Your privacy, your choice

We use essential cookies to make sure the site can function. We also use optional cookies for advertising, personalisation of content, usage analysis, and social media.

By accepting optional cookies, you consent to the processing of your personal data - including transfers to third parties. Some third parties are outside of the European Economic Area, with varying standards of data protection.

See our privacy policy for more information on the use of your personal data.

for further information and to change your choices.

Skip to main content

Plant In Vitro Culture Factories for Pentacyclic Triterpenoid Production

  • Chapter
  • First Online:
Plants as Factories for Bioproduction

Abstract

Pentacyclic triterpenoids are a diverse subclass of naturally occurring terpenes with various biological activities and applications. These compounds are broadly distributed in natural plant resources, but their low abundance and the slow growth cycle of plants pose challenges to their extraction and production. The biosynthesis of pentacyclic triterpenoids occurs through two main pathways, the mevalonic acid (MVA) pathway and the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway, which involve several enzymes and modifications. Plant in vitro cultures, including elicited and hairy root cultures, have emerged as an effective and sustainable system for pentacyclic triterpenoid production, circumventing the limitations associated with natural plant resources. Bioreactor systems and controlling key parameters, such as media composition, temperature, light quality, and elicitor treatments, have been optimized to enhance the production and characterization of specific pentacyclic triterpenoids. These systems offer a promising bioprocessing tool for producing pentacyclic triterpenoids characterized by a low carbon footprint and a sustainable source of these compounds for various industrial applications.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
¥17,985 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
JPY 3498
Price includes VAT (Japan)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Abbreviations

2 iP:

6-(γ,γ-dimethylallylamino)purine

2,4-D:

2,4-dichlorophenoxyacetic acid

BA:

6-Benzyladenine

BeA:

Betulinic acid

CMC:

Cambial meristematic cells

HR:

Hairy roots

JA:

Jasmonic acid and its methyl ester

LS:

Linsmaier and Skoog medium

MeJA:

Methyl jasmonate

MS:

Murashige and Skoog medium

NAA:

Naphthaleneacetic acid

OA:

Oleanolic acid

UA:

Ursolic acid

Wdbr:

Wave-mixed disposable bioreactors

References

  1. Thimmappa R, Geisler K, Louveau T et al (2014) Triterpene biosynthesis in plants. Annu Rev Plant Biol 65:225–257

    Article  CAS  PubMed  Google Scholar 

  2. Hemmerlin A, Harwood JL, Bach TJ (2012) A raison d’etre for two distinct pathways in the early steps of plant isoprenoid biosynthesis? Prog Lipid Res 51:95–148

    Article  CAS  PubMed  Google Scholar 

  3. Moses T, Pollier J, Almagro L et al (2014) Combinatorial biosynthesis of sapogenins and saponins in Saccharomyces cerevisiae using a C-16alpha hydroxylase from Bupleurum falcatum. Proc Natl Acad Sci U S A 111:1634–1639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hill RA, Connolly JD (2020) Triterpenoids. Nat Prod Rep 37:962–998

    Article  CAS  PubMed  Google Scholar 

  5. Xu R, Fazio GC, Matsuda SP (2004) On the origins of triterpenoid skeletal diversity. Phytochemistry 65:261–291

    Article  CAS  PubMed  Google Scholar 

  6. Falginella L, Andre CM, Legay S et al (2021) Differential regulation of triterpene biosynthesis induced by an early failure in cuticle formation in apple. Hortic Res 8:75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Checker R, Sandur SK, Sharma D et al (2012) Potent anti-inflammatory activity of ursolic acid, a triterpenoid antioxidant, is mediated through suppression of NF-κB, AP-1 and NF-AT. PloS One 7:e31318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hordyjewska A, Ostapiuk A, Horecka A et al (2019) Betulin and betulinic acid: triterpenoids derivatives with a powerful biological potential. Phytochem Rev 18:929–951

    Article  CAS  Google Scholar 

  9. Laszczyk MN (2009) Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy. Planta Med 75:1549–1560

    Article  CAS  PubMed  Google Scholar 

  10. Bensaddek L, Villarreal ML, Fliniaux M-A (2008) Induction and growth of hairy roots for the production of medicinal compounds. Electron J Integr Biosci 3:2–9

    Google Scholar 

  11. Li Y, Wang J, Li L et al (2023) Natural products of pentacyclic triterpenoids: from discovery to heterologous biosynthesis. Nat Prod Rep

    Google Scholar 

  12. Zhou LG, Wu JY (2006) Development and application of medicinal plant tissue cultures for production of drugs and herbal medicinals in China. Nat Prod Rep 23:789–810

    Article  CAS  PubMed  Google Scholar 

  13. Chandra S, Chandra R (2011) Engineering secondary metabolite production in hairy roots. Phytochem Rev 10:371–395

    Article  CAS  Google Scholar 

  14. Altaf H, Iqbal Ahmed Q, Hummera N et al (2012) Plant tissue culture: current status and opportunities. In: Annarita L, Laura MRR (eds) Recent advances in plant in vitro culture. IntechOpen, Rijeka

    Google Scholar 

  15. Rogowska A, Szakiel A (2021) Enhancement of phytosterol and triterpenoid production in plant hairy root cultures-simultaneous stimulation or competition? Plants (Basel) 10

    Google Scholar 

  16. Ghosh S (2017) Triterpene structural diversification by plant cytochrome P450 enzymes. Front Plant Sci 8

    Google Scholar 

  17. Isah MB, Ibrahim MA, Mohammed A et al (2016) A systematic review of pentacyclic triterpenes and their derivatives as chemotherapeutic agents against tropical parasitic diseases. Parasitology 143:1219–1231

    Article  CAS  PubMed  Google Scholar 

  18. Dewick PM (2009) A biosynthetic approach. In: Medicinal natural products. Wiley

    Chapter  Google Scholar 

  19. Chung PY (2020) Novel targets of pentacyclic triterpenoids in Staphylococcus aureus: a systematic review. Phytomedicine 73

    Google Scholar 

  20. Sommano SR, Chittasupho C, Ruksiriwanich W et al (2020) The cannabis terpenes. Molecules 25

    Google Scholar 

  21. Sheng H, Sun H (2011) Synthesis, biology and clinical significance of pentacyclic triterpenes: a multi-target approach to prevention and treatment of metabolic and vascular diseases. Nat Prod Rep 28:543–593

    Article  CAS  PubMed  Google Scholar 

  22. Jager S, Trojan H, Kopp T et al (2009) Pentacyclic triterpene distribution in various plants – rich sources for a new group of multi-potent plant extracts. Molecules 14:2016–2031

    Article  PubMed  PubMed Central  Google Scholar 

  23. Parmar SK, Sharma T, Airao V et al (2013) Neuropharmacological effects of triterpenoids. Phytopharmacology 4:354–372

    CAS  Google Scholar 

  24. Mandal A, Ghosh S, Bothra AK et al (2012) Synthesis of friedelan triterpenoid analogs with DNA topoisomerase IIα inhibitory activity and their molecular docking studies. Eur J Med Chem 54:137–143

    Article  CAS  PubMed  Google Scholar 

  25. Abe I, Rohmer M, Prestwich GD (1993) Enzymatic cyclization of squalene and oxidosqualene to sterols and triterpenes. Chem Rev 93:2189–2206

    Article  CAS  Google Scholar 

  26. Sawai S, Saito K (2011) Triterpenoid biosynthesis and engineering in plants. Front Plant Sci 2:25

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kushiro T, Ebizuka Y (2010) 1.18 – triterpenes. In: Liu H-W, Mander L (eds) Comprehensive natural products II. Elsevier, Oxford

    Google Scholar 

  28. Kahn RA, Durst F (2000) Function and evolution of plant cytochrome P450. Recent Adv Phytochem 34:151–189

    Article  CAS  Google Scholar 

  29. Andre CM, Greenwood JM, Walker EG et al (2012) Anti-inflammatory procyanidins and triterpenes in 109 apple varieties. J Agric Food Chem 60:10546–10554

    Article  CAS  PubMed  Google Scholar 

  30. Romero C, García A, Medina E et al (2010) Triterpenic acids in table olives. Food Chem 118:670–674

    Article  CAS  Google Scholar 

  31. Trivedi P, Nguyen N, Klavins L et al (2021) Analysis of composition, morphology, and biosynthesis of cuticular wax in wild type bilberry (Vaccinium myrtillus L.) and its glossy mutant. Food Chem 354

    Google Scholar 

  32. Szakiel A, Paczkowski C, Huttunen S (2012) Triterpenoid content of berries and leaves of bilberry vaccinium myrtillus from Finland and Poland. J Agric Food Chem 60:11839–11849

    Article  CAS  PubMed  Google Scholar 

  33. Dashbaldan S, Becker R, Pączkowski C et al (2019) Various patterns of composition and accumulation of steroids and triterpenoids in cuticular waxes from screened Ericaceae and Caprifoliaceae berries during fruit development. Molecules 24

    Google Scholar 

  34. Szakiel A, Paczkowski C, Koivuniemi H et al (2012) Comparison of the triterpenoid content of berries and leaves of lingonberry vaccinium vitis-idaea from Finland and Poland. J Agric Food Chem 60:4994–5002

    Article  CAS  PubMed  Google Scholar 

  35. Awad R, Muhammad A, Durst T et al (2009) Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity. Phytother Res 23:1075–1081

    Article  CAS  PubMed  Google Scholar 

  36. Da Silva Filho AA, De Sousa JP, Soares S et al (2008) Antimicrobial activity of the extract and isolated compounds from Baccharis dracunculifolia D. C. (Asteraceae). Z Naturforsch C J Biosci 63:40–46

    Article  PubMed  Google Scholar 

  37. Abe F, Yamauchi T, Nagao T et al (2002) Ursolic acid as a trypanocidal constituent in rosemary. Biol Pharm Bull 25:1485–1487

    Article  CAS  PubMed  Google Scholar 

  38. Siddiqui BS, Sultana I, Begum S (2000) Triterpenoidal constituents from Eucalyptus camaldulensis var. obtusa leaves. Phytochemistry 54:861–865

    Article  CAS  PubMed  Google Scholar 

  39. Jager S, Laszczyk MN, Scheffler A (2008) A preliminary pharmacokinetic study of Betulin, the main Pentacyclic triterpene from extract of outer bark of birch (Betulae alba cortex). Molecules 13:3224–3235

    Article  PubMed  PubMed Central  Google Scholar 

  40. Nguyen HN, Ullevig SL, Short JD et al (2021) Ursolic acid and related analogues: triterpenoids with broad health benefits. Antioxidants (Basel):10

    Google Scholar 

  41. Banerjee S, Bose S, Mandal SC et al (2019) Pharmacological property of pentacyclic triterpenoids. Egypt J Chem 62:13–35

    Google Scholar 

  42. Lee D, Lee SR, Kang KS et al (2019) Betulinic acid suppresses ovarian cancer cell proliferation through induction of apoptosis. Biomol Ther 9

    Google Scholar 

  43. Patočka J (2003) Biologically active pentacyclic triterpenes and their current medicine signification. J Appl Biomed 1:7–12

    Article  Google Scholar 

  44. Pisha E, Chai H, Lee IS et al (1995) Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat Med 1:1046–1051

    Article  CAS  PubMed  Google Scholar 

  45. Fulda S (2009) Betulinic acid: a natural product with anticancer activity. Mol Nutr Food Res 53:140–146

    Article  CAS  PubMed  Google Scholar 

  46. Fulda S (2008) Betulinic acid for cancer treatment and prevention. Int J Mol Sci 9:1096–1107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Rabi T, Shukla S, Gupta S (2008) Betulinic acid suppresses constitutive and TNFalpha-induced NF-kappaB activation and induces apoptosis in human prostate carcinoma PC-3 cells. Mol Carcinog 47:964–973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Xiang D, Zhao M, Cai X et al (2020) Betulinic acid inhibits endometriosis through suppression of estrogen receptor β signaling pathway. Front Endocrinol (Lausanne) 11:604648

    Article  PubMed  Google Scholar 

  49. Guo YY, Zhu HY, Weng M et al (2020) Chemopreventive effect of Betulinic acid via mTOR -caspases/Bcl2/Bax apoptotic signaling in pancreatic cancer. BMC Complement Med 20

    Google Scholar 

  50. Wang YJ, Liu JB, Dou YC (2015) Sequential treatment with betulinic acid followed by 5-fluorouracil shows synergistic cytotoxic activity in ovarian cancer cells. Int J Clin Exp Pathol 8:252–259

    PubMed  PubMed Central  Google Scholar 

  51. Ehrhardt H, Fulda S, Führer M et al (2004) Betulinic acid-induced apoptosis in leukemia cells. Leukemia 18:1406–1412

    Article  CAS  PubMed  Google Scholar 

  52. Wu QL, He J, Fang J et al (2010) Antitumor effect of betulinic acid on human acute leukemia K562 cells in vitro. J Huazhong U Sci-Med 30:453–457

    Article  Google Scholar 

  53. Sawada N, Kataoka K, Kondo K et al (2004) Betulinic acid augments the inhibitory effects of vincristine on growth and lung metastasis of B16F10 melanoma cells in mice. Br J Cancer 90:1672–1678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhou R, Zhang Z, Zhao L et al (2011) Inhibition of mTOR signaling by oleanolic acid contributes to its anti-tumor activity in osteosarcoma cells. J Orthop Res 29:846–852

    Article  CAS  PubMed  Google Scholar 

  55. De Angel RE, Smith SM, Glickman RD et al (2010) Antitumor effects of ursolic acid in a mouse model of postmenopausal breast cancer. Nutr Cancer 62:1074–1086

    Article  PubMed  Google Scholar 

  56. Shan JZ, Xuan YY, Ruan SQ et al (2011) Proliferation-inhibiting and apoptosis-inducing effects of ursolic acid and oleanolic acid on multi-drug resistance cancer cells in vitro. Chin J Integr Med 17:607–611

    Article  CAS  PubMed  Google Scholar 

  57. Yeh CT, Wu CH, Yen GC (2010) Ursolic acid, a naturally occurring triterpenoid, suppresses migration and invasion of human breast cancer cells by modulating c-Jun N-terminal kinase, Akt and mammalian target of rapamycin signaling. Mol Nutr Food Res 54:1285–1295

    Article  CAS  PubMed  Google Scholar 

  58. Kim KH, Seo HS, Choi HS et al (2011) Induction of apoptotic cell death by ursolic acid through mitochondrial death pathway and extrinsic death receptor pathway in MDA-MB-231 cells. Arch Pharm Res 34:1363–1372

    Article  CAS  PubMed  Google Scholar 

  59. He XJ, Liu RH (2006) Cranberry phytochemicals: isolation, structure elucidation, and their antiproliferative and antioxidant activities. J Agric Food Chem 54:7069–7074

    Article  CAS  PubMed  Google Scholar 

  60. Ullevig SL, Zhao QW, Zamora D et al (2011) Ursolic acid protects diabetic mice against monocyte dysfunction and accelerated atherosclerosis. Atherosclerosis 219:409–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Pyo JS, Roh SH, Kim DK et al (2009) Anti-cancer effect of Betulin on a human lung cancer cell line: a pharmacoproteomic approach using 2 D SDS PAGE coupled with nano-HPLC tandem mass spectrometry. Planta Med 75:127–131

    Article  CAS  PubMed  Google Scholar 

  62. Gautam R, Jachak SM (2009) Recent developments in anti-inflammatory natural products. Med Res Rev 29:767–820

    Article  CAS  PubMed  Google Scholar 

  63. Costa JFO, Barbosa JM, Maia GLD et al (2014) Potent anti-inflammatory activity of betulinic acid treatment in a model of lethal endotoxemia. Int Immunopharmacol 23:469–474

    Article  PubMed  Google Scholar 

  64. Viji V, Shobha B, Kavitha SK et al (2010) Betulinic acid isolated from Bacopa monniera (L.) Wettst suppresses lipopolysaccharide stimulated interleukin-6 production through modulation of nuclear factor-kappaB in peripheral blood mononuclear cells. Int Immunopharmacol 10:843–849

    Article  CAS  PubMed  Google Scholar 

  65. Shishodia S, Majumdar S, Banerjee S et al (2003) Ursolic acid inhibits nuclear factor-κB activation induced by carcinogenic agents through suppression of IκBα kinase and p65 phosphorylation: correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D11. Cancer Res 63:4375–4383

    CAS  PubMed  Google Scholar 

  66. Chun J, Lee C, Hwang SW et al (2014) Ursolic acid inhibits nuclear factor-κB signaling in intestinal epithelial cells and macrophages, and attenuates experimental colitis in mice. Life Sci 110:23–34

    Article  CAS  PubMed  Google Scholar 

  67. Feng L, Liu X, Zhu W et al (2013) Inhibition of human neutrophil elastase by pentacyclic triterpenes. PloS One 8:e82794

    Article  PubMed  PubMed Central  Google Scholar 

  68. Ullevig SL, Kim HS, Short JD et al (2016) Protein S-glutathionylation mediates macrophage responses to metabolic cues from the extracellular environment. Antioxid Redox Signal 25:836–851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ullevig S, Kim HS, Asmis R (2013) S-Glutathionylation in monocyte and macrophage (Dys) function. Int J Mol Sci 14:15212–15232

    Article  PubMed  PubMed Central  Google Scholar 

  70. Nguyen HN, Ahn YJ, Medina EA et al (2018) Dietary 23-hydroxy ursolic acid protects against atherosclerosis and obesity by preventing dyslipidemia-induced monocyte priming and dysfunction. Atherosclerosis 275:333–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Radhiga T, Rajamanickam C, Senthil S et al (2012) Effect of ursolic acid on cardiac marker enzymes, lipid profile and macroscopic enzyme mapping assay in isoproterenol-induced myocardial ischemic rats. Food Chem Toxicol 50:3971–3977

    Article  CAS  PubMed  Google Scholar 

  72. Zhang S, Liu Y, Wang X et al (2020) Antihypertensive activity of oleanolic acid is mediated via downregulation of secretory phospholipase A2 and fatty acid synthase in spontaneously hypertensive rats. Int J Mol Med 46:2019–2034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Soler F, Poujade C, Evers M et al (1996) Betulinic acid derivatives: a new class of specific inhibitors of human immunodeficiency virus type 1 entry. J Med Chem 39:1069–1083

    Article  CAS  PubMed  Google Scholar 

  74. Wang Q, Li Y, Zheng L et al (2020) Novel betulinic acid-nucleoside hybrids with potent anti-HIV activity. ACS Med Chem Lett 11:2290–2293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kanamoto T, Kashiwada Y, Kanbara K et al (2001) Anti-human immunodeficiency virus activity of YK-FH312 (a betulinic acid derivative), a novel compound blocking viral maturation. Antimicrob Agents Chemother 45:1225–1230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Kashiwada Y, Chiyo J, Ikeshiro Y et al (2000) Anti-AIDS agents, part 43 – synthesis and anti-HIV activity of 3-alkylamido-3-deoxy-betulinic acid derivatives. Chem Pharm Bull 48:1387–1390

    Article  CAS  Google Scholar 

  77. Fujioka T, Kashiwada Y, Kilkuskie RE et al (1994) Anti-aids agents .11. Betulinic acid and platanic acid as anti-HIV principles from syzigium-claviflorum, and the anti-HIV activity of structurally related triterpenoids. J Nat Prod 57:243–247

    Article  CAS  PubMed  Google Scholar 

  78. Akihisa T, Ogihara J, Kato J et al (2001) Inhibitory effects of triterpenoids and sterols on human immunodeficiency virus-1 reverse transcriptase. Lipids 36:507–512

    Article  CAS  PubMed  Google Scholar 

  79. Jain M, Kapadia R, Jadeja RN et al (2012) Hepatoprotective potential of Tecomella undulata stem bark is partially due to the presence of betulinic acid. J Ethnopharmacol 143:194–200

    Article  CAS  PubMed  Google Scholar 

  80. Yi J, Xia W, Wu J et al (2014) Betulinic acid prevents alcohol-induced liver damage by improving the antioxidant system in mice. J Vet Sci 15:141–148

    Article  PubMed  PubMed Central  Google Scholar 

  81. Preetha SP, Kanniappan M, Selvakumar E et al (2006) Lupeol ameliorates aflatoxin B1-induced peroxidative hepatic damage in rats. Comp Biochem Physiol C Toxicol Pharmacol 143:333–339

    Article  CAS  PubMed  Google Scholar 

  82. Huang S, Mo C, Zeng T et al (2021) Lupeol ameliorates LPS/D-GalN induced acute hepatic damage by suppressing inflammation and oxidative stress through TGFβ1-Nrf2 signal pathway. Aging (Albany NY) 13:6592–6605

    Article  CAS  PubMed  Google Scholar 

  83. Kim SJ, Quan HY, Jeong KJ et al (2014) Beneficial effect of betulinic acid on hyperglycemia via suppression of hepatic glucose production. J Agric Food Chem 62:434–442

    Article  CAS  PubMed  Google Scholar 

  84. Yoon JJ, Lee YJ, Han BH et al (2017) Protective effect of betulinic acid on early atherosclerosis in diabetic apolipoprotein-E gene knockout mice. Eur J Pharmacol 796:224–232

    Article  CAS  PubMed  Google Scholar 

  85. Xie R, Zhang H, Wang XZ et al (2017) The protective effect of betulinic acid (BA) diabetic nephropathy on streptozotocin (STZ)-induced diabetic rats. Food Funct 8:299–306

    Article  CAS  PubMed  Google Scholar 

  86. Wang XT, Gong Y, Zhou B et al (2018) Ursolic acid ameliorates oxidative stress, inflammation and fibrosis in diabetic cardiomyopathy rats. Biomed Pharmacother 97:1461–1467

    Article  CAS  PubMed  Google Scholar 

  87. Bamuamba K, Gammon DW, Meyers P et al (2008) Anti-mycobacterial activity of five plant species used as traditional medicines in the Western Cape Province (South Africa). J Ethnopharmacol 117:385–390

    Article  PubMed  Google Scholar 

  88. Singh A, Venugopala KN, Khedr MA et al (2017) Antimycobacterial, docking and molecular dynamic studies of pentacyclic triterpenes from Buddleja saligna leaves. J Biomol Struct Dyn 35:2654–2664

    Article  CAS  PubMed  Google Scholar 

  89. Rojas R, Caviedes L, Aponte JC et al (2006) Aegicerin, the first oleanane triterpene with wide-ranging antimycobacterial activity, isolated from Clavija procera. J Nat Prod 69:845–846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Scalon Cunha LC, Andrade e Silva ML, Cardoso Furtado NA et al (2007) Antibacterial activity of triterpene acids and semi-synthetic derivatives against oral pathogens. Z Naturforsch C J Biosci 62:668–672

    Article  PubMed  Google Scholar 

  91. Mallavadhani UV, Mahapatra A, Jamil K et al (2004) Antimicrobial activity of some pentacyclic triterpenes and their synthesized 3-O-lipophilic chains. Biol Pharm Bull 27:1576–1579

    Article  CAS  PubMed  Google Scholar 

  92. Horiuchi K, Shiota S, Hatano T et al (2007) Antimicrobial activity of oleanolic acid from Salvia officinalis and related compounds on vancomycin-resistant enterococci (VRE). Biol Pharm Bull 30:1147–1149

    Article  CAS  PubMed  Google Scholar 

  93. Furtado NJC, Pirson L, Edelberg H et al (2017) Pentacyclic triterpene bioavailability: an overview of in vitro and in vivo studies. Molecules 22

    Google Scholar 

  94. Patra JK, Das G, Fraceto LF et al (2018) Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol 16

    Google Scholar 

  95. Bozzuto G, Molinari A (2015) Liposomes as nanomedical devices. Int J Nanomedicine 10:975–999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Shu Q, Wu J, Chen Q (2019) Synthesis, characterization of liposomes modified with biosurfactant MEL-A loading betulinic acid and its anticancer effect in HepG2 cell. Molecules 24

    Google Scholar 

  97. Gao DW, Tang SN, Tong Q (2012) Oleanolic acid liposomes with polyethylene glycol modification: promising antitumor drug delivery. Int J Nanomedicine 7:3517–3526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Wang S, Meng X, Dong Y (2017) Ursolic acid nanoparticles inhibit cervical cancer growth in vitro and in vivo via apoptosis induction. Int J Oncol 50:1330–1340

    Article  CAS  PubMed  Google Scholar 

  99. Li DY, Cui RX, Xu SN et al (2020) Synergism of cisplatin-oleanolic acid co-loaded hybrid nanoparticles on gastric carcinoma cells for enhanced apoptosis and reversed multidrug resistance. Drug Deliv 27:191–199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Bao YM, Zhang S, Chen Z et al (2020) Synergistic chemotherapy for breast cancer and breast cancer brain metastases via paclitaxel-loaded oleanolic acid nanoparticles. Mol Pharm 17:1343–1351

    Article  CAS  PubMed  Google Scholar 

  101. Colombo E, Polito L, Biocotino M et al (2020) New class of betulinic acid-based nanoassemblies of cabazitaxel, podophyllotoxin, and thiocolchicine. ACS Med Chem Lett 11:895–898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Csuk R (2014) Betulinic acid and its derivatives: a patent review (2008-2013). Expert Opin Ther Pat 24:913–923

    Article  CAS  PubMed  Google Scholar 

  103. Johnson M, Jewell RC, Peppercorn A et al (2018) The safety, tolerability, and pharmacokinetic profile of GSK2838232, a novel 2nd generation HIV maturation inhibitor, as assessed in healthy subjects. Pharmacol Res Perspect 6

    Google Scholar 

  104. Moses T, Pollier J, Thevelein JM et al (2013) Bioengineering of plant (tri)terpenoids: from metabolic engineering of plants to synthetic biology in vivo and in vitro. New Phytol 200:27–43

    Article  CAS  PubMed  Google Scholar 

  105. Lim EK, Bowles D (2012) Plant production systems for bioactive small molecules. Curr Opin Biotechnol 23:271–277

    Article  CAS  PubMed  Google Scholar 

  106. Wilson SA, Roberts SC (2012) Recent advances towards development and commercialization of plant cell culture processes for the synthesis of biomolecules. Plant Biotechnol J 10:249–268

    Article  CAS  PubMed  Google Scholar 

  107. Georgiev MI, Weber J, Maciuk A (2009) Bioprocessing of plant cell cultures for mass production of targeted compounds. Appl Microbiol Biotechnol 83:809–823

    Article  CAS  PubMed  Google Scholar 

  108. Rao SR, Ravishankar GA (2002) Plant cell cultures: chemical factories of secondary metabolites. Biotechnol Adv 20:101–153

    Article  CAS  PubMed  Google Scholar 

  109. Ahad Hedayati MHM, Hadian J (2015) Quantification of betulinic, oleanolic and ursolic acid as medicinally important triterpenoids in wild and in vitro callus culture of Salvia sahendica (Lamiaceae): a comparative study. J Biodivers Environ Sci 4:327–333

    Google Scholar 

  110. Bolta Z, Baricevic D, Bohanec B et al (2000) A preliminary investigation of ursolic acid in cell suspension culture of Salvia officinalis. Plant Cell Tiss Org 62:57–63

    Article  CAS  Google Scholar 

  111. Akashi T, Furuno T, Takahashi T et al (1994) Biosynthesis of triterpenoids in cultured-cells, and regenerated and wild plant organs of taraxacum-officinale. Phytochemistry 36:303–308

    Article  CAS  Google Scholar 

  112. Srivastava P, Kasoju N, Bora U et al (2010) Accumulation of betulinic, oleanolic, and ursolic acids in in vitro cell cultures of Lantana camara L. and their significant cytotoxic effects on HeLa cell lines. Biotechnol Bioproc E 15:1038–1046

    Article  CAS  Google Scholar 

  113. Haas C, Hengelhaupt KC, Kummritz S et al (2014) Salvia suspension cultures as production systems for oleanolic and ursolic acid. Acta Physiol Plant 36:2137–2147

    Article  CAS  Google Scholar 

  114. Marchev A, Ivanov I, Georgiev V et al (2012) Determination of di- and triterpenes in Salvia tomentosa mill. Cell suspension culture by high performance liquid chromatography. Sci Works Univ Food Technol Plovdiv 59:229–233

    Google Scholar 

  115. Grzelak A, Janiszowska W (2002) Initiation and growth characteristics of suspension cultures of Calendula officinalis cells – changes in the level of oleanolic acid during the cell growth cycle of the culture. Plant Cell Tiss Org 71:29–40

    Article  CAS  Google Scholar 

  116. Wiktorowska E, Dlugosz M, Janiszowska W (2010) Significant enhancement of oleanolic acid accumulation by biotic elicitors in cell suspension cultures of Calendula officinalis L. Enzyme Microb Technol 46:14–20

    Article  CAS  Google Scholar 

  117. Kamisako W, Morimoto K, Makino I et al (1984) Changes in triterpenoid content during the growth cycle of cultured plant cells. Plant Cell Physiol 25:1571–1574

    Article  CAS  Google Scholar 

  118. Marchev A, Georgiev V, Badjakov I et al (2011) Triterpenes production by rhizogenic callus of Salvia scabiosifolia Lam. Obtained via agrobacterium rhizogenes mediated genetic transformation. Biotechnol Biotechnol Equip 25:30–33

    Article  Google Scholar 

  119. Flores-Sanchez IJ, Ortega-Lopez J, Montes-Horcasitas MD et al (2002) Biosynthesis of sterols and triterpenes in cell suspension cultures of Uncaria tomentosa. Plant Cell Physiol 43:1502–1509

    Article  CAS  PubMed  Google Scholar 

  120. Pandey P, Singh S, Banerjee S (2019) Ocimum basilicum suspension culture as resource for bioactive triterpenoids: yield enrichment by elicitation and bioreactor cultivation. Plant Cell Tiss Org 137:65–75

    Article  CAS  Google Scholar 

  121. Norrizah JS, Suhaimi MY, Rohaya A et al (2012) Ursolic acid and Oleanolic acid productions in elicited cell suspension cultures of Hedyotis corymbosa. Biotechnology 11:238–242

    Article  CAS  Google Scholar 

  122. Mehring A, Haffelder J, Chodorski J et al (2020) Establishment and triterpenoid production of Ocimum basilicum cambial meristematic cells. Plant Cell Tiss Organ Cult 143:573–581

    Article  CAS  Google Scholar 

  123. Baek S, Han JE, Ho TT et al (2022) Development of hairy root cultures for biomass and triterpenoid production in Centella asiatica. Plants (Basel) 11

    Google Scholar 

  124. Kuzma L, Skrzypek Z, Wysokinska H (2006) Diterpenoids and triterpenoids in hairy roots of Salvia sclarea. Plant Cell Tiss Org 84:171–179

    Article  CAS  Google Scholar 

  125. Nader BL, Taketa AT, Pereda-Miranda R et al (2006) Production of triterpenoids in liquid-cultivated hairy roots of Galphimia glauca. Planta Med 72:842–844

    Article  CAS  PubMed  Google Scholar 

  126. Marzouk AM (2009) Hepatoprotective triterpenes from hairy root cultures of Ocimum basilicum L. Z Naturforsch C 64:201–209

    Article  CAS  PubMed  Google Scholar 

  127. Ochoa-Villarreal M, Howat S, Hong S et al (2016) Plant cell culture strategies for the production of natural products. BMB Rep 49:149–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Vrancheva R, Ivanov I, Aneva I et al (2018) Food additives and bioactive substances from in vitro systems of edible plants from the Balkan peninsula. Eng Life Sci 18:799–806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Steingroewer J, Bley T, Georgiev V et al (2013) Bioprocessing of differentiated plant in vitro systems. Eng Life Sci 13:26–38

    Article  CAS  Google Scholar 

  130. Ono NN, Tian L (2011) The multiplicity of hairy root cultures: prolific possibilities. Plant Sci 180:439–446

    Article  CAS  PubMed  Google Scholar 

  131. Shanks JV, Morgan J (1999) Plant 'hairy root' culture. Curr Opin Biotechnol 10:151–155

    Article  CAS  PubMed  Google Scholar 

  132. Markowski M, Dlugosz M, Szakiel A et al (2019) Increased synthesis of a new oleanane-type saponin in hairy roots of marigold (Calendula officinalis) after treatment with jasmonic acid. Nat Prod Res 33:1218–1222

    Article  CAS  PubMed  Google Scholar 

  133. Georgiev MI, Pavlov AI, Bley T (2007) Hairy root type plant in vitro systems as sources of bioactive substances. Appl Microbiol Biotechnol 74:1175–1185

    Article  CAS  PubMed  Google Scholar 

  134. Feria-Romero I, Lazo E, Ponce-Noyola T et al (2005) Induced accumulation of oleanolic acid and ursolic acid in cell suspension cultures of Uncaria tomentosa. Biotechnol Lett 27:839–843

    Article  CAS  PubMed  Google Scholar 

  135. Pereira PS, Ticli FK, Franca SDC et al (2007) Enhanced triterpene production in Tabernaemontana catharinensis cell suspension cultures in response to biotic elicitors. Quim Nova 30:1849–1852

    Article  CAS  Google Scholar 

  136. Sharan S, Sarin NB, Mukhopadhyay K (2019) Elicitor-mediated enhanced accumulation of ursolic acid and eugenol in hairy root cultures of Ocimum tenuiflorum L. is age, dose, and duration dependent. S Afr J Bot 124:199–210

    Article  CAS  Google Scholar 

  137. Vergara-Martinez VM, Estrada-Soto SE, Valencia-Diaz S et al (2021) Methyl jasmonate enhances ursolic, oleanolic and rosmarinic acid production and sucrose induced biomass accumulation, in hairy roots of Lepechinia caulescens. Peerj 9

    Google Scholar 

  138. Valdiani A, Hansen OK, Nielsen UB et al (2019) Bioreactor-based advances in plant tissue and cell culture: challenges and prospects. Crit Rev Biotechnol 39:20–34

    Article  CAS  Google Scholar 

  139. Eibl R, Eibl D (2008) Design of bioreactors suitable for plant cell and tissue cultures. Phytochem Rev 7:593–598

    Article  CAS  Google Scholar 

  140. Werner S, Maschke RW, Eibl D et al (2018) Bioreactor technology for sustainable production of plant cell-derived products. Ref Ser Phytochem:413–432

    Google Scholar 

  141. Badjakov I, Georgiev V, Georgieva M et al (2020) Bioreactor technology for in vitro berry plant cultivation. In: Ramawat KG, Ekiert HM, Goyal S (eds) Plant cell and tissue differentiation and secondary metabolites: fundamentals and applications. Springer, Cham

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2024 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Badjakov, I., Dincheva, I., Vrancheva, R., Georgiev, V., Pavlov, A. (2024). Plant In Vitro Culture Factories for Pentacyclic Triterpenoid Production. In: Steingroewer, J. (eds) Plants as Factories for Bioproduction. Advances in Biochemical Engineering/Biotechnology, vol 188. Springer, Cham. https://doi.org/10.1007/10_2023_245

Download citation

Publish with us

Policies and ethics