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Objective(s): The study aims to estimate the neuroprotective effect of chromone derivatives in the sporadic form of Alzheimer’s disease in the context of the relationship between changes in mitochondrial function and neuroinflammation.Materials and Methods: Alzheimer’s disease was modeled by injecting Aβ 1-42 fragments into the CA1 part of the hippocampus of animals. The test compounds and memantine were administered orally for 60 days from the moment the pathology was reproduced. The change in cognitive deficit in rats was assessed in the Y-maze test. In the hippocampus of rats, intensity of cellular respiration, activity of mitochondrial enzymes (citrate synthase, aconitase, cytochrome-c-oxidase, and succinate dehydrogenase), concentrations of IL - 6; IL -1β; TNF -α; IL – 10, and cardiolipin were determined.Results: Of the 18 substances, only C3AACP6 and C3AACP7 compounds contributed to the recovery of aerobic metabolism, increased activity of mitochondrial enzymes, and reduced neuroinflammation in the hippocampus of rats. Furthermore, administration of these substances reduced the manifestation of cognitive deficit in animals with Alzheimer’s disease to a degree comparable with memantine. Moreover, in terms of the effect on changes in the activity of mitochondrial enzymes and aerobic metabolism, these substances significantly exceeded memantine.Conclusion: The study showed that from the analyzed chromone derivatives, two compounds C3AACP6 and C3AACP7 could have a neuroprotective effect in Alzheimer’s disease, which is realized through the axis: recovery of mitochondrial function, decrease extramitochondrial cardiolipin, decrease neuroinflammation, neuroprotection.

Introduction: Neuroprotection is a promising area of adjuvant therapy of ischemic brain lesions. At the same time, among potentially effective neuroprotectors, herbal remedies are distinguished due to their high efficiency and safety of use. In this work, some aspects of the neuroprotective effect of 40% ethanol extract of black walnut bark were investigated in comparison with its major component juglone . Materials and methods: The work was performed on male Wistar rats, which were simulated with cerebral ischemia by irreversible occlusion of the middle cerebral artery. The acute toxicity of the extract was preliminarily evaluated. During the work, the following parameters were determined: changes in the behavior of animals in the Morris water maze, cerebral blood flow, brain necrosis zone area, the activity of mitochondrial complexes, citrate synthase activity, lactic, pyruvic, and ATP concentrations. The activity of the studied extract was compared with juglone in a concentration of 1 mg/kg (per os). Discussion: The study showed that the use of black walnut bark extract in conditions of cerebral ischemia contributed to an increase in the activity of mitochondrial complexes I-V, citrate synthase, which in turn led to the normalization of aerobic-anaerobic metabolism reactions. The increase in the activity of respiratory complexes is probably mediated by the antioxidant properties of juglone , which is a major component of the test extract of black walnut bark. Conclusion: Thus, the test extract can be a potentially effective neuroprotective agent and requires further study.

Introduction: The aim of the study was to investigate the dose-dependent actoprotective effect of ATACL on physical performance and psychoemotional status of animals under conditions of exhausting exercise. Materials and methods: Outbred male mice (23–25 g) were used in the experiment. The test compound in various dosages, as well as the reference drug, were administered intragastrically 60 minutes before the forced swimming test for 10 days of the experiment. At the end of the physical activity, the psychoemotional status of the animals was assessed in the Open Field (OF) and Elevated plus maze (EPM) tests. Results and discussion: In the course of the experiment, it was found that under conditions of exhausting physical execise, a smooth increase in performance was observed in the group that had received the test compound 4-hydroxy-3,5-di-tert butyl cinnamic acid (ATACL) at a dosage of 100 mg/kg for 10 days. The peak of performance was recorded on the 8th day, which was 47.3% (p

Neurodegenerative processes of the central nervous system are an important socially significant problem of modern society. They cause many diseases, such as Alzheimer's disease and cerebral ischemia, which significantly reduce the quality of human life and can lead to disability or death. The aim of this study was to synthesize novel 6,7-dimethoxyquinazolin-4(3H)-one derivatives with the remains of neuroactive amino acids and dipeptides in order to investigate their cerebroprotective properties. As a result of the study, 13 novel 6,7-dimetho-xyquinazolin-4(3H)-one derivatives were synthesized. Cerebral ischemia in rats was reproduced by irreversible right-sided occlusion of the middle cerebral artery using the Tamura method, and the area of brain necrosis was evaluated. Cognitive functions were evaluated in the Y-maze test. Among the studied quinazolinone derivatives, compounds 3i, 3j and 3k have the most pronounced cerebrotropic activity, which is not inferior to ethylmethylhydroxypyridine succinate in terms of pharmacological activity, making them promising objects for further research.

Introduction: In this study, the neuroprotective effect of L-carnitine administered per os in a dose of 25 mg/kg – 800 mg/kg was evaluated. The effects of L-carnitine on changes in mitochondrial function were also studied. Materials and Methods: The neuroprotective effect and mitochondrial function were evaluated in a model of permanent focal ischemia in Wistar-line rats. L-carnitine was administered to rats orally for 72 hours from the moment of modeling ischemia. On the 4th day after the ischemia simulation, the change in the respiratory function of the mitochondria, the opening time of the mitochondrial permeability transition pore, the mitochondrial membrane potential, the concentration of intracellular calcium and the size of the cerebral necrosis zone were determined in rats’ brain supernatant. Results: As a result, it was found that the administration of L-carnitine contributed to the restoration of mitochondrial function and a decrease in the size of the brain necrosis zone. At the same time, the administration of L-carnitine in low doses (25 mg/kg – 100 mg/kg) did not have a significant effect on the change in the concentration of intracellular calcium. It should be noted that an increase in the dose of L-carnitine from 200 mg/kg to 800 mg/kg was not accompanied by a significant increase in the therapeutic effect. Discussion: L-carnitine is one of the key biomolecules that directly affect metabolic processes. It is known that L-carnitine acts as a ”shuttle” for long-chain fatty acids and thus can affect the alteration of mitochondrial function. However, the detailed nature of the mitochondriotropic action of L-carnitine has not been yet established. This was the focus of this study, which showed that the mitochondrion-oriented effect of L-carnitine is dose-dependent and expressed in the form of restoring the respiratory function of mitochondria, restoring the mitochondrial potential and increasing the latent opening time of the mitochondrial permeability transition pore, reducing the level of intracellular calcium. Conclusion: The study allowed us to expand our understanding of the L-carnitine neuroprotective effect and the effect of this compound on changes in mitochondrial function. Graphical abstract

Alzheimer's disease is a chronic neurodegenerative disease, which is characterized mainly by a progressive decrease in intellectual abilities, memory impairment and a change in a person's personality. Unfortunately, there are practically no medicines that act on pathogenesis of Alzheimer's disease. The development of new highly effective medicines for the treatment of this pathology is an actual area of pharmaceutical research. The aim of this work is to search among 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one effective compounds with an anticholinesterase and an antiamyloid activities. As a result, it was found that compounds 4d, 4e and 4f have the high anticholinesterase ability, which in their structure contain residues of hydroxy-methoxyphenyl fragments. Structures 4c, 4g, 4h, 4j, 4k, 4m, 4n and 4p showed slightly less activity, the effect of which did not differ statistically from that of Donepezil. Compounds 4c, 4e, 4k and 4m have the greatest ability to inhibit the formation of the amyloid, comparable to GV-971. It should be noted that the molecular docking data are consistent with the results of the determination of the anticholinesterase activity of the studied compounds obtained in vitro. Thus, the prospects for future studies of these compounds in the possibility of creating a pharmaceutical active substance for the treatment of neurodegenerative diseases have been revealed.

Background and objectives: To evaluate the effect of a new pyrimidine derivative on the change of mitochondrial function in experimental chronic traumatic encephalopathy. Materials and methods: The study was performed on male mice of the BALB/c line (acute toxicity was assessed) and male rats of the Wistar line, which were modeled chronic traumatic encephalopathy by the method of free fall of the load (weight 150 g from a 50 cm height). The injury to rats was reproduced once a day for 7 days. Further, cognitive functions, changes in sensorimotor deficiency, cerebral blood flow, neuron-specific enolase(NSE), S100β, glial fibrillary acidic protein (GFAP) (in blood serum) and β-amyloid, adenosine triphosphate (ATP) (in brain tissue supernatant) were evaluated. Mitochondrial respiration was also measured. Choline alfoscerate (100 mg/kg) was used as a reference drug. Results: The study found that the use of a new pyrimidine derivative contributed to the preservation of the mitochondrial respirometric function and cognitive functions in rats. In addition, against the administration of test-object marked increase in the concentration of ATP, the velocity of cerebral blood flow was 4.2 times (p < 0.05) and 35.6% (p < 0.05), respectively, as well as reduced concentration and GFAP, NSE, S100β, β-amyloid and sensorimotor deficit at 2.7 (p < 0.05) times; 2 times (p < 0.05); 2.4 times (p < 0.05); of 30.4% (p < 0.05 and 46.5% (p < 0.05), respectively. The LD50 (per os) for the test-object was 4973.56 ± 573.72 mg/kg. Conclusion: Based on the obtained data, high therapeutic efficacy and low systemic toxicity of the application are assumed 4-{2-[2-(3,4-dimethoxyphenyl)-vinyl]-6-ethyl-4-oxo-5-phenyl-4H-pyrimidine-1-Il}benzsulfamide in chronic traumatic encephalopathy.