Hairy Root Culture an Alternative for Bioactive Compound Production from Medicinal Plants

Arpita       Roy
Abstract

Medicinal plants produce a diverse group of phytocompounds like anthraquinones, alkaloids, anthocyanins, flavonoids, saponins, and terpenes which are used in pharmaceutical, perfume, cosmetics, dye and flavor industries. Commercial source of these metabolites is field-grown plants, which are generally influenced by seasonal changes. Biotechnology possesses a significant role in production of high-value secondary metabolites. By incorporating biotechnological methods, it is feasible to manage biosynthetic pathways of the plant to enhance phytocompound production that is of pharmaceutical interest. Plant cell suspension, shoot, adventitious root and hairy root culture are considered as alternative methods for important bioactive compound production. These methods are controllable, sustainable and overcome several inconveniences for large scale secondary metabolites production. At present research on hairy root culture for valuable bioactive compound production has gained a lot of attention. Agrobacterium rhizogenes is an agent which causes hairy root disease in a plant and this leads to the neoplastic growth of root which is characterized by higher growth rate and genetic stability. Various studies explore the hairy root culture for production of a wide range of bioactive compounds. Scale-up of hairy root culture using bioreactors has provided an opportunity to enhance bioactive compound production at the commercial level. The present review discusses the role of hairy root culture in the production of valuable bioactive compounds, the effect of culture parameters on bioactive compound production and bioreactor applications.
Keywords: Medicinal plants, bioactive compounds, Agrobacterium rhizogenes, elicitors, scale up, bioreactor.
Graphical Abstract

[1] 
Roy, A.; Bharadvaja, N. Biotechnological approaches for the production of pharmaceutically important compound: plumbagin. Curr. Pharm. Biotechnol.,  2018, 19(5), 372-381.
[http://dx.doi.org/10.2174/1389201019666180629143842] [PMID:  29956626] 
[2] 
Roy, A.; Bharadvaja, N. Medicinal plants in the management of cancer: a review. Int J Complement Alt Med,  2017, 9(2), 00291.
[3] 
Hussain, M.S.; Fareed, S.; Ansari, S.; Rahman, M.A.; Ahmad, I.Z.; Saeed, M. Current approaches toward production of secondary plant metabolites. J. Pharm. Bioallied Sci.,  2012, 4(1), 10-20.
[http://dx.doi.org/10.4103/0975-7406.92725] [PMID:  22368394] 
[4] 
Charlwood, B.V.; Charlwood, K.A. Terpenoid production in plant cell culture.Ecological Chemistry and Biochemistry of Plant Terpenoids; Harborne, J.B.; Tomas-Barberan, F., Eds.; Clarendon Press: Oxford, 1991, pp. 95-132.
[5] 
Rudrappa, T.; Neelwarne, B.; Kumar, V.; Lakshmanan, V.; Venkataramareddy, S.R.; Aswathnarayana, R.G. Peroxidase production from hairy root cultures of red beet (Beta vulgaris). Electron. J. Biotechnol.,  2005, 8, 185-197.
[http://dx.doi.org/10.2225/vol8-issue2-fulltext-12] 
[6] 
Steward, F.C.; Rolfs, F.M.; Hall, F.H. A fruit disease survey of western New York in 1900. New York Agric. Exp. Sta. Bact,  1900, 191, 291-331.
[7] 
Ackermann, C. Pflanzen aus Agrobacterium rhizogenes- Tumoren an Nicotiana tabacum. Plant Sci. Lett.,  1977, 8, 23-30.
[http://dx.doi.org/10.1016/0304-4211(77)90167-5] 
[8] 
Balandrin, M.F.; Klocke, J.A.; Wurtele, E.S.; Bollinger, W.H. Natural plant chemicals: sources of industrial and medicinal materials. Science,  1985, 228(4704), 1154-1160.
[http://dx.doi.org/10.1126/science.3890182] [PMID:  3890182] 
[9] 
Cardillo, A.B.; Perassolo, M.; Minoia, J.M.; Talou, J.R.; Giulietti, A.M. Tropane alkaloid production by the establishment of hairy root cultures of Brugmansia candida and elicitation.Hairy Root Cultures Based Applications; Springer: Singapore, 2020, pp. 123-132.
[10] 
Baek, S.; Ho, T.T.; Lee, H.; Jung, G.; Kim, Y.E.; Jeong, C.S.; Park, S.Y. Enhanced biosynthesis of triterpenoids in Centella asiatica hairy root culture by precursor feeding and elicitation. Plant Biotechnol. Rep.,  2020, 14(1), 45-53.
[http://dx.doi.org/10.1007/s11816-019-00573-w] 
[11] 
Perassolo, M.; Cardillo, A.B.; Busto, V.D.; Rivière, S.; Cerezo, J.; Giulietti, A.M.; Talou, J.R. Elicitation as an essential strategy for enhancing anthraquinone accumulation in hairy root cultures of Rubia tinctorum.Hairy Root Cultures Based Applications; Springer: Singapore, 2020, pp. 133-152.
[http://dx.doi.org/10.1007/978-981-15-4055-4_10] 
[12] 
Srivastava, V.; Mehrotra, S.; Mishra, S. Biotransformation through hairy roots: Perspectives, outcomes, and major challenges; Transgenesis and Secondary Metabolism, 2017, pp. 1-24.
[13] 
Sidwa-Gorycka, M.; Krolicka, A.; Orlita, A.; Malinski, E.; Golebiowski, M.; Kumirska, J.; Chromik, A.; Biskup, E.; Stepnowski, P.; Lojkowska, E. Genetic transformation of Ruta graveolens L. by Agrobacterium rhizogenes: hairy root cultures a promising approach for production of coumarins and furanocoumarins. Plant Cell Tissue Organ Cult.,  2009, 97, 59-69.
[http://dx.doi.org/10.1007/s11240-009-9498-x] 
[14] 
Moghadam, A.Y.; Piri, K.; Bahramnejad, B.; Ghiasvand, T. Dopamine production in hairy root cultures of Portulaca oleracea (Purslane) using Agrobacterium rhizogenes. J. Agric. Sci. Technol.,  2014, 16, 409-420.
[15] 
Skała, E.; Kicel, A.; Olszewska, M.A.; Kiss, A.K.; Wysokińska, H. Establishment of hairy root cultures of Rhaponticum carthamoides (Willd.) Iljin for the production of biomass and caffeic acid derivatives. BioMed Res. Int.,  2015, 2015181098
[http://dx.doi.org/10.1155/2015/181098] [PMID:  25811023] 
[16] 
Wilhelmson, A.; Häkkinen, S.T.; Kallio, P.T.; Oksman-Caldentey, K.M.; Nuutila, A.M. Heterologous expression of Vitreoscilla hemoglobin (VHb) and cultivation conditions affect the alkaloid profile of Hyoscyamus muticus hairy roots. Biotechnol. Prog.,  2006, 22(2), 350-358.
[http://dx.doi.org/10.1021/bp050322c] [PMID:  16599546] 
[17] 
Verma, P.C.; Singh, H.; Negi, A.S.; Saxena, G.; Rahman, L.U.; Banerjee, S. Yield enhancement strategies for the production of picroliv from hairy root culture of Picrorhiza kurroa Royle ex Benth. Plant Signal. Behav.,  2015, 10(5)e1023976
[http://dx.doi.org/10.1080/15592324.2015.1023976] [PMID:  26039483] 
[18] 
Bais, H.P.; George, J.; Ravishankar, G.A.; Sudha, G. Influence of exogenous hormones on growth and secondary metabolite production in hairy root cultures of Cichorium intybus L. cv. Lucknow local. In Vitro Cell. Dev. Biol. Plant,  2001, 37, 293-299.
[http://dx.doi.org/10.1007/s11627-001-0052-8] 
[19] 
Manuhara, Y.S.W.; Kristanti, A.N.; Utami, E.S.W.; Yachya, A. Effect of sucrose and potassium nitrate on biomass and saponin content of Talinum paniculatum Gaertn. hairy root in balloon-type bubble bioreactor. Asian Pac. J. Trop. Biomed.,  2015, 5(12), 1027-1032.
[http://dx.doi.org/10.1016/j.apjtb.2015.09.009] 
[20] 
Kochan, E.; Szymczyk, P.; Szymańska, G. Nitrogen and phosphorus as the factors affecting ginsenoside production in hairy root cultures of Panax quinquefolium cultivated in shake flasks and nutrient sprinkle bioreactor. Acta Physiol. Plant.,  2016, 38(6), 149.
[http://dx.doi.org/10.1007/s11738-016-2168-9] 
[21] 
Yu, K.W.; Hahna, E.J.; Paek, K.Y. Ginsenoside production by hairy root cultures of Panax ginseng: influence of temperature and light quality. J Biochem Eng,  2005, 23, 53-56.
[http://dx.doi.org/10.1016/j.bej.2004.07.001] 
[22] 
Pavlov, A.; Georgiev, V.; Kovatcheva, P. Relationship between type and age of the inoculum cultures and betalains biosynthesis by Beta vulgaris hairy root culture. Biotechnol. Lett.,  2003, 25(4), 307-309.
[http://dx.doi.org/10.1023/A:1022397317504] [PMID:  12882542] 
[23] 
Jeong, G.T.; Park, D.H.; Ryu, H.W.; Hwang, B.; Woo, J.C. Effects of inoculum conditions on growth of hairy roots of Panax ginseng C.A. Meyer. Appl. Biochem. Biotechnol.,  2004, 113-116, 1193-1203.
[http://dx.doi.org/10.1385/ABAB:116:1-3:1193] [PMID:  15054227] 
[24] 
Gai, Q.Y.; Jiao, J.; Luo, M.; Wei, Z.F.; Zu, Y.G.; Ma, W.; Fu, Y.J. Establishment of hairy root cultures by Agrobacterium rhizogenes mediated transformation of Isatis tinctoria L. For the efficient production of flavonoids and evaluation of antioxidant activities. PLoS One,  2015, 10(3)e0119022
[http://dx.doi.org/10.1371/journal.pone.0119022] [PMID:  25785699] 
[25] 
Jose, B.; Silja, P.K.; Pillai, D.B.; Satheeshkumar, K. In vitro cultivation of hairy roots of Plumbago rosea L. in a customized reaction kettle for the production of plumbagin-An anticancer compound. Ind. Crops Prod.,  2016, 87, 89-95.
[http://dx.doi.org/10.1016/j.indcrop.2016.04.023] 
[26] 
Sivakumar, G.; Yu, K.W.; Hahn, E.J.; Paek, K.Y. Optimization of organic nutrients for ginseng hairy roots production in large-scale bioreactors. Curr. Sci.,  2005, 89, 641-649.
[27] 
Amdoun, R.; Khelifi, L.; Khelifi-Slaoui, M.; Amroune, S.; Benyoussef, E.H.; Thi, D.V.; Assaf-Ducrocq, C.; Gontier, E. Influence of minerals and elicitation on Datura stramonium L. tropane alkaloid production: Modelization of the in vitro biochemical response. Plant Sci.,  2009, 177(2), 81-87.
[http://dx.doi.org/10.1016/j.plantsci.2009.03.016] 
[28] 
Wang, J.P.; Zhou, Y.M.; Zhang, Y.H. Kirenol production in hairy root culture of Siegesbeckea orientalis and its antimicrobial activity. Pharmacogn. Mag.,  2012, 8(30), 149-155.
[http://dx.doi.org/10.4103/0973-1296.96569] [PMID:  22701289] 
[29] 
Petrova, M.; Zayova, E.; Dincheva, I.; Badjakov, I.; Vlahova, M. Influence of carbon sources on growth and GC–MS based metabolite profiling of Arnica montana L. hairy roots. Turk. J. Biol.,  2015, 39, 469-478.
[http://dx.doi.org/10.3906/biy-1412-37] 
[30] 
Reis, A.; Boutet-Mercey, S.; Massot, S.; Ratet, P.; Zuanazzi, J.A.S. Isoflavone production in hairy root cultures and plantlets of Trifolium pratense. Biotechnol. Lett.,  2019, 41(3), 427-442.
[http://dx.doi.org/10.1007/s10529-018-02640-8] [PMID:  30661155] 
[31] 
Solis-Castañeda, G.J.; Zamilpa, A.; Cabañas-García, E.; Bahena, S.M.; Pérez-Molphe-Balch, E.; Gómez-Aguirre, Y.A. Identification and quantitative determination of feruloyl-glucoside from hairy root cultures of Turbinicarpus lophophoroides (Werderm.) Buxb. & Backeb. (Cactaceae). In Vitro Cell. Dev. Biol. Plant,  2020, 56(1), 8-17.
[http://dx.doi.org/10.1007/s11627-019-10029-z] 
[32] 
Guerriero, G.; Berni, R.; Muñoz-Sanchez, J.A.; Apone, F.; Abdel-Salam, E.M.; Qahtan, A.A.; Alatar, A.A.; Cantini, C.; Cai, G.; Hausman, J.F.; Siddiqui, K.S.; Hernández-Sotomayor, S.M.T.; Faisal, M. Production of plant secondary metabolites: Examples, tips and suggestions for biotechnologists. Genes (Basel),  2018, 9(6), 309.
[http://dx.doi.org/10.3390/genes9060309] [PMID:  29925808] 
[33] 
Murthy, H.N.; Lee, E.J.; Paek, K.Y. Production of secondary metabolites from cell and organ cultures: strategies and approaches for biomass improvement and metabolite accumulation. Plant Cell Tiss Organ,  2014, 118, 1-16.
[http://dx.doi.org/10.1007/s11240-014-0467-7] 
[34] 
Wielanek, M.; Urbanek, H. Enhanced glucotropaeolin production in hairy root cultures of Tropaeolum majus L. by combining elicitation and precursor feeding. Plant Cell Tissue Organ Cult.,  2006, 86, 177-186.
[http://dx.doi.org/10.1007/s11240-006-9106-2] 
[35] 
Srivastava, S.; Srivastava, A.K. Effect of elicitors and precursors on azadirachtin production in hairy root culture of Azadirachta indica. Appl. Biochem. Biotechnol.,  2014, 172(4), 2286-2297.
[http://dx.doi.org/10.1007/s12010-013-0664-6] [PMID:  24357500] 
[36] 
Ahmadian Chashmi, N.; Sharifi, M.; Behmanesh, M. Lignan enhancement in hairy root cultures of Linum album using coniferaldehyde and methylenedioxycinnamic acid. Prep. Biochem. Biotechnol.,  2016, 46(5), 454-460.
[http://dx.doi.org/10.1080/10826068.2015.1068802] [PMID:  26444150] 
[37] 
Renouard, S.; Corbin, C.; Drouet, S.; Medvedec, B.; Doussot, J.; Colas, C.; Maunit, B.; Bhambra, A.S.; Gontier, E.; Jullian, N.; Mesnard, F.; Boitel, M.; Abbasi, B.H.; Arroo, R.R.J.; Lainé, E.; Hano, C. Investigation of Linum flavum (L.) hairy root cultures for the production of anticancer aryltetralin lignans. Int. J. Mol. Sci.,  2018, 19(4), 990.
[http://dx.doi.org/10.3390/ijms19040990] [PMID:  29587452] 
[38] 
Kundu, S.; Salma, U.; Ali, M.N.; Hazra, A.K.; Mandal, N. Development of transgenic hairy roots and augmentation of secondary metabolites by precursor feeding in Sphagneticola calendulacea (L.). Pruski. Ind. Crops Prod.,  2018, 121, 206-215.
[http://dx.doi.org/10.1016/j.indcrop.2018.05.009] 
[39] 
Demirci, T.; Akçay, U.Ç.; Baydar, N.G. Effects of 24-epibrassinolide and L-phenylalanine on growth and caffeic acid derivative production in hairy root culture of Echinacea purpurea L. Moench. Acta Physiol. Plant.,  2020, 42(66), 66.
[http://dx.doi.org/10.1007/s11738-020-03055-7] 
[40] 
Chen, G.; Chunchao, L.; Hechun, Y.; Guofeng, L. Effect of temperature on growth and artemisinin biosynthesis in hairy root cultures of \sl Artemisia annua. Xibei Zhiwu Xuebao,  2004, 24(10), 1828-1831.
[41] 
Zárate, R.; Cequier-Sánchez, E.; Rodríguez, C.; Dorta-Guerra, R.; Jaber-Vazdekis, E.; Ravelo, Á.G. Improvement of polyunsaturated fatty acid production in Echium acanthocarpum transformed hairy root cultures by application of different abiotic stress conditions. International Scholarly Research Notices,  2013, 2013
[42] 
Rahimi, S.; Hasanloo, T. The effect of temperature and pH on biomass and bioactive compounds production in Silybum marianum hairy root cultures. Research Journal of Pharmacognosy,  2016, 3(2), 53-59.
[43] 
Zhong, J.J.; Seki, T.; Kinoshita, S.; Yoshida, T. Effect of light irradiation on anthocyanin production by suspended culture of Perilla frutescens. Biotechnol. Bioeng.,  1991, 38(6), 653-658.
[http://dx.doi.org/10.1002/bit.260380610] [PMID:  18604883] 
[44] 
Taya, M.; Yakura, K.; Kino-Oka, M.; Tone, S. Influence of medium constituents on enhancement of pigment production by batch culture of red beet hairy roots. J. Ferment. Bioeng.,  1994, 77, 215-217.
[http://dx.doi.org/10.1016/0922-338X(94)90329-8] 
[45] 
Wang, Y.C.; Zhang, H.X.; Zhao, B.; Yuan, X.F. Improved growth of Artemisia annua L hairy roots and artemisinin production under red light conditions. Biotechnol. Lett.,  2001, 23(23), 1971-1973.
[http://dx.doi.org/10.1023/A:1013786332363] 
[46] 
Abbasi, B.H.; Tian, C.L.; Murch, S.J.; Saxena, P.K.; Liu, C.Z. Light-enhanced caffeic acid derivatives biosynthesis in hairy root cultures of Echinacea purpurea. Plant Cell Rep.,  2007, 26(8), 1367-1372.
[http://dx.doi.org/10.1007/s00299-007-0344-5] [PMID:  17396238] 
[47] 
Jacob, A.; Malpathak, N. Green hairy root cultures of Solanum khasianum Clarke-a new route to in vitro solasodine production. Curr. Sci.,  2004, 87, 1442-1447.
[48] 
Marsh, Z.; Yang, T.; Nopo-Olazabal, L.; Wu, S.; Ingle, T.; Joshee, N.; Medina-Bolivar, F. Effect of light, methyl jasmonate and cyclodextrin on production of phenolic compounds in hairy root cultures of Scutellaria lateriflora. Phytochemistry,  2014, 107, 50-60.
[http://dx.doi.org/10.1016/j.phytochem.2014.08.020] [PMID:  25236693] 
[49] 
Jiao, J.; Gai, Q.Y.; Yao, L.P.; Niu, L.L.; Zang, Y.P.; Fu, Y.J. Ultraviolet radiation for flavonoid augmentation in Isatis tinctoria L. hairy root cultures mediated by oxidative stress and biosynthetic gene expression. Ind. Crops Prod.,  2018, 118, 347-354.
[http://dx.doi.org/10.1016/j.indcrop.2018.03.046] [PMID:  32288266] 
[50] 
Roy, A.; Bharadvaja, N. Establishment of root suspension culture of Plumbago zeylanica and enhanced production of plumbagin. Ind. Crops Prod.,  2019, 137, 419-427.
[http://dx.doi.org/10.1016/j.indcrop.2019.05.007] 
[51] 
Thakur, M.; Sohal, B.S. Role of elicitors in inducing resistance in plants against pathogen infection: a review. ISRN biochemistry,  2013, 2013
[http://dx.doi.org/10.1155/2013/762412] 
[52] 
Zhao, J.; Davis, L.C.; Verpoorte, R. Elicitor signal transduction leading to production of plant secondary metabolites. Biotechnol. Adv.,  2005, 23(4), 283-333.
[http://dx.doi.org/10.1016/j.biotechadv.2005.01.003] [PMID:  15848039] 
[53] 
Bais, H.P.; Walker, T.S.; Schweizer, H.P.; Vivanco, J.A. Root specific elicitation and antimicrobial activity of rosmarinic acid in hairy root cultures of Ocimum basilicum. Plant Physiol. Biochem.,  2002, 40, 983-995.
[http://dx.doi.org/10.1016/S0981-9428(02)01460-2] 
[54] 
Jeong, G.T.; Park, D.H.; Ryu, H.W.; Hwang, B.; Woo, J.C.; Kim, D.; Kim, S.W. Production of antioxidant compounds by culture of Panax ginseng C.A. Meyer hairy roots: I. Enhanced production of secondary metabolite in hairy root cultures by elicitation. Appl. Biochem. Biotechnol.,  2005, 121-124, 1147-1157.
[http://dx.doi.org/10.1385/ABAB:124:1-3:1147] [PMID:  15930588] 
[55] 
Stojakowska, A.; Burczyk, J.; Kisel, W.; Zych, M.; Banas, A.; Duda, T. Effect of various elicitors on the accumulation and secretion of spiroketal enol ether diacetylenes in fever few hariy root culture. Acta Soc. Bot. Pol.,  2008, 77, 17-21.
[http://dx.doi.org/10.5586/asbp.2008.002] 
[56] 
Wu, J.Y.; Ng, J.; Shi, M.; Wu, S.J. Enhanced secondary metabolite (tanshinone) production of Salvia miltiorrhiza hairy roots in a novel root-bacteria coculture process. Appl. Microbiol. Biotechnol.,  2007, 77(3), 543-550.
[http://dx.doi.org/10.1007/s00253-007-1192-5] [PMID:  17882415] 
[57] 
Zhao, J.L.; Zhou, L.G.; Wu, J.Y. Promotion of Salvia miltiorrhiza hairy root growth and tanshinone production by polysaccharide–protein fractions of plant growth-promoting rhizobacterium Bacillus cereus. Process Biochem.,  2010, 45, 1517-1522.
[http://dx.doi.org/10.1016/j.procbio.2010.05.034] 
[58] 
Shakeran, Z.; Keyhanfar, M.; Ghanadian, M. Biotic elicitation for scopolamine production by hairy root cultures of Datura metel. Mol. Biol. Res. Commun.,  2017, 6(4), 169-179.
[PMID:  29417086] 
[59] 
Yang, D.; Fang, Y.; Xia, P.; Zhang, X.; Liang, Z. Diverse responses of tanshinone biosynthesis to biotic and abiotic elicitors in hairy root cultures of Salvia miltiorrhiza and Salvia castanea Diels f. tomentosa. Gene,  2018, 643, 61-67.
[http://dx.doi.org/10.1016/j.gene.2017.11.067] [PMID:  29196256] 
[60] 
Pitta-Alvarez, S.I.; Spollansky, T.C.; Giulietti, A.M. The influence of different biotic and abiotic elicitors on the production and profile of tropane alkaloids in hairy root cultures of Brugmansia candida. Enzyme Microb. Technol.,  2000, 26(2-4), 252-258.
[http://dx.doi.org/10.1016/S0141-0229(99)00137-4] [PMID:  10689085] 
[61] 
Jeong, G.T.; Park, D.H. Enhanced secondary metabolite biosynthesis by elicitation in transformed plant root system: effect of abiotic elicitors. Appl. Biochem. Biotechnol.,  2006, 129-132, 436-446.
[http://dx.doi.org/10.1385/ABAB:130:1:436] [PMID:  16915660] 
[62] 
Binder, B.Y.K.; Peebles, C.A.M.; Shanks, J.V.; San, K.Y. The effects of UV-B stress on the production of terpenoid indole alkaloids in Catharanthus roseus hairy roots. Biotechnol. Prog.,  2009, 25(3), 861-865.
[http://dx.doi.org/10.1002/btpr.97] [PMID:  19479674] 
[63] 
Gangopadhyay, M.; Dewanjee, S.; Bhattacharya, S. Enhanced plumbagin production in elicited Plumbago indica hairy root cultures. J. Biosci. Bioeng.,  2011, 111(6), 706-710.
[http://dx.doi.org/10.1016/j.jbiosc.2011.02.003] [PMID:  21382748] 
[64] 
Patra, N.; Srivastava, A.K. Enhanced production of artemisinin by hairy root cultivation of Artemisia annua in a modified stirred tank reactor. Appl. Biochem. Biotechnol.,  2014, 174(6), 2209-2222.
[http://dx.doi.org/10.1007/s12010-014-1176-8] [PMID:  25172060] 
[65] 
Srivastava, M.; Sharma, S.; Misra, P. Elicitation based enhancement of secondary metabolites in Rauwolfia serpentina and Solanum khasianum hairy root cultures. Pharmacogn. Mag.,  2016, 12(Suppl. 3), S315-S320.
[http://dx.doi.org/10.4103/0973-1296.185726] [PMID:  27563218] 
[66] 
Gai, Q.Y.; Jiao, J.; Wang, X.; Zang, Y.P.; Niu, L.L.; Fu, Y.J. Elicitation of Isatis tinctoria L. hairy root cultures by salicylic acid and methyl jasmonate for the enhanced production of pharmacologically active alkaloids and flavonoids. Plant Cell Tissue Organ Cult.,  2019, 137(1), 77-86.
[http://dx.doi.org/10.1007/s11240-018-01553-8] 
[67] 
Thimmaraju, R.; Bhagyalakshmi, N.; Narayan, M.S.; Ravishankar, G.A. Kinetics of pigment release from hairy root cultures of Beta vulgaris under the influence of pH, sonication, temperature and oxygen stress. Process Biochem.,  2003, 38(7), 1069-1076.
[http://dx.doi.org/10.1016/S0032-9592(02)00234-0] 
[68] 
Sivanandhan, G.; Rajesh, M.; Arun, M.; Jeyaraj, M.; Dev, G.K.; Manickavasagam, M.; Selvaraj, N.; Ganapathi, A. Optimization of carbon source for hairy root growth and withaferin A and withanone production in Withania somnifera. Nat. Prod. Commun.,  2012, 7(10), 1271-1272.
[http://dx.doi.org/10.1177/1934578X1200701005] [PMID:  23156987] 
[69] 
Gutierrez-Valdes, N.; Häkkinen, S.T.; Lemasson, C.; Guillet, M.; Oksman-Caldentey, K.M.; Ritala, A.; Cardon, F. Hairy Root Cultures-A Versatile Tool With Multiple Applications. Front. Plant Sci.,  2020, 11, 33.
[http://dx.doi.org/10.3389/fpls.2020.00033] [PMID:  32194578] 
[70] 
Paek, K.Y.; Chakrabarty, D.; Hahn, E.J. Application of bioreactor systems for large scale production of horticultural and medicinal plants. Plant Cell Tissue Organ Cult.,  2005, 81(3), 287-300.
[http://dx.doi.org/10.1007/s11240-004-6648-z] 
[71] 
Kim, Y.J.; Wyslouzil, B.E.; Weathers, P.J. Invited review: secondary metabolism of hairy root cultures in bioreactors. In Vitro Cell. Dev. Biol. Plant,  2002, 38, 1-10.
[http://dx.doi.org/10.1079/IVP2001243] 
[72] 
Souret, F.F.; Kim, Y.; Wyslouzil, B.E.; Wobbe, K.K.; Weathers, P.J. Scale-up of Artemisia annua L. hairy root cultures produces complex patterns of terpenoid gene expression. Biotechnol. Bioeng.,  2003, 83(6), 653-667.
[http://dx.doi.org/10.1002/bit.10711] [PMID:  12889030] 
[73] 
Ali, M.B.; Hahn, E.J.; Paek, K.Y. Methyl jasmonate and salicylic acid induced oxidative stress and accumulation of phenolics in Panax ginseng bioreactor root suspension cultures. Molecules,  2007, 12(3), 607-621.
[http://dx.doi.org/10.3390/12030607] [PMID:  17851415] 
[74] 
Cui, X.H.; Chakrabarty, D.; Lee, E.J.; Paek, K.Y. Production of adventitious roots and secondary metabolites by Hypericum perforatum L. in a bioreactor. Bioresour. Technol.,  2010, 101(12), 4708-4716.
[http://dx.doi.org/10.1016/j.biortech.2010.01.115] [PMID:  20171884] 
[75] 
Rahimi, S.; Hasanloo, T.; Najafi, F.; Khavari-Nejad, R.A. Methyl jasmonate influence on silymarin production and plant stress responses in Silybum marianum hairy root cultures in a bioreactor. Nat. Prod. Res.,  2012, 26(18), 1662-1667.
[http://dx.doi.org/10.1080/14786419.2011.593518] [PMID:  21988074] 
[76] 
Li, L.; Wang, J.; Wang, W.; Lu, Y.; Wang, Y.; Zhou, G.; Kai, G. Optimization of induction and culture conditions and tropane alkaloid production in hairy roots of Anisodus acutangulus. Biotechnol. Bioprocess Eng.; BBE,  2008, 13(5), 606-612.
[http://dx.doi.org/10.1007/s12257-008-0035-2] 
[77] 
Habibi, P.; Piri, K.; Deljo, A.; Moghadam, Y.A.; Ghiasvand, T. Increasing scopolamine content in hairy roots of Atropa belladonna using bioreactor. Braz. Arch. Biol. Technol.,  2015, 58(2), 166-174.
[http://dx.doi.org/10.1590/S1516-8913201400276] 
[78] 
Kim, J.S.; Lee, Y.S.; Park, S. Resveratrol production in hairy root culture of peanut, Arachis hypogaea L. transformed with different Agrobacterium rhizogenes strains. Afr. J. Biotechnol.,  2008, 7(20), 3788-3790.
[79] 
Brijwal, L.; Tamta, S. Agrobacterium rhizogenes mediated hairy root induction in endangered Berberis aristata DC. Springerplus,  2015, 4, 443.
[http://dx.doi.org/10.1186/s40064-015-1222-1] [PMID:  26312208] 
[80] 
Cardillo, A.B.; María Otalvaro Alvarez, A.; Calabró Lopez, A.; Enrique Velásquez Lozano, M.; Rodríguez Talou, J.; María Giulietti, A. Anisodamine production from natural sources: seedlings and hairy root cultures of Argentinean and Colombian Brugmansia candida plants. Planta Med.,  2010, 76(4), 402-405.
[http://dx.doi.org/10.1055/s-0029-1186164] [PMID:  19790035] 
[81] 
Lorence, A.; Medina-Bolivar, F.; Nessler, C.L. Camptothecin and 10-hydroxycamptothecin from Camptotheca acuminata hairy roots. Plant Cell Rep.,  2004, 22(6), 437-441.
[http://dx.doi.org/10.1007/s00299-003-0708-4] [PMID:  13680137] 
[82] 
Kim, O.T.; Bang, K.H.; Shin, Y.S.; Lee, M.J.; Jung, S.J.; Hyun, D.Y.; Kim, Y.C.; Seong, N.S.; Cha, S.W.; Hwang, B. Enhanced production of asiaticoside from hairy root cultures of Centella asiatica (L.) Urban elicited by methyl jasmonate. Plant Cell Rep.,  2007, 26(11), 1941-1949.
[http://dx.doi.org/10.1007/s00299-007-0400-1] [PMID:  17632725] 
[83] 
Bais, H.P.; Govindaswamy, S.; Ravishankar, G.A. Enhancement of growth and coumarin production in hairy root cultures of witloof chicory (Cichorium intybus L.cv. Lucknow local) under the influence of fungal elicitors. J. Biosci. Bioeng.,  2000, 90(6), 648-653.
[http://dx.doi.org/10.1016/S1389-1723(00)90011-2] [PMID:  16232926] 
[84] 
Fathi, R.; Mohebodini, M.; Chamani, E. High-efficiency Agrobacterium rhizogenes-mediated genetic transformation in Cichorium intybus L. via removing macronutrients. Ind. Crops Prod.,  2019, 128, 572-580.
[http://dx.doi.org/10.1016/j.indcrop.2018.11.050] 
[85] 
Kedari, P.; Malpathak, N.P. Hairy root cultures of Chonemorpha fragrans (Moon) Alston.: a potential plant for camptothecin production. Indian J. Biotechnol.,  2014, 13(2), 231-235.
[86] 
Parizi, K.J.; Rahpeyma, S.A.; Pourseyedi, S. The novel paclitaxel-producing system: establishment of Corylus avellana L. hairy root culture. In Vitro Cell; Dev. Biol. Plant, 2020, pp. 1-8.
[87] 
Yoon, J.Y.; Chung, I.M.; Thiruvengadam, M. Evaluation of phenolic compounds, antioxidant and antimicrobial activities from transgenic hairy root cultures of gherkin (Cucumis anguria L.). S. Afr. J. Bot.,  2015, 100, 80-86.
[http://dx.doi.org/10.1016/j.sajb.2015.05.008] 
[88] 
Dechaux, C.; Boitel-Conti, M. A strategy for overaccumulation of scopolamine in Datura innoxia hairy root culture. Acta Biol. Cracov. Ser.; Bot.,  2005, 47, 101-107.
[89] 
Peng, C.X.; Gong, J.S.; Zhang, X.F.; Zhang, M.; Zheng, S.Q. Production of gastrodin through biotransformation of p-hydroxybenzyl alcohol using hairy root cultures of Datura tatula L. Afr. J. Biotechnol.,  2008, 7(3), 211-216.
[90] 
Kastell, A.; Schreiner, M.; Knorr, D.; Ulrichs, C.; Mewis, I. Influence of nutrient supply and elicitors on glucosinolate production in E. sativa hairy root cultures. Plant Cell Tissue Organ Cult.,  2018, 132(3), 561-572.
[http://dx.doi.org/10.1007/s11240-017-1355-8] 
[91] 
Thwe, A.; Valan Arasu, M.; Li, X.; Park, C.H.; Kim, S.J.; Al-Dhabi, N.A.; Park, S.U. Effect of different Agrobacterium rhizogenes strains on hairy root induction and phenylpropanoid biosynthesis in tartary Buckwheat (Fagopyrum tataricum Gaertn). Front. Microbiol.,  2016, 7, 318.
[http://dx.doi.org/10.3389/fmicb.2016.00318] [PMID:  27014239] 
[92] 
Triplett, B.; Moss, S.; Bland, J.; Dowd, M. Induction of hairy root cultures from Gossypium hirsutum and Gossypium barbadense to produce gossypol and related compounds. In Vitro Cell. Dev. Biol. Plant,  2008, 44, 508-517.
[http://dx.doi.org/10.1007/s11627-008-9141-2] 
[93] 
Dhakulkar, S.; Ganapathi, T.R.; Bhargava, S.; Bapat, V.A. Induction of hairy roots in Gmelina arborea Roxb and production of verbascoside in hairy roots. Plant Sci.,  2005, 169, 812-818.
[http://dx.doi.org/10.1016/j.plantsci.2005.05.014] 
[94] 
Grabkowska, R.; Krolicka, A.; Mielicki, W.; Wielanek, M.; Wysokin, H. Genetic transformation of Harpagophytum procumbens by Agrobacterium rhizogenes: iridoid and phenylethanoid glycoside accumulation in hairy root cultures. Acta Physiol. Plant.,  2010, 32, 665-673.
[http://dx.doi.org/10.1007/s11738-009-0445-6] 
[95] 
Georgiev, M.; Heinrich, M.; Kerns, G.; Pavlov, A.; Bley, T. Production of iridoids and phenolics by transformed Harpagophytum procumbens root cultures. Eng. Life Sci.,  2006, 6, 593-596.
[http://dx.doi.org/10.1002/elsc.200620160] 
[96] 
Komarovská, H.; Giovannini, A.; Kosutha, J.; Cellárovia, E. Agrobacterium rhizogenes-mediated transformation of Hypericum tomentosum L and Hypericum tetrapterum Fries. Z. Natforsch. C J. Biosci.,  2009, 64(11-12), 864-868.
[http://dx.doi.org/10.1515/znc-2009-11-1218] [PMID:  20158159] 
[97] 
Lin, H.W.; Kwok, K.H.; Doran, P.M. Development of Linum flavum hairy root cultures for production of coniferin. Biotechnol. Lett.,  2003, 25(7), 521-525.
[http://dx.doi.org/10.1023/A:1022821600283] [PMID:  12882138] 
[98] 
Samadi, A.; Carapetian, J.; Heidari, R.; Jafari, M.; Gorttapeh, A.H. Hairy root induction in Linum mucronatum ssp mucronatum, an anti-tumor lignans producing plant. Not. Bot. Horti Agrobot. Cluj-Napoca,  2012, 40(1), 125-131.
[http://dx.doi.org/10.15835/nbha4017312] 
[99] 
Phongprueksapattana, S.; Putalun, W.; Keawpradub, N.; Wungsintaweekul, J. Mitragyna speciosa: hairy root culture for triterpenoid production and high yield of mitragynine by regenerated plants. Z. Natforsch. C J. Biosci.,  2008, 63(9-10), 691-698.
[http://dx.doi.org/10.1515/znc-2008-9-1014] [PMID:  19040109] 
[100] 
Ha, P.C.; Su, K.N.; Ji, Y.H.; Ju, B.S.; Seok, P.J.; Il, P.N.; Un, P.S. Effects of Culture Medium on Growth and Glucosinolate Accumulation in the Hairy Root Cultures of Watercress (Nasturtium officinale). Res. J. Biotechnol.,  2019, 14(2), 61-66.
[101] 
Saito, K.; Sudo, H.; Yamazaki, M.; Koseki-Nakamura, M.; Kitajima, M.; Takayama, H.; Aimi, N. Feasible production of camptothecin by hairy root culture of Ophiorrhiza pumila. Plant Cell Rep.,  2001, 20, 267-271.
[http://dx.doi.org/10.1007/s002990100320] 
[102] 
Park, S.U.; Facchini, P.J. Agrobacterium rhizogenes-mediated transformation of opium poppy, Papaver somniferum l., and California poppy, Eschscholzia californica cham., root cultures. J. Exp. Bot.,  2000, 51(347), 1005-1016.
[http://dx.doi.org/10.1093/jexbot/51.347.1005] [PMID:  10948228] 
[103] 
Rostampour, S.; Sohi, S.H.; Jourabchi, E.; Ansari, E. Influence of Agrobacterium rhizogenes on induction of hairy roots and benzylisoquinoline alkaloids production in Persian poppy (Papaver bracteatum Lindl.): preliminary report. World J. Microbiol. Biotechnol.,  2009, 25, 1807-1814.
[http://dx.doi.org/10.1007/s11274-009-0081-8] 
[104] 
Alejandro, Y.P.; Alberto, S.A.; de los Santos-Castillo, J.E.; Elidé, A.B.; Karlina, G.S.; Manuel, P.R.; Luisa, V.O.; Gregorio, G.H. Establishment of Hairy Root Cultures of Pentalinon andrieuxii for the Production of Betulinic Acid.Hairy Root Cultures Based Applications; Springer: Singapore, 2020, pp. 99-122.
[http://dx.doi.org/10.1007/978-981-15-4055-4_8] 
[105] 
Nayak, P.; Sharma, M.; Behera, S.N.; Thirunavoukkarasu, M.; Chand, P.K. High-performance liquid chromatographic quantification of plumbagin from transformed rhizoclones of Plumbago zeylanica L.: inter-clonal variation in biomass growth and plumbagin production. Appl. Biochem. Biotechnol.,  2015, 175(3), 1745-1770.
[http://dx.doi.org/10.1007/s12010-014-1392-2] [PMID:  25424284] 
[106] 
Giri, A.; Giri, C.C.; Dhingra, V.; Narasu, M.L. Enhanced podophyllotoxin production from Agrobacterium rhizogenes transformed cultures of Podophyllum hexandrum. Nat. Prod. Lett.,  2001, 15(4), 229-235.
[http://dx.doi.org/10.1080/10575630108041286] [PMID:  11833617] 
[107] 
Ru, M. An, Y.; Wang, K.; Peng, L.; Li, B.; Bai, Z.; Wang, B. Liang Z. Prunella vulgaris L. hairy roots: Culture, growth, and elicitation by ethephon and salicylic acid. Eng. Life Sci.,  2016, 16(5), 494-502.
[http://dx.doi.org/10.1002/elsc.201600001] 
[108] 
Hwang, S.J. Catapol production in Chinese foxglove (Rehmannia glutinosa Libos.) hairy roots transformed with Agrobacterium rhizogenes ATCC15834. Methods Mol. Biol.,  2009, 547, 263-273.
[http://dx.doi.org/10.1007/978-1-60327-287-2_21] [PMID:  19521851] 
[109] 
Perassolo, M.; Alejandra, B.; Cardillo, M. Laura Mugas, Susana C.; Núñez Montoya.; Julián Rodríguez Talou. Enhancement of anthraquinone production and release by combination of culture medium selection and methyl jasmonate elicitation in hairy root cultures of Rubia tinctorum. Ind. Crops Prod.,  2017, 105, 124-132.
[http://dx.doi.org/10.1016/j.indcrop.2017.05.010] 
[110] 
Karolak, I.G.; Kuźma, L.; Skała, E.; Kiss, A.K. Hairy root cultures of Salvia viridis L. for production of polyphenolic compounds. Ind. Crops Prod.,  2018, 117, 235-244.
[http://dx.doi.org/10.1016/j.indcrop.2018.03.014] 
[111] 
Figlan, S.; Makunga, N.P. Genetic transformation of the medicinal plant Salvia runcinata L. f. using Agrobacterium rhizogenes. S. Afr. J. Bot.,  2017, 112, 193-202.
[http://dx.doi.org/10.1016/j.sajb.2017.05.029] 
[112] 
Kang, Y.M.; Park, D.J.; Min, J.Y.; Song, H.J.; Jeong, M.J.; Kim, Y.D.; Kang, S.M.; Karigar, C.S.; Choi, M.S. Enhanced production of tropane alkaloids in transgenic Scopolia parviflora hairy root cultures over-expressing putrescine N-methyl transferase (PMT) and hyoscyamine-6β-hydroxylase (H6H). In Vitro Cell. Dev. Biol. Plant,  2011, 47, 516.
[http://dx.doi.org/10.1007/s11627-011-9367-2] 
[113] 
Rahnama, H.; Hasanloo, T.; Shams, M.R.; Sepehrifar, R. Silymarin production by hairy root culture of Silybum marianum (L.). Gaertn. Int. J. Biotechnol.,  2008, 6(2), 113-118.
[114] 
Kim, Y.B.; Reed, D.W.; Covello, P.S. Production of triterpenoid sapogenins in hairy root cultures of Silene vulgaris. Nat. Prod. Commun.,  2015, 10(11), 1919-1922.
[http://dx.doi.org/10.1177/1934578X1501001129] [PMID:  26749827] 
[115] 
Shilpha, J.; Satish, L.; Kavikkuil, M.; Joe Virgin Largia, M.; Ramesh, M. Methyl jasmonate elicits the solasodine production and anti-oxidant activity in hairy root cultures of Solanum trilobatum L. Ind. Crops Prod.,  2015, 71, 54-64.
[http://dx.doi.org/10.1016/j.indcrop.2015.03.083] 
[116] 
Putalun, W.; Yusakul, G.; Patanasethanont, D. Dicentrine production from a hairy roots culture of Stephania suberosa. Z. Natforsch. C J. Biosci.,  2009, 64(9-10), 692-696.
[http://dx.doi.org/10.1515/znc-2009-9-1014] [PMID:  19957438] 
[117] 
Sharifi, S.; Sattari, T.N.; Zebarjadi, A.; Majd, A.; Ghasempour, H. The influence of Agrobacterium rhizogenes on induction of hairy roots and ß-carboline alkaloids production in Tribulus terrestris L. Physiol. Mol. Biol. Plants,  2014, 20(1), 69-80.
[http://dx.doi.org/10.1007/s12298-013-0208-0] [PMID:  24554840] 
[118] 
Kumar, A.M.; Sravanthi Pammi, S.S.; Sukanya, M.S.; Giri, A. Enhanced production of pharmaceutically important isoflavones from hairy root rhizoclones of Trifolium pratense L. In Vitro Cell. Dev. Biol. Plant,  2018, 54(1), 94-103.
[http://dx.doi.org/10.1007/s11627-017-9873-y] 
[119] 
Zolfaghari, F.; Rashidi-Monfared, S.; Moieni, A.; Abedini, D.; Ebrahimi, A. Improving diosgenin production and its biosynthesis in Trigonella foenum-graecum L. hairy root cultures. Ind. Crops Prod.,  2020, 145112075
[http://dx.doi.org/10.1016/j.indcrop.2019.112075] 
[120] 
Chaudhuri, K.N.; Ghosh, B.; Tepfer, D.; Jha, S. Genetic transformation of Tylophora indica with Agrobacterium rhizogenes A4: growth and tylophorine productivity in different transformed root clones. Plant Cell Rep.,  2005, 24(1), 25-35.
[http://dx.doi.org/10.1007/s00299-004-0904-x] [PMID:  15660269] 
[121] 
Kim, J.; Baek, K.; Son, Y.; Son, S.; Shin, H. Hairy root cultures of Taxus cuspidate for enhanced production of paclitaxel. J Appl Biol Chem,  2009, 52, 144-150.
[122] 
Mirjalili, H.; Fakhr-Tabatabaei, S.; Bonfill, M.; Alizadeh, H.; Cusido, R.; Ghassempour, A.; Palazon, J. Morphology and withanolide production of Withania coagulans hairy root cultures. Eng. Life Sci.,  2009, 9, 197-204.
[http://dx.doi.org/10.1002/elsc.200800081] 
[123] 
Murthy, H.N.; Dijkstra, C.; Anthony, P.; White, D.A.; Davey, M.R.; Power, J.B.; Hahn, E.J.; Paek, K.Y. Establishment of Withania somnifera hairy root cultures for the production of withanolide A. J. Integr. Plant Biol.,  2008, 50(8), 975-981.
[http://dx.doi.org/10.1111/j.1744-7909.2008.00680.x] [PMID:  18713347] 
[124] 
Shajahan, A.; Thilip, C.; Mehaboob, V.M.; Faizal, K.; Raja, P.; Thiagu, G.; Aslam, A. Protocol for Enhanced Withaferin-A Production in Elicited Withania somnifera (L.) Dunal Hairy Root Cultures.Hairy Root Cultures Based Applications; Springer: Singapore, 2020, pp. 87-98.
[http://dx.doi.org/10.1007/978-981-15-4055-4_7] 
[125] 
Bhagwath, S.G.; Hjortsø, M.A. Statistical analysis of elicitation strategies for thiarubrine A production in hairy root cultures of Ambrosia artemisiifolia. J. Biotechnol.,  2000, 80(2), 159-167.
[http://dx.doi.org/10.1016/S0168-1656(00)00256-X] [PMID:  10908796] 
[126] 
Jiao, J.; Gai, Q.Y.; Wang, W.; Luo, M.; Zu, Y.G.; Fu, Y.J.; Ma, W. Enhanced astragaloside production and transcriptional responses of biosynthetic genes in Astragalus membranaceus hairy root cultures by elicitation with methyl jasmonate. Biochem. Eng. J.,  2016, 105, 339-346.
[http://dx.doi.org/10.1016/j.bej.2015.10.010] 
[127] 
Putalun, W.; Luealon, W.; De-Eknamkul, W.; Tanaka, H.; Shoyama, Y. Improvement of artemisinin production by chitosan in hairy root cultures of Artemisia annua L. Biotechnol. Lett.,  2007, 29(7), 1143-1146.
[http://dx.doi.org/10.1007/s10529-007-9368-8] [PMID:  17426924] 
[128] 
Lee, K.T.; Hirano, H.; Yamakawa, T.; Kodama, T.; Igarashi, Y.; Shimomura, K. Responses of transformed root culture of Atropa belladonna to salicylic acid stress. J. Biosci. Bioeng.,  2001, 91(6), 586-589.
[http://dx.doi.org/10.1016/S1389-1723(01)80178-X] [PMID:  16233044] 
[129] 
Zhang, L.; Yang, B.; Lu, B.; Kai, G.; Wang, Z.; Xia, Y.; Ding, R.; Zhang, H.; Sun, X.; Chen, W.; Tang, K. Tropane alkaloids production in transgenic Hyoscyamus niger hairy root cultures over-expressing putrescine N-methyltransferase is methyl jasmonate-dependent. Planta,  2007, 225(4), 887-896.
[http://dx.doi.org/10.1007/s00425-006-0402-1] [PMID:  17004056] 
[130] 
Zeynali, Z.; Hosseini, B.; Rezaei, E. Effect of elicitation on antioxidant activity and production of tropane alkaloids in Hyoscyamus reticulatus hairy root cultures. Res. J. Pharmacog.,  2016, 3(3), 43-53.
[131] 
Chung, I.M.; Thiruvengadam, M.; Kaliyaperumal, R.; Govindasamy, R. Elicitation enhanced the production of phenolic compounds and biological activities in hairy root cultures of bitter melon (Momordica charantia L.). Braz. Arch. Biol. Technol.,  2016, 59.
[http://dx.doi.org/10.1590/1678-4324-2016160393] 
[132] 
Yousefian, Z.; Golkar, P.; Mirjalili, M.H. Production Enhancement of medicinally active coumarin and phenolic compounds in hairy root cultures of Pelargonium sidoides: The effect of elicitation and sucrose. J. Plant Growth Regul., 2020.
[http://dx.doi.org/10.1007/s00344-020-10127-y] 
[133] 
Shinde, A.N.; Malpathak, N.; Fulzele, D.P. Enhanced production of phytoestrogenic isoflavones from hairy root cultures of Psoralea corylifolia L. using elicitation and precursor feeding. Biotechnol Bioproc Eng,  2009, 14, 288-294.
[http://dx.doi.org/10.1007/s12257-008-0238-6] 
[134] 
Pirian, K.; Piri, K. Effect of methyl jasmonate and salicylic acid on noradrenalin accumulation in hairy roots of Portulaca oleracea L. Int. Res. J. Appl. Basic Sci.,  2012, 3, 213-218.
[135] 
Yaoya, S.; Kanho, H.; Mikami, Y.; Itani, T.; Umehara, K.; Kuroyanagi, M. Umbelliferone released from hairy root cultures of Pharbitis nil treated with copper sulfate and its subsequent glucosylation. Biosci. Biotechnol. Biochem.,  2004, 68(9), 1837-1841.
[http://dx.doi.org/10.1271/bbb.68.1837] [PMID:  15388957] 
[136] 
Krstić-Milošević, D.; Janković, T.; Uzelac, B.; Vinterhalter, D.; Vinterhalter, B. Effect of elicitors on xanthone accumulation and biomass production in hairy root cultures of Gentiana dinarica. Plant Cell Tissue Organ Cult.,  2017, 130(3), 631-640.
[http://dx.doi.org/10.1007/s11240-017-1252-1] 
[137] 
Kochan, E.; Balcerczak, E.; Lipert, A.; Szymańska, G.; Szymczyk, P. Methyl jasmonate as a control factor of the synthase squalenegene promoter and ginsenoside production in American ginseng hairy root cultured in shake flasks and a nutrient sprinkle bioreactor. Ind. Crops Prod.,  2018, 115, 182-193.
[http://dx.doi.org/10.1016/j.indcrop.2018.02.036] 
[138] 
Zhao, J.L.; Zhou, L.G.; Wu, J.Y. Effects of biotic and abiotic elicitors on cell growth and tanshinone accumulation in Salvia miltiorrhiza cell cultures. Appl. Microbiol. Biotechnol.,  2010, 87(1), 137-144.
[http://dx.doi.org/10.1007/s00253-010-2443-4] [PMID:  20195862] 
[139] 
Liang, Z.S.; Yang, D.F.; Liang, X.; Zhang, Y.J.; Liu, Y.; Liu, F.H. Roles of reactive oxygen species in methyl jasmonate and nitric oxide-induced tanshinone production in Salvia miltiorrhiza hairy roots. Plant Cell Rep.,  2012, 31(5), 873-883.
[http://dx.doi.org/10.1007/s00299-011-1208-6] [PMID:  22189441] 
[140] 
Wu, J.Y.; Shi, M. Ultrahigh diterpenoid tanshinone production through repeated osmotic stress and elicitor stimulation in fed-batch culture of Salvia miltiorrhiza hairy roots. Appl. Microbiol. Biotechnol.,  2008, 78(3), 441-448.
[http://dx.doi.org/10.1007/s00253-007-1332-y] [PMID:  18189134] 
[141] 
Gabr, A.M.M.; Ghareeb, H.; El Shabrawi, H.M.; Smetanska, I.; Bekheet, S.A. Enhancement of silymarin and phenolic compound accumulation in tissue culture of Milk thistle using elicitor feeding and hairy root cultures. J Genet Eng Biotechnol,  2016, 14(2), 327-333.
[http://dx.doi.org/10.1016/j.jgeb.2016.10.003] [PMID:  30647631] 
[142] 
Khalili, G.M.; Hasanloo, T.; Tabar, S.K.K. Ag+ enhanced silymarin production in hairy root cultures of Silybum marianum L. Plant Omics,  2010, 3, 109-114.
[143] 
Gharari, Z.; Bagheri, K.; Danafar, H.; Sharafi, A. Enhanced flavonoid production in hairy root cultures of Scutellaria bornmuelleri by elicitor induced over-expression of MYB7 and FNSП2 genes. Plant Physiol. Biochem.,  2020, 148, 35-44.
[http://dx.doi.org/10.1016/j.plaphy.2020.01.002] [PMID:  31926388] 
[144] 
Sivanandhan, G.; Selvaraj, N.; Ganapathi, A.; Manickavasagam, M. Elicitation Approaches for Withanolide Production in Hairy
Root Culture of Withania somnifera (L.) Dunal. In: Biotechnology of Plant Secondary Metabolism. Methods in Molecular Biology, 1405; Fett-Neto, A., Ed.; Humana Press: New York, NY, 2016. 
[http://dx.doi.org/10.1007/978-1-4939-3393-8_1] 
[145] 
Palazon, J.; Cusido, R.M.; Bonfill, M.; Mallol, A.; Moyano, E.; Morales, C.; Pinol, M.T. Elicitation of different Panax ginseng transformed root phenotypes for an improved ginsenoside production. Plant Physiol. Biochem.,  2003, 41, 1019-1025.
[http://dx.doi.org/10.1016/j.plaphy.2003.09.002] 
[146] 
Jeong, G.T.; Park, D.H.; Hwang, B.; Woo, J.C. Comparison of growth characteristics of Panax ginseng hairy roots in various bioreactors. Appl. Biochem. Biotechnol.,  2003, 105(108), 493-503.
[http://dx.doi.org/10.1385/ABAB:107:1-3:493] [PMID:  12721430] 
[147] 
Ramakrishnan, D.; Curtis, W.R. Trickle-bed root culture bioreactor design and scale-up: growth, fluid-dynamics, and oxygen mass transfer. Biotechnol. Bioeng.,  2004, 88(2), 248-260.
[http://dx.doi.org/10.1002/bit.20231] [PMID:  15449296] 
[148] 
Kintzios, S.; Makri, O.; Pistola, E.; Matakiadis, T.; Shi, H.P.; Economou, A. Scale-up production of puerarin from hairy roots of Pueraria phaseoloides in an airlift bioreactor. Biotechnol. Lett.,  2004, 26(13), 1057-1059.
[http://dx.doi.org/10.1023/B:BILE.0000032963.41208.e8] [PMID:  15218379] 
[149] 
Suresh, B.; Bais, H.P.; Raghavarao, K.S.; Ravishankar, G.A.; Ghildyal, N.P. Comparative evaluation of bioreactor design using Tagetes patula L. hairy roots as a model system. Process Biochem.,  2005, 40(5), 1509-1515.
[http://dx.doi.org/10.1016/j.procbio.2003.10.017] 
[150] 
Zhong, J.J.; Zhang, Z.Y. High-density cultivation of Panax notoginseng cell cultures with methyl jasmonate elicitation in cenrifugal impeller bioreactor. Eng. Life Sci.,  2005, 5, 471-547.
[http://dx.doi.org/10.1002/elsc.200520093] 
[151] 
Georgiev, M.I.; Pavlov, A.I.; Bley, T. Hairy root type plant in vitro systems as sources of bioactive substances. Appl. Microbiol. Biotechnol.,  2007, 74(6), 1175-1185.
[http://dx.doi.org/10.1007/s00253-007-0856-5] [PMID:  17294182] 
[152] 
Mehrotra, S.; Kumar Kukreja, A.; Singh Khanuja, S.; Nath Mishra, B. Genetic transformation studies and scale up of hairy root culture of Glycyrrhiza glabra in bioreactor. Electron. J. Biotechnol.,  2007, 11(2), 1-7.
[153] 
Kuźma, Ł.; Bruchajzer, E.; Wysokińska, H. Methyl jasmonate effect on diterpenoid accumulation in Salvia sclarea hairy root culture in shake flasks and sprinkle bioreactor. Enzyme Microb. Technol.,  2009, 44(6-7), 406-410.
[http://dx.doi.org/10.1016/j.enzmictec.2009.01.005] 
[154] 
Sivakumar, G.; Liu, C.; Towler, M.J.; Weathers, P.J. Biomass production of hairy roots of Artemisia annua and Arachis hypogaea in a scaled-up mist bioreactor. Biotechnol. Bioeng.,  2010, 107(5), 802-813.
[http://dx.doi.org/10.1002/bit.22892] [PMID:  20687140] 
[155] 
Lee, E.J.; Paek, K.Y. Effect of nitrogen source on biomass and bioactive compound production in submerged cultures of Eleutherococcus koreanum Nakai adventitious roots. Biotechnol. Prog.,  2012, 28(2), 508-514.
[http://dx.doi.org/10.1002/btpr.1506] [PMID:  22213626] 
[156] 
Mišić, D.; Šiler, B.; Skorić, M.; Djurickovic, M.S.; Živković, J.N.; Jovanović, V.; Giba, Z. Secoiridoid glycosides production by Centaurium maritimum (L.) Fritch hairy root cultures in temporary immersion bioreactor. Process Biochem.,  2013, 48(10), 1587-1591.
[http://dx.doi.org/10.1016/j.procbio.2013.07.015] 
[157] 
Jaremicz, Z.; Luczkiewicz, M.; Kokotkiewicz, A.; Krolicka, A.; Sowinski, P. Production of tropane alkaloids in Hyoscyamus niger (black henbane) hairy roots grown in bubble-column and spray bioreactors. Biotechnol. Lett.,  2014, 36(4), 843-853.
[http://dx.doi.org/10.1007/s10529-013-1426-9] [PMID:  24322778] 
[158] 
Thakore, D.; Srivastava, A.K.; Sinha, A.K. Mass production of Ajmalicine by bioreactor cultivation of hairy roots of   Catharanthus roseus. Biochem. Eng. J.,  2017, 119, 84-91.
[http://dx.doi.org/10.1016/j.bej.2016.12.010] 
Cite As
Current Pharmaceutical Biotechnology

Hairy Root Culture an Alternative for Bioactive Compound Production from Medicinal Plants

Abstract

Graphical Abstract
