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Plant Science Today (PST)

Research Articles

Early Access

Effect of heavy metal elicitation on antioxidants and andrographolide content in cell suspension cultures of Andrographis paniculata

DOI
https://doi.org/10.14719/pst.3473
Submitted
2 March 2024
Published
26-05-2025
Versions

Abstract

Andrographolide, a bicyclic diterpene from Andrographis paniculata is of immense pharmaceutical importance. A. paniculata, an annual herb from Acanthaceae is widespread in the Indian subcontinent. Heavy metals act as abiotic elicitors. The study deals with the effect of mercury (Hg), cadmium (Cd) and arsenic (As) on andrographolide content, phenols and flavonoids and each of their correlation with the metal chelating and radical scavenging activity, in cell suspension cultures of A. paniculata. Andrographolide was estimated using HPLC, while other estimation methods were used for other metabolites. Four different concentrations of each of the heavy metal salts CdCl2, As2O3 and HgCl2, were administered in liquid MS media containing 1 g of cells. Media without any metal served as control. Higher concentrations of Cd and As imparted a positive effect on andrographolide content, Hg imparted a negative effect. The cells were most sensitive to Hg and most tolerant to Cd. Cd could be the best choice as an elicitor for increased production of andrographolide. While phenols show a positive correlation with antioxidants, flavonoids and andrographolides do not show a positive correlation with antioxidants.

References

  1. 1. Rao YK, Koteswara Rao Y, Vimalamma G, et al. Flavonoids and andrographolides from Andrographis paniculata. Phytochem. 2004;65:2317–21. https://doi.org/10.1016/j.phytochem.2004.05.008
  2. 2. Xu C, Chou GX, Wang ZT. A new diterpene from the leaves of Andrographis paniculata Nees. Fitoterapia. 2010; 81:610–13. https://doi.org/10.1016/j.fitote.2010.03.003
  3. 3. Subramanian R, Asmawi MZ, Sadikun A. A bitter plant with a sweet future? A comprehensive review of an oriental medicinal plant: Andrographis paniculata. Phytochem Rev. 2012;11:39–75. https://doi.org/10.1007/s11101-011-9219-z
  4. 4. Hossain MS, Urbi Z, Sule A, Hafizur Rahman KM. Andrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacology. Scientific World Journal. 2014;274905. https://doi.org/10.1155/2014/274905
  5. 5. Liu MY. Insight into the pharmacological effects of andrographolide in musculoskeletal disorders. Biomed. Pharmacother. 2022; 146:112583. https://doi.org/10.1016/j.biopha.2021.112583
  6. 6. Tundis R. Anti-Cancer agent: The labdane diterpenoid-andrographolide. Plants. 2023;12. https://doi.org/10.3390/plants12101969
  7. 7. Wang T, Liu B, Zhang W, Wilson B, Hong JS. Andrographolide reduces inflammation-mediated dopaminergic neurodegeneration in mesencephalic neuron-glia cultures by inhibiting microglial activation. J Pharmacol Exp Ther. 2004;308:975–83. https://doi.org/10.1124/jpet.103.059683
  8. 8. Yang S, Evens AM, Prachand S, Singh ATK, Bhalla S, David K, Gordon LI Mitochondrial-mediated apoptosis in lymphoma cells by the diterpenoid lactone andrographolide, the active component of Andrographis paniculata. Clin Cancer Res. 2010;16:4755–68. https://doi.org/10.1158/1078-0432.CCR-10-0883
  9. 9. Zhou J, Lu GD, Ong CS, Ong CN, Shen HM. Andrographolide sensitizes cancer cells to TRAIL-induced apoptosis via p53-mediated death receptor 4 up-regulation. Mol Cancer Ther. 2008; 7:2170–2180. https://doi.org/10.1158/1535-7163.MCT-08-0071
  10. 10. Lin TP, Chen SY, Duh PD Inhibition of the Epstein-Barr virus lytic cycle by andrographolide. Biol Pharm Bulletin. 2008; 31:2018–23. https://doi.org/10.1248/bpb.31.2018
  11. 11. Manikam ST, Stanslas J. Andrographolide inhibits growth of acute promyelocytic leukaemia cells by inducing retinoic acid receptor-independent cell differentiation and apoptosis. J Pharm Pharmacol. 2010;61:69–78. https://doi.org/10.1211/jpp/61.01.0010
  12. 12. Shi MD, Lin HH, Lee YC, Chao JK, Lin RA, Chen JH. Inhibition of cell-cycle progression in human colorectal carcinoma Lovo cells by andrographolide. Chem Biol Interact. 2008; 174:201–10. https://doi.org/10.1016/j.cbi.2008.06.006
  13. 13. Ji L, Liu T, Liu J. Andrographolide inhibits human hepatoma-derived Hep3B cell growth through the activation of c-Jun N-terminal kinase. Planta Med. 2007;73:1397–1401. https://doi.org/10.1055/s-2007-990230
  14. 14. Kishore PH, Kishore P, Reddy MVB. Flavonoids from Andrographis lineata. Phytochem. 2003;63:457–61. https://doi.org/10.1016/S0031-9422(02)00702-1
  15. 15. Li J, Huang W, Zhang H. Synthesis of andrographolide derivatives and their TNF-alpha and IL-6 expression inhibitory activities. Bioorg Med Chem Lett. 2007;17:6891–94. https://doi.org/10.1016/j.bmcl.2007.10.009
  16. 16. Cheung HY, Cheung CS, Kong CK. Determination of bioactive diterpenoids from Andrographis paniculata by micellar electrokinetic chromatography. J Chromatography A. 2001;930:171–76. https://doi.org/10.1016/S0021-9673(01)01160-8
  17. 17. Pholphana N, Rangkadilok N, Thongnest, Ruchirawat S, Ruchirawat M, Satayavivad J. Determination and variation of three active diterpenoids in Andrographis paniculata (Burm.f.) Nees. Phytochem Anal. 2004;15:365–71. https://doi.org/10.1002/pca.789
  18. 18. Reddy MVB. New 2‘-Oxygenated flavonoids from Andrographis affinis. J Nat Prod. 2003; 66:295–97. https://doi.org/10.1021/np020331k
  19. 19. Radhika P, Prasad YR, Lakshmi KR. Flavones from the stem of Andrographis paniculata Nees. Nat Prod Commun. 2010; 5:1934578X1000500. https://doi.org/10.1177/1934578X1000500115
  20. 20. Das D, Bandhopadhyay M. Novel approaches towards over-production of andrographolide in in vitro seedling cultures of Andrographis paniculata. South African J Bot. 2021;128:77-86. https://doi.org/10.1016/j.sajb.2019.10.015
  21. 21. 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;44:406–10. https://doi.org/10.1016/j.enzmictec.2009.01.005
  22. 22. Frankfater CR, Dowd MK, Triplett BA. Effect of elicitors on the production of gossypol and methylated gossypol in cotton hairy roots. Plant Cell Tiss Org Cult. 2009;3:341–49. https://doi.org/10.1007/s11240-009-9568-0
  23. 23. Zaheer M, Giri CC. Enhanced diterpene lactone (andrographolide) production from elicited adventitious root cultures of Andrographis paniculata. Res Chem Intermed. 2017; 43:2433–44. https://doi.org/10.1007/s11164-016-2771-9
  24. 24. Cusido RM, Onrubia M, Sabater-Jara AB. A rational approach to improving the biotechnological production of taxanes in plant cell cultures of Taxus spp. Biotechnol Adv. 2014;32:1157–67. https://doi.org/10.1016/j.biotechadv.2014.03.002
  25. 25. Gandi S, Rao K, Chodisetti B, Giri A. Elicitation of andrographolide in the suspension cultures of Andrographis paniculata. Appl Biochem Biotechnol. 2012;168:1729–38. https://doi.org/10.1007/s12010-012-9892-4
  26. 26. Lu X, Tang K, Li P. Plant metabolic engineering strategies to produce pharmaceutical terpenoids. Front Plant Sci. 2016;7(2016). https://doi.org/10.3389/fpls.2016.01647
  27. 27. Vijayakumar J, Ponmanickam P, Samuel P. Metabolite profiles of arsenic tolerant plants regenerated from stem calli of Andrographis paniculata (Burm.f.) Nees using HPLC and 1D 1H NMR. Am. J Biochem Biotechnol. 2017;13:195–207. https://doi.org/10.3844/ajbbsp.2017.195.207
  28. 28. Anna A, Nagella P. Heavy metal stress influence the andrographolide content, phytochemicals and antioxidant activity of A. paniculata. Plant Sci Today. 2012;8. https://doi.org/10.14719/pst.2021.8.2.1034
  29. 29. Ahmed N, Nagella P. Effect of elicitors on andrographolide content in cell suspension cultures of A. paniculata. J Appl Biol Biotechnol. 2023; 11:198-203. https://doi.org/10.7324/JABB.2023.110220
  30. 30. Zaheer M, Giri CC. Multiple shoot induction and jasmonic versus salicylic acid driven elicitation for enhanced andrographolide production in Andrographis paniculata. Plant Cell Tiss Org Cult. 2015;122:553–63. https://doi.org/10.1007/s11240-015-0787-2
  31. 31. Singleton VL, Orthofer R, Lamuela-Raventós RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent. Oxid Antioxid Part A. 1999;152–78. https://doi.org/10.1016/S0076-6879(99)99017-1
  32. 32. Zhishen J, Mengcheng T, Jianming W. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chem. 1999;64:555–59. https://doi.org/10.1016/S0308-8146(98)00102-2
  33. 33. Shen Q, Zhang B, Xu R, Wang Y, Ding X, Li P. Antioxidant activity in vitro of the selenium-contained protein from the Se-enriched Bifidobacterium animalis 01. Anaerobe. 2010;16:380–86. https://doi.org/10.1016/j.anaerobe.2010.06.006
  34. 34. Chew YL, Goh JK, Lim YY. Assessment of in vitro antioxidant capacity and polyphenolic composition of selected medicinal herbs from Leguminosae family in Peninsular Malaysia. Food Chem. 2009;116:13–18. https://doi.org/10.1016/j.foodchem.2009.01.091
  35. 35. Finnegan PM, Chen W. Arsenic toxicity: the effects on plant metabolism. Front Physiol. 2012;3:182. https://doi.org/10.3389/fphys.2012.00182
  36. 36. Azevedo R, Rodriguez E. Phytotoxicity of mercury in plants: A Review. J Bot. 2012;1–6. https://doi.org/10.1155/2012/848614
  37. 37. Savage DF, Stroud RM. Structural basis of aquaporin inhibition by mercury. J Mol Biol. 2007;368:607–17. https://doi.org/10.1016/j.jmb.2007.02.070
  38. 38. Manquián-Cerda K, Escudey M, Zúñiga G, Arancibia-Miranda N, Molina M, Cruces E. Effect of cadmium on phenolic compounds, antioxidant enzyme activity and oxidative stress in blueberry (Vaccinium corymbosum L.) plantlets grown in vitro. Ecotoxicol Environ Safety. 2016;133:316–26. https://doi.org/10.1016/j.ecoenv.2016.07.029
  39. 39. Lafuente A, Pérez‐Palacios P, Doukkali B. Unraveling the effect of arsenic on the model Medicago ensifer interaction: a transcriptomic meta‐analysis. New Phytol. 2015; 205:255–72. https://doi.org/10.1111/nph.13009
  40. 40. Siatka T. Production of anthocyanins in callus cultures of Angelica archangelica. Natur Prod Commun. 2018;13. https://doi.org/10.1177/1934578X1801301219
  41. 41. Banadka A, Nagella P. Effect of heavy metals on germination, biochemical, and L-DOPA content in Mucuna pruriens (L.) DC. J Appl Biol Biotechnol. 2022. https://doi.org/10.7324/JABB.2022.100613
  42. 42. Murthy HN, Dalawai D. Biotechnological production of diterpenoid lactones from cell and organ cultures of Andrographis paniculata. Appl Microbiol Biotechnol. 2021;105:7683–94. https://doi.org/10.1007/s00253-021-11599-y
  43. 43. Wu S, Chen W, Lu S, Zhang H, Yin L. Metabolic engineering of shikimic acid biosynthesis pathway for the production of shikimic acid and its branched products in microorganisms: Advances and prospects. Molecules. 2022;27. https://doi.org/10.3390/molecules27154779
  44. 44. Rezaie M, Farhoosh R, Iranshahi M. Ultrasonic-assisted extraction of antioxidative compounds from Bene (Pistacia atlantica subsp. mutica) hull using various solvents of different physicochemical properties. Food Chem. 2015;173:577–83. https://doi.org/10.1016/j.foodchem.2014.10.081
  45. 45. Pirbalouti AG, Nekoei M, Rahimmalek M, Malekpoor F. Chemical composition and yield of essential oil from lemon balm (Melissa officinalis L.) under foliar applications of jasmonic and salicylic acids. Biocatal Agric Biotechnol. 2019;19:101144. https://doi.org/10.1016/j.bcab.2019.101144
  46. 46. Karimkhani MM, Salarbashi D, Sefidy S, Mohammadzadeh A. Effect of extraction solvents on lipid peroxidation, antioxidant, antibacterial and antifungal activities of Berberis orthobotrys Bienerat ex C.K. Schneider. J Food Measur. Char. 2019;13:357–67. https://doi.org/10.1007/s11694-018-9951-9
  47. 47. Tan WSD. Andrographolide simultaneously augments Nrf2 antioxidant defense and facilitates autophagic flux blockade in cigarette smoke-exposed human bronchial epithelial cells. Toxicol Appl Pharmacol. 2018;360:120–30. https://doi.org/10.1016/j.taap.2018.10.005
  48. 48. Li B, Jiang T, Liu H. Andrographolide protects chondrocytes from oxidative stress injury by activation of the Keap1–Nrf2–Are signalling pathway. J Cell Physiol. 2019;234:561–71. https://doi.org/10.1002/jcp.26769
  49. 49. Mussard E, Cesaro A, Lespessailles E, Legrain B, Berteina-Raboin S, Toumi H. Andrographolide, a natural antioxidant: An Update. Antioxidants (Basel). 2019;8. https://doi.org/10.3390/antiox8120571
  50. 50. Tohge T, Yonekura-Sakakibara K, Niida R. Watanabe-Takahashi A, Saito K. Phytochemical genomics in Arabidopsis thaliana: A case study for functional identification of flavonoid biosynthesis genes. Pure Appl Chem. 2007;79:811–23. https://doi.org/10.1351/pac200779040811

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