Introduction: The aim of the study was to investigate the effects of myrtle secondary metabolites (hydrolate, syrup I, and syrup II) on overall brain electrical activity and the severity of neurological deficits in rats in simulated ischemia-reperfusion. Materials and Methods: Ischemia-reperfusion was modeled in 60 male Wistar rats using 30-minute occlusion of the left common carotid artery followed by restoration of blood flow. The animals were divided into six groups (n=10): sham-operated (SO); ischemia control (I/C); a comparison group Thiocetam; and experimental groups that received intragastrically administered myrtle hydrolate (Hydrolate), syrup I (Syrup I), and syrup II (Syrup II) at a dose of 2.5 mL/kg daily for 21 days. Results: Ischemia caused persistent suppression of EEG amplitudes (by 40–61%), spectrum restructuring with a predominance of delta (+47–63%) and theta rhythms (+41–119%) and suppression of alpha rhythm (–54–75%), as well as severe neurological deficit. Hydrolate had a moderate effect in the early period, but by day 21, amplitudes had fallen by 12–14% below the ischemia control (I/C) levels. Syrup I restored amplitudes (+29–82%), spectrum (alpha rhythm +151–345%, delta rhythm –36%), and neurological status by days 7–14. Syrup II restored neurological deficit by day 2 (0.08 points on the Bederson scale versus 1.67 in I/C); by day 7, the neurological deficit was fully restored, with EEG amplitudes increasing by 17–63% and alpha rhythm – by 104–272%. Discussion: The differences revealed in the neuroprotective activity of the three myrtle secondary metabolite compositions correlate with their chemical profiles. In terms of the intensity of their neuroprotective effect, the myrtle secondary metabolites were ranked in the following order: Hydrolate < Syrup I ≈ Thiocetam < Syrup II. Conclusion: Myrtle secondary metabolites, particularly Syrup II with its high flavonoid content, exert a complex neuroprotective effect, which manifests in the coordinated restoration of electrophysiological and behavioral parameters.
Introduction: The aim of the study was the effect of solid herbal extract of Primula veris L. and comparison drugs phenotropil and mildronate on the psycho-emotional state of rats after chronic alcohol intoxication (CAI). Materials and Methods: CAI was modeled by replacing drinking water with a 10% solution of ethyl alcohol with sucrose (50 g/L) for 6 months. After alcoholization, rats at the age of 16 months were divided into the following groups: 1 – intact – animals without CAI received oral 0.9% sodium chloride solution for 14 days; 2 – control – rats after ethanol withdrawal, which were injected with a 0.9% sodium chloride solution in a similar regimen; 3, 4 and 5 – experimental – females after CAI received oral solid herbal extract of Primula veris L. at a dose of 30 mg/kg, phenotropil 25 mg/kg, mildronate 50 mg/kg, respectively. After the end of treatment, to assess the psycho-emotional state of the animals, the Open field test, Elevated plus maze test, Marble burying test and Porsolt forced swim test were performed. Results and Discussion: In animals after CAI, increased anxiety is observed, which manifested itself in a greater number of stands with support, urinations and boluses in the Open field test compared to the intact group. In the Elevated plus maze test, the trend remained the same: rats in the control group entered the open compartment installation less often, hung from it less often, and spent less time in the open compartment. In addition, females after CAI exhibited compulsive behavior in the Marble burying test. In the Porsolt forced swim test, animals in the control group had a shorter period of active swimming compared to intact females and a longer period of immobilization, which indicates depressive behavior in the former. Solid herbal extract of Primula veris L., phenotropil and mildronate contributed to the improvement of the psycho-emotional state of animals after CAI. Conclusion: Thus, solid herbal extract of Primula veris L. at a dose of 30 mg/kg, which was administered orally once a day to female rats for 14 days after the withdrawal of ethanol, has a pronounced anxiolytic and antidepressant effect, while phenotropil and mildronate (25 mg/kg and 50 mg/kg, respectively, in a similar regimen) had a greater anticompulsive effect.
Introduction: Apoptosis resistance in non-small cell lung cancer is frequently sustained by pro-survival Bcl-2 family proteins such as Mcl-1, motivating the search for new Mcl-1 inhibitors from natural products, including diterpenoids from Rabdosia serra. Materials and Methods: An integrated in silico approach was applied to evaluate R. serra diterpenoids as putative Mcl-1 (PDB: 6QFQ) inhibitors, integrating molecular docking, molecular dynamics simulation, MM/GBSA rescoring, pkCSM-based ADMET prediction, and DFT calculations at the B3LYP/6-31G(d,p) level, with Tivantinib as the reference ligand. Results and Discussion: Docking prioritized CPD1 (-10.31 kcal/mol) over Tivantinib (-9.09 kcal/mol). Molecular dynamics simulation indicated stable complexes, with CPD1-6QFQ showing a more compact, less solvent-exposed ensemble (Rg 1.42-1.45 nm; SASA 83-89 nm²; RMSD 0.09-0.15 nm). MM/GBSA favored CPD1 (ΔTOTAL -26.17 ± 2.79 kcal/mol) versus Tivantinib (-24.25 ± 4.50 kcal/mol). ADMET predicted high intestinal absorption for CPD1 (98.243%), a higher unbound fraction, and fewer liabilities (negative hepatotoxicity; negative hERG II inhibition). DFT supported CPD1 with a smaller ΔE (3.7165 eV) and higher softness (0.5381 eV⁻¹) than Tivantinib. Conclusion: Convergent computational evidence nominates CPD1 as a leading putative Mcl-1 inhibitor for optimization, while target engagement, efficacy, and safety require experimental validation.
Introduction: The problem of cardiorenal syndrome (CRS) in patients with acute coronary syndrome (ACS) and arterial hypertension (AH) is highly relevant. Early diagnosis, based on cystatin C, microalbuminuria, and arterial stiffness, is key for prognosis and therapy selection. Aim: To assess CRS marker dynamics and arterial stiffness in patients with ACS, AH, and chronic kidney disease (CKD) on standardized therapy, and to develop a treatment selection algorithm. Materials and Methods: A prospective study included 148 patients after percutaneous coronary intervention for ACS with AH. The main group (n=118) had CKD stages 2-3; controls (n=30) had no CKD. All received initial therapy with a fixed-dose combination of amlodipine 5 mg/perindopril 5 mg once daily, with possible uptitration to a triple combination including indapamide 1.25 mg (amlodipine 5 mg/perindopril 5 mg/indapamide 1.25 mg once daily). Markers were assessed at days 10-12 and 3 months. Results: Cystatin C and microalbuminuria correlated with ACS severity and arterial stiffness. After 3 months, the main group showed significant improvement: cystatin C decreased from 1.35±0.33 to 1.02±0.29 mg/L; microalbuminuria – from 41.24±3.56 to 25.56±2.99 mg/L; pulse wave velocity – from 9.31 to 8.20 m/s (all p<0.001). Triple therapy provided a more pronounced effect. Baseline cystatin C >1.3 mg/L and microalbuminuria >30 mg/L are criteria for considering early triple therapy initiation. Conclusion: Standardized therapy with perindopril/amlodipine, with the possible addition of indapamide, significantly improves cardiorenal status and vascular stiffness. The developed algorithm, based on initial biomarkers, allows for a personalized approach to managing these comorbid patients.
Introduction: Anthracyclines and anthracenedione derivatives are a group of anticancer drugs that are widely used in clinical practice. Their application is frequently limited by cardiotoxic effects. The aim of this study was to evaluate the cardiotoxicity of the new anthracenedione derivative Anthrafuran (AF) in comparison with Doxorubicin (Dox) and Mitoxantrone (MT). Materials and Methods: The study was conducted on 50 adult female Wistar rats. AF, MT, and Dox were administered in therapeutic doses and regimens for this animal species (AF: 20 mg/kg x 3/48 per os; MT: 1 mg/kg x 3/96 i.v.; Dox: 2.5 mg/kg x 3/72 i.v.). Electrocardiographic (ECG) parameters and heart weight index were determined; histological evaluation of the myocardium was performed on days 1 and 30 post-treatment. Results: Dox intravenous injections in therapeutic doses caused a pronounced cardiotoxic effect. The signs of cardiac decompensation manifested as a significant decrease in heart rate (HR) (Dox 486±6, control 522±12.8), prolongation of the QT interval (Dox 0.06±0.002, control 0.048±0.001), an increase in weight index of the heart (Dox 0.41±0.03, control 0.36±0.006), and myocardial damage. Although the cardiotoxicity of MT was less pronounced, it nevertheless negatively affected both ECG parameters (HR 465±15, QT 0.056±0.002) and the structure of the heart muscle. The use of AF did not cause any pathological changes and had no effect on the heart weight index or ECG parameters (HR 498±7.3, QT 0.052±0.003, weight index of the heart 0.35±0.009). Conclusion: Unlike Dox (2.5 mg/kg x 3/72 i.v.) and MT (1 mg/kg x 3/96 i.v.), the new anthracenedione derivative AF (20 mg/kg x 3/48 per os) in therapeutic doses does not possess cardiotoxic properties, supporting its potential for clinical study.
