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.

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.

Anxiety disorders represent one of the most prevalent categories of psychiatric illnesses, affecting individuals regardless of gender, age, or social standing. They result in substantial personal and societal costs. The pursuit of novel pharmacological approaches for treating these disorders is driven by the increasing medical necessity to enhance the effectiveness and safety profiles of anxiolytic medications. Due to the fact that benzodiazepines and their derivatives have anti-anxiety, hypnotic-sedative, antidepressant, anticonvulsant, and muscle relaxant properties, they occupy a leading place in the treatment of anxiety disorders. An essential aspect of investigating the pharmacological activity of new triazolobenziazepine derivatives is assessing their impact on rodent muscle tone and coordination of movements. The aim of the work is to find out the influence of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the muscle tone of rodents in the “vertical grid” test and coordination of movements using the rotarod test. Materials and methods. The objects of the study were 5 new derivatives of 1,2,3-triazolo-1,4-benzodiazepines. Before conducting in vivo experiments, these derivatives were mixed with lactose at a ratio of 1:1000. The “vertical grid” test and rotarod test (rotating rod test) were used to reproduce the model of motor behavior of rodents. Results. The presence of a tendency to the manifestation of a myorelaxant effect in the “vertical grid” test was established. The indicator of the total duration of detention at the facilities was similar and did not differ significantly in the control and experimental groups at doses of 0.50 mg/kg and 0.75 mg/kg. Derivatives MA-252, MA-253 and MA-254 at a dose of 1 mg/kg reduced the total duration of retention on the vertical grid, which indicates their mild muscle relaxant effect. In the rotating rod test, MA-253 derivative at a dose of 1 mg/kg increased the retention time on the rotarod, which demonstrates greater physical endurance of the animals of these experimental groups. Conclusions. The study’s findings indicated that the 1,2,3-triazolo-1,4-benzodiazepine derivatives did not exhibit an adverse impact on movement coordination. Some of these derivatives demonstrated a mild muscle relaxant effect. These results support the need for further research into their influence on spontaneous motor activity. Additionally, there’s a necessity to determine the dosage regimen, establish an effective dose, and adapt it for human use.

Anxiety disorders are the most prevalent psychiatric disorders and are associated with a high burden of illness. Combining synthetic and native-origin compounds in treating such disorders could provide true benefits in terms of therapeutic efficacy. In the present study, we combined triazolobenzodiazepine and motherwort (Leonurus cardiaca L.) dry extract for such applications. The aim. The aim of this study was to develop aqueous polyethylene oxide (PEO) composite gels loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and a valine-modified motherwort herb dry extract for semi-solid extrusion (SSE) 3D printing. The printability of such gels and the physicochemical properties of the final 3D-printed drug preparations were investigated. Materials and methods. A new drug substance, 1,2,3-triazolo-1,4-benzodiazepine (MA-253) was synthesized and used to formulate oleogels and electrospun nanofibers for 3D printing. The plant-origin dry extract was prepared from a motherwort tincture and valine. The aqueous PEO gels loaded with a synthetic drug (MA-253) containing nanofibers and a valine-modified motherwort extract were prepared and subsequently used in the SSE 3D printing experiments. The homogeneity, viscosity and 3D printability of composite PEO gels were verified. The phytochemical assay of flavonoids in the 3D-printed drug preparations was conducted with the European pharmacopoeia spectrophotometric method. Research results. Three experimental gel formulations loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and a valine-modified motherwort dry extract were developed and tested for the SSE 3D printing applications. The present three gels showed good SSE 3D printability without any significant printing flaws. The SSE 3D-printed lattices prepared from the aqueous PEO gels containing 100 mg/ml of motherwort extract showed the most promising 3D printing performance. The 3D-printed drug preparations were entirely dissolved in purified water (22±2 °C) within 20 minutes, thus suggesting their applicability in oral administration. Conclusions. Novel aqueous PEO gel formulations loaded with nanofibrous 1,2,3-triazolo-1,4-benzodiazepine nanofibers and valine-modified motherwort herb extract are feasible for pharmaceutical SSE 3D printing. The present composite PEO gels enable the preparation of printed oral immediate-release drug delivery systems for new triazolobenzodiazepine derivatives and a drug therapy supportive plant extract Тривожні розлади є найбільш поширеними психіатричними розладами і пов'язані з великою кількістю захворювань. Поєднання синтетичних і природних субстанцій у лікуванні таких розладів може забезпечити значні переваги у терапевтичній ефективності. У цьому дослідженні ми поєднали похідні триазолобензодіазепінів та сухий екстракт собачої кропиви трави (Leonurus cardiaca L.). Мета. Метою цього дослідження була розробка композитних водних гелів на основі поліетиленоксиду (ПEO) з 1,2,3-тріазоло-1,4-бензодіазепіновими нановолокнами та сухим екстрактом собачої кропиви трави, модифікованого валіном, придатних для напівтвердого екструзійного 3D друку. Було досліджено можливість 3D друку таких гелів, їх фізико-хімічні властивості та надруковані на 3D-принтері лікарські форми. Матеріали та методи. Нове похідне 1,2,3-триазоло-1,4-бензодіазепіну (МА-253) було синтезовано та використано для створення олеогелів з нановолоконами, які були завантажені ним. Сухий екстракт готували з настойки собачої кропиви та валіну. Були виготовлені водні ПЕО-гелі, до складу яких входили нановолокна з синтетичним препаратом MA-253 та екстракт собачої кропиви трави, модифікований валіном, які згодом використовувалися для екструзійниого 3D друку. Було перевірено однорідність, в’язкість і можливість 3D-друку цих композитних ПЕО-гелів. Фітохімічний аналіз флавоноїдів у надрукованих на 3D-принтері лікарських формах проводили спектрофотометричним методом згідно методики Європейської фармакопеї. Результати досліджень. Три експериментальні гелеві композиції з нановолокнами 1,2,3-тріазоло-1,4-бензодіазепінів та сухим екстрактом собачої кропиви, модифікованим валіном, були розроблені та досліджені на придатність для екструзійного 3D друку. Ці три гелі продемонстрували гарну друкованість без будь-яких суттєвих недоліків. Аналіз решіток, надрукованих на 3D принтері, показав, що ПЕО-гель, який містив 100 мг/мл екстракту собачої кропиви, є найбільш...

Anxiety-depressive disorders are among the most common mental health conditions and often cause significant functional impairment, affecting a person’s quality of life. Research conducted in recent years indicate the importance of studying and searching for new substances based on benzodiazepines, in particular triazolobenzodiazepines, for the treatment of anxiety states and disorders, as well as determining the presence of other biological activities of these compounds. Aim. To study the antidepressant activity of new derivatives of 1,2,3-triazolo-1,4-benzodiazepines in the Porsolt forced swim and tail suspension tests. Materials and methods. The antidepressant activity of new 1,2,3-triazolo-1,4-benzodiazepine derivatives under the code MA-252, MA-253, MA-254, MA-255 and MA-261 was studied in the Porsolt forced swim and tail suspension tests. The following behavioral reactions, such as the latent period of the first immobility (more than 5 seconds), the total duration of immobility (staying in a stationary state), the number of immobile episodes, were recorded. Results and discussion. During the study, a decrease in the total duration of immobility, the main indicator of “despair” of animals, and an increase in the latent period of the first immobility were monitored. It may indicate the manifestation of antidepressant properties of new 1,2,3-triazolo-1,4-benzodiazepine derivatives. The indicator of the antidepressant activity in groups of animals administered MA-253, MA-254 and MA-255 derivatives in all doses was higher among the groups studied. The depression index was the lowest when MA-253 and MA-254 derivatives were used in the dose of 1 mg/kg, and was not statistically significantly different from that in the group receiving imipramine in the dose of 25 mg/kg. According to the results of the tail suspension test, 1,2,3-triazolo-1,4-benzodiazepine derivatives MA-253, MA-254 and MA-255 showed a significant decrease in the total duration of immobilization by 69.4 %, 47.1 % and 33.1 %, respectively, in relation to the control group (p<0.05), as well as an increase in the latent period of the onset of the first immobility episode by several times. Conclusions. A decrease in the duration of immobility in mice injected with 1,2,3-triazolo-1,4-benzodiazepine derivatives gives grounds to draw a conclusion that animals develop a state of “behavioral despair” and exhibit antidepressant properties. Тривожно-депресивні розлади є одними з найпоширеніших станів психічного здоров’я і часто викликають значні функціональні порушення, впливаючи на якість життя людини. Дослідження останніх років свідчать про важливість вивчення та пошуку нових речовин на основі бензодіазепінів, зокрема триазолобензодіазепінів, для лікування тривожних станів та розладів, а також виявлення інших біологічних активностей цих сполук. Метою роботи було дослідити антидепресивну активність нових похідних 1,2,3-триазоло-1,4-бензодіазепінів у тестах примусового плавання за Порсолтом та «підвішування за хвіст». Матеріали та методи. Антидепресивну активність нових похідних 1,2,3-триазоло-1,4-бензодіазепінів під шифром МА-252, МА-253, МА-254, МА-255 та МА-261 досліджували в тестах примусового плавання за Порсолт та «підвішування за хвіст». Реєстрували такі поведінкові реакції, як: латентний період першого зависання (понад 5 секунд), загальна тривалість іммобілізації (перебування в нерухомому стані), кількість зависань. Результати та їх обговорення. Під час дослідження відстежували зменшення загальної тривалості завмирання, основного показника «відчаю» тварин, та збільшення латентного періоду першого зависання, що може свідчити про прояв антидепресивних властивостей нових похідних 1,2,3-триазоло-1,4-бензодіазепінів. Показник антидепресивної активності в групах тварин, яким вводили МА-253, МА-254 та МА-255 в усіх досліджуваних дозах, був вищий серед досліджуваних груп. Індекс депресивності був найнижчий за застосування похідних МА-253 та МА-254 в дозі 1 мг/кг та статистично значуще не відрізнявся від такого в групі, тварини якої отримували іміпрамін в дозі 25 мг/кг. За результатами тесту «підвішування за хвіст» похідні 1,2,3-триазоло-1,4-бензодіазепінів МА-253, МА-254 та МА-255 продемонстрували помітне зменшення загальної тривалості іммобілізації на 69,4 %, 47,1 % та 33,1 % відповідно, якщо порівнювати з групою контролю (р<0,05), а також збільшення латентного періоду...

Inflammation accompanies huge numbers of diseases. In case of inflammation, non-steroidal anti-inflammatory drugs are used, but they have a number of side effects and disadvantages. In turn, medicines based on the medicinal plant raw material that exhibit the anti-inflammatory activity, on the contrary, are underestimated and insufficientlystudied. An interesting object in this direction is large cranberry leaves of Ericaceae family. Aim. To study the chemical composition and the anti-inflammatory activity of extracts from large cranberry leaves to establish the prospect of creating new drugs with the anti-inflammatory activity. Materials and methods. The study objects were dry extracts from large cranberry (Oxycoccus macrocarpus (Ait.)) leaves. The chemical analysis of the extracts was studied by TLC and spectrophotometry methods. The anti-inflammatory activity of the extracts was studied on the model of carrageenan edema. Results and discussion. Hyperoside and chlorogenic acid were identified in the extracts. In the dry extract from large cranberry leaves, the content of the total amount of derivatives of hydroxycinnamic compounds was 11.60 ± 0.05 %, and in the modified extract – 3.09 ± 0.05 %. The anti-exudative activity was more pronounced in the group of animals that received the cranberry extract with arginine in the dose of 100 mg/kg. Conclusions. Identification and the quantification of biologically active substances in large cranberry leaves extracts have been carried out; their anti-inflammatory activity has been determined.