Vol 23, No 4 (2025)

The most prevalent chronic liver diseases are metabolic disorders, which lead to the development of the so-called nonalcoholic fatty liver disease (renamed metabolic dysfunction–associated steatotic liver disease in 2020) with subsequent progression from steatosis, steatohepatitis, and fibrosis to cirrhosis and hepatocellular carcinoma. The disease is more common in developed countries and, according to some estimates, affects approximately one third of the global population. Metabolic dysfunction–associated fatty liver disease is recognized worldwide as the leading cause of chronic liver disease, which remains asymptomatic in many patients and is often diagnosed incidentally. The disease is typically comorbid with obesity, type 2 diabetes mellitus, dyslipidemia, atherosclerosis, and other cardiovascular disorders. Key pathogenetic factors include oxidative stress followed by hepatocyte apoptosis, insulin resistance, cytokine imbalance, mitochondrial dysfunction, impaired autophagy, and other abnormalities that promote the development of inflammatory processes. The disease pathogenesis is complex and not fully understood. Current hypotheses do not fully elucidate the relationships among the individual pathogenetic mechanisms. The management of metabolic dysfunction–associated fatty liver disease is challenging and is primarily aimed at correcting insulin resistance, hepatoprotection, and reducing the risks of progression of associated comorbidities. To date, no unified disease-specific pharmacological strategies have been developed. From a pharmacotherapeutic perspective, melatonin has attracted increasing attention in recent years owing to its capacity to alleviate most of the manifestations of the metabolic syndrome. This review summarizes experimental data and clinical experience regarding the use of melatonin (an indole compound synthesized in the pineal gland) for the correction of metabolic dysfunction of the liver. Melatonin is capable of controlling many physiological processes in hepatic tissue both through activation of its specific receptors and through direct modulation of intracellular pathways, thereby exerting a broad modulatory effect. In experimental models across various animal species, melatonin has demonstrated pronounced hepatoprotective activity. A considerable advantage of melatonin is its ability to alleviate emotional disturbances characteristic of chronic conditions (including anxiety, depressive symptoms, and insomnia). The accumulated evidence has already facilitated the introduction of melatonin into clinical practice and supports further expansion of its applications in hepatic diseases.

Currently, there are neither generally accepted approaches to the therapy of gaming disorder nor any medication officially approved for this indication. Available treatment strategies include psychotherapeutic interventions and pharmacotherapy using antidepressants, opioid receptor antagonists, mood stabilizers, N-methyl-D-aspartate receptor antagonists, and antipsychotics. This review analyzes the prospects for investigating the neurochemistry and pharmacology of gaming disorder. The dopaminergic and serotonergic systems make the greatest contribution to the functional state underlying gambling behavior. Of particular interest are the effects of activating dopamine D3 receptors and serotonin receptors 5-HT1A, 5-HT2A, and 5-HT1B. The investigation of the effects of antagonists of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) appears promising for the treatment of gaming disorder. Neuropeptide systems, particularly endogenous opioids, remain insufficiently studied. The study of the neuropeptides ghrelin, orexin, neurotrophin family peptides, corticotropin-releasing factor (CRF), oxytocin, neuropeptide Y, glucagon-like peptide-1 (GLP-1), and kisspeptin is also considered highly promising. A directed search for peptide targets that influence neurotransmitter systems of the brain may identify critical links for the correction of gambling addiction (pathological gambling) and gaming disorder resulting from excessive computer game use (pathological gaming).

Background: Obesity and stress are widespread today and have a significant impact on public health. Moreover, these diseases are closely interconnected, including through such eating disorders as binge eating and food addiction. A promising target for the treatment of obesity is the ghrelin receptor, which is involved in both appetite regulation and stress response.

Aim: The aim of the research was to estimate the impact of novel peptide ghrelin antagonist agrelax on rats eating behavior in the limited access model under electric foot shock stress conditions.

Methods: Eating behavior was studied in limited access to high-caloric foods model. To evaluate anxiety and compulsivity of rats the marble burying and elevated plus maze tests were employed. As stress exposure the electric stimulation of limbs (foot-shock) was used. Agrelax was administered intranasally at a dosage of 1 mg / ml, 10 μl in each nostril.

Results: The elevated plus maze and marble burying tests results demonstrated more pronounced anxiety and comulsivity in rats, consuming more than 36 kcal of chocolate treat per hour in contrast to those who consumed less or didn’t obtain treat, p < 0.05. Same, rats prone to overeating, in contrast to those who ate less than 36 kcal/hour, demonstrated a reaction to foot shock stress by increasing the consumption of chocolate treat from 47.9 ± 4.0 to 56.0 ± 5.4 kcal, while agrelax reduced this amount to 41.0 ± 3.6 kcal.

Conclusion: The results of the present study indicate that agrelax reduces the consumption of chocolate treat increased by the effect of electrical stimulation of the limbs (foot-shock) in rats prone to overeating high-calorie foods.

Background: Emotional stress impairs both mental and reproductive health, being accompanied by hormonal dysregulation that is difficult to correct. Kisspeptin is a neuropeptide that regulates the reproductive system through its effects on hypothalamic–pituitary mechanisms. Although the incidence of stress-induced reproductive disorders is increasing, effective approaches targeting the central components of neuroendocrine regulation remain limited. The role of kisspeptin in restoring the hypothalamic–pituitary–gonadal axis under chronic stress has not been sufficiently studied, creating a significant gap in the understanding of pathogenesis and the potential for its pharmacological correction.

Aim: The work aimed to investigate the effect of kisspeptin-10 on the activity of the kisspeptin–gonadotropin-releasing hormone system in male rats (Rattus norvegicus) in a model of posttraumatic stress disorder.

Methods: The study included 42 Wistar rats, which were divided into 7 groups and exposed to restraint stress or vital stress. Kisspeptin-10 was administered intranasally or intraperitoneally. The levels of selected neuropeptides and their receptors in the hypothalamus and amygdala were assessed using enzyme-linked immunosorbent assay.

Results: Kisspeptin-10 increased the levels of gonadotropin-releasing hormone, kisspeptin, and the kisspeptin receptor in the brain. An activating effect on androgen receptor expression was observed, predominantly in the hypothalamus.

Conclusions: The findings indicate a central mechanism of action of kisspeptin-10 that is independent of sex steroids and demonstrate its potential in the treatment of stress-induced reproductive dysfunction.

Among the many symptoms accompanying vibration disease (whole-body vibration, WBV effect), cognitive and memory dysfunction is particularly important because of its association with an increased risk of severe dementia. The energy from technogenic oscillatory (vibrational) exposure induces multistage phase transitions of albumins, conformational changes of synaptic proteins, active zones of synapses, and alterations in the density and sensitivity of glutamatergic, GABAergic, dopaminergic, and cholinergic receptors. Uncoupling of oxidative phosphorylation, mitochondrial de-energization, activation of nitric oxide synthases, hypercalcemia, elements of glutamate excitotoxicity, disturbances in the levels of neurotransmitters (5-hydroxytryptamine and 5-hydroxyindoleacetic acid), and imbalance in the system of pro- and anti-inflammatory cytokines disrupt the mechanisms of generation and conduction of nerve impulses, promote neuronal degeneration, increase the permeability of the blood–brain barrier, and often irreversibly transform the functioning of integrative neural networks. A generalized analysis of the neuropsychological testing, measures of direct current potential and slow-wave rhythm power, electroencephalography, and topographic mapping of brain electrical activity indicates the involvement of the frontal, inferior temporal, and inferior parietal lobes, the parieto–temporo–occipital region of the left hemisphere, as well as subcortical structures, including the hippocampus and corpus callosum, in the formation of cognitive dysfunction in patients with vibration disease. The data presented in this review indicate the need for active detection of cognitive impairment in individuals exposed to vibration and the implementation of neuroprotective therapy. It is possible that the greatest importance in protecting the brain from the destructive effects of vibrational energy may belong to regulatory peptides and peptide-based pharmacological agents possessing a synactonic mechanism of action, exerting multiple effects on intermolecular processes, transcriptional regulation, and the integration of the nervous, endocrine, and immune systems into a unified functional continuum, thereby restoring higher brain functions.

Background: Interest in the study of polysaccharides derived from higher plants is due to their high biological activity coupled with low toxicity. Polysaccharides and oligosaccharides extracted from the fruits and flowers of various hawthorn species (Crataegus spp.) exhibit diverse effects, including anticoagulant and hypolipidemic activities, as well as antioxidant and probiotic properties. Therefore, the study of the immunomodulatory properties of polysaccharides derived from the shoots of Alma-Ata hawthorn (Crataegus almaatensis Pojark.) and soft hawthorn (Crataegus submollis Sarg.) is of particular interest.

Aim: The work aimed to study the immunotropic effects of water-soluble polysaccharides derived from the shoots of Alma-Ata hawthorn (Crataegus almaatensis Pojark.) and soft hawthorn (Crataegus submollis Sarg.).

Methods: Water-soluble polysaccharides were derived from the shoots of Alma-Ata hawthorn and soft hawthorn by extraction followed by filtration, dialysis, and lyophilization. The water-soluble polysaccharides were injected intraperitoneally to C57BL/6 mice at a dose of 10 mg/kg; animals in the control group received 0.9% sodium chloride solution, and the comparison group received glucosaminylmuramyl dipeptide at a dose of 20 µg/kg for 10 days. The effects of the water-soluble polysaccharides on humoral and cell-mediated immune responses induced by sheep red blood cell immunization were evaluated. In in vitro experiments, water-soluble polysaccharides were added to the culture medium at a concentration of 20 µg/mL, and the production of IL-1β, TNF-α, and NO, arginase activity, cell proliferation in cultures of peritoneal macrophages, and the production of IL-2 and IFN-γ by cultures of mouse splenocytes were assessed.

Results: Course administration of water-soluble polysaccharides derived from the shoots of Alma-Ata hawthorn and soft hawthorn stimulated the humoral immune response in experimental animals and did not affect the cell-mediated immune response. Addition of the polysaccharides derived from the shoots of Alma-Ata hawthorn and soft hawthorn to the culture medium increased the production of IL-1β and TNF-α, enhanced nitric oxide synthase activity, reduced arginase induction in macrophages, and increased both spontaneous IL-2 secretion and stimulated IFN-γ production by splenocytes from C57BL/6 mice.

Conclusions: Administration of water-soluble polysaccharides derived from the shoots of Alma-Ata hawthorn and soft hawthorn resulted in an increased number of antibody-forming cells after immunization with sheep red blood cells and enhanced production of IL-1β, TNF-α, and NO by macrophages and IL-2 and IFN-γ by splenocytes from C57BL/6 mice. The studied polysaccharide samples showed no cytotoxicity against macrophages.