Zuriyadda Sakipova’s research while affiliated with Kazakh National Medical University and other places

Adonis tianschanica is a lesser-known plant species belonging to the genus Adonis that grows in Kazakhstan. The aim of this study was to characterize the composition of the ethanolic, water, and hydroethanolic extracts from the aerial parts of A. tianschanica by HPLC-ESI-QTOF-MS/MS to isolate the major compound isoquercitrin by HSCCC (High-Speed Counter-Current Chromatography) and to determine the cytotoxicity and anti-inflammatory potential of the extracts produced with this plant. Fingerprinting of the analyzed extracts showed the presence of a multitude of metabolites comprising polyphenols, organic acids, and coumarins, and only trace quantities of cardiac glycosides in the analyzed samples. Flavonoids were certainly the best-represented group, with kaempferol, quercetin, and their derivatives as the major components of the extracts. Key findings in this paper were that the ethanol: water (50:50 v/v) extract of A. tianschanica and its major compound isoquercitrin were able to reduce the production of NO induced by LPS, in addition to demonstrating anti-inflammatory effects by reducing cytokines such as IL-6, TNF-α, and IL-1β.

The paper presents the results of anatomo-morphological studies of vegetative (leaves) and generative (fruits) organs of endemic plants of the genus Cotoneaster, black-fruited cotoneaster (Cotoneaster melanocarpus Fisch. ex Btytt) [1] and multifloral cotoneaster (Cotoneaster multiflorus Bunge) [2], growing in the foothills of the Zailiyskiy Alatau mountains of the Almaty region, the Republic of Kazakhstan. Species traits of the plants, which make it possible to identify the objects, were determined. Ground parts of both species, collected during the phenological phase of flowering and fruit ripening, were studied. The macroscopic and microscopic diagnostic features allowing the identification of plant raw materials within the framework of pharmacopoeial standardization were determined. The study of promising endemic plants of the Republic of Kazakhstan, expansion of the nomenclature list of sources of biologically active substances, development of pharmaceutical substances and preparations on their basis, as well as their use in modern pharmacy, are promising areas of pharmaceutical research [3]. In the pharmaceutical market of the Republic of Kazakhstan, foreign medicines have a significant share. The creation and introduction of competitive import-substituting fullcycle medicines from plant substances will contribute to the carrying out of the Comprehensive Plan for the Development of the Pharmaceutical and Medical Industry in the Republic of Kazakhstan for 2020-2025 and the realization of quality and affordable healthcare for every citizen. Within the framework of the research on the Kazakhstani flora, conducted at S.D. Asfendiyarov Kazakh National Medical University, plants of the genus Cotoneaster were studied [4, 5]. Representatives of the genus Cotoneaster are promising sources of biologically active substances C. melanocarpus Fisch. ex Btytt and C. multiflorus Bunge grow in Almaty region and are used in ethnotraditional medicine as antibacterial and antifungal agents. Infusions and decoctions of cotoneasters are used for gastrointestinal disorders, acute and chronic gastritis, gastroenteritis and diarrhoea [1]. Justification of inclusion of Cotoneaster melanocarpus Fisch. ex Btytt and Cotoneaster multiflorus Bunge as plant pharmaceutical substances in the nomenclature of sources of biologically active substances entails the establishment of quality criteria and standardization according to pharmacopoeial requirements.

The development of optimal technology for collecting and drying raw materials of Semenov's sweetvetch (Hedysarum semenowii Regel & Herder) ensures the preservation of pharmacological properties, quality consistency, increased efficiency, and environmental sustainability. This process requires consideration of the influence of a large number of different factors and their assessment. The inclusion of the concept “Quality by Design” (QbD) in the development process, which focuses on obtaining finished products with multi-factor quality risks, can facilitate and enable improvements. The application of QbD provides a systematic, risk-reducing, efficient structure that helps support continuous process improvement. The aim is the development of technology for collecting and drying Hedysarum semenowii Regel & Herder medicinal plant materials of pharmacopoeial quality using the “Quality by Design” concept. Materials and methods. The research materials were plant parts from Semenov's sweetvetch: aerial parts collected during the flowering period and roots collected at the end of fruiting. All collected plant specimens were identified by employees of the RSE REM “Institute of Botany and Phytointroduction”. According to QbD principles, to create a Design Space (DSp) of the process of obtaining herbal materials of Semenov's sweetvetch, Minitab statistical software was used. Results and discussion. Introduction of QbD principles in the development of a method for the procurement of H. semenowii herbalmaterials – H. semenowii aerial parts and H. semenowii roots – made it possible to develop the most optimal drying method. By adhering to best practices of the Good agricultural and collection practices for medicinal plants (GACP) and using Minitab statistical software, the relationship between quality and critical process parameters such as temperature and drying time was determined. This approach facilitated the determination of DSp, ensuring controlled and high-quality implementation of the technological process. Conclusion. Integration of the QbD concept into the development of technology for collecting and drying Semenov’s sweetvetch herbal materials has proven its effectiveness. The defined DSp, generated taking into account optimal process parameters, lays the foundation for a controlled and reproducible production process. This study demonstrates the potential of QbD to improve quality, efficiency, and control in herbal medicine development.

In recent years, there has been a significant increase in demand for herbal medicines, due to the growing interest of consumers in natural and safe alternatives to synthetic medicines. In response to these trends, manufacturers are focusing on developing new formulas and extraction technologies to meet the increased demand for herbal medicines. Modern extraction methods make it possible to efficiently extract secondary metabolites from plant raw materials, maintaining an almost complete chemical composition and ensuring a high yield of extractives. The possibility of regulating the concentration of extracted biologically active substances during the process opens up new prospects for the use of plant raw materials as basic pharmaceutical substances. It was found that all the studied plant species of the genus Crocus L. demonstrate antioxidant, anti-inflammatory and cardioprotective activity. Crocus alatavicus, which is a representative of the flora of Kazakhstan, is of particular interest. The purpose of this study is to select the optimal extraction method for obtaining extracts with the maximum content of flavonoids and carotenoids from the aboveground part of Crocus alatavicus. The study of the technological parameters of obtaining an extract from this plant active substance is of practical importance for the further development of medicines and the formation of a scientific justification for their use.

Currently, parasitic diseases are among the most widespread in the world. Statistical analysis of the recent years’ epidemic situation among the population of the Eurasian Economic Union countries has demonstrated a dynamic increase in the incidence of parasitic invasions. This situation indicates the need to analyze the satisfaction of the population of the Republic of Kazakhstan with antiparasitic medicines and to introduce into domestic production new innovative pharmaceutical developments of scientists of S.D. Asfendiyarov KazNMU School of Pharmacy, worked out based medicinal plant raw materials. Purpose. Analysis of the pharmaceutical market of antiparasitic drugs registered in the territory of Kazakhstan. Materials and methods. The object of the study is the list of trade names in the State Register of Medicines and Medical Devices registered in the territory of Kazakhstan, in the “i-teka. kz” database and other pharmacy markets, and the “IQVIA” database. Results. Based on the results of the analysis, it was established that the share of antiparasitic drugs in the context of all registered ones was only 1.49%, with only 10% of domestic production, represented by 5 Kazakh pharmaceutical companies. Analysis of the studied drugs according to the ATC classification showed that a large subgroup includes antimicrobial drugs and antiseptics used in gynecology. Among all registered drugs, tablets and suppositories are the most common. The cost of drugs and their course of treatment varies widely. According to sales analysis, the leader is albendazole, with a sales volume of 500 thousand packs annually. Conclusion. Thus, the market of antiparasitic drugs is represented mainly by imported products. Therefore, one of the most significant tasks of the domestic pharmaceutical industry is to ensure import substitution, which is to develop and create antiparasitic products based on domestic raw materials.

Introduction. Choosing the optimal method for drying medicinal plants is an important aspect of obtaining herbal materials of pharmacopoeial quality. At the site of the pharmaceutical enterprise Fitoleum LLP (Esik, Kazakhstan), a technology for obtaining herbal materials from autumn wormwood ( Artemisia serotina Bunge) was developed, within the framework of which the optimal drying method was studied using IR radiation, convective drying and shadow drying in natural conditions. In parallel with the experimental approach, a method for simulating drying conditions was implemented. The development of technology for the obtaining of herbal materials is implemented using the "Quality by Design" concept, one of the principles of which is the modeling of experiments (Design of experiments, DoE). The advantage of modeling when studying the processes is that this technique allows you to simultaneously analyze several input parameters and their impact on quality indicators, while significantly reducing the number of experiments. Aim. To choose the optimal method for drying autumn wormwood herb for further production of herbal medicine or herbal materials. Materials and methods. During the experiment, the following equipment was used: a manual harvester for collecting plants, pallets or racks with a mesh bottom, infrared substrates, a convective drying oven, racks with pallets under a canopy in natural conditions, a grass cutter, vibrating sieves. Also, the study was carried out in accordance with the principles of the "Quality by Design" concept using the Minitab Statistical Software 21 program, using a statistical tool – Design of experiments (DoE). Results and discussion. The results of studies of various drying methods have shown that the most optimal is drying with IR radiation, which allows to maintain the content of essential oils (the main group of biologically active substances) at the optimal level – about 1,7 % with a raw material moisture content of no more than 13 %. The data obtained by simulating the experiment in the Minitab program were comparable to the results of the classical experimental design. The optimal method and technological parameters for drying autumn wormwood have been established – the use of IR radiation, temperature of 35–45 °C and drying time of 14–17 hours. Comparable data on the studied technological parameters of three sequentially produced series were obtained and the validity of the technological process for drying autumn wormwood was confirmed. Conclusion. Comparative analysis of the methods of drying medicinal plants – IR radiation, convective and shadow drying in natural conditions – of autumn wormwood ( Artemisia serotina Bunge) was carried out. It has been established that the maximum content of essential oils (as the main group of biologically active substances) in raw materials is observed when using drying using IR radiation at a temperature of 35–45 °C for 14– 17 hours. At the same time, the residual moisture content of the drug is no higher than 13 %, which corresponds to pharmacopoeial requirements. Conducted studies of predicting optimal drying parameters using the Minitab Statistical Software 21 program showed comparability with the experimental results. Based on the results obtained, an optimal method for drying autumn wormwood herb was proposed for use in production and obtaining pharmacopoeial quality medicinal products.

Introduction. Innovative technologies, new approaches to the creation of medicines, a combination of classic technological methods with the latest trends makes pharmaceutical production a direction with positive dynamics of development. But along with the emergence of new synthetic drugs, as well as biotech products, the use of herbal raw materials for the production of medicines remains relevant. Phytopreparations have a number of undeniable advantages over synthetic drugs and are the drugs of choice in different age groups, including for preventive medicine. The flora of Kazakhstan is distinguished by the presence of endemic plants with a sufficient source of raw materials, which creates the prerequisites for their phytochemical profiling and the subsequent development of phytopreparations. In this regard, Ferula akitschkensis B. Fedtsch. ex Koso-Pol., which is widespread in Kazakhstan, is distinguished by the accumulation of various classes of biologically active substances (flavonoids, coumarins, essential oils) and has experience in folk medicine. Aim. To study the component composition of ethanol extracts of Ferula akitschkensis roots by GC/MS using the Wiley 7th edition, NIST’02 library and to predict the pharmacological activity of identified compounds using the PASS Online web resource Materials and methods. Ethanol extraction of roots was obtained by extraction of raw materials with 80 % ethanol in the ratio of raw materials : extractant 1 : 10 and under ultrasonic exposure at a frequency of 15–25 kHz for 10–20 min, followed by separation of the extract from the meal. The obtained extract was analyzed by gas chromatography-mass spectrometry (GC/MS) in full current scanning mode. The obtained mass spectra were interpreted using the Wiley 7th edition and NIST’02 libraries. To predict the biological activity of the identified compounds, the PASS Online web resource was used. Results and discussion. The composition of the ethanol extract of the roots of Ferula akitschkensis B. Fedtsch. ex Koso-Pol. is characterized by a metabolomic profile of compounds that differs from other members of the Ferula genus. Thus, o -cymene, the oxygen derivative of p -cymene – thymol and 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methylphenol accumulate in the roots. These compounds can form a marker profile of the roots of Ferula akitschkensis and be used for species identification within the genus Ferula. The prognostic evaluation of the pharmacological activity of the identified compounds of Ferula akitschkensis showed the presence of an effect on metabolic and biochemical processes, in particular, the creation of a proton potential on the mitochondrial membrane, catalysis, redox processes, and stabilization of cell membranes. In addition, antispasmodic, fibrinolytic, and antioxidant activities can be predicted for the roots of Ferula akitschkensis . And in the focus of creating potential drugs based on the raw materials of this species of Ferula, it is advisable to consider the development of dermatological and carminative drugs. Conclusion. Study of the phytochemical profile of ethanol extracts from the roots of Ferula akitschkensis B. Fedtsch. ex Koso-Pol. by GC-MS made it possible to establish the presence of o -cymene and p -cymene derivatives – thymol and 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methylphenol. These compounds make up the marker profile of the roots of Ferula akitschkensis and can be used to identify the species within the genus Ferula, since thymol is not the main component of the essential oil of other representatives of this genus. Prediction of the pharmacological activity of the identified compounds in silico showed the possibility of using Ferula akitschkensis raw materials in complex therapy as a means of improving tissue respiration in conditions accompanied by a violation of redox processes in the body. It has been shown that potential medicinal candidates based on the roots of Ferula akitschkensis will be characterized by antispasmodic, fibrinolytic and antioxidant effects. The development of dermatological drugs may also be in the focus of scientific groups due to the anti-eczematous activity of most compounds of the ethanolic extract of the roots of Ferula akitschkensis .

At the pharmaceutical company Fitoleum LLP (Esik, Kazakhstan) a technology for obtaining thick and dry extracts of ferula penninervis or Keller’s ferula was developed, and the technological process of the pilot series was transferred and validated. As a result of the research, the regulating normative documentation for the proper production process under the established conditions was developed. Comparable data were obtained on the studied technological parameters of three successively produced batches of each product, and the validity of the considered technological processes for the production of extracts was confirmed. Introduction. The ferula plant (lat. Ferula) belongs to the umbrella family (Apiaceae). In folk medicine, it is widely used to treat dermatological, neuropsychiatric, ophthalmic and infectious diseases. Ferula penninervis (Ferula penninervis Regel & Schmalh.) and Keller’s ferula (Ferula Kelleri Koso-Pol) are of scientific and practical importance, having a wide distribution area in the southern region of the Republic of Kazakhstan, in areas with high solar insolation. Full-scale studies of representatives of the genus Ferula — ferula penninervis and Keller’s ferula, and the development of herbal pharmaceutical substances from their roots were carried out at S.D. Asfendiyarov Kazakh National Medical University. The aim of the study is to develop an optimal technology for obtaining an extract from the roots of the ferula penninervis (Ferula penninervis Regel & Schmalh.) or Keller’s ferula (Ferula Kelleri Koso-Pol) and its validation at the Fitoleum LLP enterprise in accordance with national requirements [1]. Materials and methods. Description of the production process. In the production of extracts, the following ingredients are used: dried roots of ferula penninervis or Keller’s ferula, collected in late autumn 2017 in the Kordai Pass, in accordance with the requirements of the relevant standard of cultivation and collection practice (GACP) [2]; purified water and ethanol 96% of pharmacopoeial quality . The technological process consists of the following classical operations: preparation of medicinal plant materials (MPM), preparation of the extractant, obtaining an extract from the MPM, purification of the extract, removal of the extractant, packaging and labeling (Figure 1).

A review of Kazakhstani species of the genus Hedysarum L. (sweetvetch) has been conducted, that includes 28 plant species with scientific names recognized by international floristic bases, 10 of which are endemics. The ranges of distribution, botanical characteristics, phytochemical composition and profile of pharmacological activity of some represented species were studied. The life form of all the studied sweetvetches is represented by perennial herbs, the chemical composition of which is characterized by such phenolic compounds as three isoflavonoids – ononin, formonononetin, formonononetin-7-O-β-D-glucoside-6′- O-malonate and pterocarpan – medicarpin. It is established that the pharmacopoeial species of the genus is Hedysarum polybotrys Hand.-Mazz, the most phylogenetically close to it is Hedysarum semenowii Regel & Herder species, which commonly grows on the territory of the Central Tien Shan. This species is used in folk medicine and is not inferior in its valuable properties to pharmacopoeial species, but it has not been widely studied, which was the reason for its selection as an object for further research.