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ВЕСТНИК КАЗНМУ #1-2022 ФАРМАЦИЯ
PHARMACY
UDC 581.91
DOI 10.53065/kaznmu.2022.90.50.085
K.E. Zhuzzhan, A.K. Kydyrvaeva, A. Zh. Moldakaryzova, Zh.A. Kashaganova, K.K. Yerkekulova, G.A.Tussupbekova
Asfendiyarov Kazakh National medical university, Almaty, Kazakhstan MAuezov South Kazakhstan university, Shymkent, Kazakhstan аl-Farabi Kazakh National University, Kazakhstan
kuralai.zhuzzhan.80@mail.ru asem.kydyrbaeva@mail.ru aijan202@mail.ru http://abaizhazira@gmail.com ekk.33@mail.ru gulmira.274@mail.ru
PHYTOCHEMICAL STUDIES OF FERULA FOETIDA PLANT AND ITS MEDICAL
SIGNIFICANCE
Resume. There are many different types of medicinal plants in the world. Since time immemorial, mankind has been creating unique plants with medicinal and healing properties, located in such a diverse geographical area. The ancient Greek physician Hippocrates was the first to write extensively about medicinal plants. He believed that any plant tree is very useful, they can be widely used to treat various chronic diseases, and also described more than one hundred and ninety plants that he used in his time. However, the scientist did not pay attention to the healing properties of the plants he described. [1].
The pharmaceutical industry of the country originated in the study of plants in the production of ephedrine, salcolin, ephyzimine and other valuable drugs.
Of course, before being introduced into medical practice, each medicinal plant undergoes a thorough examination of modern medicine. In particular, the chemical composition is checked, to what extent the factors affecting the body affect the function of each of the human organs and systems. They determine the harmfulness of certain chemicals obtained in the plant as a whole or in each of its parts, and also carefully check the medicinal properties of the plant. Then, the medicinal properties of the plant and preparations from it are evaluated experimentally in various ways. After that, the medicinal plant is tested in many clinics only under special instructions. The Pharmacological Committee of the Ministry of Health will allow the wide distribution and use of the plant for medicinal purposes, and its preparations will be developed on an industrial scale.
In this regard, the study of the current chemical composition of the plant Ferula foetida, which we took as the object of study, is an important issue in assessing the healing properties of the plant.
Keywords: plant resources, distribution, useful plants, rational use, soap root, saponins, foetida, storage, stocks, annual volume of collection, recommendations.
К-Е. Жузжан, Э-К- Кыдырбаева, А.Ж. Молдакарызова, Ж.А. Кашаганова Р.М.,К.К. Еркекулова, Г.А. Тусупбекова
С. Ж. Асфендияров атындагы Цазац ¥лттыц медицина университету
Алматы, Цазацстан М.Эуезов атындагы Оцтустк Цазацстан мемлекетткуниверситету
Шымкент, Цазацстан Зл-Фараби атындагы Цазац ¥лттыц университетi Алматы, Цазацстан Шымкент, Цазацстан kuralai.zhuzzhan.80@mail.ru asem.kydyrbaeva@mail.ru aijan202@mail.ru abaizhazira@gmail.com ekk.33@mail.ru gulmira.274@mail.ru
FERULA FOETIDA 6С1МД1ГШЩ ФИТОХИМИЯЛЫК ЗЕРТТЕУЛЕР1 ЖЭНЕ ОНЫН,
МЕДИЦИНАЛЫК МАНЫЗЫ
Тушн. Элемнщ кез-келген жерлертде шипалыц цасиетке ие квптеген тyрлi вамдктер кедеседь Осындай алуан тyрлi географиялыц аумацта орын тепкен емдЫ шипалыц касиеттерi бар ерекше всiмдiктердi вте ерте заманнан-ац адамзат баласы вз цажеттшгте жаратып келген. Дэршк всiмдiктер жайында алгашрет бiздiц заманымызга дейiнгi
ВЕСТНИК КАЗНМУ #1-2022 -
ертедегi грек dap^epi Гиппократ кец ауцымды ецбекжазды. Ол еамдктщ кез-келген дарацтары вте пайдалы, оларды эр тypлi созылмалы ауруларды емдеу мацсатына кещтен пайдалануга болады деп есептеген. Сонымен цатар ол ез кезещтде пайдаланган жуз тоцсаннан астам естджке сипаттама бердь Бipац галым сол езтщ сипаттама берген естджтердщ цандай емдк цасиeтi бар екендтне назар аудармады [1].
Елiмiздeгi фармацевтикалыц енеркэст эфедрин, сальсолин, эфизимин жэне тагыда басца багалы препараттарды дайындауда есiмдiктepдi зерттеу барысында дуниеге экелдь
Элбетте, эpбip дэршк есiмдiктep емдеу тэжipибeсiнe eнгiзiлмeс бурын заманауи медицинада тъщгылыцты зерттеудщ сараптамасынан етедь Атап айтцанда химиялыц цурамы тексерыед1 агзага эсер eтушi факторлары адамныщ эpбip мyшeлepi мен жуйелертщ цызметте цаншалыцты эсер ететтдт жт бацыланады. всшджтердщ тугелдей езiндeгi немесе оныщ эpбip белiгiндeгi алынган кеü6íp химиялыц заттардыщ цаншалыцты зиянды екендг аныцталады, сонымен цатар еамдктщ емдк цасиeтi жан-жацты муцият тексерыедь Содан кешн эр тypлiжолмен тэжipибe жасау арцылы еамдктщ жэне содан жасалган препараттардыщ дэршк цасиеттерте бага берыедь Осыдан кешн барып цана арнаулы нусцау бойынша дэршк еамдШ кептеген клиникаларда сынацтан етедь Сынацтан сэттi еткен есiмдiктiДенсаулыц сацтауминистрлтнщ фармакологиялыц комитeтiхалыц арасына кещтен таратугажэне емдеу мацсатында цолдануга, ал оныщ препараттарын ендipiстiкжолмен жасауга руцсат берыедь Соган байланысты бiз зерттеу нысаны реттде алынган Ferula foetida еамдтнщ цaзipгi кeздeгi химиялыц цурамын зерттей отырып ол еамдктщ шипалыц цасиетт багалау езeктiмэселе болып табылады.
Tyürndi свздер: еамдк ресурстары, таралуы, пайдалы есiмдiктep, утымды пайдалану, сабын тамыры, сапониндер, сацтау, цорлар, жыл сайынгы жинау келем1 усыныстар.
К.Е. Жузжан, А.К. Кыдырбаева , А, Ж. Молдакарызова, Ж.А.Кашаганова, К.К. Еркекулова, Г.А. Тусупбекова
Казахский Национальный медицинский университет имени С. Д. Асфендиярова
Алматы, Казахстан Южно-Казахстанский университет имени М.Ауэзова, Шымкент, Казахстан Казахский Национальный университет имени аль-Фараби, Алматы, Казахстан
kuralai.zhuzzhan.80@mail.ru asem.kydyrbaeva@mail.ru aijan202@mail.ru http://abaizhazira@gmail.com ekk.33@mail.ru gulmira.274@mail.ru
ФИТОХИМИЧЕСКИЕ ИССЛЕДОВАНИЯ РАСТЕНИЯ FERULA FOETIDA И ЕГО
МЕДИЦИНСКОЕ ЗНАЧЕНИЕ
Резюме. В мире существует множество различных видов лекарственных растений. Человечество с незапамятных времен создавало уникальные растения, обладающие лечебными и целебными свойствами, расположенные в столь разнообразном географическом ареале. Древнегреческий врач Гиппократ был первым, кто много писал о лекарственных растениях. Он считал, что любое дерево растения очень полезно, их можно широко использовать для лечения различных хронических заболеваний, а также описал более ста девяноста растений, которые использовал в свое время. Однако ученый не обратил внимания на целебные свойства описанных им растений. [1]. Фармацевтическая промышленность страны зародилась при изучении растений при получении эфедрина, салколина, эфизимина и других ценных лекарств.
Безусловно, каждое лекарственное растение перед внедрением в медицинскую практику проходит тщательную экспертизу современной медицины. В частности, проверяется химический состав, в какой степени воздействующие на организм факторы влияют на функцию каждого из органов и систем человека. Определяют вредность тех или иных химических веществ, полученных в растении в целом или в каждой его части, а также тщательно проверяют лечебные свойства растения. Затем оценивают лечебные свойства растения и препаратов из него опытным путем разными способами. После этого лекарственное растение испытывают во многих клиниках только по особым указаниям. Фармакологический комитет Минздрава разрешит широкое распространение и использование растения в лечебных целях, а его препараты будут разрабатываться в промышленных масштабах.
В связи с этим изучение современного химического состава растения Ferula foetida, взятого нами в качестве объекта исследования, является важным вопросом в оценке целебных свойств растения.
Ключевые слова: растительные ресурсы, распространение, полезные растения, рациональное использование, мыльный корень, сапонины, хранение, запасы, ежегодный объем сбора, рекомендации.
Introduction. Ferula L. is a relative of many promising medicinal plants, which are widely used in practice (fodder, food, essential oils, medicinal, etc.). The plant Ferula foetida L. has great prospects in traditional oriental medicine as a medicinal plant and as a new medicinal plant. In Kazakhstan, the locusts are called stink bugs. Although the medicinal plant is widespread in South Kazakhstan (Turkestan region), it has not been fully studied. It is collected without losses only for export to foreign countries (China, India, Pakistan, etc.) [3].
From an experimental point of view, feruls are aromatic, essential oil plants as a food plant that cannot be replaced by other plants, as well as a medicinal plant in traditional oriental medicine, being the primary source of medicines. Some species of ferula have been used in Central Asia in the past centuries as a food plant (F. karelinii. F. sibirica, F. dubjanskyi, F. schtschurowasiana), as a kind of spice (mainly garlic and garlic-flavored species). as a material; In recent years, it has been found that their particularly large deciduous species can be used for decorative purposes
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(Rakhimov, 2010): (F. Kokanica Regel & Schmalh and others) and others., for decorative purposes: F.dissecta (Ledeb.) F.karatavica Regel & Schmaih, F.kelleri Koso-pol. (Sikura, 1982) species are also important; The people of Central Asia also have a special place in the flora of Kazakhstan, where they made musical instruments from the lessons of the century. On the one hand, the plants of this genus are used for economic purposes and are not absent in the data on their importance [6]. The current use of sage as a medicinal plant in the future proves that it contains high concentrations of biologically active substances in its roots and seeds. Roots and seeds of safflower are a real source of raw materials, as well as the purposeful use of seeds in terms of preservation of natural shoots proves the high germination of seeds. [5]. Ferula foetida is a monocarpic, propagated only by seeds, flowering seeds only once in 5 years. Therefore, it is important to study and protect the medicinal plant that stinks, to prevent its extinction. Research area: Tole bi district of South Kazakhstan region. South Kazakhstan region as an administrative - territorial unit is mainly geographically a rising undulating plain with an altitude of 190 to 450 m above sea level, with islands of small mountain formations (height from 500 to 875-1000 m). Therefore, the South Kazakhstan region is a very complex formation with alternating areas of flat, Foothill and mountainous terrain. [8].
South Kazakhstan region belongs to Zone III (semi-desert landscape zone of the temperate zone). In this region, it occupies the territory of the physical and geographical country of Central Asia-the Tien Shan physical and geographical region, where there are two provinces. One of these provinces includes the south-western Tien Shan physical and geographical province and the territory of the South Kazakhstan region [10]. The southwestern Tien Shan physical and geographical province is part of the desert zone of vegetation in the Southern subzone. Ephemeral-sagebrush deserts are characterized by the predominance of ephemeroids and ephemeroids in the vegetation cover, various types of sagebrush, as well as shrubs.
Methods. F.foetida (Bung.) Regel. - Fragrant - broad-leaved, found in Almaty, Kyzylorda, South Kazakhstan, present-day Turkestan region and Zhambyl region. For medicinal purposes, dried milky juice (gum) is used in the Results and discussion
air coming out of the roots and flowering parts. The juice is known in pharmacological practice as "Gummi Assa-foetida". Condensed milk juice consists of resin (9-65%), comedy (12-48%) and ephemeral oil (5-20%). From resin are obtained lactic acid, resin (asarezen), resitanol (asarezitanol) and resinol (asarezinol) and their esters with tartaric acid.
The phytochemical composition of plants belonging to the genus Ferula.L in the Turkestan region has not been scientifically determined. Therefore, the study of the accumulation of biologically active compounds and other additives in the roots of Ferula foetida, a relative of Ferula.L, has aroused interest. To date, vascular extracts have been prepared and their composition (Table 3) has been studied to determine the amount of biologically active compounds and other additives that are useful for accurate knowledge of their medicinal properties. Analysis of the plant Ferula foetida by phytochemistry. Method of analysis: gas chromatography with mass spectrometric detection
Conditions of analysis: sample volume 1.0 |l, sample introduction temperature 260 ° s.
Separation was performed at a constant velocity of 1 ml / min of carrier gas (helium) through a chromatographic capillary tube with a length of 30 m, an inner diameter of 0.25 mm and a film (transparent shell) thickness of 0.25 |m.
Chromatography temperature is planned from 40 ° C (holding 10 min), heating rate from 5 ° C / min to 270 ° C (holding 10 min).
Detection is performed in SCAN m / z mode 34-750. Agilent MSD ChemStation software (version 1701ea) was used to control the gas chromatography system, record and process the results and data obtained. Data processing, time storage, determination of peak areas, as well as processing of spectral information obtained with the help of mass spectrometric detector. Wiley 7th edition and NIST'02 libraries were used to open the obtained mass spectra (the total number of spectra in the libraries is more than 550 thousand). Sample preparation: 10 g of plant roots were obtained by ultrasonic bath with 96% ethanol for 30 minutes. Grinded plant roots, ethyl alcohol as an extractant and repercolation method were used to obtain a liquid extract.
Results of c chromatographic analysis of Ferula foetida root extract
№ Retention time min Chemical name Probability of identification, % Percentage of content,%
1 9,39 2-Cyclopenten-1-one, 2-hydroxy 76 0,41
2 9,67 Methyl sec-butyl disulphide 86 1,14
3 11,86 Ethyl n-butyl disulphide 80 0,21
4 12,79 2,4,6-Octatriene, 2,6-dimethyl- 82 0,34
5 12,96 2-Hydroxy-gamma-butyro lactone 74 0,67
6 13,19 Thiophene, tetrahydro-2-methyl- 65 0,68
7 14,72 1,2-Dithiolane 62 11,03
8 15,58 Disulfide, bis(1-methylpropyl) 96 8,42
9 16,62 Tioxolone 62 0,48
10 17,12 1,4-Dithiane-2,5-dione, 3,6-dimethyl- 64 1,93
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11 19,14 3-Thiatricyclo [3.1.1.0(2,4)] heptane 3-oxide 60 1,05
12 20,85 Caryophyllene 92 1,77
13 21,75 Thiophene, 2-ethyltetrahydro- 60 3,30
14 22,20 Trisulfide, bis(1,1-dimethylethyl) 64 1,89
15 24,06 Thiocyanic acid, ethyl ester 68 2,55
16 24,33 6-(Methylthio) hexa-1,5-dien-3-ol 61 1,66
17 24,84 Thiophene, 2-butyltetrahydro- 60 0,74
18 27,77 Thiocyanic acid, ethyl ester 71 56,68
19 30,24 Acetic acid, 3-hydroxy-2,2-dimethoxy-propyl ester 64 0,49
20 31,07 Oxalic acid, 2-phenylethyl tetradecyl ester 60 2,98
21 31,38 Butanoic acid, 3-methyl-, 2-phenylethyl ester 60 0,88
22 32,37 Malonic acid, 3-methylbutyl pentadecyl ester 61 0,70
Figure- Extract chromatogram
Phytochemical analysis revealed 22 elements in the root extract of Ferula foetida.
People use substances with a pungent odor, similar to rubber, when using drugs.
These include: 2-Cyclopenten-1-one, 2-hydroxy-0.41%, methyl sec-butyl disulphide (methyl ester) -1.14%, Ethyl n-butyl disulphide-0.21% and 2,4,6 -Octatriene, 2.6-dimethyl-0.34%, Thiophene, tetrahydro-2-methyl-0.68%. Chemical properties:
2-Cyclopenten is an organic compound with a molecular formula (C5H8). It is a colorless liquid that tastes like gasoline. The structure is not smooth, but flexible. Cyclopenten is produced in large quantities at industrial sites. It is used as a monomer to synthesize plastics in addition to other chemical syntheses.
Ethyl methyl disulfide has a pungent, white truffle-like aroma. It is found in cabbage, kohlrabi, cheese, beef, pork and coffee.
Thiophene is an important heterocyclic compound that is widely used as a building material in many agrochemicals and pharmaceutical products. The benzene ring of the biologically active compound can often be replaced with thiophene without losing its activity. At room temperature, thiophene is a colorless liquid with a moderate odor, reminiscent of benzene, 2-Hydroxy-gamma-butyrolactone-0.67% is gamma hydroxybutyric acid, in short. GHB, as well as 4-hydroxybutanoic acid is an organic compound, a natural hydroxyl acid that plays an important role in the human central nervous system, and these compounds are found in wine, citrus fruits, etc. there is. Gamma hydroxybutyric acid is used in anesthesia, but is banned in many countries.
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1,2-Dithiolane-11.03%. In medicine, it is found in drugs for the treatment of atherosclerosis, liver disease and diabetes and polyneuritis.
Caryophyllene 1.77%. Caryophylline is found in some essential oils.
It is often used to create perfume compositions, to obtain fragrances for soaps and cosmetics, and to synthesize certain fragrances.
Trisulfide, bis (1.1-dimethylethyl) - 1.89%. In medicine, in particular, as a substance with anti-inflammatory and anti-arthritic activity.
Oxalic acid 2.98% and Malonic acid 0.70%. It is used in the production of oxalic acid, which is a valuable product in the food and chemical industries. It is also used in medicine as an antimicrobial.
-«P-
Conclusion. It is the richest in coumarin compounds, which have a wide range of biological activity in plants belonging to the genus Rose. Many coumarins, even in relatively small amounts, are lethal to horses, cattle, and sheep, and are used as pharmacological agents for humans. In pharmacology, coumarins are used to treat leukoderma (furocoumarins - peuedanin, prangenin) and other cancers. (Nikonov, 1964; Georgievsky, Komisarenko, 1990). Coumarins - treat skin burns (photophytodermatitis). This property is based on the ability of coumarins to make the skin sensitive to light. Coumarins such as pastinacin, bergapten, imporerin, isopimpinelline, xanthoxol, angiesin have antispasmodic activity.
1 "Ferula assa-foetida L." Plants of the World Online. Kew Science. Retrieved 2021-05-20.
2 The Red Book of Kazakhstan. 2 vols. Section 1. Plants. -Astana, 2014. - P.357.
3 Rémi Safi , Marwan El-Sabban, Fadia Najjar, Ferula hermonis: A Review of Current Use and Pharmacological Studies of its Sesquiterpene Ester Ferutinin// Curr Drug Targets.2020;21(5):499-508.doi: 10.2174/1389450120666191029155053.
4 Grudzinskaya LM, Gemedzhieva NG, Nelina NV, Karzhaubekova Zh.Zh. Annotated list of medicinal plants of Kazakhstan: Reference book. Almaty, 2014. - 200 p.
5 Saidova NG, Kodirova GH, Karomatov IJ Medicinal plant ferula stinking. //Biology and Integrative Medicine, 2017. - № 9. - P. 58-69.
6 Syed Nadeem Badar , Zafar Iqbal , Muhammad Sohail Sajid et all, Comparative anthelmintic efficacy of Arundo donax, Areca catechu, and Ferula assa-foetida against Haemonchus contortus// Rev Bras Parasitol Vet,2021 May 28;30(2):e001221. doi: 10.1590/S1984-29612021028. eCollection 2021.
7 Bandana Rath, Maharana C.S., Sadananda Rath, Mahakul D.J. Evaluation of Bronchoprotective Effect of Ferula Asafetida in Guinea pigs. OSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-ISSN: 2279-0853, p-ISSN: 2279-0861.Volume 16, Issue 3 Ver. XIII (March, 2017). P. 19.
8 Barzegar, Alireza; Salim, Mohammad Amin; Badr, Parmis; Khosravi, Ahmadreza; Hemmati, Shiva; Seradj, Hassan; Iranshahi, Mehrdad; Mohagheghzadeh, Abdolali (April 2020). "Persian Asafoetida vs. Sagapenum: Challenges and Opportunities". Research Journal of Pharmacognosy. 7 (2). doi:10.22127/rjp.2019.
9 Chandran S., Sakthivel M., Thirumavalavan M., Thota J.R., Mariappanadar V., Raman P. A facile approach to the isolation of proteins in Ferula asafoetida and their enzyme stabilizing, anti-microbial and antioxidant activity //Int. J. Biol. Macromol., 2017. № 102. P. 1211-1219.
10 Nausheen Nazir, Mohammad Nisar, Muhammad Zahoor, Phytochemical Analysis, In Vitro Anticholinesterase, Antioxidant Activity and In Vivo Nootropic Effect of Ferula ammoniacum ( Dorema ammoniacum) D. Don. in Scopolamine-Induced Memory Impairment in Mice// Brain Sci.2021 Feb 19;11(2):259. doi: 10.3390/brainsci11020259.
11 Farhadi, Faegheh; Asili, Javad; Iranshahy, Milad; Iranshahi, Mehrdad (November 2019). "NMR-based metabolomic study of asafoetida". Fitoterapia. 139: 104361. doi:10.1016/j.fitote.2019.104361
12 Alireza Daneshkazemi , Hengameh Zandi , Abdolrahim Davari, Antimicrobial Activity of the Essential Oil Obtained
from the Seed and Oleo-Gum-Resin of Ferula Assa-Foetida against Oral Pathogens// Front Dent. Mar-Apr 2019;16(2):113-120. doi: 10.18502/fid.v16i2.1362. Epub 2019 Apr 30.
13 Roberta Macri , Vincenzo Musolino , Micaela Gliozzi, Ferula L. Plant Extracts and Dose-Dependent Activity of Natural Sesquiterpene Ferutinin: From Antioxidant Potential to Cytotoxic Effects//Molecules,2020 Dec 7;25(23):5768.doi: 10.3390/molecules25235768.
14 Bagheri S.M., Dashti-R M.H., Morshedi A. Antinociceptive effect of Ferula assa-foetida oleo-gum-resin in mice.//Res. Pharm. Sci, 2017. № 9(3). Р. 207-212
15 Bagheri S.M., Dashti-R M.H. Influence of asafoetida on prevention and treatment of memory impairment induced by D-galactose and NaNO2 in mice.//Am J Alzheimers Dis Other Demen, 2015. - № 30. - Р. 607-612.
Authors' Contributions. All authors participated equally
in the writing of this article.
No conflicts of interest have been declared.
This material has not been previously submitted for
publication in other publications and is not under
consideration by other publishers.
There was no third-party funding or medical representation in the conduct of this work. Funding - no funding was provided.
Авторлардьщ улесь Барлык; авторлар осы мак;аланы
жазуга тен, дэрежеде катысты.
Мудделер цацтьгеысы - мэлiмделген жок;.
Бул материал баск;а басылымдарда жариялау ушш
бурын мэлiмделмеген жэне бас;а басылымдардын,
;арауына усынылмаган.
Осы жумысты журпзу кезшде сырт;ы уйымдар мен медициналык; екшджтердщ каржыландыруы жасалган жок;.
Царжыландыру журпзшмедь
Вклад авторов. Все авторы принимали равносильное участие при написании данной статьи. Конфликт интересов - не заявлен. Данный материал не был заявлен ранее, для публикации в других изданиях и не находится на рассмотрении другими издательствами. При проведении данной работы не было финансирования сторонними организациями и медицинскими представительствами. Финансирование - не проводилось.
BECTHHK KA3HMY # 1-2022
Information about the authors:
Zhuzzhan K.E, A.K.Kydyrvaeva, A. Zh.Moldakaryzova, Zh. A. Kashaganova , K.K. Yerkekulova, G.A.Tussupbekova
Zhuzhan Kuralay Ermakkyzy, Master of Biological Sciences, lecturer, Asfendiyarov Kazakh National medical university, Almaty, Kazakhstan; kuralai.zhuzzhan.80@mail.ru,
https://orcid.org/0000-0002-2358-9626 Kydyrbaeva Asem Kiyashkyzy, Master of Biological Sciences, lecturer, Asfendiyarov Kazakh National medical university, Almaty, Kazakhstan; Kydyrbaeva.a@kaznmu.kz,
https://orcid.org/0000-0002-1622-3626
Moldakaryzova Aizhan Zhanarbekova, Cand. Sc. Biology, associate professor, Asfendiyarov Kazakh National medical university, Almaty, Kazakhstan; http://aijan202@mail.ru, https://orcid.org/0000-0003-0186-978X
Kashaganova Zhazira Abaevna, Master of Biological Sciences, lecturer, Asfendiyarov Kazakh National medical university, Almaty, Kazakhstan; http://abaizhazira@ gmail.com,
https://orcid.org/0000-000 2-9510-2565 Yerkekulova Kaliya Kudaykulovna, PhD student, department of Biotechnology, M.Auezov South Kazakhstan University, Shymkent, Kazakhstan, ekk.33@mail.ru, https://orcid.org/0000-0001-5086-5019
Tussupbekova Gulmira Ablaevna associate professor, department of Biophysics, biomedicine and neuroscience, al-Farabi Kazakh National University, Almaty, Kazakhstan gulmira.274@mail.ru, https://orcid.org/0000-0001-9379-4687
