eISSN: 2221-6197 DOI: 10.31301/2221-6197

Перспективы использования лекарственного растения Withania somnifera для производства фармацевтических препаратов биотехнологическим способом

Год: 2022

Страницы: 192-208

Номер: Том 14, № 3

Тип: научная статья

Аннотация:

Withania somnifera (L.) Dunal – Витания снотворная, называемая также ашвагандой или индийским женьшенем - растение, широко используемое в традиционной восточной медицине. Современные научные исследования подтверждают применимость витанолидов и других веществ, содержащихся в корнях витании, в лечении различных заболеваний. Однако огромные масштабы сбора W. somnifera для использования в традиционной медицине на данный момент ставят вид под угрозу вымирания. Поскольку это растение требовательно к климатическим условиям, наиболее перспективным представляется выращивание культуры "волосовидных корней" (hairy roots) W. somnifera в биореакторах. Несомненным преимуществом данного метода является получение биоматериала высокой степени чистоты, со стабильным содержанием биологически активных веществ. Было накоплено большое количество данных об оптимальных условиях культивирования корней W. somnifera как для ускоренного накопления биомассы, так и для повышения содержания витанолидов, а также о методах их экстракции. Совокупность научных данных позволяет говорить о перспективности производства из витании фармацевтических препаратов для лечения широкого спектра заболеваний.

Ключевые слова:

Withania somnifera, волосовидные (бородатые) корни

Библиографический список:

  1. Михайлова Е.В. , Кулуев Б.Р. , Ясыбаева Г.Р., Чемерис А.В. Создание культур бородатых корней Withania somnifera и оценка параметров их роста при выращивании на твердых и жидких питательных средах // Вестник биотехнологии и физико-химической биологии имени Ю.А. Овчинникова. 2017. Т. 13. №2. С. 40-46.
  2. Ahmad M, Saleem S, Ahmad AS, Ansari MA, Yousuf S, Hoda MN, et al. Neuroprotective effects of Withania somnifera on 6-hydroxydopamine induced Parkinsonism in rats. Hum Exp Toxicol 2005;24: 137–47 
  3. Andallu, B. and Radhika, B. (2000) Hypoglycemic, Diuretic and Hypocholesterolemic Effect of Winter Cherry (Withania somnifera) Root. Indian Journal of Experimental Biology, 38, 607-609. 4 Aslam S. et al. Current Status of Withania somnifera (L.) Dunal: An Endangered Medicinal Plant from Himalaya // AJPS. 2017. Vol. 08, № 05. P. 1159– 1169. https://doi.org/10.4236/ajps.2017.85076
  4. Baba I. A. et al. In vitro propagation of Withania Somnifera (L.) Dunal (Ashwagandha) an endangered medicinal plant //International Journal of Pharmaceutical Science Invention. – 2013. – Т. 2. – №. 3. – С. 6-11.
  5. Banerjee S., Naqvi A.A., Mandal S., Ahuja P.S. Transformation of Withania somnifera (L.) Dunal by Agrobacterium rhizogenes: Infectivity and phytochemical studies // Phytother. Res. 1994. Vol. 8, № 8. P. 452–455. https://doi.org/10.1002/ptr.2650080803
  6. Cho C.-W., Kim Y.-C., Rhee Y.K., Lee Y.-C., Kim K.-T., Hong H.-D. Chemical composition characteristics of Korean straight ginseng products // Journal of Ethnic Foods. 2014. V. 1(1). P. 24–28. https://doi.org/10.1016/j.jef.2014.11.007 
  7. Choudhary MI, Nawaz SA, ul-Haq Z, Lodhi MA, Ghayur MN, Jalil S, et al. Withanolides a new class of natural cholinesterase inhibitors with calcium antagonistic properties // Biochem Biophys Res Commun 2005. V.334. P.276–287 
  8. Dar N.J., Bhat J.A., Satti N.K., Sharma P.R., Hamid A., Ahmad M. Withanone, an Active Constituent from Withania somnifera, Affords Protection Against NMDA-Induced Excitotoxicity in Neuron-Like Cells // Mol Neurobiol. 2017. V. 54(7). P. 5061–5073. https://doi.org/10.1007/s12035-016-0044-7
  9. Dar P.A., Mir S.A., Bhat J.A., Hamid A., Singh L.R., Malik F., Dar T.A. An anti-cancerous protein fraction from Withania somnifera induces ROS- dependent mitochondria-mediated apoptosis in human MDA-MB-231 breast cancer cells // International Journal of Biological Macromolecules. 2019. V. 135. P. 77–87. https://doi.org/10.1016/j.ijbiomac.2019.05.120
  10. Dehdashti S.M., Acharjee S., Kianamiri S., Deka M. An efficient Agrobacterium rhizogenes-mediated transformation protocol of Withania somnifera // Plant Cell Tiss Organ Cult. 2017. V. 128(1). P. 55–65. https://doi.org/10.1007/s11240-016-1081-7
  11. Dehdashti S.M., Acharjee S., Nomani A., Deka M. Production of pharmaceutical active recombinant globular adiponectin as a secretory protein in Withania Somnifera hairy root culture // Journal of Biotechnology. 2020. V. 323. P. 302–312. https://doi.org/10.1016/j.jbiotec.2020.07.012
  12. Dhanani T., Shah S., Gajbhiye N.A., Kumar S. Effect of extraction methods on yield, phytochemical constituents and antioxidant activity of Withania somnifera // Arabian Journal of Chemistry. 2017. V. 10. P. S1193–S1199. https://doi.org/10.1016/j.arabjc.2013.02.015
  13. Dhar N. et al. Dynamics of withanolide biosynthesis in relation to temporal expression pattern of metabolic genes in Withania somnifera (L.) Dunal: a comparative study in two morpho-chemovariants // Mol Biol Rep. 2013. V. 40(12). P. 7007–7016. https://doi.org/10.1007/s11033-013-2820-z
  14. Dhar N., Razdan S., Rana S., Bhat W.W., Vishwakarma R., Lattoo S.K. A Decade of Molecular Understanding of Withanolide Biosynthesis and In vitro Studies in Withania somnifera (L.) Dunal: Prospects and Perspectives for Pathway Engineering // Front. Plant Sci. 2015. V. 6. https://doi.org/10.3389/fpls.2015.01031
  15. Ganguly B., Kumar N., Ahmad A.H., Rastogi S.K. Influence of phytochemical composition on in vitro antioxidant and reducing activities of Indian ginseng [Withania somnifera (L.) Dunal] root extracts // Journal of Ginseng Research. 2018. V. 42(4). P. 463–469. https://doi.org/10.1016/j.jgr.2017.05.002 
  16. Ganeshan S., Natesan S., Andy G., Markandan M. An efficient hairy root culture system for Withania somnifera (L.) Dunal // Afr. J. Biotechnol. 2014. V. 13(43). P. 4141–4147. https://doi.org/10.5897/AJB2014.14128
  17. Garg S., Huifu H., Kumari A., Sundar D., Kaul S.C., Wadhwa R. Induction of Senescence in Cancer Cells by a Novel Combination of Cucurbitacin B and Withanone: Molecular Mechanism and Therapeutic Potential // The Journals of Gerontology: Series A / ed. Anderson R. 2020. V. 75(6). P. 1031–1041. https://doi.org/10.1093/gerona/glz077
  18. Gaur S.K., Kumar K. Toxicity and insect growth regulatory effects of root extract from the medicinal plant, Withania somnifera (Linnaeus) against red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae) // Archives of Phytopathology and Plant Protection. 2020. V. 53(17–18). P. 856–875. https://doi.org/10.1080/03235408.2020.1802566
  19. Giri K. R. Comparative study of anti- inflammatory activity of Withania somnifera (Ashwagandha) with hydrocortisone in experimental animals (Albino rats) //J Med Plants Studies. 2016. V. 4. P. 78-83.
  20. Guillon S., Trémouillaux-Guiller J., Pati P.K., Rideau M., Gantet P. Harnessing the potential of hairy roots: dawn of a new era // Trends in Biotechnology. 2006. V. 24(9). P. 403–409. https://doi.org/10.1016/j.tibtech.2006.07.002
  21. Gupta P., Goel R., Agarwal A.V., Asif M.H., Sangwan N.S., Sangwan R.S., Trivedi P.K. Comparative transcriptome analysis of different chemotypes elucidates withanolide biosynthesis pathway from medicinal plant Withania somnifera // Sci Rep. 2015. V. 5(1). P. 18611. https://doi.org/10.1038/srep18611
  22. Gupta M., Kaur G. Withania somnifera as a Potential Anxiolytic and Anti-inflammatory Candidate Against Systemic Lipopolysaccharide-Induced Neuroinflammation // Neuromol Med. 2018. V. 20(3). P. 343–362. https://doi.org/10.1007/s12017-018-8497-7 
  23. Gupta M., Kaur G. Withania somnifera (L.) Dunal ameliorates neurodegeneration and cognitive impairments associated with systemic inflammation // BMC Complement Altern Med. 2019. V. 19(1). P. 217. https://doi.org/10.1186/s12906-019-2635-0
  24. Gupta A., Singh S. Evaluation of anti- inflammatory effect of Withania somnifera root on collagen-induced arthritis in rats // Pharmaceutical Biology. 2014. V. 52(3). P. 308–320. https://doi.org/10.3109/13880209.2013.835325
  25. Halder B., Thakur S.S. Withania somnifera Has Potential to Treat Cancer // Science of Ashwagandha: Preventive and Therapeutic Potentials / ed. Kaul S.C., Wadhwa R. Cham: Springer International Publishing, 2017. P. 213–226. https://doi.org/10.1007/978-3-319-59192-6_10  
  26. Henley A.B., Yang L., Chuang K.-L., Sahuri- Arisoylu M., Wu L.-H., Bligh S.W.A., Bell J.D. Withania somnifera Root Extract Enhances Chemotherapy through ‘Priming’ // PLoS ONE 2017. V. 12(1). P. e0170917. https://doi.org/10.1371/journal.pone.0170917
  27. Jain S., Shukla S.D., Sharma K., Bhatnagar M. Neuroprotective Effects of Withania somnifera Dunn. in Hippocampal Sub-regions of Female Albino Rat // Phytother. Res. 2001. V. 15(6). P. 544–548. https://doi.org/10.1002/ptr.802
  28. Johny L., Conlan X.A., Adholeya A., Cahill D.M. Growth kinetics and withanolide production in novel transformed roots of Withania somnifera and measurement of their antioxidant potential using chemiluminescence // Plant Cell Tiss Organ Cult. 2018. V. 132(3). P. 479–495. https://doi.org/10.1007/s11240-017-1344-y 
  29. Johny L., Conlan X., Cahill D., Adholeya A. In vitro and in situ screening systems for morphological and phytochemical analysis of Withania somnifera germplasms // Plant Cell Tiss Organ Cult. 2015. V. 120, P.1191–1202. https://doi.org/10.1007/s11240-014-0673-3
  30. Kambizi L., Adebola P.O., Afolayan A.J. Effects of temperature, pre-chilling and light on seed germination of Withania somnifera; a high value medicinal plant // South African Journal of Botany. 2006. V. 72(1). P. 11– 14. https://doi.org/10.1016/j.sajb.2005.03.001
  31. Kashyap S., Agarwal G., Kumar M., Kant Awasthi K. Extraction of bioactive compounds from Withania somnifera using hydrothermal technique // Materials Today: Proceedings. 2022. P. S2214785322055304. https://doi.org/10.1016/j.matpr.2022.08.385 
  32. Kaur A. et al. Organic cultivation of Ashwagandha with improved biomass and high content of active Withanolides: Use of Vermicompost // PLoS ONE / ed. Sundar D. 2018. V. 13(4). P. e0194314. https://doi.org/10.1371/journal.pone.0194314
  33. Khan M.A., Ahmed R.S., Chandra N., Arora V.K., Ali A. In vivo, Extract from Withania somnifera Root Ameliorates Arthritis via Regulation of Key Immune Mediators of Inflammation in Experimental Model of Arthritis // AIAAMC. 2019. V. 18(1). P. 55–70. https://doi.org/10.2174/1871523017666181116092934
  34. Khanal P. et al. Withanolides from Withania somnifera as an immunity booster and their therapeutic options against COVID-19 // Journal of Biomolecular Structure and Dynamics. 2022. V. 40(12). P. 5295–5308. https://doi.org/10.1080/07391102.2020.1869588
  35. Khanchandani N., Shah P., Kalwani T., Ardeshna A., Dharajiya D. Antibacterial and Antifungal Activity of Ashwagandha (Withania somnifera L.): A review // J. Drug Delivery Ther. 2019. V. 9(5-s). P. 154– 161. https://doi.org/10.22270/jddt.v9i5-s.3573
  36. Khanna P.K., Kumar A., Chandra R., Verma V. Germination behaviour of seeds of Withania somnifera (L.) Dunal: a high value medicinal plant // Physiol Mol Biol Plants. 2013. V. 19(3). P. 449–454. https://doi.org/10.1007/s12298-013-0169-3
  37. Kim S.-H., Singh K.B., Hahm E.-R., Lokeshwar B.L., Singh S.V. Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cells // Journal of Traditional and Complementary Medicine. 2020. V. 10. P. 188–197. https://doi.org/10.1016/j.jtcme.2020.02.002
  38. Kuboyama T., Tohda C., Komatsu K. Withanoside IV and its active metabolite, sominone, attenuate Aβ(25-35)-induced neurodegeneration: Neuroregeneration by withanoside IV and its metabolite, sominone // European Journal of Neuroscience. 2006. V. 23(6). P. 1417–1426. https://doi.org/10.1111/j.1460-9568.2006.04664.x 
  39. Kulkarni S.K., Dhir A. Withania somnifera: An Indian ginseng // Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2008. V. 32(5). P. 1093–1105. https://doi.org/10.1016/j.pnpbp.2007.09.011 
  40. Kumar B., Yadav R., Singh S.C., Singh H.P. Seed Germination Behavior of Withania spp. under Different Temperature Regimes // Journal of Crop Improvement. 2016. V. 30(3). P. 287–292. https://doi.org/10.1080/15427528.2016.1151849
  41. Kumar S., Singh R., Gajbhiye N., Dhanani T. Extraction Optimization for Phenolic- and Withanolide- Rich Fractions from Withania somnifera Roots: Identification and Quantification of Withaferin A, 12- Deoxywithastromonolide, and Withanolide A in Plant Materials and Marketed Formulations Using a Reversed- Phase HPLC–PhotodiodeArray Detection Method // Journal of AOAC INTERNATIONAL. 2018. V. 101(6). P. 1773–1780. https://doi.org/10.5740/jaoacint.18-0081 
  42. Kushwaha R.K., Singh S., Pandey S.S., Kalra A., Babu C.S.V. Fungal endophytes attune withanolide biosynthesis in Withania somnifera, prime to enhanced withanolide A content in leaves and roots // World J Microbiol Biotechnol. 2019. V. 35(2). P. 20. https://doi.org/10.1007/s11274-019-2593-1 
  43. Kwon J.-H., Lee G.-D., Belanger J.M.R., Jocelyn Pare J.R. Effect of ethanol concentration on the efficiency of extraction of ginseng saponins when using a microwave-assisted process (MAPtm) // Int J Food Sci Tech. 2003. V. 38(5). P. 615–622. https://doi.org/10.1046/j.1365-2621.2003.00688.x 
  44. Malhotra CL, Mehta VL, Das PK, Dhalla NS. Studies on Withania-ashwagandha Kaul V The effect of total alkaloids (ashwagandholine) on the central nervous system. Indian J Physiol Pharmacol 1965. V.9. P.127– 136.
  45. Mishra S., Bansal S., Mishra B., Sangwan R.S., Asha, Jadaun J.S., Sangwan N.S. RNAi and Homologous Over-Expression Based Functional Approaches Reveal Triterpenoid Synthase Gene-Cycloartenol Synthase Is Involved in Downstream Withanolide Biosynthesis in Withania somnifera // PLoS ONE. 2016. V. 11(2). P. e0149691. https://doi.org/10.1371/journal.pone.0149691
  46. Mirjalili H.M., Fakhr-Tabatabaei S.M., Bonfill M., Alizadeh H., Cusido R.M., Ghassempour A., Palazon J. Morphology and withanolide production of Withania coagulans hairy root cultures // Eng. Life Sci. 2009. V. 9, P. 197–204. https://doi.org/10.1002/elsc.20080008
  47. Mirjalili M., Moyano E., Bonfill M., Cusido R., Palazón J. Steroidal Lactones from Withania somnifera, an Ancient Plant for Novel Medicine // Molecules. 2009. V. 14(7). P. 2373–2393. https://doi.org/10.3390/molecules14072373
  48. Murthy H.N. et al. Establishment of Withania somnifera Hairy Root Cultures for the Production of Withanolide A // Journal of Integrative Plant Biology. 2008. V. 50(8). P. 975–981. https://doi.org/10.1111/j.1744-7909.2008.00680.x
  49. Musin Kh.G., Gumerova G.R., Gorte E., Baimukhametova E.A., Mikhaylova E.V., Kuluev B.R. Using stress factors for storage of Withania somnifera L. hairy roots without passages // Russian Journal of Plant Physiology. 2021. V. 68. P. 536–544. https://doi.org/10.1134/S1021443721030146 
  50. Naidoo D.B., Chuturgoon A.A., Phulukdaree A., Guruprasad K.P., Satyamoorthy K., Sewram V. Withania somnifera modulates cancer cachexia associated inflammatory cytokines and cell death in leukaemic THP- 1 cells and peripheral blood mononuclear cells (PBMC’s) // BMC Complement Altern Med. 2018. V. 18(1). P. 126. https://doi.org/10.1186/s12906-018-2192-y 
  51. Nile S.H., Nile A., Gansukh E., Baskar V., Kai G. Subcritical water extraction of withanosides and withanolides from ashwagandha (Withania somnifera L) and their biological activities // Food and Chemical Toxicology. 2019. V. 132. P. 110659. https://doi.org/10.1016/j.fct.2019.110659
  52. Owais M., Sharad K.S., Shehbaz A., Saleemuddin M. Antibacterial efficacy of Withania somnifera (ashwagandha) an indigenous medicinal plant against experimental murine salmonellosis // Phytomedicine. 2005. V. 12(3). P. 229–235. https://doi.org/10.1016/j.phymed.2003.07.012
  53. Palaniyandi S., Suh J.-W., Yang S. Preparation of ginseng extract with enhanced levels of ginsenosides Rg1 and Rb1 using high hydrostatic pressure and polysaccharide hydrolases // Phcog Mag. 2017. V. 13(49). P. 142. https://doi.org/10.4103/0973-1296.203992
  54. Palliyaguru D.L., Singh S.V., Kensler T.W. Withania somnifera : From prevention to treatment of cancer // Mol. Nutr. Food Res. 2016. V. 60(6). P. 1342– 1353. https://doi.org/10.1002/mnfr.201500756
  55. Pandey V., Srivastava R., Akhtar N., Mishra J., Mishra P., Verma P.C. Expression of Withania somnifera Steroidal Glucosyltransferase gene Enhances Withanolide Content in Hairy Roots // Plant Mol Biol Rep. 2016. V. 34(3). P. 681–689. https://doi.org/10.1007/s11105-015-0955-x  
  56. Pandey V., Ansari W.A., Misra P., Atri N. Withania somnifera: Advances and Implementation of Molecular and Tissue Culture Techniques to Enhance Its Application // Front. Plant Sci. 2017. V. 8. P. 1390. https://doi.org/10.3389/fpls.2017.01390  
  57. Pandey S.S. et al. Endophytes of Withania somnifera modulate in planta content and the site of withanolide biosynthesis // Sci Rep. 2018. V. 8. P. 5450. https://doi.org/10.1038/s41598-018-23716-5  
  58. Patel N., Patel P., Kendurkar S.V., Thulasiram H.V., Khan B.M. Overexpression of squalene synthase in Withania somnifera leads to enhanced withanolide biosynthesis // Plant Cell Tiss Organ Cult. 2015. V. 122, P. 409–420. https://doi.org/10.1007/s11240-015-0778-3 
  59. Pavan Kumar Achar G.S., Prabhakar B.T., Rao S., George T., Abraham S., Sequeira N., Baliga M.S. Scientific Validation of the Usefulness of Withania somnifera Dunal in the Prevention and Treatment of Cancer // Anticancer plants: Properties and Application / ed. Akhtar M.S., Swamy M.K. Singapore: Springer Singapore, 2018. P. 285–301. https://doi.org/10.1007/978-981-10-8548-2_12 
  60. Prakash J., Gupta S.K., Dinda A.K. Withania somnifera Root Extract Prevents DMBA-Induced Squamous Cell Carcinoma of Skin in Swiss Albino Mice // Nutrition and Cancer. 2002. V. 42(1). P. 91–97. https://doi.org/10.1207/S15327914NC421_12  
  61. Praveen N., Murthy H.N. Withanolide A production from Withania somnifera hairy root cultures with improved growth by altering the concentrations of macro elements and nitrogen source in the medium // Acta Physiol Plant. 2013. V. 35(3). P. 811–816. https://doi.org/10.1007/s11738-012-1125-5
  62. Rasool M., Varalakshmi P. Immunomodulatory role of Withania somnifera root powder on experimental induced inflammation: An in vivo and in vitro study // Vascular Pharmacology. 2006. V. 44(6). P. 406–410. https://doi.org/10.1016/j.vph.2006.01.015 
  63. Roja G., Heble M.R., Sipahimalani A.T. Tissue cultures ofWithania somnifera: Morphogenesis and withanolide synthesis // Phytother. Res. 1991. V. 5(4). 185–187. https://doi.org/10.1002/ptr.2650050411 
  64. Sabir F., Sangwan N.S., Chaurasiya N.D., Misra L.N., Sangwan R.S. In vitro Withanolide Production by Withania somnifera L. Cultures // Zeitschrift für Naturforschung C. 2008. V. 63(5-6). P. 409–412. https://doi.org/10.1515/znc-2008-5-616 
  65. Saggam A., Limgaokar K., Borse S., Chavan- Gautam P., Dixit S., Tillu G., Patwardhan B. Withania somnifera (L.) Dunal: Opportunity for Clinical Repurposing in COVID-19 Management // Front. Pharmacol. 2021. V. 12. P. 623795. https://doi.org/10.3389/fphar.2021.623795  
  66. Saravanakumar A., Aslam A., Shajahan A. Development and optimization of hairy root culture systems in Withania somnifera (L.) Dunal for withaferin- A production //African journal of Biotechnology. 2012. V. 11(98). DOI: https://doi.org/10.5897/AJB11.3867 
  67. Sehgal N. et al. Withania somnifera reverses Alzheimer’s disease pathology by enhancing low-density lipoprotein receptor-related protein in liver // Proc. Natl. Acad. Sci. U.S.A. 2012. V. 109(9). P. 3510–3515. https://doi.org/10.1073/pnas.1112209109 
  68. Setty Balakrishnan A., Nathan A.A., Kumar M., Ramamoorthy S., Ramia Mothilal S.K. Withania somnifera targets interleukin-8 and cyclooxygenase-2 in human prostate cancer progression // Prostate International. 2017. V. 5(2). P. 75–83. https://doi.org/10.1016/j.prnil.2017.03.002 
  69. Shah D.D., Palaskar S.J., Pawar R., Punse R.R. WithaniaSomnifera: A New Approach To Cancer // AABS. 2018. V. 5(1). P. R1-8. https://doi.org/10.21276/AABS.1838 
  70. Shree P., Mishra P., Selvaraj C., Singh S.K., Chaube R., Garg N., Tripathi Y.B. Targeting COVID-19 (SARS-CoV-2) main protease through active phytochemicals of ayurvedic medicinal plants – Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi) – a molecular docking study // Journal of Biomolecular Structure and Dynamics. 2022. V. 40(1). P. 190–203. https://doi.org/10.1080/07391102.2020.1810778  
  71. Sivanandhan G. et al. Optimization of Carbon Source for Hairy Root Growth and Withaferin A and Withanone Production inWithania somnifera // Natural Product Communications. 2012. V. 7(10). P. 1934578X1200701. https://doi.org/10.1177/1934578X1200701005 
  72. Shasmita, Rai M.K., Naik S.K. Exploring plant tissue culture in Withania somnifera (L.) Dunal: in vitro propagation and secondary metabolite production // Critical Reviews in Biotechnology. 2018. V. 38(6). P. 836–850. https://doi.org/10.1080/07388551.2017.1416453  
  73. Singh P. et al. Biotechnological interventions in Withania somnifera (L.) Dunal // Biotechnology and Genetic Engineering Reviews. 2015. V. 31(1–2). P. 1–20. https://doi.org/10.1080/02648725.2015.1020467 
  74. Singh G., Tiwari M., Singh S.P., Singh S., Trivedi P.K., Misra P. Silencing of sterol glycosyltransferases modulates the withanolide biosynthesis and leads to compromised basal immunity of Withania somnifera // Sci Rep. 2016. V. 6(1). P. 25562. https://doi.org/10.1038/srep25562  
  75. Singh P. et al. Addressing Challenges to Enhance the Bioactives of Withania somnifera through Organ, Tissue, and Cell Culture Based Approaches // BioMed Research International. 2017. V. 2017. P. 1–15. https://doi.org/10.1155/2017/32784941 
  76. Singh V. et al. Leaf spot disease adversely affects human health-promoting constituents and withanolide biosynthesis in Withania somnifera (L.) Dunal // J Appl Microbiol. 2017. V. 122(1). P. 153–165. https://doi.org/10.1111/jam.13314  
  77. Sivanandhan G., Selvaraj N., Ganapathi A., Lim Y.P. Withanolide Production in Hairy Root Culture of Withania somnifera (L.) Dunal: A Review // Plant Cell and Tissue Differentiation and Secondary Metabolites / ed. Ramawat K.G., Ekiert H.M., Goyal S. Cham: Springer International Publishing, 2021. P. 607–624. https://doi.org/10.1007/978-3-030-30185-9_26  
  78. Sumantran V.N., Chandwaskar R., Joshi A.K., Boddul S., Patwardhan B., Chopra A., Wagh U.V. The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro // Phytother. Res. 2008. V. 22(10). P. 1342–1348. https://doi.org/10.1002/ptr.2498 
  79. Tata S.S., Jyothirmayee G., Kumar O.A. In vitro Plant Regeneration from Mature Seed Explants of Withania somnifera (L.) Dunal, an Important, Rare and Endangered Medicinal Plant // Not Sci Biol. 2019. V. 11, P. 387–391. https://doi.org/10.15835/nsb11410512 
  80. Thilip C., Mehaboob V.M., Varutharaju K., Faizal K., Raja P., Aslam A., Shajahan A. Elicitation of withaferin-A in hairy root culture of Withania somnifera (L.) Dunal using natural polysaccharides // Biologia. 2019. V. 74(8). P. 961–968. https://doi.org/10.2478/s11756-019-00236-9 
  81. Thilip C., Soundar Raju C., Varutharaju K., Aslam A., Shajahan A. Improved Agrobacterium rhizogenes-mediated hairy root culture system of Withania somnifera (L.) Dunal using sonication and heat treatment // 3 Biotech. 2015. V. 5(6). P. 949–956. https://doi.org/10.1007/s13205-015-0297-2 
  82. Thorat S.A. et al. Differential Gene Expression and Withanolides Biosynthesis During in vitro and ex vitro Growth of Withania somnifera (L.) Dunal // Front. Plant Sci. 2022. V. 13. P. 917770. https://doi.org/10.3389/fpls.2022.917770 
  83. Tomar V., Beuerle T., Sircar D. A validated HPTLC method for the simultaneous quantifications of three phenolic acids and three withanolides from Withania somnifera plants and its herbal products // Journal of Chromatography B. 2019. V. 1124. P. 154– 160. https://doi.org/10.1016/j.jchromb.2019.06.009 
  84. Tripathi M.K., Singh P., Sharma S., Singh T.P., Ethayathulla A.S., Kaur P. Identification of bioactive molecule from Withania somnifera (Ashwagandha) as SARS-CoV-2 main protease inhibitor // Journal of Biomolecular Structure and Dynamics. 2021. V. 39(15). P. 5668–5681. https://doi.org/10.1080/07391102.2020.1790425 
  85. Trivedi M.K., Panda P., Sethi K.K., Jana S. Metabolite Profiling in Withania somnifera Roots Hydroalcoholic Extract Using LC/MS, GC/MS and NMR Spectroscopy // Chem. Biodiversity. 2017. V. 14(3). P. e1600280. https://doi.org/10.1002/cbdv.201600280 
  86. Yadav B., Bajaj A., Saxena M., Saxena A. In Vitro anticancer activity of the root, stem and leaves of Withania Somnifera against various human cancer cell lines // Indian J Pharm Sci. 2010. V. 72(5). P. 659. https://doi.org/10.4103/0250-474X.78543 
  87. Yadava S. A. et al. Antioxidant activity of Withania somnifera (L.) Dunal by different solvent extraction methods //J Pharm Res. 2011. V. 4(5). P. 1428- 1430. 
  88. Yousefian Z., Hosseini B., Rezadoost H., Palazón J., Mirjalili M.H. Production of the Anticancer Compound Withaferin A from Genetically Transformed Hairy Root Cultures of Withania Somnifera // Natural Product Communications. 2018. V. 13(8). P. 1934578X1801300. https://doi.org/10.1177/1934578X1801300806 
  89. Yu Y., Wang J., Kaul S.C., Wadhwa R., Miyako E. Folic Acid Receptor-Mediated Targeting Enhances the Cytotoxicity, Efficacy, and Selectivity of Withania somnifera Leaf Extract: In vitro and in vivo Evidence // Front. Oncol. 2019. V. 9. P. 602. https://doi.org/10.3389/fonc.2019.00602 
  90. Zhao J., Nakamura N., Hattori M., Kuboyama T., Tohda C., Komatsu K. Withanolide Derivatives from the Roots of Withania somnifera and Their Neurite Outgrowth Activities. // Chem. Pharm. Bull. 2002. V. 50(6). P. 760–765. https://doi.org/10.1248/cpb.50.760 
Скачать pdf
наверх
eISSN: 2221-6197 DOI: 10.31301/2221-6197