidneys, the content of uric acid in these organs and blood plasma, as well as its renal excretion under conditions of water loading were measured.Results. In rats receiving the atherogenic diet combined with protamine sulfate the uric acid level in the kidneys and its renal excretion moderately decreased, while the XO activity and the uric acid level in the liver and blood plasma remained unchanged. Against the background of metformin, the goutweed tincture, or their combination, as well as the combination of metformin with the extract the inhibition of the liver XO activity was registered, against the background of the tincture (per se and in the combination with metformin), as well as the extract, there was also suppression of the kidney XO activity. The content of uric acid in the liver did not change significantly in all groups, uricemia decreased only after administration of the tincture per se and slightly increased against the background of metformin combined with the extract (compared to other groups of treated animals, but not with the intact control); the uric acid level in the kidneys significantly reduced in rats treated with the combination of metformin and the extract, the similar tendency was observed in the untreated control group and both groups receiving the tincture. Against the background of the tincture and the extract per se the uric acid excretion increased (in rats receiving the tincture diuresis was elevated, so there were no increase in the uric acid concentration in the urine, which occurred against the background of the extract). After the combined administration of the extract with metformin there was no change of the uric acid excretion although its urinary content remained elevated against the background of low diuresis. The stimulatory effect of the tincture on the renal excretion of uric acid was not revealed when combining with metformin, while normourocemia and the effect on the XO activity in the liver and kidneys maintained. Conclusions. The combination of goutweed tincture with metformin is promising for further studies.

The effects of goutweed (Aegopodium podagraria L.) tincture (1 ml/kg intragastrically), metformin (100 mg/kg intraperitoneally) or their combination were studied in alloxan-induced diabetic rats.On the 4th day after alloxan injection, β-cells underwent destructive changes and death, the number of pancreatic islets was reduced, proliferation processes were intensified in the places of typical α-cells localization.The studied combination normalized the state of the islets counteracting cell death and limiting excessive proliferation foci (evidently α-cells), the last effect was not observed after monotherapy in both cases.The tincture and metformin normalized the histological structure of the liver counteracting hepatocytes death, which was intensified in diabetic rats.The protective effect of metformin on the structure of the vascular wall both in the pancreas and the liver was maintained after combined use of this drug with the tincture.This combination also partially restored insulinemia and insulin resistance index, while the effect on glycemia and TNF-α level in plasma was not manifested within the term of the study and under conditions of anaesthesia.The correlation between TNF-α and insulinemia indicates the possible participation of the mechanisms related to this cytokine in the tincture protective effect in regard to β-cells.Combined use of goutweed tincture with metformin allowed increasing plasma albumin level, which was not observed after monotherapy with metformin.Abbreviations: ALTalanine aminotransferase,

This study addressed the influence of Aegopodium podagraria L. (goutweed) aerial part extract (100 mg/kg and 1 g/kg) and tincture (1 and 5 ml/kg) on the course of ethanol-induced as well as thiopental sodium induced narcosis. It has been shown that the extract at a dose of 1 g/kg, but not 100 mg/kg, significantly reduces the duration of ethanol-induced narcosis in male mice, the extract at a low dose decreases the onset of the loss of righting reflex. The tincture does not influence on the course of ethanol-induced narcosis, but significantly reduces the duration of sleep caused by thiopental sodium in male mice (at a dose of 1 ml/kg, but not 5 ml/kg), by this effect it is comparable with Hypericum perforatum L. extract at a dose of 100 mg/kg. Goutweed extract does not influence on the duration of thiopental-induced sleep.

Diabetes mellitus and metabolic syndrome are the common problems of the modern society. The interest in herbal medicines increases, and often they are used in combination with conventional drugs. Aegopodium podagraria L. (goutweed) is a plant widely used in traditional medicine. Hypoglycemic effect of goutweed aerial part tincture has been previously shown in alloxan-induced diabetic mice and in rats receiving excess of fructose and hydrochlorothiazide. The effects of co-administration of the tincture with widely used antihyperglycemic drugs have not been verified. The objective of this study is to determine the efficacy of goutweed tincture and its combination with metformin using the model reproducing the pathogenetic mechanisms of the metabolic syndrome and type 2 diabetes.

The effect of the extract (100 mg/kg and 1 g/kg) and the tincture (1 and 5 ml/kg) of the goutweed (Aegopodium podagraria L.) aerial part on the physical endurance, the level of depression and cognitive functions has been studied using the weight-loaded forced swimming test, the extrapolation escape test, and the reserpine-induced depression model. The goutweed extract in the dose of 100 mg/kg, but not in the dose of 1 g/kg, significantly increases the exhaustive swimming time (10% and 20% load) in male mice. In female mice the augmentation of exhaustive swimming time is registered with 20% load against the background of the extract in both doses. The goutweed tincture does not change the results of this test. Goutweed medicines have the ambiguous effect on the results of the extrapolation escape test: the extract and the tincture do not change the percentage of mice that succeed in completing the task, still the average time spent for the task performance is significantly decreased in these animals (but not within the whole group) against the background of the extract in the doses of 100 mg/kg and 1 g/kg. The extract in the dose of 100 mg/kg significantly reduces the number of rats capable of completing the task, the extract (1 g/kg) and the tincture (1 ml/kg) increase the time spent for performing the extrapolation escape task by rats. The extract and the tincture do not change the body temperature reduction and blepharoptosis induced by reserpine in rats. Thus, the goutweed extract is able to increase the physical endurance, exert a moderate positive effect on cognitive functions in mice (but not in rats) without any significant changes in the level of depression. The goutweed tincture worsens the results of the extrapolation escape test in the dose of 1 ml/kg, does not change them in the dose of 5 ml/kg and does not influence on the level of depression and physical endurance in both doses.

Aegopodium podagraria is used as a sedative in trad itional medicine. The effect of its aerial part ext ract and tincture on levels of depression and anxiety, as we ll as on locomotor activity, exploratory behaviour and memory of male and female mice was investigated. The extract showed dose-dependent and sex specific antidepressi ve effect (at a dose of 100 mg/kg but not at a dose of 1 g/kg in female mice) with the worsening of the results of the passive avoidance test. The extract at a dose of 100 mg/kg tended to reduce anxiety signs in the animals of b oth sexes , in male mice such reduction was also seen under the in fluence of the extract at a dose of 1 g/kg and the tincture at doses of 1 and 5 ml/kg (the latter did not consider ably changed the other parameters measured). The re sults indicate favourable central activity of A. podagraria extrac t in mice.

The influence of the goutweed dry extract (1 g/kg), goutweed tincture (1 and 5 ml/kg) and “Arphasetin” tea infusion (18 ml/kg) on the histological structure of the kidneys and liver in alloxan-induced diabetic mice has been investigated. In three weeks after the pathological process induction in the nontreated mice dystrophic changes with the partial transition to necrobiosis and necrosis in the kidneys and liver, protein casts within the renal tubuli and lympholeucocytal infiltration in the liver were found. The goutweed dry extract (1 g/kg) and “Arphasetin” tea infusion (18 ml/kg) normalize the structure of the renal tubuli (granular dystrophy of the kidney epithelium and necrobiosis foci in some histological samples were evident), prevent pathological changes of hepatocytes (on the background of the extract the vascular plethora, hepatocytes granular dystrophy and hypertrophy of some cells were detected, on the background of “Arphasetin”, in addition to the abovementioned changes, single necrobiosis foci were registered). Necrobiosis and necrosis were not detected in the kidneys and liver of the animals treated with the goutweed tincture in the of dose of 5 ml/kg, but the vascular plethora was present. Granular dystrophy of the epithelium and protein casts within some tubuli were seen in the kidneys, granular dystrophy of hepatocytes was registered in the liver. The goutweed tincture in the dose of 1 ml/kg did not show the protective action on the histological structure of the kidneys and liver. Thus, a dry extract of goutweed (1 g/kg), the goutweed tincture (5 ml/kg, but not 1 ml/kg) and “Arphasetin” tea infusion (18 ml/kg) improve the histological structure of the kidneys and liver in alloxan-induced diabetic mice, prevent necrosis development and infiltration of tubuli with protein casts. The goutweed extract in the dose of 1 g/kg is considered to be the most promising medicine for further research.

The high level of uric acid in blood distinguishes humans from other studied species of mammals. The reason behind this is the absence of the enzyme uricase, which is evolutionary determined. Today, hyperuricemia can be considered as a factor of “diseases of civilization.” However, uric acid can also have positive effects, because it intensifies cognitive processes. The high level of uric acid in blood probably facilitated the emergence of intellectually advanced primates. Later, it enhanced the human’s motivation for active work. In the present review, these points are substantiated using data by V.P. Efroimson on the role of hyperuricemia and gout in the development of genius, V.S. Rotenberg’s Search Activity Concept, and the R. Johnson’s hypothesis on the role of uric acid as a messenger when it is necessary to change the behavioral responses of animals upon transition to active feeding. The nonspecific activating role of hyperuricemia is the factor that links all three hypotheses together. In addition, the enhancement of cognitive functions and motivations in hyperuricemia has been confirmed in different population samples. The biochemical basis for such effects is the potential for uric acid synthesis in the central nervous system and the penetration of the blood-brain barrier by its precursors, the interrelations between the metabolism of uric acid in the central nervous system and the metabolism of catecholamines and dopamine, and the neuroprotective and antioxidative properties of uric acid.