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doi: 10.15389/agrobiology.2023.1.114eng

UDC: 633.8:58.144:58.01:57.017.6:574.45:581.192

 

EXPERIENCE OF Rhaponticum carthamoides (Willd.) Iliin CULTIVATION AS A NATURAL SOURCE OF ECDYSTERONE UNDER THE CONDITIONS OF THE ARKHANGELSK REGION

N.P. Timofeev

KKh BIO, 47, ul, Lenina, Koryazhma, 165650 Russia, e-mail sciens@leuzea.ru (✉ corresponding author)

ORCID:
Timofeev N.P. orcid.org/0000-0003-4565-7260

Final revision received May 15, 2022
Accepted July 7, 2022

In 2021, the global market for ecdysterone-containing substances amounted to $100 billion and is expected to grow significantly in the next 5 years. The aboveground and underground parts of Rhaponticum carthamoides (Willd.) Iliin are primarily suitable to obtain ecdysterone-containing products of pharmaceutical quality. However, both in Russia and abroad, сommon technologies for R. carthamoides cultivation and study are not focused on the quality of the medicinal raw materials. In this paper, we have implemented for the first time an alternative technology for the production of ecdysterone-containing substance from the leaf parts of R. carthamoides. The technology is simple and can be scaled up in agropopulations of the Northern European Russia and meets the key requirements for industrial raw materials and end ecdysterone products set by international experts. Our goal was to summarize 32 years of experience in growing R. carthamoides on a plantation located in the European Northeast of Russia (Arkhangelsk Province). We assessed the potential for longevity and productivity of the agricultural population by life cycle stages and age, the regularities of ecdysterone accumulation in annually harvested aboveground plant parts, and the quality of obtained plant raw material for the content of standardized substances. The study was performed in the southeast of the Arkhangelsk Province (the Middle Taiga subzone, Kotlass District; 61°20'' N, 47°E) in an agropopulation of R. carthamoides (the field area of 1 ha) in 1989-2022. The seeds obtained from the Botanical Garden of the Komi Scientific Center, UB RAS (Syktyvkar) were initially originated from the Altai natural population (first collected in 1956). Autumn sowing was performed in mid-October after the beginning of autumn frosts (row spacing of 70 cm, seed embedding depth of 2-3 cm, seed rate of 2.7 kg/ha; 58 % field germination of seeds). Mineral fertilizers (NPK60-90) were applied during the first three years after sowing followed by organic farming without use of mineral and organic fertilizers, chemical pesticides, and plant growth regulators. The aboveground parts were annually harvested during budding. A set of population, agrochemical, morphoanatomical, biochemical and statistical methods were used to asses parameters of the plant population (age states in ontogenesis, population density, gross production of above-ground and under-ground organs, seed yield) and individual plants (growth, development, morphological structure, productivity of roots, leaves, and seeds). Samples were collected at optimal phases of plant development, the aboveground phytomass during budding (I-II decade of June), rhizomes in autumn, after the end of vegetation (October), or in early spring, before the beginning of vegetation (April). Shortened vegetative (rosette) and stem generative (reproductive) shoots with inflorescences were morphologically heterogeneous organs separated in the aboveground part. Industrial harvesting of plant raw materials was carried out in late May-early June, during budding. Plant material (organs, elements and fractions) was dried at 23-25 to 35-40 °С and relative humidity of 25-40 % in accordance with the procedure for harvesting and drying medicinal raw materials. The samples of air-dry raw materials for further determination of the content of primary and secondary metabolites were formed by quartering method. The amount of ecdysterone in dry samples was determined by reverse phase high performance liquid chromatography with the internal standards (a liquid microcolumn chromatograph Milichrom-5, column 80½2 mm, Nucleosil C18 sorbent with a particle size of 5 μm; LLC «Medicant», Russia). Potentially dangerous substances were also assessed. Duration of agropopulation ontogenesis was close to parameters of natural populations in subalpine meadows and is more than 30 years without transition to senile age on the 33rd year of life, plant density reached optimum values of 28-23 thousand pcs/ha, starting from the 3-4 years of life. Diseases and pests did not affect vegetative aboveground mass and roots with rhizomes. The average root mass with rhizomes during the period of relatively stable mass production (from the 5th to the 32nd year of life) was 246.3 g/plant, aboveground mass was 223.4 g/plant. Calculated annual productivity of the agropopulation during the same period averaged approximately 5300 kg/ha for aboveground parts, and approximately 6100 kg/ha for underground parts. Vegetative type of reproduction was most pronounced for subsenile age state (from the 13th to the 32nd year and onwards), when seed production was extremely low, 1.3 kg/ha. The seed type of reproduction was characteristic of the generative period from years 4-5 (8-30 kg/ha) with a peak during years 6-7 (108 and 78 kg/ha). In general, the percent of generative shoots in total plant biomass was insignificant throughout the life cycle. Ecdysterone biosynthesis and accumulation in the leaves of rosellate shoots were directly related to vegetative reproduction, namely to the aboveground mass value (R2 = 0,768, or close to 80 %). More than 90 % of annually synthesized ecdysterone (22 kg/ha) was concentrated in the aboveground part of plants at optimal harvesting age (from year 5 to year 32), or about 600 kg of ecdysterone for 27 years of operation. Qualitative indicators of medicinal raw materials from leaves of R. carthamoides were high and met the requirements for the manufacture of pharmaceuticals with a relative purity of ecdysterone 97 %. The plant material met all the regulatory requirements of the supervisory authorities. The levels of heavy metals (Hg, Cd, As, Zn; Ni, Cu, Cr) did no exceeded the permissible level, there were no prohibited organochlorine and phosphorus compounds, the content of radionuclides 90Sr and 137Cs and nitrites were below the permissible limit. Ecdysterone from the dried flour of the R. carthamoides leaves was well extracted into aqueous and alcohol solutions and was well preserved (up to 93-98 % within 24 hours) without preservatives. Its use significantly improved animal health (a 1.6-2.5-fold decrease in mortality), had an anabolic and economic effects (i.e., a 24-33 % higher daily weight gain and a decrease in feed consumption by 11-17 %).

Keywords: phytoecdysteroids, 20-hydroxyecdysone, Rhaponticum carthamoides, Leuzea safflower, maral root, feed additives, anabolic substances.

 

REFERENCES

  1. Rhaponticum carthamoides. V knige: Rastitel’nye resursy SSSR. Tsvetkovye rasteniya, ikh khimicheskiy sostav, ispol’zovanie. Semeystvo Asteraceae (Compositae) /Otvetstvennyy redaktor P.D. Sokolov [In: Plant resources of the USSR. Flowering plants, their chemical composition and use. Family Asteraceae (Compositae). P.D. Sokolov (ed.)]. St. Petersburg, 1993, iss. 7: 161-163 (in Russ.).
  2. Hidalgo O., Garcia-Jacas N., Garnatje T., Susanna A. Phylogeny of Rhaponticum (Asteraceae, Cardueae-Centaureinae) and related genera inferred from nuclear and chloroplast DNA sequence data: taxonomic and biogeographic implications. Annals of Botany,2006, 97(5): 705-714 CrossRef
  3. Rhapontici carthamoides rhizomata cum radicibus. V knige: Gosudarstvennaya farmakopeya Rossiyskoy Federatsii [In: State Pharmacopoeia of the Russian Federation].XIV edition. Moscow, 2018, Vol. 4: 6360-6368 (in Russ.).
  4. Rhapontici carthamoides folium (Leuzea leaf). V knige: Gosudarstvennaya Farmakopeya Respubliki Belarus’ [In: State Pharmacopoeia of the Republic of Belarus]. 2nd edition. Molodechno, 2016, Vol. 2: 1257-1258 (in Russ.).
  5. Shikov A.N., Narkevich I.A., Flisyuk E.V., Luzhanin V.G., Pozharitskaya O.N. Medicinal plants from the 14th edition of the Russian Pharmacopoeia, recent updates. Journal of Ethnopharmacology, 2021, 268: 113685 CrossRef
  6. Todorova V., Ivanov K., Ivanova S. Comparison between the biological active compounds in plants with adaptogenic properties (Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus and Panax ginseng). Plants,2022, 11(1): 64 CrossRef
  7. Liu X.X., Chen C.Y., Li L., Guo M.M., He Y.F., Meng H., Dong Y.M., Xiao P.G., Yi F. Bibliometric study of adaptogens in dermatology: pharmacophylogeny, phytochemistry, and pharmacological mechanisms, drug design. Development and Therapy, 2023, 17: 341-361 CrossRef
  8. Głazowska J., Kaminski M.M., Kamiński M. Chromatographic separation, determination and identification of ecdysteroids: focus on maral root (Rhaponticum carthamoides, Leuzea carthamoides). Journal of Separation Science, 2018, 41(23): 4304-4314 CrossRef
  9. Dinan L., Dioh W., Veillet S., Lafont R. 20-Hydroxyecdysone, from plant extracts to clinical use: therapeutic potential for the treatment of neuromuscular, cardio-metabolic and respiratory diseases. Biomedicines, 2021, 9(5): 492 CrossRef
  10. Lafont R., Dilda P., Dioh W., Dupont P., Signore S.D., Veillet S. 20-hydroxyecdysone extract of pharmaceutical quality, use and preparation thereof. Patent France FR 3065644A1. Publ. 2020-02-21.
  11. Lafont R., Serova M., Didry-Barca B., Raynal S., Guibout L., Dinan L., Veillet S., Latil M., Dioh W., Dilda P.J. 20-Hydroxyecdysone activates the protective arm of the RAAS via the MAS receptor. Journal of Molecular Endocrinology, 2021, 68(2): 77-87 CrossRef
  12. Latil M., Camelo S., Veillet S., Lafont R., Dilda P.J.Developing new drugs that activate the protective arm of the renin-angiotensin system as a potential treatment for respiratory failure in COVID-19 patients — review. Drug Discovery Today, 2021, 26(5): 1311-1318 CrossRef
  13. Sláma K. Vitamin D1 versus ecdysteroids: growth effects on cell regeneration and malignant growth in insects are similar to those in humans. European Journal of Entomology, 2019, 116: 16-32 CrossRef
  14. Slama K.Approaching a time we can prevent pernicious malignant tumors? Mini review. EC Pharmacology and Toxicology, 2020, 8(3): 01-09.
  15. Shuvalov O., Fedorova O., Tananykina E., Gnennaya Y., Daks A., Petukhov A., Barlev N.A. An arthropod hormone, ecdysterone, inhibits the growth of breast cancer cells via different mechanisms. Frontiers in Pharmacology, 2020, 11: 561537 CrossRef
  16. Panossian A.G., Efferth T., Shikov A.N., Pozharitskaya O.N., Kuchta K., Mukherjee P.K., Banerjee S., Heinrich M., Wu W., De-An Guo D.A., Wagner H. Evolution of the adaptogenic concept from traditional use to medical systems: pharmacology of stress‐ and aging‐related diseases. Medicinal Research Reviews, 2021, 41(1): 630-703 CrossRef
  17. Isenmann E., Ambrosio G., Joseph J.F., Mazzarino M., Torre X., Zimmer Ph., Kazlauskas R., Goebel C., Botre F., Diel P., Parr M.K. Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans. Archives of Toxicology, 2019, 93: 1807-1816 CrossRef
  18. Parr M.K., Müller-Schöll A. Pharmacology of doping agents — mechanisms promoting muscle hypertrophy (review). AIMS Molecular Science, 2018, 5(2): 131-159 CrossRef
  19. Parr M.K., Ambrosio G., Wuest B., Mazzarino M., Torre X., Sibilia F., Joseph J.F., Diel P., Botrè F. Targeting the administration of ecdysterone in doping control samples. Forensic Toxicology, 2020, 38: 172-184 CrossRef
  20. Marciniak A., Nemeczek S., Walczak K., Walczak P., Merkisz K., Grzybowski Ja., Grzywna N., Jaskuła K., Orłowski W. Adaptogens — use, history and future. Quality in Sport, 2023, 9(1): 19-28 CrossRef
  21. World anti-doping code. International standard. Prohibited List 2023. Available: https://www.wada-ama.org/sites/default/files/2022-09/2023list_en_final_9_september_2022.pdf. Accessed: 10.05.2022.
  22. Ivanovskiy A.A., Timofeev N.P., Ermolina S.A. Agrarnaya nauka Evro-Severo-Vostoka, 2019, 20(4): 387-397 CrossRef (in Russ.).
  23. Timofeev N.P.Agrarnaya nauka Evro-Severo-Vostoka, 2021, 22(6): 804-825 CrossRef (in Russ.).
  24. Bathori M., Toth N., Hunyadi A., Marki A., Zador E. Phytoecdysteroids and anabolic-androgenic steroids – structure and effects on humans. Current Medicinal Chemistry, 2008; 15(1): 75-91 CrossRef
  25. Lafont R., Dinan L. Practical uses for ecdysteroids in mammals including humans: and update. Journal of Insect Science, 2003, 3(7): 1-30 CrossRef
  26. Hornok, S., Csorba, A., Kováts, D., Csörgő T., Hunyadi A. Ecdysteroids are present in the blood of wild passerine birds. Scientific Reports, 2019, 9: 17002 CrossRef
  27. Ecdysterone market, by type (0.95, 0.98, other), by application (pharma & healthcare, cosmetic & skin care, other), by region (North America, Europe, Asia Pacific, Middle East & Africa, and South America) — Market Size & Forecasting To 2028. Report Code: CH2066906. Quince Market Insights. Hadapsar, Pune, India, 2021. Available: https://www.quincemarketinsights.com/industry-analysis/ecdysterone-marke. Accessed: 10.05.2022.
  28. Ambrosio G., Wirth D., Joseph J.F., Mazzarino M., Torre X., Botre F., Parr M.K. How reliable is dietary supplement labelling? Experiences from the analysis of ecdysterone supplements. Journal of Pharmaceutical and Biomedical Analysis, 2020, 177: 112877 CrossRef
  29. Tóth G., Herke I., Gáti T., Vágvölgyi M., Berkecz R., Parfenova L.V., Ueno M., Yokoi T., Nakagawa Y., Hunyadi A.A Commercial extract of Cyanotis arachnoidea roots as a source of unusual ecdysteroid derivatives with insect hormone receptor binding activity. Journal of Natural Products, 2021, 84(7): 1870-1881 CrossRef
  30. Hunyadi A., Herke I., Lengyel K., Báthori M., Kele Z., Simon A., Tóth G., Szendrei K. Ecdysteroid-containing food supplements from Cyanotis arachnoidea on the European market: evidence for spinach product counterfeiting. Scientific Reports, 2016, 6: 37322 CrossRef
  31. Kraiem S., Al-Jaber M.Y., Al-Mohammed H., Al-Menhali A.S., Al-Thani N.J., Helaleh M., Samsam W., Touil S., Beotra A., Georgakopoulas C., Bouabdallah S., Mohamed-Ali V., Al Maadheed M. Analytical strategy for the detection of ecdysterone and its metabolites in vivo in uPA(+/+)-SCID mice with humanised liver, human urine samples and estimation of prevalence of its use in anti-doping samples. Drug Testing and Analysis, 2021, 13(7): 1341-1353 CrossRef
  32. 20-Hydroxyecdysone. Product No H5142 (³93 %, HPLC, powder). 2022. Available: https://www.sigmaaldrich.com/RU/en/product/sigma/h5142. Accessed: 10.05.2022.
  33. Timofeev N.P. Achievements and problems in investigation of biology in medicinal herbs of Rhaponticum carthamoides (Willd.) Iljin and Serratula coronata L. (review). Sel'skokhozyaistvennaya biologiya [Agricultural Biology], 2007, 3: 3-17 CrossRef (in Russ.).
  34. Dinan L., Balducci C., Guibout L., Foucault A.-S., Bakrim A., Kumpun S., Girault J.-P., Tourette C., Dioh W., Dilda P.J., Veillet S., Lafont R. Ecdysteroid metabolism in mammals: The fate of ingested 20-hydroxyecdysone in mice and rats. The Journal of Steroid Biochemistry and Molecular Biology,2021, 212: 105896 CrossRef
  35. A double-blind, placebo controlled, randomized interventional clinical trial (SARA-INT) (SARA-INT). ClinicalTrials.gov Identifier: NCT0345248. Available: https://clinicaltrials.gov/ct2/show/NCT03452488. Accessed: 10.05.2022.
  36. Timofeev N.P.International Agricultural Journal, 2021, 64(6): 46-112 CrossRef (in Russ.).
  37. Compendiumof botanicals reported to contain naturally occuring substances of possible concern for human health when used in food and food supplements. EFSA Journal, 2012, 10(5): 2663 CrossRef
  38. Das N., Mishra S.K., Bishayee A., Ali E.S., Bishayee A. The phytochemical, biological, and medicinal attributes of phytoecdysteroids: an updated review. Acta Pharmaceutica Sinica B, 2021, 11(7): 1740-1766 CrossRef
  39. Zhang X.-P., Zhang J., Dong M., Zhang M.-L., Huo C.-H., Shi Q.-W., Gu Y.-C. Chemical constituents of plants from the genus  Rhaponticum. Chemistry & Biodiversity, 2010, 7(3): 594-609 CrossRef
  40. Carasso V., Mucciarelli M., Dovana F., Müller J.V. Comparative germination ecology of two endemic Rhaponticum species (Asteraceae) in different climatic zones of the Ligurian and Maritime Alps (Piedmont, Italy). Plants, 2020, 9(6): 708 CrossRef
  41. Timofeev N.P., Punegov V.V., Bindasova T.N. V sbornike: Khimiya i tekhnologiya rastitel’nykh veshchestv [In: Chemistry and technology of plant substances]. Syktyvkar, 2022: 197-197 (in Russ.).
  42. Tekhnicheskiy reglament Tamozhennogo soyuza. TR TS № 021/2011 «O bezopasnosti pishchevoy produktsii». Reshenie KTS ot 09.12.2011 № 880, v red. ot 14.07.2021 [Technical regulations of the Customs Union. TR CU No. 021/2011 "On food safety". Decision of the CCC dated 12/09/2011 No. 880, amended 07/14/2021]. Astana, Kazakhstan (in Russ.).
  43. Barnaulov O.D. Traditsionnaya meditsina, 2015, 3: 52-56 (in Russ.).
  44. Peschel W., Kump A., Prieto J.M. Effects of 20-hydroxyecdysone, Leuzea carthamoides extracts, dexamethasone and their combinations on the NF-κB activation in HeLa cells. Journal of Pharmacy and Pharmacology,2011,63(11): 1483-1495 CrossRef
  45. Girault J.-P., Lafont R., Varga E., Hajdu Zs., Herke I., Szendrei K. Ecdysteroids from Luzea carthamoides. Phytochemistry, 1988, 27(3): 737-741 CrossRef
  46. Bili A.Sh., Meyer M., Sheval’e K., Lorenson L., Fol’er N., Roller M., Birtik S., Fansa-Berton P.Е.R, Fal’ko L.D. Kompozitsii i sposoby dlya uluchshennogo myshechnogo metabolizma. Patent RU 2730853 C2. NATUREKS SA. Frantsiya.Zayavl. 03.02.2016. Opubl. 26.08.2020. Byul. № 24 [Substances and methods to improve muscle metabolism. Patent RU 2730853 C2. NATUREX SA. France. Appl. 02/03/2016. Published 08/26/2020. Bull. No. 24](in Russ.).
  47. Píš J., Buděšínsky̌ M., Vokáč K., Laudová V., Harmatha J. Ecdysteroids from the roots of Leuzea carthamoides. Phytochemistry, 1994, 37(3): 707-711 CrossRef
  48. Mamatkhanov A.U., Shamsutdinov M.-R., Shakirov T.T. Khimiya prirodnykh soedineniy, 1980, 5: 528-529 (in Russ.).
  49. Baltaev U.A., Abubakirov N.K. Khimiya prirodnykh soedineniy, 1987, 5: 681-684 (in Russ.).
  50. Vokáč K., Buděšínsky̌ M., Harmatha J. Minor ecdysteroid components of Leuzea carthamoides. Collection of Czechoslovak Chemical Communications, 2002, 67(1): 124-139 CrossRef
  51. Timofeev N.P., Lapin A.A., Zelenkov V.N. Quality assessment of Rhaponticum carthamoides (Willd.) Iljin as medicinal raw material by the bromic antioxidant capacity estimation. In: Functional foods for chronic diseases. The modern day cure without the side effects of traditionall treatments. D.M. Martirosyan (ed.). Richardson (Texas, USA), D&A Incorporated, 2006: 164-172. Accessed: 10.05.2022.
  52. Protokol issledovaniya na soderzhanie еkdisteroidov № 18 ot 31.03.2021 g. Syktyvkar, IB FITs Komi NTs UrO RAN. Available: https://leuzea.ru/pdf/drug_leuzea-p_from_the_pharmacy.pdf. No date (in Russ.).
  53. Sevko D.A. Kontsentrirovanie i opredelenie fitosteroidov s pomoshch’yu molekulyarno-imprintirovannykh sorbentov i tandemnoy mass-spektrometrii vysokogo razresheniya. Avtoreferat kandidatskoy dissertatsii [Concentration and determination of phytosteroids using molecularly imprinted sorbents and high resolution tandem mass spectrometry. PhD Thesis]. Moscow, 2016 (in Russ.).
  54. Potanin G.N. Ocherki Severo-zapadnoy Mongolii: rezul’taty puteshestviya, ispolnennye v 1876-1877 g. po porucheniyu Imp. Rus. geogr. o-va chl. sotr. onogo G.N. Potaninym. Vyp. 4. Materialy еtnograficheskie [Essays on North-Western Mongolia: the results of a journey completed in 1876-1877 by member-employee G.N. Potanin on behalf of Imp. Rus. geogr. society. Issue. 4. Ethnographic materials]. St. Petersburg, 1883: 188-189 (in Russ.).
  55. Postnikov B.A. Maraliy koren’ i osnovy vvedeniya ego v kul’turu [Maral root and the basics of its introduction into culture]. Novosibirsk, 1995 (in Russ.).
  56. Terekhin A.A., Vandyshev V.V. Tekhnologiya vozdelyvaniya lekarstvennykh rasteniy [Technology of cultivation of medicinal plants]. Moscow, 2008 (in Russ.).
  57. Galambozi B., Kirakosyan G.M., Luzhanin V.G., Flisyuk E.V., Makarov V.G., Pozharitskaya O.N., Shikov A.N. Vyrashchivanie еfiromaslichnykh i lekarstvennykh rasteniy v usloviyakh Severa: monografiya [Growing essential oil plants and medicinal plants in the conditions of the North: monograph]. St. Petersburg, 2018 (in Russ.).
  58. Kubentaev S.A., Danilova A.N. Vestnik Tomskogo gosudarstvennogo universiteta, 2017, 37: 31-46 (in Russ.).
  59. Timofeev N.P. Rastitel’nye resursy, 2006, 42(2): 17-36 (in Russ.).
  60. Timofeev N.P. Ecological relations of the agropopulations of ecdysteroid-containing plants Rhaponticum carthamoides (Willd.) Iljin and Serratula coronata L. with the insects-phytophagans. Report 1. Contemporary Problems of Ecology, 2009, 2(5):489-500 CrossRef
  61. Timofeev N.P. Composition variability of phytoecdysteroids in agrocenoses and their role in the vulnerability of plants to phytophagans. Report 2. Ecological relations of the agropopulations of ecdysteroid-containing plants Rhaponticum carthamoides (Willd.) Iljin and Serratula coronata L. with the insects-phytophagans. Contemporary Problems of Ecology, 2009, 2(6): 531-541 CrossRef
  62. Baù A., Bottex B. EFSA's compendium of botanicals. Zenodo, 2018. CrossRef
  63. Yang J., Wang, L. Safety pharmacology and toxicity study of herbal medicines. In: Traditional herbal medicine research methods: identification, analysis, bioassay, and pharmaceutical and clinical sciences. W.J.H. Liu (ed.). Wiley, 2011 CrossRef
  64. Brown A.C. An overview of herb and dietary supplement efficacy, safety, and government regulation in the United States with suggested improvements. Part 1 of 5 series. Food and Chemical Toxicology, 2017, 107(Part A): 449-471 CrossRef
  65. Brown A.C. Liver toxicity related to herb and dietary supplements: online table of medical case reports. Part 2 of 5 series. Food and Chemical Toxicology, 2017, 107(Part A): 472-501 CrossRef
  66. Brown A.C. Kidney toxicity related to herb and dietary supplements: online table of medical case reports. Part 3 of 5 series. Food and Chemical Toxicology, 2017, 107(Part A): 502-519 CrossRef
  67. Brown A.C. Heart toxicity related to herb and dietary supplements: online table of case reports. Part 4 of 5. Journal of Dietary Supplements,2018, 15(4): 516-555 CrossRef
  68. Brown A.C. Cancer related to herbs and dietary supplements: online table of case reports. Part 5 of 5. Journal of Dietary Supplements, 2018, 15(4): 556-581 CrossRef
  69. IPNI (International Plant Names Index). Available: https://www.ipni.org/. Accessed: 10.05.2022.
  70. Mamaev S.A. V kn.: Individual’naya i еkologo-geograficheskaya izmenchivost’ rasteniy. Trudy Instituta еkologii rasteniy i zhivotnykh UNTs AN SSSR. Tom 94 [In: Individual and ecogeographical variability of plants. Proceedings of the Institute of Plant and Animal Ecology, UNC, USSR Academy of Sciences. Vol. 94]. Sverdlovsk, 1975: 3-14 (in Russ.).
  71. Ecdybase: The ecdysone handbook. R. Lafont, J. Harmatha, F. Marion-Poll, L. Dinan, I.D. Wilson (eds.). Available: https://ecdybase.org/. Accessed: 10.05.2022.
  72. Polozhiy A.V., Nekratova N.A.V knige: Biologicheskie osobennosti rasteniy Sibiri, nuzhdayushchikhsya v okhrane [In: Biological features of Siberian plants in need of protection]. Novosibirsk, 1986: 198-226 (in Russ.).
  73. Myrzangalieva A.B., Samarkhanov T.N. Vestnik Evraziyskogo natsional’nogo universiteta imeni L.N. Gumileva. Seriya Biologicheskie nauki, 2018, 124(3): 55-64 (in Russ.).
  74. Matolinets D.A., Voloshin V.A. Sibirskiy vestnik sel’skokhozyaystvennoy nauki, 2017, 47(6): 66-72 CrossRef (in Russ.).
  75. Maysak G.P., Matolinets D.A. Kormoproizvodstvo, 2021, 2: 32-35 (in Russ.).
  76. Crouzet S., Maria A., Dinan L., Lafont R., Girault J.-P. Ecdysteroids from Cyanotis longifolia Benth. (Commelinaceae). Archives of Insect Biochemistry and Physiology, 2009, 72(4): 194-209 CrossRef
  77. Kokoska L., Janovska D. Chemistry and pharmacology of Rhaponticum carthamoides: a review. Phytochemistry, 2009, 70(7): 842-855 CrossRef
  78. Timofeev N.P. Agrarnaya nauka Evro-Severo-Vostoka, 2022, 23(4): 480-495 CrossRef (in Russ.).
  79. Timofeev N.P. Materialy III Mezhdunarodnoy konferentsii po selektsii, tekhnologii vozdelyvaniya i pererabotki netraditsionnykh rasteniy [Proceedings of III International Conference on breeding, cultivation technology and processing of non-traditional plantsных растений]. Simferopol’, 1994: 166-167 (in Russ.).
  80. Kratky F., Opletal L., Hejhalek J., Kucharova S. Effect of 20-hydroxyecdysone on the protein synthesis of pigs. Zivocisna Vyroba, 1997, 42: 445-451.

 

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