2024, Issue 1, Volume 16

VARIOUS APPROACHES FOR ENHANCING THE ARTEMISININ CONTENT AND AROMATIC OIL OF ARTEMISIA ANNUA L.

Shivani*, Dutt B. and Sood M.

Department of Forest Products, Dr Yashwant Singh Parmar University of Horticulture and Forestry, Nauni, Solan Himachal Pradesh. India. Pi n-173230

Email:  shivanibains7@gmail.com

Received-06.01.2024, Revised-17.01.2024, Accepted-30.01.2024

Abstract: The Artemisia annua L. plant is well-known for yielding “artemisinin,” a crucial ingredient in the treatment of malaria. Artemisinin, isolated from Artemisia annua L., is potentially being effective against multidrug-resistant strains of the malarial parasite, Plasmodium. The essential oils of the plant work well to keep mosquitoes away. The majority of efforts have been focused on increasing the content of artemisinin. Since wild Artemisia spp. produce limited amount of this metabolite, the artemisinin-based drugs remain exorbitantly costly despite tremendous efforts. An overview of the several initiatives to enhance these antimalarial chemicals is provided in this article.

Keywords: Artemisia annua, Artemisinin, Biotechnological tools, Fertilizers, Phytohormones

References

Aftab, A., Mansoor, M., Khan, A., Idrees, M., Naeem, M. and Moinuddin (2010). Salicylic acid acts as potent enhancer of growth, photosynthesis and artemisinin production in Artemisia annua L. Journal of Crop Science and Biotechnology, 13:183-188.

Google Scholar

Aftab, T., Mansoor, M., Khan, A., Idrees, M., Naeem, M., Hashmi, N. and Moinuddin (2011). Effect of Giberellic acid on growth, photosynthetic efficiency and artemisinin content of Artemisia annua L. Medicinal and Aromatic Plant Science and Biotechnology, 5(1):25-29.

Google Scholar

Al-Khayri JM, Sudheer WN, Lakshmaiah VV, Mukherjee E, Nizam A, Thiruvengadam M, Nagella P, Alessa FM, Al-Mssallem MQ and Rezk AA. (2022). Biotechnological approaches for production of artemisinin, an anti-malarial drug from Artemisia annua L. Molecules, 27, 3040.

Google Scholar

Arora, M., Saxena, P., Choudhary, D.K., Abdin, M.Z. and Varma, A. (2016). Dual symbiosis between Piriformospora indica and Azotobacter chroococcum enhances the artemisinin content in Artemisia annua L. World Journal of Microbiology and Biotechnology 32:1-10.

Google Scholar

Ayanoglu F, Mert A and Kirici S. (2002). The Effects of Different Nitrogen Doses on Artemisia annua L. Journal of Herbs, Spices and Medicinal Plants, 9(4):399-404.

Google Scholar

Ayman EL, Sabagh, Islam MS, Hossain A, Iqbal MA, Mubeen M, Waleed M, Reginato M, Battaglia M, Ahmed S, Rehman A, Arif M, Athar HUR, Ratnasekera D, Danish S, Raza MA, Rajendran K, Mushtaq M, Skalicky M, Brestic M, Soufan W, Fahad S, Pandey S, Kamran M, Datta R and Abdelhamid MT. (2022). Phytohormones as growth regulator during abiotic stress tolerance in plants. Frontiers in Agronomy 4:1-16. https://doi.org/10.3389/fagro.2022.765068

Google Scholar

Bi B, Tang J, Han S, Guo J and Miao Y. (2017). Sinapic acid or its derivatives interfere with abscisic acid homeostasis during Arabidopsis thaliana seed germination. BMC Plant Biology 17(1):99.

Google Scholar

Billa AR, Flamini G, Morgenni F, Isacchi B and Franco F. (2008). GC-MS analysis of the volatile constituents of essential oil and aromatic waters of Artemisia annua L. at different developmental stages. Natural Product Communications, 3: 2075-2078.

Google Scholar

Brisibe EA, Uyoh EA, Brisibe F, Magakhaes PM and Ferreira JFS. (2008). Building a golden triangle for the production and use of artemisinin derivatives against malaria in African Journal of Biotechnology, 7(25):4884-4896.

Google Scholar

Chen M, Yan T, Shen Q, Lu X, Pan Q, Huang Y, Tang Y, Fu X, Liu M, Jiang W, Lv Z, Shi P, Hao X, Zhang L, Li L and Tang K. (2017). Glandular trichome-specific wrky 1 promotes artemisinin biosynthesis in Artemisia annua. New Phytologist 214(1):304-316. https://doi.org/10.1111/nph.14373

Google Scholar

Cockram J, Hill C, Burns C, Arroo, RRJ, Woolley JG, Flockart I and Bentley S. (2012). Screening a diverse collection of Artemisia annua germplasm accessions for the antimalarial compound, artemisinin. Plant Genetic Resources: Characterisation and Utilisation, 10(2):152–154. doi:10.1017/S1479262112000159

Google Scholar

Creelman RA and Mullet JE. (1995). Jasmonic acid distribution and action in plants: regulation during development and response to biotic and abiotic stress. Proceedings of the National Academy of Sciences of USA 92:4114-4119. https:// doi. org/ 10. 1073/ pnas. 92. 10. 4114

Google Scholar

Dai Y, Zhou WW, Meng J, Du XL, Sui YP, Dai L, Wang PQ, Huo HR and Sui F. (2017). The pharmacological activities and mechanisms of artemisinin and its derivatives: A systematic review. Medicinal Chemistry Research, 26:867–880.

Google Scholar

Davies MJ, Atkinson CJ, Burns C, Woolley JG, Hipps  NAJ, Arroo RR, Dungey N, Robinson T, Brown P, Flockart I, Hill C, Smith L and Bentley S. (2009). Enhancement of artemisinin concentration and yield in response to optimization of nitrogen and potassium supply to Artemisia annua. Annals of Botany,104(2):315-323. https://doi.org/10.1093/aob/mcp126

Google Scholar

Damtew Z, Tesfaye B and Bisrat D. (2011). Leaf essential oil and artemisinin yield of artemisia (Artemisia annua L) as influenced by harvesting age and plant population density. World Journal of Agricultural Sciences 7(4):404-412.

Google Scholar

Ewulo BS. (2005). Effect of poultry dung and cattle manure on chemical properties of clay and sandy clay loam soil. Journal of Animal Veterinary advances 4:839-841.

Google Scholar

Frey-Klett P and Garbaye J. (2005). Mycorrhizal helper bacteria: a promising model for the genomic analysis of fungal bacteria interactions. New Phytologist 168: 4–8.

Google Scholar

Fulzele DP, Heble MR and Rao PS. (1995). Production of terpenoids from Artemisia annua L. plantlet cultures in bioreactor. Journal of Biotechnology 40:139-143.

Google Scholar

Gaibi ZL, Roviqowati F, Yunus A and Purwanto E. (2019). Vermicompost and arbuscular mycorrhiza application on growth and yield of Artemisia annua in the low land. IOP Conference Series: Earth and Environmental Science 250:1-6.

Google Scholar

Garbaye J. (1994). Helper bacteria: a new dimension to the mycorrhizal symbiosis. New Phytologist 128:197–210.

Google Scholar

Ghassemi B, Nayeri FD and Hosseini R. (2021). The effects of chitosan nanoparticles on genes expression of artemisinin synthase in suspension culture of Artemisia annua L: A comparative study. International Journal of Advanced Biological and Biomedical Research 9 (2):190-203. Doi:10.22034/ijabbr.2021.523524.1343

Google Scholar   

Huang JH, Tan JF, Jie HK and Zeng R. (2011). Effects of inoculating arbuscular mycorrhizal fungi on Artemisia annua growth and its officinal components. The journal of applied ecology 22(6):1443-9.

Google Scholar

Ikram NKBK and Simonsen HT. (2017). A review of biotechnological artemisinin production in plants. Frontiers in Plant Science 8: 1966.

Google Scholar

Jain DC, Jain HC, Mathur AK, Gupta AK, Gupta MM, Singh AK, Verma RK Gupta AP and Kumar S. (1996). Isolation of high artemisinin-yirlding clones of Artemisia annua. Phytochemistry 43(5):993-1001.

Google Scholar

Jha P, Ram M, Khan MA, Kiran U, Mahmooduzzafar and Abdin MZ. (2011). Impact of organic manure and chemical fertilizers on artemisinin content and yield of Artemisia annua L. Industrial crops and products 33:296-301.

Google Scholar

Kaminska M. (2021). Role and activity of jasmonates in plants under in vitro conditions. Plant Cell, Tissue and Organ Culture  146:425-447. https://doi.org/10.1007/s11240-021-02091-6

Google Scholar

Kapoor R, Chaudhary V and Bhatnagar AK. (2007). Effects of arbuscular mycorrhiza and phosphorus application on artemisinin concentration in Artemisia annua L. Mycorrhiza 17:581–587.

Google Scholar

Kuntyastuti H, Sutrisno S and Ayu Dwi Lestari S. (2020). Effect of application of organic and inorganic fertilizer on soybean yield in lowland vertisols, Journal of Degraded and Mining Lands Management 8(1): pp. 2439–2450.

Google Scholar  

Liu Q, Yang ZY, Deng ZB, Sa G, Wang X. (1988). Preliminary analysis on chemical constituents of essential oil from inflorescence of of Artemisia annua L. Acta Botanica Sinica (Zhiwu Xuebao) 30:223-225.

Google Scholar

Liu H, He W, Yao X, Yan X, Wang X, Peng B, Zhang Y, Shao J, Hu X, Miao Q, Li  L and Tang K. (2023). The Light- and Jasmonic Acid-Induced AaMYB108-like Positive Regulates the Initiation of Glandular Secretory Trichome in Artemisia annua L. International Journal of Molecular Sciences 24:1-13.12929. https:// doi.org/10.3390/ijms241612929

Google Scholar

Ma C, Wang H, Lu X, Xu G and Liu B. (2008). Metabolic fingerprinting investigation of Artemisia annua L. in different stages of development by gas chromatography and gas chromatographymass spectrometry. Journal of Chromatography A1186:412-419.

Google Scholar

Ma D, Li G, Alejos-Gonzalez F, Zhu Y, Xue Z and Wang A. (2017). Overexpression of a type I isopentenyl pyrophosphate isomerase of Artemisia annua in the cytosol leads to high arteannuin B production and artemisinin increase. The Plant Journal 91:466-479. 10.1111/tpj.13583

Google Scholar

Mahanty T, Bhattacharjee S, Goswami M, Bhattacharyya P, Das B, Ghosh A and Tribedi P. (2016). Biofertilizers: a potential approach for sustainable agriculture development. Environmental Science and pollution Research: 1-21. DOI 10.1007/s11356-016-8104-0

Google Scholar

Malik AA, Ahmad J, Mir SR, Ali M and MZ Abdin. (2009). Influence of chemical and biological treatments on volatile oil composition of Artemisia annua Linn. Industrial Crops and Products 30:380–383.

Google Scholar

Malik AA, Ahmed J, Suryapani S, Abdin MZ, Mir SR and Ali M. (2012). Volatiles of Artemisia annua L. as influenced by soil applications of organic residues. Research Journal of Medicinal Plants  6(6):433-440.

Google Scholar

Malusa E and Vassilev N. (2014). A contribution to set a legal framework for biofertilisers. Applied Microbiology and Biotechnology 98(15):6599–6607.

Google Scholar

Mandal S, Upadhyay S, Wajid S, Ram M, Jain DC, Singh VP, Abdin MZ and  Kapoor R. (2014). Arbuscular mycorrhiza increase artemisinin accumulation in Artemisia annua by higher expression of key biosynthesis genes via enhanced jasmonic acid levels. Mycorrhiza:1-13.DOI 10.1007/s00572-014-0614-3

Google Scholar

Mercke P, Bengtsson M, Bouwmeester HJ, Posthumus MA and Brodelius PE. (2000). Molecular cloning, expression, and characterization of amorpha-4,11-diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L. Archives of Biochemistry and Biophysics 381 173-180. 

Google Scholar

Moyin- Jesu EI. (2007). Use of plant residues for improving soil fertility, pod nutrients, root growth and pod weight of Okra (Abelmoshchus esculentum L.) Bioresource Technology 98: 2057-2064.

Google Scholar

Namul A, Bazira J, Casim TU and Engeu PO. (2018). A review of various efforts to increase artemisinin and other antimalarial compounds in Artemisia annua L. plant. Cogent Biology 4:1-8. DOI: 10.1080/23312025.2018.1513312

Google Scholar

Omer EA, Abou Hussein E, Hendawy SF, Ezz El-din, Azza A and El-Gendy AG. (2014). Effect of nitrogen and potassium fertilizers on growth, yield, essential oil and artemisinin of Artemisia Annua L Plant. International Research Journal of Horticulture2(2):11-20.

Google Scholar

Ozguven M, Sener B, Orhan I, Sekeroglu N, Kirpik M, Kartal M, Pesin I and Kaya Z. (2008). Effects of varying nitrogen doses on yield, yield components and artemisinin content of Artemisia annua L. Industrial crops and products 27:60-64.

Google Scholar

Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, Leavell MD, Tai A, Main A and Eng D. (2013). High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496:528-532.

Google Scholar

Pauwels L, Morreel K, De Witte E, Lammertyn F, Van Montagu M, Boerjan W, Inze D and Goossens A. (2008). Mapping methyl jasmonate-mediated transcriptional reprogramming of metabolism and cell cycle progression in cultured Arabidopsis cells. Proceedings of the National Academy of Sciences 105:1380-1385. 10.1073/pnas.0711203105

Google Scholar

Perotto S, Bonfante P. (1997). Bacterial associations with mycorrhizal fungi: close and distant friends in the rhizosphere. Trends in Microbiology 12: 496–501.

Google Scholar

Rapparini F, Lludia J and Penuelas J. (2008). Effect of Arbuscular mycorrhizal (AM) colonization on terpene emission and content of Artemisia annua L. Plant Biology 10:108-122.

Google Scholar

Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL Ndungu JM, Ho KA, Eachus RA, Ham TS and Kirby J. (2006). Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440:940-943.

Google Scholar

Sa G, Mi M, He-chun Y, Ben-ye L, Guo-feng L and Kang C. (2001). Effects of ipt gene expression on the physiological and chemical characteristics of Artemisia annua L. Plant Science 160:691-698.

Google Scholar

Mohamed SM, Mohamed YFY, Saleh DM and Abou-El- Ghait EM. (2023). Influence of Planting Distances in Presence of  Chemical Fertilization And Compost on Growth, Essential Oil , Artemisinin Content and Chemical Constituents of Artemisia annua L. Plant. Journal of Plant Production 14 (2):31-43.

Google Scholar

Saxena A and Singh JN. (1998). Effect of irrigation, mulch and nitrogen on yield and composition of Japanese mint (Mentha arvensis) oil. Indian Journal of Agronomy 43:179-182.

Google Scholar

Schramek N, Wang H, Ro misch-Margl W, Keil B, Radykewicz T, Winzenho rlein B, Beerhues L, Bacher A, Rohdich F, Gershenzon J, Liu B and Eisenreich W. (2010). Artemisinin biosynthesis in growing plants of Artemisia annua. A13CO2 study. Phytochemistry 71:179-187.

Google Scholar

Sharma G and Agrawal V. (2013). Marked enhancement in the artemisinin content and biomass productivity in Artemisia annua L. shoots co-cultivated with Piriformospora indica World Journal of Microbiology and Biotechnology 29:1133–1138.DOI 10.1007/s11274-013-1263-y

Google Scholar

Shen Q, Lu X, Yan T, Fu X, Lv Z, Zhang F and Tang K. (2016). The jasmonate-responsive Aa MYC 2 transcription factor positively regulates artemisinin biosynthesis in Artemisia annua. New Phytologist 210:1269-1281. https:// doi. org/ 10. 1111/ nph. 13874

Google Scholar

Singh M. (2000). Effect of nitrogen, phosphorous and potassium nutrition on herb, oil and artemisinin yield of Artemisia annua  under semi-rid tropical conditions. Journal of Medicinal  and Aromatic Plants Sciences 22:368-369.

Google Scholar

Smith TC, Weathers PJ and Cheetham RD. (1997). Effects of gibberallic acid on hairy root cultures of artemisinin yield in Artemisia annua growth and artemisinin production. In Vitro Cellular and  Development Biology 33:75-79.

Google Scholar

Sun LR, Wang YB, He SB and Hao FS. (2018). Mechanisms for abscisic acid inhibition of root growth. Plant Signaling and Behavior 13(9) e1500069. doi: 10.1080/15592324.2018.1500069

Google Scholar

Teoh KH, Polichuk DR, Reed DW, Nowak G and Covello PS. (2006). Artemisia annua L. (Asteraceae) trichome-specific cDNAs reveal CYP71AV1, a cytochrome P450 with a key role in the biosynthesis of the antimalarial sesquiterpene lactone artemisinin. Federation of European Biochemical Societies Letters 580:1411-1416.

Google Scholar

Tian J, Feng W and He B. (2007). Study on volatile constituents of herba Artemisia annua and its preparation by GC-MS. Shizen Guoyi Guoyao 18:1840-1842.

Google Scholar

Towler MJ and Weathers PJ. (2007). Evidence of artemisinin production from IPP stemming from both the mevalonate and the nonmevalonate pathways. Plant Cell Reports 26:2129-2136.

Google Scholar

Verma RK, Chauhan A, Verma RS and Gupta AK. (2011). Influence of planting date on growth, artemisinin yield, seed and oil yield of Artemisia annua L. under temperate climate conditions. Industrial crops and products Industrial crops and products Industrial crops and products 34:860-864. doi.org/10.1016/j.indcrop.2011.02.004

Google Scholar

Verma S, Varma A, Rexer KH, Kost G, Sarbhoy A, Bisen P, Butehorn B and Franken P. (1998). Piriformospora indica, gen. nov. sp. nov., a new root-colonizing fungus. Mycologia 95:896–903.

Google Scholar

Wang HH, Ma CF and Li ZQ. (2010). Effects of exogenous methyl jasmonate on artemisinin biosynthesis and secondary metabolites in Artemisia annua L. Industrial Crops and Products 31(2):214-218.

Google Scholar

Weathers PJ, Bunk G and Mccoythe MC. (2005). Effect of phytohormones on growth and artemisinin production in Artemisia annua hairy roots. In Vitro Cellular and Biology-Plant 41:47-53. DOI: 10.1079/IVP2004604

Google Scholar

WHO. (2005). Susceptibility of Plasmodium falciparum to antimalarial drugs. Reports on global monitoring, 1996-2004. Geneva. World Health Organisation.pp.1-33.

Google Scholar

Woerdenbag HJ, Bos R, Salomons MC, Hendriks H, Pras N and Malingre TM. (1993). Volatile constituents of Artemisia annua L. (Asteraceae). Flavour and Fragrance Journal 8:131-137.

Google Scholar

Wright CW. (2002). Artemisia. Taylor and Francis Inc., New York.

Google Scholar

Wyk BE and Wink M. (2004). Medicinal Plants of the World. Timber Press, Portland OR. P.188.

Google Scholar

Yuan M, Shu G, Zhou J, He P, Xiang L, Yang C, Chen M, Liao Z and Zhang F. (2022). AabHLH113 integrates jasmonic acid and abscisic acic signaling to positively regulate artemisinin biosynthesis in Artemisia annua. New Phytologists 237:885-899. https://doi.org/10.1111/nph.18567

Google Scholar

Zhang F, Lu X, Lv Z, Zhang L, Zhu M and Jiang W. (2013). Overexpression of the Artemisia Orthologue of ABA Receptor, AaPYL9, Enhances ABA Sensitivity and Improves Artemisinin Content in Artemisia annua L. PLoS ONE 8(2): e56697. https://doi.org/10.1371/journal.pone.0056697

Google Scholar

Zhao L, Zhu Y, Jia H, Han Y, Zheng X, Wang M and Feng W. (2022). From Plant to Yeast-Advances in Biosynthesis of Artemisinin. Molecules 27:1-23. DOI:https:// doi.org/10.3390/molecules27206888

Google Scholar