Abstract
Plants are a rich source of valuable chemicals that are used as herbal and modern medicines. Shikonin, a naphthoquinone red pigment, produced from roots of Arnebia hispidissima, A. euchroma, Lithospermum erythrorhizon and other Boraginaceous species was the first phytochemical to be produced on commercial scale using biotechnological approach. Plant cell culture technologies were the only tools employed for secondary metabolites production in other cases in past. Shikonin production and localization is tissue specific with stringent metabolic regulation. Hence, the differentiated cultures such as those of hairy root cultures offer a great promise for secondary metabolite production. A. rhizogenes-mediated transformed roots are characterized by high growth rate, genetic stability and growth in hormone free media. These genetically transformed root cultures can produce larger amounts of secondary metabolites. The present review deliberates upon potential and prospects of diverse physico-chemical factors that affect shikonin production in tissue culture, as well as, the genetic modification for enhancement of shikonin production.
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Abbreviations
- ABA:
-
Abscisic acid
- BAP:
-
6-Benzylaminopurine
- B5 :
-
Gamborg’s medium
- CaMV35S :
-
Cauliflower mosaic virus 35S promoter
- 2,4-D:
-
2,4-Dichlorophenoxy acetic acid
- DA:
-
Davydenkov arnebia medium
- DOPA:
-
L-3,4-Dihydroxyphenylalanine
- GA3 :
-
Gibberellic acid
- GUS:
-
β-Glucuronidase
- HMGR:
-
Hydroxymethylglutaryl CoA reductase
- HPLC:
-
High pressure liquid chromatography
- HPT:
-
Hygromycin phosphotransferase
- IAA:
-
Indole acetic acid
- LS:
-
Linsmaier and Skoog’s medium
- MeJa:
-
Methyl jasmonate
- MS:
-
Murashige and Skoog’s medium
- NAA:
-
α-Naphthalene acetic acid
- PAL:
-
Phenylalanine ammonia-lyase
- PFP:
-
P-fluorophenylalanine
- PVP:
-
Polyvynilpirrolidone
- RC:
-
Root culture medium
- TDZ:
-
Thidiazuron
- TLC:
-
Thin layer chromatography
References
Papageorgiou VP, Assimopoulou AN, Samanidou VF, Papadoyannis IN (2006) Recent advances in chemistry, biology and biotechnology of alkannins and shikonins. Curr Org Chem 10:2123–2142
Pietrosiuk A, Furmanowa M, Skopińska-Różewska E, Sommer E, Skurzak H, Bany J (2004) The effect of acetylshikonin isolated from Lithospermum canescens roots on tumour-induced cutaneous angiogenesis. Acta Pol Pharm 5:379–382
Pietrosiuk A, Skopińska-Różewska E, Furmanowa M, Wiedenfeld H, Sommer E, Sokolnicka I, Rogala E, Radomska-Leśniewska D, Bany J, Malinowski M (2004) Immunomodulatory effect of shikonin derivatives isolated from Lithospermum canescens on cellular and humoral immunity in Balb/c mice. Pharmazie 59:640–642
Su L, Yan GZ, Guan BJ, Xu W, Hao YY, Wang YL, Zhang Y, Liu LH (2011) Shikonin derivatives protect immune organs from damage and promote immune responses in vivo in tumour-bearing mice. Phytother Res 26:26–33
Chaudhury A, Pal M (2010) Induction of shikonin production in hairy root cultures of Arnebia hispididdima via Agrobacterium rhizogenes- mediated genetic transformation. J Crop Sci Biotechnol 13:99–106
Yadav R, Arora P, Chaudhury A (2012) Plant secondary metabolites: from diseases to health. Front Rec Dev Plant Sci 1:3–23
Manjkhola S, Dhar U, Joshi M (2005) Organogenesis, embryogenesis, and synthetic seed production in Arnebia euchroma—a critically endangered medicinal plant of the Himalaya. In Vitro Cell Dev Biol Plant 41:244–248
Sykłowska-Baranek K, Pietrosiuk A, Naliwajski MR, Kawiak A, Jeziorek M, Wyderska S, Łojkowska E, Chinou I (2012) Effect of l-phenylalanine on PAL activity and production of naphthoquinone pigments in suspension cultures of Arnebia euchroma (Royle). Johnst. In Vitro Cell Dev Biol Plant 48:555–564
Jiang B, Yang YG, Guo YM, Guo ZC, Chen YZ (2005) Thidiazuroninduced in vitro shoot organogenesis of the medicinal plant Arnebia euchroma (Royle) Johnst. In Vitro Cell Dev Biol Plant 41:677–681
Ge F, Wang X, Zhao B, Wang Y (2006) Effects of rare earth elements on the growth of Arnebia euchroma cells and the biosynthesis of shikonin. Plant Growth Regul 48:283–290
Kumar R, Sharma N, Malik S, Bhushan S, Kumar Sharma U, Kumari D, Sinha Kumar A, Sharma M, Singh Ahuja P (2011) Cell suspension culture of Arnebia euchroma (Royle) Johnston—a potential source of naphthoquinone pigments. J Med Plant Res 5:6048–6054
Malik S, Bhushan S, Sharma M, Ahuja PS (2011) Physico-chemical factors influencing the shikonin derivatives production in cell suspension cultures of Arnebia euchroma (Royle) Johnston, a medicinally important plant species. Cell Biol Int 35:153–158
Shekhawat MS, Shekhawat NS (2011) Micropropagation of Arnebia hispidissima (Lehm). DC. and production of alkannin from callus and cell suspension culture. Acta Physiol Plant 33:1445–1450
Zou A, Zhang W, Pan Q, Zhu S, Yin J, Tian R, Gu H, Wang X, Qi J, Yang Y (2011) Cloning, characterization, and expression of LeEIL-1, an Arabidopsis EIN3 homolog, in Lithospermum erythrorhizon. Plant Cell, Tissue Organ Cult 106:71–79
Zare K, Nazemiyeh H, Movafeghi A, Khosrowshahli M, Motallebi-Azar A, Dadpour M, Omidi Y (2010) Bioprocess engineering of Echium italicum L.: induction of shikonin and alkannin derivatives by two-liquid-phase suspension cultures. Plant Cell, Tissue Organ Cult 100:157–164
Roychowdhury D, Majumder A, Jha S (2013) Agrobacterium rhizogenes-mediated transformation in medicinal plants: prospects and challenges. In: Chandra S et al (eds) Biotechnol med plants. Springer, Berlin, pp 29–68
Srivastava S, Srivastava AK (2007) Hairy root culture for mass-production of high-value secondary metabolites. Crit Rev Biotechnol 27:29–43
Vanisree M, Lee CY, LoS Manohar S, Nalawade Lin CY, Tsay HS (2004) Studies on the production of some important secondary metabolites from medicinal plants by plant tissue cultures. Bot Bull Acad Scinica 45:1–22
Charlwood BV, Charlwood KA, Torres JM (1990) Accumulation of secondary compounds organized plant cultures. In: Charlwood V, Rhodes MJC (eds) Progress in plant cellular and molecular biology. Clarendon Press, Oxford, pp 167–300
Rhodes MJC (1989) Secondary metabolites. In: Kurz WGW (ed) Primary and secondary metabolism of plant cell cultures. Springer, Berlin, pp 58–72
Phulwaria M, Rai MK, Shekhawat NS (2013) An improved micropropagation of Arnebia hispidissima (lehm.) dc. and assessment of genetic fidelity of micropropagated plants using dna-based molecular markers. App. Biochem. https://doi.org/10.1007/s12010-013-0266-3
Pal M, Chaudhury A (2010) High frequency direct plant regeneration, micropropagation and shikonin induction in Arnebia hispidissima. J Crop Sci Biotech 13(1):13–20
Yazaki K, Matsuoka H, Shimomura K, Bechthold A, Sato F (2001) A novel dark inducible protein, LeDI-2 and its involvement in root specific secondary metabolism in Lithospermum erythrorhizon. Plant Physiol 125:1831–1841
Chung MS, Lee MS (1994) Stability and sensory evaluation of naphthaquinones pigments from the roots of Lithospermum erythrorhizon. Korean J Food Sci Technol 26:157–161
Bulgakov VP, Kozyrenko MM, Fedoreyev SA, Mischenko NP, Denisenko VA, Zvereva LV, Pokushalova TV, Zhuravlev YN (2001) Shikonin production by p-fluorophenylalanine resistant cells of Lithospermum erythrorhizon. Fitoterapia 72(4):394–401
Shibata D, Liu YG (2000) Agrobacterium-mediated plant transformation with large DNA fragments. Trends Plant Sci 5:354–357
Shimomura K, Sudo H, Saga H, Komada H (1991) Shikonin production and secretion by hairy root cultures of Lithospermum erythrorhizon. Plant Cell Rep 10:282–285
Yazaki K, TanakaS Matsuoka H, Sato F (1998) Stable transformation of Lithospermum erythrorhizon by Agrobacterium rhizogenes and shikonin production of transformants. Plant Cell Rep 18:214–219
Fukui H, Hasan AFMF, Kyo M (1999) Formation and secretion of a unique quinone by hairy root cultures of Lithospermum erythrorhizon. Phytochem 51:511–515
Yamamoto H, Inouye K, Yazaki K (2000) Caffeic acid oligomers in Lithospermum erythrorhizon cell suspension cultures. Phytochem 53:651–657
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The infrastructural facility provided during writing of this manuscript by Director, Centre for Plant Biotechnology, HSCST, is duly acknowledged.
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Significance statement ‘Shikonin, a naphthoquinone red pigment, produced from roots of A. hispidissima and other Boraginaceous species was first phytochemical produced on commercial scale. This review describes enhanced shikonin production strategies from medicinal plants’.
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Pal, M., Kumar, V., Yadav, R. et al. Potential and Prospects of Shikonin Production Enhancement in Medicinal Plants. Proc. Natl. Acad. Sci., India, Sect. B Biol. Sci. 89, 775–784 (2019). https://doi.org/10.1007/s40011-017-0931-3
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DOI: https://doi.org/10.1007/s40011-017-0931-3