Sodium alginate is a polymer with unique ability to gel with different cross-linking agents in result of ionic and electrostatic interactions. Chitosan cross-linked alginate provides improvement of swelling and mucoadhesive properties and might be used to design sustained release dosage forms. Therefore, the aim of this research was to develop and evaluate possibility of preparing chitosan cross-linked alginate microparticles containing metformin hydrochloride by the spray-drying method. In addition, influence of cross-linking agent on the properties of microparticles was evaluated. Formulation of microparticles prepared by the spray drying of 2% alginate solution cross-linked by 0.1% chitosan was characterized by good mucoadhesive properties, high drug loading and prolonged metformin hydrochloride release. It was shown that designed microparticles reduced rat glucose blood level, delayed absorption of metformin hydrochloride and provided stable plasma drug concentration. Additionally, histopathological studies of pancreas, liver and kidneys indicated that all prepared microparticles improved degenerative changes in organs of diabetic rats. Moreover, no toxicity effect and no changes in rats behavior after oral administration of chitosan cross-linked alginate microparticles were noted.

The aim of this study was to evaluate the therapeutic effects of chlorogenic acid (CGA) in rats with advanced alcoholic steatohepatitis. The rats were fed on a high-fat diet and gavaged with ethanol (4 g/kg) for 8 weeks. The livers of ethanol-treated rats showed steatosis; necrosis and mononuclear infiltration; and significant upregulation of the mRNA expression of the prooxidant (Cyp2e1, iNos), lipogenic (Srebp1, Acc), proinflammatory (Tlr4, Nf-κb, TnfA, Il-1B, and Il-6), and profibrogenic (TgfB, Col1, VegfA) genes. Simultaneously, a downregulation of level of Sod and Nrf2 was observed, which was accompanied by increased serum transaminase, TnfA, and serum and liver triglycerides levels. CGA administration (40 and 80 mg/kg, 8 weeks) to ethanol-fed group reduced the liver expression levels of Cyp2e1 and iNos, whereas it markedly enhanced the expression of Sod, Nrf2, and Ho-1. CGA at both doses downregulated the expressions of lipogenic, proinflammatory, and profibrogenic genes, while the expression of Tlr4 was lowered only after the higher dose of CGA. The higher dose of CGA efficiently prevented the progression of alcohol-induced steatosis and reduced inflammation through regulation of the expression of genes encoding the proteins involved in the Tlr4/Nf-κB signaling pathway and fibrosis. The study revealed hepatoprotective and anti-inflammatory effects of CGA through the regulation of expression of genes encoding Cyp2e1/Nrf2 involved in oxidative stress modulation. These results demonstrate CGA as a therapeutic candidate for the prevention and treatment of alcoholic steatohepatitis.

Central nervous system disorders, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, are associated with complex pathophysiological mechanisms involving oxidative stress, inflammation, and protein misfolding. According to the literature, betulin, a natural compound derived from the bark of birch trees, demonstrates promising neuroprotective effects. This study investigates the neuroprotective potential of betulin and its complex with cyclodextrin, referred to as Betula Forte, using an in vitro model of differentiated SH-SY5Y neuroblastoma cells. Specifically, the study explores the antioxidant and antiapoptotic properties of these compounds under oxidative stress induced by hydrogen peroxide (H₂O₂). Our results indicated that Betula Forte exhibited lower cytotoxicity compared to betulin alone. Both substances enhanced cell viability in pre-incubation and co-incubation models, with Betula Forte showing superior efficacy under severe oxidative stress. Additionally, both substances exhibited protective effects against H₂O₂-induced oxidative stress and apoptosis, as evidenced by reduced levels of reactive oxygen species (ROS) and a lower number of apoptotic cells compared with the H₂O₂-treated cells. These findings suggest that Betula Forte, due to lower cytotoxicity, may offer a more effective neuroprotective strategy than betulin alone, highlighting its potential as a therapeutic agent for neurodegenerative diseases.

We investigated the role of aldosterone (ALDO) in the development of arterial thrombosis in streptozotocin-induced diabetic rats. To evaluate the effect of endogenous ALDO, the rats underwent adrenalectomy (ADX). ADX reduced the development of arterial thrombosis. A 1 h infusion of ALDO (30 μg/kg/h) enhanced thrombosis in adrenalectomized rats, while this effect was potentiated in diabetic rats. ALDO shortened bleeding time, increased plasma levels of tissue factor (TF) and plasminogen activator inhibitor, decreased plasma level of nitric oxide (NO) metabolites, and increased oxidative stress. Moreover, 2 h incubation of human umbilical vein endothelial cells (HUVECs) with ALDO (10⁻⁷ M) disrupted hemostatic balance in endothelial cells in normoglycemia (glucose 5.5 mM), and this effect was more pronounced in hyperglycemia (glucose 30 mM). We demonstrated that the acute ALDO infusion enhances arterial thrombosis in rats and hyperglycemia potentiates this prothrombotic effect. The mechanism of ALDO action was partially mediated by mineralocorticoid (MR) and glucocorticoid (GR) receptors and related to impact of the hormone on primary hemostasis, TF-dependent coagulation cascade, fibrinolysis, NO bioavailability, and oxidative stress balance. Our in vitro study confirmed that ALDO induces prothrombotic phenotype in the endothelium, particularly under hyperglycemic conditions.

Betulin is natural pentacyclic triterpenoids lupane-structure, which shows a wide range of biological activity, including possibly hypoglycemic effects. Diabetes mellitus is a metabolic disease, accompanied by chronic hyperglycemia caused by absolute or relative insulin deficiency. The main effective drug in the treatment of type 1 diabetes is insulin injections. In the case of type 2 diabetes, it is an adjuvant therapy. To purpose of this study was to show hypoglycemic action of betulin in a model of experimentally induced diabetes in rats. For the induction of diabetes, alloxan at a dose of 170 mg/kg, i.p. was used. The hypoglycemic effect of betulin was evaluated using doses of 50 and 100 mg/kg/day for 30 days. The activity of glucose metabolism enzymes: liver glycogen phosphorylase, hexokinase and liver and skeletal muscle phosphofructokinase in rats, glucose-6-phosphate dehydrogenase (DG-6-P) of the liver was also evaluated. Betulin in a dose-dependent manner normalized of glycemia, increased the basal insulin concentration in the blood serum, increased the activity of carbohydrate metabolizing enzymes and on the gene expression profile of enzymes involved in carbohydrate metabolism. Betulin also significant improved the morphology of the pancreas. In particular, there was an increase in the area of the islands, their diameter, an increase in the number of β cells in the composition of the islands. We conclude that betulin has hypoglycemic properties, improving glycemia and carbohydrate metabolizing enzymes and pancreatic morphology.