Abstract
Andrographis paniculata (AP) is a medicinal plant that is traditionally used in Indian, Chinese, Malay, Thai, and Oriental system of medicines to treat various disorders. AP consists of andrographolide (AD), 14-deoxy-11,12-didehydroandrographolide (DDAD), and neoandrographolide (NAD) as major diterpene lactones which has extremely bitter properties; therefore, AP is commonly called “King of bitters.” AD, DDAD, and NAD are reported to possess therapeutic values such as antioxidant, immunostimulatory, hepatoprotective, anti-cancer, anti-inflammatory, anti-rheumatoidal, anti-malarial, anti-leishmanial, anti-fertility, anti-obesity, antipyretic, and antimicrobial attributes. According to the Indian Pharmacopoeia, the leaves and tender shoots of AP yield up to 1%, 0.16%, and 0.11% of AD, DDAD, and NAD, respectively, on a dry-weight basis. However, variability in the accumulation of AD, DDAD, and NAD in plants has been reported with respect to species, genotype, season, phenological stage, plant part used, and geography of a region of cultivation. Therefore, cell and tissue culture systems especially cell, shoot, and adventitious root cultures are explored as alternatives for constant and higher production of AD, DDAD, and NAD. This review explores the prospects of exploiting the plant cell and tissue culture systems for the controlled production of AD, DDAD, and NAD. Various strategies such as elicitation by using biological and chemical elicitors are explored for the enhancement of accumulation of AD, DDAD, and NAD in cell and organ cultures.
Key points
• This review explores the possibilities of diterpene lactone production from cell and organ cultures.
• Various strategies are explored for the enhanced accumulation of AD, DDAD, and NAD in cell and organ cultures.
• Prospects of diterpene lactone production are highlighted.
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References
Al Batran R, Al-Bayaty F, Al-obaidi MMJ, Ashrafi A (2014) Insights into the antiatherogenic molecular mechanism of andrographolide against Porphyromonas gingivalis-induced atherosclerosis in rabbits. Naunys-Schmiederberg’s Arch Pharmacol 387:1141–1152
Aromdee C (2014) Andrographolide: progression in its modifications and applications – a patent review (2012-2-14). Expert OpinTher Pat 24:1129–1138
Arpita M, Zenu J (2018) Effective method of Ri plasmid transformation for hairy root induction in kalmegh. Res J Biotech 13:58–64
Bansi TS, Rout GR (2013) Plant regeneration protocol of Andrographis paniculata (Burm. f.) – an important medicinal plant. Afr J Biotechnol 12:5738–5742
Batkhuuu J, Hattori K, Takano F, Fushiya S, Oshiman K, Fujimiya Y (2002) Suppression of NO production in activated macrophages in vitro and ex vivo by neoandrographolide isolated from Andrographis paniculata. Biol Pham Bull 25:1169–1174
Chang RS, Ding L, Chen GQ, Pan QC, Zhao ZL, Smith KM (1991) Dehydroandrographolide succinic acid monoester as an inhibitor against the human immunodeficiency virus. Proc Soc Exp Biol Med 197:59–66
Chao WW, Kuo YH, Hsieh SL, Lin BF (2011) Inhibitory effects of ethyl acetate extract of Andrographis paniculata on NF-kB trans-activation activity and LPS-induced acute inflammation in mice. Evid Based Complement Alternat Med 2011: 254531
Chao WW, Lin BF (2010) Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian). Chinese Med 5:17
Dalawai D, Aware C, Jadhav JP, Murthy HN (2019) RP-HPLC analysis of diterpene lactones in leaves and stem of different species of Andrographis. Nat Prod Res 2019:1–4. https://doi.org/10.1080/14786419.2019.1662004
Dandin VS, Murthy HN (2012a) Regeneration of Andrographis paniculata Nees: analysis of genetic fidelity and andrographolide content in micropropagated plants. Afr J Biotechnol 11:12464–12471
Dandin VS, Murthy HN (2012b) Enhanced in vitro multiplication of Nothapodytes nimmoniana Graham using semisolid and liquid cultures and estimation of camptothecin in regenerated plants. Acta Physiol Plant 34:1381–1386
Das D, Bandyopadhyay M (2015) Tissue organization is necessary for accumulation of andrographolide in in vitro cultures of Andrographis paniculata (Burm. f.) Wall. ex Nees. J Botan Soc Bengal 69:27–34
Dawande AA, Sahay S (2020) Copper sulphate elicitation of optimized suspension culture of Andrographis paniculata Nees yields unprecedented level of andrographolide. J Microbiol Biotech Food Sci 9:688–694
Dwivedi MK, Mishra S, Sonter S, Singh PK (2021) Diterpenoids as potential anti-malarial compounds from Andrographis paniculata. Beni-Suef Univ J Basic Appl Sci 10:7
Efferth T (2019) Biotechnology applications of plant callus cultures. Engineering 5:50–59
Enfissi EMA, Fraser PD, Lois L, Boronat A, Schuch W, Bramley PM (2005) Metabolic engineering of the mevolanate and ion-mevolanate isopentenyl diphosphate-forming pathways for the production of health-promoting isoprenoids in tomato. Plant Botechnol J 3:17–27
Espinosa-Leal CA, Puente-Garza CA, Gracia-Lara S (2018) In vitro plant tissue culture: means for production of bioactive compounds. Planta 248:1–18
Estevez JM, Cantero A, Reindl A, Reichler S, Leon P (2001) 1-deoxy-d-xylulose-5-phosphate synthase, a limiting enzyme for plastidic isoprenoid biosynthesis in plants. J Bio Chem 276:22901–22909
Fardiyah Q, Ersam T, Suynta SA, Suprapto KF (2020) New potential and characterization of Andrographis paniculata L. Ness plant extracts as photoprotective agent. Arabian J Chem 13:8888–8897
Ganeshkumar Y, Kavitha P, Ramarao A, Veeresham C (2019) Enhanced production of andrographolide from cell cultures of Andrographis paniculata by the elicitation with arachidonic acid. Indian J Nat Prod 33:18–23
Garg A, Agarwal L, Misra RC, Sharma S, Ghosh S (2015) Andrographis paniculata transcriptome provides molecular insights into tissue-specific accumulation of medicinal diterpenes. BMC Genomics 16:659
Gutierrez-Valdes N, Hakkinen T, Lemasson C, Guillet M, Oksman-Caldentey KM, Ritala A, Cardon F (2020) Hairy root cultures – a versatile tool with multiple applications. Front Plant Sci 11:33
Handa SS, Dharma A, Chakraborti KK (1986) Natural products and plants as liver protecting drugs. Fitoterapia 57:347–351
Jarukamjorn K, Nemoto N (2008) Pharmacological aspects of Andrographis paniculata on health and its major diterpenoid constituent Andrographolide. J Health Sci 54:370–381
Jayakumar T, Hsieb CY, Lee JJ, Sheu JR (2013) Experimental and clinical pharmacology of Andrographis paniculata and its major bioactive phytoconstituent Andrographolide. Evid-Based Coml Alt 2013, Article ID 846740
Kadapatti SS, Murthy HN (2021) Rapid regeneration, analysis of genetic fidelity, and neoandrographolide content of micropropagated plants of Andrographis alata (Vahl) Nees. J Genet Eng Biotechnol 19:20
Kandanur SGS, Tamang N, Golakoti NR, Nanduri S (2019) Andrographolide: a natural product template for the generation of structurally and biologically diverse diterpenes. Eur J Med Chem 176:513–533
Li J, Chen X, Zhan R, He R (2019) Transcriptome profiling reveals metabolic alteration of Andrographis paniculata in response to continuous cropping. Ind Crops Prod 137:585–596
Lim JCW, Chan TK, Ng DSW, Sagineedu SR, Stanslas J, Wong WSF (2012) Andrographolide and its analogs: versatile bioactive molecules for combating inflammation and cancer. Clin Exp PharmacolPhysiol 39:300–310
Liu J, Wang ZT, Ji LL (2007) In vivo and In vitro anti-inflammatory activities of neoandrographolide. Am J Clin Med 35:317–328
Lu J, Ma Y, Wu J, Huang H, Wang X, Chen Z, Chen J, He H, Huang C (2019) A review for the neuroprotective effects of andrographolide in the central nervous system. Biomed Pharmacother 117: 109078
Martin KP (2004) Plant regeneration protocol of medicinally important Andrographis paniculata (Burm. f.) Wallich ex Nees via somatic embryogenesis. In Vitro Cell Dev Biol – Plant 40: 204–209
Marwani E, Pratiwi D, Wardhani K, Esyanti, (2015) Development of hairy root culture of Andrographis paniculata for in vitro andrographolide production. J Med Bioeng 4:446–450
Mishra N, Yadav KS, Rai VK, Yadav NP (2017) Polysaccharide encrusted multilayered nano-colloidal system of andrographolide for improved hepatoprotection. AAPS Pharm Sci Tech 18:381–392
Misra RJ, Garg A, Roy S, Chanotiya CS, Vasudev PG, Ghosh S (2015) Involvement of an ent-copalyl diphosphate synthase in tissue-specific accumulation of specialized diterpenes in Andrographis paniculata. Plant Sci 24); 50–64
Morris WL (2006) Overexpression of a bacterial 1-deoxy-D-xylulose-5-phosphate synthase gene in potato tubers perturbs the isoprenoid metabolic network: implications for the control of the tuber life cycle. J Exp Bot 57:3007–3018
Murthy HN, Lee EJ, Paek KY (2014) Production of secondary metabolites from cell and organ cultures: strategies and approaches for biomass improvement and metabolite accumulation. Plant Cell Tiss Organ Cult 118:1–16
Murthy HN, Dandin VS, Paek KY (2016) Tools for biotechnological production of useful phytochemicals from adventitious root cultures. Phytochem Rev 15:129–145
Murthy HN, Dalawai D, Bhat MA, Dandin VS, Paek KY, Park SY (2021) Biotechnological production of useful phytochemicals from adventitious root cultures. In: Ramawath KG, Ekiert HM, Goyal S (ed) Plant cell and tissue differentiation and secondary metabolites: fundamentals and applications. Springer Nature Switzerland AG, pp. 469–486
Nagegowda DA (2010) Plant volatile terpenoid metabolism: biosynthetic genes, transcriptional regulation, and subcellular compartmentation. FEB Lett 584:2965–2973
Okhuarobo A, Falodun JE, Erharuyi O, Imieje V, Falodun A, Langer P (2014) Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology. Asian Pac J Trop Dis 4:213–222
Paritala V, Mohammed A, Kayat F (2017) In vitro plant regeneration of Andrographis paniculata Nees using mature zygotic embryonic explants. Agri Res Tech: Open Access J 5: 555674
Prathanturarug S, Soonthornchareonnon N, Chuakul W, Saralamp P (2007) Variation in growth and diterpene lactones among field-cultivated Andrographis paniculata. J Nat Med 61:159–163
Praveen N, Manohar SH, Naik PM, Nayeem A, Jeong JH, Murthy HN (2009) Production of andrographolide from adventitious root cultures of Andrographis paniculata. Curr Sci 96:694–697
Purkayastha J, Sugla T, Paul A, Solleti A, Sahoo L (2008) Rapid in vitro multiplication and plant regeneration from nodal explants of Andrographis paniculata: a valuable medicinal plant. In Vitro Cell Dev Biol – Plant 44: 442–447
Rafi M, DevieAf SUD, Heryanto R, Suparto IH, Arman MB, Rohman A, Prajogo B, Lim LW (2020) Classification of Andrographis paniculata extracts by solvent extraction using HPLC fingerprinting and chemometric analysis. BMC Res Notes 13:56
Rodriguez-Concepcion M (2006) Early steps in isoprenoid biosynthesis: multilevel regulation of the supply of common precursors in plant cells. Phytochem ‘Rev 5: 1–15
Roy PK (2014) In vitro propagation of Andrographis paniculata Nees. – a threatened medicinal plant of Bangladesh. Jahandgirnagar University J Biol Sci 3:67–73
Roy S, Giri A, Bhubaneswari C, Lakshmi Narasu M, Giri CC (2009) High-frequency plantlet regeneration via direct organogenesis in Andrographis paniculata. Med Aromatic Plant Sci Biotechnol 3:94–96
Sangwan RS, Chaurasiya ND, Lal P, Misra L, Uniyal GC, Tuli R, Sangwan NS (2007) Withanolide A biogeneration in in vitro shoot cultures of ashwagandha (Withania somnifera Dunal), a main medicinal plant. Chem Pharm Bull 55:1371–1375
Sareer O, Ahmad S, Umar S (2014) Andrographis paniculata: a critical appraisal of extraction, isolation appraisal of extraction, isolation, and quantification of and other active constituents. Nat Prod Res 28:2061–2101
Sharma SN, Jha Z, Sinha RK (2013) Establishment of in vitro adventitious root cultures and analysis of andrographolide in Andrographis paniculata. Nat Prod Commun 8:1045–1047
Sharma SN, Jha Z, Sinha RK, Geda AK (2015) Jasmonate-induced biosynthesis of andrographolide in Andrographis paniculata. Physiol Plant 153:221–229
Shen Q, Li L, Jiang Y, Wang Q (2016a) Functional characterization of ent-copalyl diphosphate synthase from Andrographis paniculata with putative involvement in andrographolides biosynthesis. Biotechnol Lett 38:131–137
Shen Q, Liu Q, Li L, Fu Y, Wnag Q (2016b) Functional characterization of ApCPS involved in andrographolides biosynthesis by virus-induced gene silencing. Acta Bot BorealOccid Sin 36:17–22
Shukla B, Visen PK, Patnaik GK, Dhawan BN (1992) Choleretic effects of andrographolide in rats and guinea pigs. Planta Med 58:146–149
Singh S, Pandey P, Ghosh S, Banerjee S (2018) Anti-cancer labdane diterpenoids from adventitious roots of Andrographis paniculata: augmentation of production prospect endowed with pathway gene expression. Protoplasma 255:1387–1400
Sinha RK, Sharma SN, Verma SS, Zha J (2018) Effects of lovastatin, fosmidomycin, and methyl jasmonate on andrographolide biosynthesis in the Andrographis paniculata. Acta Physiol Plant 40:165
Sivakumar V, Rajeshkumar S (2015) Protective effect of Andrographis paniculata on hyperglycemic mediated oxidative damage in renal tissues of diabetic rats. J Phyto 4:287–294
Srinath M, Shilaja A, Bindu BBV, Giri CC (2021) Molecular cloning and differential gene expression analysis of 1-deody-D-xylulose 5-phosphate synthase (DXS) in Andrographis paniculata (Burm. f.) Nees Mol Biotechnol 63: 109–124
Srivastava N, Akhila A (2010) Biosynthesis of andrographolide in Andrographis paniculata. Phytochemistry 71:1298–1304
Srivastava P, Garg A, Misra RC, Chanotiya CS, Ghosh S (2021) UGT86C11 is a novel plant UDP-glycosyltransferase involved in labdane diterpene biosynthesis. J Biol Chem 297: 101045
Su P, Tong Y, Cheng Q, Hu Y, Zhang M, Yang J, Teng Z, Gao W, Huang L (2016) Functional characterization of ent-copalyl-diphosphate synthase, kaurene synthase and kaurene oxidase in the Salvia miltiorrhiza gibberellins biosynthetic pathway. Sci Rep 6:23057
Sukardiman H, Widyawaruyanti A, Sismindari ZNC (2007) Apoptosis-inducing effect of andrographolide on TD-47 human breast cancer cell line. Afr J Trait Complement Altern Med 16:345–351
Sun W, Leng L, Yin Q, Xu M, Huang M, Xu Z, Zhang Y, Yao H, Wang C, Xiong C, Chen S, Jiang C, Xie N, Zheng X, Wang Y, Song C, Peters RJ, Chen S (2019) The genome of the medicinal plant Andrographis paniculata provides insight into the biosynthesis of the bioactive diterpenoid neoandrographolide. The Plant J 97:841–857
Tajidin NEA, Shaari K, Maulidiani M, Salleh NS, Ketaren BR, Mohamad M (2019) Metabolite profiling of Andrographis paniculata (Burm. f.) Nees. young and mature leaves at different harvest ages using 1H NMR-based metabolomics approach. 9: 16766
Thakur AK, Rai G, Chatterjee SS, Kuamr V (2016) Beneficial effects of an Andrographis paniculata extract and andrographolide on cognitive functions in streptozotocin-induced diabetic rats. Pharm Biol 54:1528–1538
Thanh NT, Murthy HN, Paek KY (2014) Optimization of ginseng cell culture in airlift bioreactors and developing the large-scale production system. Ind Crops Prod 60:343–348
Tran QTN, Tan WSD, Wong WSF, Chai CLL (2021) Polypharmacology of andrographolide: beyond one molecule one target. Nat Prod Rep 38:682–692
Tritsch D, Hemmerlin A, Bach TJ, Rohmer M (2010) Plant isoprenoid biosynthesis via the MEP pathway: in vivo IPP/DMAPP ratio produced by (E)-4hydroxy-3-methylbut-2-enyl diphosphate reductase in tobacco BY-2 cell cultures. FEBS Lett 584:129–134
Vakil MMA, Mendhulkar VD (2013b) Enhanced synthesis of andrographolide by Aspergillus niger and Penicillium expansum elicitors in cell suspension culture of Andrographis paniculata (Burm. f.) Nees Bot Stud 54: 49
Vakil MMA, Mendhulkar VD (2013a) Salicylic acid and chitosan mediated abiotic stress in cell suspension culture of Andrographis paniculata (Burm. f.) Nees for andrographolide synthesis. Int J Pharma Sci Res 4:3453–3459
Wang Z, Chen Y, Wu F (2016) Oligo-polyethene glycol (PEG)-modified 14-deoxy-11,12-didehydroandrographolide derivatives: synthesis, solubility and anti-bacterial activity. Tetrahedron 72:2265–2270
Widyawaruyanti A, Asrory M, Ekasari W, Setiawan D, Radjaram A, Tumewu L, Hafid AF (2014) In vivo antimalarial activity of Andrographis paniculata tablets. Procedia Chem 13:101–104
Xu Y, Marshall RL, Mukkar TK (2006) An investigation on the antimicrobial activity of Andrographis paniculata extracts and andrographolide in vitro. Asian J Plant Sci 5:527–530
Yamamura Y, Taguchi Y, Ichitani K, Umebara I, Ohshita A, Kurosaki F, Lee J (2018) Characterization of ent-kaurene synthase and kaurene oxidase involved in gibberellins biosynthesis form Scoparia dulcis. J Nat Med-Tokyo 72:456–463
Zaheer M, Giri CC (2015) Multiple shoot induction and jasmonic versus salicylic acid-driven elicitation for enhanced andrographolide production in Andrographis paniculata. Plant Cell Tiss Organ Cult 122:553–563
Zaheer M, Giri CC (2017) Enhanced diterpene lactone (andrographolide) production form elicited adventitious root cultures of Andrographis paniculata. Res Chem Intermed 43:2433–2444
Zhang CY, Tan BK (1996) Hypotensive activity of aqueous extract of Andrographis paniculata in rats. Clin Exp PharmacolPhysiol 23:675–678
Zhao J, Davis LC, Verpoorte R (2005) Elicitor signal transduction leading to production of plant secondary metabolites. Biotechnol Adv 23:283–333
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HNM and DD screened and selected literature. All the authors developed the manuscript and read and approved the final version.
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Murthy, H.N., Dalawai, D. Biotechnological production of diterpenoid lactones from cell and organ cultures of Andrographis paniculata. Appl Microbiol Biotechnol 105, 7683–7694 (2021). https://doi.org/10.1007/s00253-021-11599-y
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DOI: https://doi.org/10.1007/s00253-021-11599-y