Phytochemical, Pharmacological, and Molecular Docking Study of Dry Extracts of Matricaria discoidea DC. with Analgesic and Soporific Activities.

Pineapple weed (Matricaria discoidea DC.) is a widespread plant in Europe and North America. In ethnomedicine, it is well-known for its anti-inflammatory and spasmolytic activities. The aim of this research was to develop novel methods of M. discoidea processing to obtain essential oil and dry extracts and to investigate their phytochemical compositions. Moreover, the molecular docking of the main substances and the in vivo studies on their soporific and analgesic activities were conducted. The essential oil and two dry extracts from M. discoidea were prepared. A total of 16 phenolic compounds (seven flavonoids, seven hydroxycinnamic acids, and two phenolic acids) in the dry extracts were identified by means of UPLC-MS/MS. In the essential oil, nine main terpenoids were identified by gas chromatography (GC). It was shown that phenolic extraction from the herb was successful when using 70% ethanol in a triple extraction method and at a ratio of 1:14-1:16. The in vivo studies with rodents demonstrated the analgesic activity of the M. discoidea extracts and improvements in the sleep of animals. The dry extracts of M. discoidea did not show any toxicity. The molecular docking analysis showed a high probability of COX-1,2 inhibition and NMDA receptor antagonism by the extracts.

Phytochemical, Technological, and Pharmacological Study on the Galenic Dry Extracts Prepared from German Chamomile (Matricaria chamomilla L.) Flowers.

Galenic preparations of German chamomile are used to treat mild skin diseases, inflammation, and spasms, and they have also been reported to have anxiolytic and sedative effects. The medicinal use of chamomile is well known in ethnomedicine. After obtaining its galenic preparations, there is lots of waste left, so it is expedient to develop waste-free technologies. The aims of this study were to gain knowledge of the ethnomedical status of chamomile in the past and present, develop methods for preparing essential oils and dry extracts from German chamomile flowers using complex processing, reveal the phytochemical composition of such extracts, and verify the analgesic and soporific activity of the extracts. Two methods for the complex processing of German chamomile flowers were developed, which allowed us to obtain the essential oil and dry extracts of the tincture and aqueous extracts as byproducts. A total of 22 phenolic compounds (7 hydroxycinnamic acids, 13 flavonoids, and 2 phenolic acids) were found in the dry extracts by using UPLC-MS/MS. In total, nine main terpenoids were identified in the chamomile oil, which is of the bisabolol chemotype. During the production of chamomile tincture, a raw material-extractant ratio of 1:14-1:16 and triple extraction are recommended for its highest yield. In in vivo studies with mice and rats, the extracts showed analgesic activity and improvements in sleep. The highest sedative and analgesic effects in rodents were found with the dry extract prepared by using a 70% aqueous ethanol solution for extraction at a dose of 50 mg/kg. The developed methods for the complex processing of German chamomile flowers are advisable for implementation into the pharmaceutical industry to reduce the volume of waste during the production of its essential oil and tincture, and to obtain new products.

Application of nanofiber-based drug delivery systems in improving anxiolytic effect of new 1,2,3-triazolo-1,4-benzodiazepine derivatives.

Anxiety disorders are highly prevalent worldwide and can affect people of all ages, genders and backgrounds. Much efforts and resources have been directed at finding new anxiolytic agents and drug delivery systems (DDSs) especially for cancer patients to enhance targeted drug delivery, reduce drug adverse effects, and provide an analgesic effect. The aim of this study was (1) to design and develop novel nanofiber-based DDSs intended for the oral administration of new 1,2,3-triazolo-1,4-benzodiazepines derivatives, (2) to investigate the physical solid-state properties of such drug-loaded nanofibers, and (3) to gain knowledge of the anxiolytic activity of the present new benzodiazepines in rodents in vivo. The nanofibers loaded with 1,2,3-triazolo-1,4-benzodiazepine derivatives were prepared by means of electrospinning (ES). Field-emission scanning electron microscopy and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy were used for the physicochemical characterization of nanofibers. The anxiolytic activity of new derivatives and drug-loaded nanofibers was studied with an elevated plus maze test and light-dark box test. New 1,2,3-triazolo-1,4-benzodiazepine derivatives showed a promising anxiolytic effect in mice with clear changes in behavioral reactions in both tests. The nanofiber-based DDS was found to be feasible in the oral delivery of the present benzodiazepine derivatives. The nanofibers generated by means of ES presented the diameter in a nanoscale, uniform fiber structure, capacity for drug loading, and the absence of defects. The present findings provide new insights in the drug treatment of anxiety disorders with new benzodiazepine derivatives.

STUDY OF POPULATION ADHERENCE TO COVID-19 VACCINATION.

OBJECTIVE: The aim: To study population adherence to COVID-19 vaccination and to identify factors influencing people's decision to vaccinate, and to develop of possible ways to increase the rate of COVID-19 vaccination. PATIENTS AND METHODS: Materials and methods: Individuals of different social groups were surveyed about adherence to COVID-19 vaccination. RESULTS: Results: Results of the study are the determination of the factors influencing the decision on vaccination. The most important were the opinion that the vaccine is not safe; fear of developing a side effect after vaccination and opinions about the low effectiveness of the vaccine. However, the almost 53% of unvaccinated persons doubted their decision or even expressed a desire to be vaccinated in the future. A possible way to increase the population's adherence to vaccination will be to increase awareness of the effectiveness and safety of vaccination. CONCLUSION: Conclusions: The results revealed the factors that influenced the positive and negative decision about COVID-19 vaccination, which made it possible to propose ways to increase the population's adherence to vaccination.

Arctostaphylos uva-ursi L. leaves extract and its modified cysteine preparation for the management of insulin resistance: chemical analysis and bioactivity.

Bearberry (Arctostaphylos uva-ursi L.) is a perennial plant of the heather family (Ericaceae). The leaves are dominated by arbutin, phenol carbonic acids flavonoids, saponins, etc. It was previously shown that the bearberry leaves extract reduced blood glucose level in healthy animals under glucose overload, so it need to be studied more detail. The aim of the study was to investigate the chemical composition and the effect of dry alcohol extract from bearberry leaves, which enriched with cysteine, on the rats pancreas under experimental dexamethasone-induced insulin resistance (IR). Arctostaphylos uva-ursi L. leaves extract and its modified cysteine preparation were obtained according to the developed method with 50% ethanol solution. Their phytochemical profile, hypoglycaemic and pancreatic protective effect were investigated. Phenologlycoside (arbutin), phenolic carboxylic acid (gallic acid), 5 flavonoids and 4 hydroxycinnamic acids were identified and quantified in the extracts by HPLC. Present data revealed that bearberry leaves alcoholic dry extract enriched with cysteine has a hypoglycaemic and pancreatic protective effect in treated animals under dexamethasone-induced IR model. Treatment improved hyperglycaemia, insulin resistance and beta cell reduction induced by dexamethasone injections.

PREVENTION OF ASTHENIC SYNDROME AS CONCOMITANT CIRCUMSTАINS IN POST-COVID-19 PATIENTS.

OBJECTIVE: The aim: Is research into development of asthenic syndrome and its effect on the productivity in post-COVID-19 patients. PATIENTS AND METHODS: Materials and methods: All patients underwent neuropsychological testing immediately after the COVID-19 treatment and one month after a comprehensive rehabilitation program. RESULTS: Results: The research proved that of all post-COVID-19 patients, who showed signs of asthenic syndrome from predominantly moderate to extreme severity, the patients who followed the complete comprehensive rehabilitation intervention significantly reduced verifiable severity of asthenic syndrome as well as the disability duration. CONCLUSION: Conclusions: Early administration of combined rehabilitation methods enables preventing the development of long-term side effects, reduces recovery time and enchases the productivity in post-COVID-19 patients.

Phytochemical and Psychotropic Research of Motherwort (Leonurus cardiaca L.) Modified Dry Extracts.

The prospect of creating a new medicine with psychotropic activity is shown as a result of studying the chemical composition and pharmacological activity of modified dry extracts of motherwort (Leonurus cardiaca L.) tincture. The most promising substances were the dry extracts, modified by adding small amounts of arginine, valine, phenylalanine, glycine, lysine, and alanine. A total of 15 main phenolic substances were found in the extracts, and eight of them were identified. There were also 10 hydroxycinnamic acids in these extracts, three of which were identified (chlorogenic, caffeic, and rosmarinic acids). The dominant hydroxycinnamic acids were chlorogenic and caffeic acids. Among flavonoids, catechin, hyperoside, and rutin were identified. It should be noted that the extracts had a significant content of ellagic acid. On the basis of the results of the phytochemical analysis of the extracts, it can be concluded that the composition of phenolic compounds does not differ significantly, and the main differences are related to amino acids, which obviously have an impact on the overall pharmacological effect. The results obtained indicate the presence of anxiolytic activity in the motherwort extracts studied in complex with amino acids. The extracts with glycine, valine, and arginine were more effective in reducing anxiety in animals.

Centrosome separation: respective role of microtubules and actin filaments.

In mammalian cells, the separation of centrosomes is a prerequisite for bipolar mitotic spindle assembly. We have investigated the respective contribution of the two cytoskeleton components, microtubules and actin filaments, in this process. Distances between centrosomes have been measured during cell cycle progression in Xenopus laevis XL2 cultured cells in the presence or absence of either network. We considered two stages in centrosome separation: the splitting stage, when centrosomes start to move apart (minimum distance of 1 microm), and the elongation stage (from 1 to 7 microm). In interphase, depolymerisation of microtubules by nocodazole significantly inhibited the splitting stage, while the elongation stage was, on the contrary, facilitated. In mitosis, while nocodazole treatment completely blocked spindle assembly, in prophase, we observed that 55% of the centrosomes separated, versus 94% in the control. Upon actin depolymerisation by latrunculin, splitting of the interphase centrosome was blocked, and cells entered mitosis with unseparated centrosomes. Cells compensated for this separation delay by increasing the length of both prophase and prometaphase stages to allow for centrosome separation until a minimal distance was reached. Then the cells passed through anaphase, performing proper chromosome separation, but cytokinesis did not occur, and binuclear cells were formed. Our results clearly show that the actin microfilaments participate in centrosome separation at the G2/M transition and work in synergy with the microtubules to accelerate centrosome separation during mitosis.