In the present study, we explored the therapeutic potential of bioreactor-grown cell cultures of the medicinal plant species Dioscorea deltoidea, Tribulus terrestris and Panax japonicus to treat carbohydrate metabolism disorders (CMDs) in laboratory rats. In the adrenaline model of hyperglycemia, aqueous suspensions of cell biomass pre-administered at a dose of 100 mg dry biomass/kg significantly reduced glucose level in animal blood 1–2.5 h (D. deltoidea and T. terrestris) or 1 h (P. japonicus) after adrenaline hydrochloride administration. In a streptozotocin-induced model of type 2 diabetes mellitus, the cell biomass of D. deltoidea and T. terrestris acted towards normalization of carbohydrate and lipid metabolism, as evidenced by a significant reduction of daily diuresis (by 39–57%), blood-glucose level (by 46–51%), blood content in urine (by 78–80%) and total cholesterol (25–36%) compared to animals without treatment. Bioactive secondary metabolites identified in the cell cultures and potentially responsible for their actions were deltoside, 25(S)-protodioscin and protodioscin in D. deltoidea; furostanol-type steroidal glycosides and quinic acid derivatives in T. terrestris; and ginsenosides and malonyl-ginsenosides in P. japonicus. These results evidenced for high potential of bioreactor-grown cell suspensions of these species for prevention and treatment of CMD, which requires further investigation.

Obesity, and its consequences for human health, is a huge and complicated problem that has no simple solution. The constant search for natural and safe compounds with systemic action that can be used for obesity prophylactics and treatment is hampered by the limited availability and variable quality of biomass of wild medicinal plants. Plant cell biotechnology is an alternative approach for the sustainable production of vegetative biomass or individual phytochemicals with high therapeutic potential. In this study, the suspension cell biomass of the medicinal plants, Dioscorea deltoidea Wall., Tribulus terrestris L., and Panax japonicus (T. Nees) C.A. Mey, produced in 20 L and 630 L bioreactors, were tested for therapeutic effects in rat models with alimentary-induced obesity. Three-month intake of water infusions of dry cell biomass (100 mg/g body weight) against the background of a hypercaloric diet reduced weight gain and the proportion of fat mass in the obese animals. In addition, cell biomass preparation reduced the intracellular dehydration and balanced the amounts of intra- and extracellular fluids in the body as determined by bioimpedance spectroscopy. A significant decrease in the glucose and cholesterol levels in the blood was also observed as a result of cell biomass administration for all species. Hypocholesterolemic activity reduced in the line P. japonicus > D. deltoidea > T. terrestris/liraglutide > intact group > control group. By the sum of parameters tested, the cell culture of D. deltoidea was considered the most effective in mitigating diet-induced obesity, with positive effects sometimes exceeding those of the reference drug liraglutide. A safety assessment of D. deltoidea cell phytopreparation showed no toxic effect on the reproductive function of the animals and their offspring. These results support the potential application of the biotechnologically produced cell biomass of medicinal plant species as safe and effective natural remedies for the treatment of obesity and related complications, particularly for the long-term treatment and during pregnancy and lactation periods when conventional treatment is often contraindicated.

Objective. To assess the efficacy and safety of long-term treatment with divozilimab in patients with relapsing multiple sclerosis (MS). Material and methods. Study No. BCD-132-EXT enrolled patients with relapsing MS who had previously received divozilimab at a dose of 500 mg in a phase II and III studies. Taking into account the participation of patients in previous studies, the total treatment duration was 4 years. The efficacy assessment was carried out using parameters associated with relapses (annualized relapse rate (ARR), time to first relapse), parameters of magnetic resonance imaging of the brain, and also included evaluation of neurological deficit. Safety monitoring included evaluation of standard laboratory parameters and reporting of adverse events. Results. A total of 44 patients were enrolled in the study, of which 93.2% (41/44) patients completed 4 years of follow-up. During the BCD-132-EXT period, the proportion of relapse-free patients was 97.7%. Over the 4 years of observation, the ARR remained consistently low, with the overall ARR over 4 years of divozilimab treatment being 0.052 (95% CI 0.028; 0.097). The 6-month confirmed disability progression (CDP) during the treatment period was observed in 4.5% (n=2) of patients. Adverse reactions, most of which were mild to moderate in severity, were reported in 59.1% (n=26) of patients. The most common adverse reactions were decreased lymphocyte count, decreased white blood cell count, decreased neutrophil count, and infusion reactions. Conclusion. The obtained results indicate the maintenance of efficacy over 4 years of therapy with divozilimab. The safety profile of divozilimab was favorable and consistent with previously obtained data.

Introduction. The development of heart failure is closely associated with the appearance of life threatening arrhythmias, which are often a terminal event for these patients. An analysis of randomized clinical trials of inhibitors of sodium-glucose cotransporter type 2 indicates the clinically significant potential of these drugs as agents with antiarrhythmic properties. However, at the moment the full mechanism by which this effect can be realized is still not fully understood.Aim. To evaluate the effect of empagliflozin on the transmembrane calcium currents and the intracellular calcium transients on isolated ventricular cardiomyocytes of mice under conditions of normoglycemia.Materials and methods. In the experiment, ventricular cardiomyocytes were isolated from 12 outbred male mice. 2 groups were formed: group № 1 – control ventricular cardiomyocytes; group № 2 – ventricular cardiomyocytes after two hours incubation with 5 µmol/L empagliflozin solution. Transmembrane calcium currents were recorded and intracellular calcium transients were assessed.Results and discussion. Incubation of ventricular cardiomyocytes with empagliflozin significantly increased I_Ca current density and accelerated Ca²⁺ temporal dynamics. The amplitude of the Ca²⁺ wave and the rate of rise and decay were increased and the duration of the Ca²⁺ wave was shortened.Conclusion. The result of the experiment indicates that empagliflozin is able to modulate Ca²⁺-dependent mechanism of the excitation-contraction-coupling, enhancing and accelerating Ca²⁺ release into cytoplasm and reuptake. This presumably can optimize, namely reduce the time of systole and enhance it, which may be one of the important elements in the manifestation of empagliflozin antiarrhythmic properties.