HDL particles are protein-rich particles that act as a vehicle for reverse cholesterol transport from tissues to the liver. The purpose of this study was to investigate age-dependent changes in the functional activity of HDL and the effect of high-energy diet on this index, as well as to correct it under the influence of grape polyphenols from “Enoant” obtained from Vitis vinifera grapes. We observed the age-dependent composition changes in HDL particle. It was shown that total lipids and triacylglycerol (TG) levels were higher in 24-month-old animals. In obese rats, HDL total lipids and TG levels were higher in 24-month-old than in the 3-month-old and 12-month-old groups but did not differ from 24-month-old group. The plasma HDL paraoxonase (PON) and lecithin:cholesterol acyltransferase (LCAT) activity levels were decreased in old-aged rats, and cholesteryl ester transfer protein (CETP) activity was higher in old rats. Keeping 12-month-old animals on high-fructose diet completely leveled the age differences in the data that have been measured between 12-month-old and 24-month-old rats. After “Enoant” administration, an increase of HDL PON and LCAT activity levels and a reduction of CETP activity were found in 24-month-old and obese rats.

Growing blueberry (Vaccinium corymbosum L., Highbush blueberry) as a berry crop is developing dynamically, especially in warm temperate, subtropical, and tropical regions of the world. When blueberry is cultivated on plantations, the bushes are pruned annually, and tons of leaves become waste. Thus, the aim of the present study was to create a preparation from blueberry leaves, study their chemical composition and determine their potential as a dietary supplement for the prophylactic and correction of the metabolic syndrome. Several schemes for obtaining extracts from blueberry leaves have been developed, including one with addition of arginine. A total of 18 phenolic substances were identified and quantified in the extracts by TLC and HPLC methods. Chlorogenic acid, hyperoside, and rutin were shown to be dominating constituents. Quantitative determination of hydroxycinnamic acid derivatives, flavonoids and other phenolics in the extracts was performed by spectrophotometric method. The extracts administration led to a significant decrease in the level of glucose, insulin and triacylglycerols in blood serum of adult mature inbred rats with insulin resistance induced by the fructose-enriched diet. The most promising one was the extract modified with arginine. The determined hypoglycemic and hypolipidemic activity of chemically standardized extracts from highbush blueberry leaves indicate the potential of this crop residue in utilization as a dietary supplement recommended in prevention of ailments associated with metabolic syndrome.

Diabetes mellitus is a global medical and social issue. In the developed countries of the world, from 5 to 12% of the population are diagnosed with diabetes mellitus and, according to WHO prognosis, the level of this disease may increase to 30-35%. Type 2 diabetes is a disease that progresses over time, but the rational and systematic use of hypoglycemic synthetic drugs and phytopreparations can significantly delay the onset of insulin therapy. A promising source of BAS with a hypoglycemic effect is the raw material of plants of the Heather family, namely, bearberry leaves. However, on the Ukrainian market there are no domestic galenic and novo-galenic preparations based on biologically active substances of this raw material, which indicates the prospects for the development of new drugs, including those with hypoglycemic action. The aim. The aim of the study was to study the phytochemical composition and to carry out a screening of the hypoglycemic activity of dry extracts from bearberry leaves modified with various amino acids to identify promising substances with hypoglycemic action. Materials and methods. The objects of the study were 11 dry extracts from bearberry leaves, 10 of which were modified with various amino acids. The study of the phenolic compounds of the extracts was carried out by TLC, HPLC, and spectrophotometry. To assess the hypoglycemic activity of the extracts, two experiments were carried out - primary screening and oral glucose tolerance test. Results. Using TLC and HPLC, in the extracts obtained arbutin, gallic acid, 5 flavonoids were identified, among which hyperoside was dominant, 4 hydroxycinnamic acids, among which chlorogenic and caffeic acids were dominant, and their content was established. In the extracts obtained, main groups of phenolic compounds were quantified using a spectrophotometric method. Dry extracts from bearberry leaves, modified with cysteine, arginine and glutamic acid, showed the strongest hypoglycemic activity. Conclusions. The chemical composition of phenolic compounds and the hypoglycemic activity of dry extracts from bearberry leaves modified with 10 different amino acids were determined. The most promising substances turned out to be extracts modified with cysteine, arginine and glutamic acid; therefore, they are promising agents for the development of new drugs.

Obesity is strongly associated with the insulin resistance development and is an integral pathogenic part of the metabolic syndrome, type 2 diabetes, atherosclerosis, and other comorbid pathologies. It is well known that the obesity causes the disorders in adipose tissue endocrine and metabolic activity, which results in the activation of free radical processes. The administration of natural origin substances with antioxidant properties could be a promising direction for obesity and overweight correction. The objective of the current study was to evaluate the usefulness of natural origin active substances with antioxidant properties' administration under the obesity and comorbid disorder treatment. This chapter presents the results of experimental studies that proved the usefulness of phenolic compounds from apple food concentrate (Malus domestica L.) and dry bilberry extract (Vaccinium myrtillus L.) application under experimental metabolic syndrome, insulin resistance syndrome, and type 2 diabetes mellitus, which are extremely associated with obesity. It has been found that due to expressive antioxidant activity, these compounds exhibit the high efficiency in carbohydrate metabolism disorders' correction (in cases of metabolic syndrome and type 2 diabetes), lipids metabolism disorders' correction (in case of metabolic syndrome), preventing of endothelial dysfunction under experimental insulin resistance, and normalization of antioxidant status in the liver (under experimental type 2 diabetes mellitus).

The unbalanced high-calorie diet can be the cause of a number of pathological states, including metabolic syndrome MS . It is well known that the risk of MS increases with age, but gender differences in age-related lipid metabolism changes under this pathology are not fully understood.In order to investigate the mechanisms of atherogenic dyslipidemia under the MS, we study the dynamics of some parameters of lipid and lipoprotein metabolism in hamsters of different sex and age. In our experiments, we found some age and gender differences in lipid and lipoprotein metabolism in healthy hamsters and hamsters with MS. In general, the obtained results demonstrate dyslipidemia development in males feeding high-calorie diet, irrespective of age. We suppose that hypertriglyceridemia in males under the high-calorie diet developed due to the accumulation of triacylglycerols T"Gs in hepatocytes and as a result very low density lipoprotein VLDL over secretion by liver. However, in females feeding high-calorie diet atherogenic dyslipoproteinemia develops only with aging. It can be assumed that the reason why high-calorie diet in females leads to the pathological changes in VLDL morphology and hypertriglyceridemia development is reducing the hepatocytes sensitivity to insulin. Herewith, insulin resistance in females does not cause lipolysis activation in adipose tissue, which is probably associated with the ability of female

Bearberry (Arctostaphylos uva-ursi L.) is a perennial plant of the heather family (Ericaceae). The leaves are dominated by arbutin, phenol carbonic acids flavonoids, saponins, etc. It was previously shown that the bearberry leaves extract reduced blood glucose level in healthy animals under glucose overload, so it need to be studied more detail. The aim of the study was to investigate the chemical composition and the effect of dry alcohol extract from bearberry leaves, which enriched with cysteine, on the rats pancreas under experimental dexamethasone-induced insulin resistance (IR). Arctostaphylos uva-ursi L. leaves extract and its modified cysteine preparation were obtained according to the developed method with 50% ethanol solution. Their phytochemical profile, hypoglycaemic and pancreatic protective effect were investigated. Phenologlycoside (arbutin), phenolic carboxylic acid (gallic acid), 5 flavonoids and 4 hydroxycinnamic acids were identified and quantified in the extracts by HPLC. Present data revealed that bearberry leaves alcoholic dry extract enriched with cysteine has a hypoglycaemic and pancreatic protective effect in treated animals under dexamethasone-induced IR model. Treatment improved hyperglycaemia, insulin resistance and beta cell reduction induced by dexamethasone injections. Graphical Abstract

Introduction. In recent decades, diabetes mellitus type 2 (DM2) has become one of the leading causes of deaths worldwide. A number of studies confirmed the causal relationship between the development of insulin resistance (IR) and DM2. At the same time, traditionally and for many years the plants or substances isolated from them have been using in the DM2 treatment and correction of its complications. The aim of the study – to find out the effect of ethanolic polyphenol Bearberry leaves (Arctostaphylos uva-ursi) extract enriched with arginine (PE50_arg) on tolerance to glucose and lipid metabolism under experimental IR in rats. Research Methods. Adult male outbred albino rats were used in the present study. Two experimental IR models were conducted: daily intraperitoneal administration of dexamethasone and a diet enriched with fructose. Treating was performed by oral administration of polyphenolic alcohol extract (PE50) and the corresponding extract with the addition of arginine (PE50_arg). IR was confirmed by measuring immunoreactive insulin (IRI) and plasma glucose levels. At the end of the experiment, the lipid profile was investigated in the obtained serum samples. The statistical processing of the data was carried out using the STATISTICA program (StatSoftInc., USA, version 6.0). Results and Discussion. A diet for 7 weeks enriched with fructose caused IR in rats. Also we observed increased triacylglycerol (TAG), free fatty acids (FFA) and cholesterol (Ch) levels. Daily injections of dexamethasone, which maintained the hormone level for 5 weeks, led to the IR development. Under hormone-induced IR also FFA and TAG levels were elevated, but Ch concentration in blood plasma did not significantly change. Both extracts, PE50 and PE50_arg, improve cell sensitivity to insulin in experimental IR models. At the same time, PE50_arg has a more pronounced normalizing effect on the lipid parameters being investigated. Conclusions. Our results suggest that PE50_arg may be a potentially promising anti-diabetic agent.

The synthesis of mono-and bis-derivatives of spiro-2-oxindole[3,3']pyrrole and the study of their antioxidant and anti-inflammatory activities Aim. To synthesize a series of mono-and bis-derivatives of spiro-2-oxindole[3,3']pyrrole and study the antioxidant and anti-inflammatory activity of the compounds obtained.Materials and methods. Methods of organic synthesis and instrumental methods for determining the structure of organic compounds were used. The antioxidant properties of the compounds synthesized were studied in vitro on the model of spontaneous lipid peroxidation (LPO); the model of acute aseptic inflammation (carrageenan edema) was used for determination of the anti-inflammatory (anti-exudative) activity.Results and discussion. A series of novel spiro-2-oxindole[3,3']pyrrole derivatives was synthesized by means of the three-component cascade interaction of isatin, α-amino acids and dipolarophils based on bis-maleimids. In order to broaden the range of compounds obtained nitroso derivatives of ethylene-N,N'-bis(spiroindole-3,3'-pyrrolo[3,4-c]pyrrole-5'-methyl-2a