Variations in key artemisinic and other metabolites throughout plant development in Artemisia annua L. for potential therapeutic use

Towler, Melissa J.; Weathers, Pamela J.

doi:10.1016/j.indcrop.2015.01.007

Cited by 51Plant biochemistry and biosynthesisSesquiterpenes and Asteraceae StudiesPhytochemical compounds biological activities

Variations in key artemisinic and other metabolites throughout plant development in Artemisia annua L. for potential therapeutic use

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Towler, Melissa J., Weathers, Pamela J.·2015·Industrial Crops and Products

DOI 10.1016/j.indcrop.2015.01.007PMC PMC4341905

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Abstract

Dried leaves of Artemisia annua show promise as an inexpensive and sustainable antimalarial therapeutic, especially for use in developing countries. Along with the potent terpene, artemisinin, many other small molecules produced by the plant seem to aid in the therapeutic response. However, little is known about the ontogenic and phenological production of artemisinin in the plant, and its plethora of other important secondary metabolites. From a consistently high artemisinin-producing A. annua clone (SAM) we extracted and analyzed by GC/MS 22 different metabolites including terpenes, flavonoids, a coumarin, and two phenolic acids as they varied during leaf development and growth of the plant from the vegetative stage through the reproductive, full flower stage. As leaves developed, the maximum amount of most metabolites was in the shoot apical meristem. Artemisinin, on the other hand, maximized once leaves matured. Leaf and apical tissues (e.g. buds, flowers) varied in their metabolite content with growth stage with maximum artemisinin and other important secondary metabolites determined to be at floral bud emergence. These results indicated that plants at the floral bud stage have the highest level of artemisinin and other therapeutic compounds for the treatment of malaria.

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Deoxyartemisinin can account for >10% of total artemisinin.
“Deoxyartemisinin can account for > 10% of total artemisinin (Towler and Weathers 2015).”
From Enhancing artemisinin content in and delivery from Artemisia annua: a review of alternative, classical, and transgenic approaches (2021) · cites this paper as Towler and Weathers 2015
The Results (§3.1.1; page unavailable) report deoxyartemisinin at less than 25% of artemisinin in young shoot tissue. That upper bound does not establish that it exceeded 10%; §3.2.1 says only that levels remained low across the measured growth stages. (LLM, conf=0.77)
Experimental — accuracy not yet measured
The amount of artemisinin varies in different cultivars of A. annua and is responsive to stage of development (peak during flowering), light intensity, and harvest time.
“The amount of artemisinin varies in different cultivars of A. annua . Its content is also responsive to the stage of development (reaching its peak during flowering), light intensity, and the harvest time (Laughlin et al. 1994; Towler and Weathers 2015).”
From Enhancing artemisinin content in and delivery from Artemisia annua: a review of alternative, classical, and transgenic approaches (2021) · cites this paper as Towler and Weathers 2015
The Discussion describes cultivar-specific differences in artemisinin content, and the Results (§3.2.1) report that leaf artemisinin peaked during floral budding. The Conclusions recommend harvesting at that stage. The paper distinguishes budding from full flowering, and although Materials and Methods (§2.1) records the light intensity used, it does not show that light intensity affects artemisinin content. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Deoxyartemisinin can account for 7.5-12% of the total measured artemisinin.
“Although not frequently measured in A. annua studies, deoxyartemisinin can account for 7.5-12% of the total measured artemisinin (Towler and Weathers 2015).”
From Enhancing artemisinin content in and delivery from Artemisia annua: a review of alternative, classical, and transgenic approaches (2021) · cites this paper as Towler and Weathers 2015
The Methods (§2.3; page unavailable) say the authors measured both deoxyartemisinin and artemisinin, and the Results (§3.2.1; page unavailable) say deoxyartemisinin remained low. Neither passage gives a deoxyartemisinin-to-artemisinin ratio or supports the specific 7.5–12% range; the copy also does not establish how frequently other studies measure it. (LLM, conf=0.78)
Experimental — accuracy not yet measured
Increased chemical variability among different plant populations has been previously documented for a number of species.
“This increased chemical variability among different plant populations have been previous documented for a number of species [33,34,35].”
From Ecdysteroid Content and Therapeutic Activity in Elicited Spinach Accessions (2020) · cites this paper as [35]

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Flavonoids from Artemisia annua L. as Antioxidants and Their Potential Synergism with Artemisinin against Malaria and Cancer
Ferreira, J., Luthria, D. L., Sasaki, T., & Heyerick, A. (2010) · Molecules · doi:10.3390/molecules15053135 · Cited by 532 · see citing works
[Standardization of propolis extract and identification of principal constituents].
Arvouet-Grand, A., Vennat, B., Pourrat, A., & Legret, P. (1994) · PubMed · Cited by 401 · see citing works
The Biosynthesis of Artemisinin (Qinghaosu) and the Phytochemistry of Artemisia annua L. (Qinghao)
Brown, G. D. (2010) · Molecules · doi:10.3390/molecules15117603 · Cited by 363 · see citing works
The Genetic Map of Artemisia annua L. Identifies Loci Affecting Yield of the Antimalarial Drug Artemisinin
Graham, I. A., Besser, K., Blumer, S., Branigan, C. A., Czechowski, T., Elias, L., Guterman, I., Harvey, D., Isaac, P. G., Khan, A. M., et al. (2010) · Science · doi:10.1126/science.1182612 · Cited by 348 · see citing works
Seasonal Variation of Artemisinin and its Biosynthetic Precursors in Plants of Artemisia annua of Different Geographical Origin: Proof for the Existence of Chemotypes
Wallaart, T. E., Pras*, N., Beekman, A., & Quax, W. J. (2000) · Planta Medica · doi:10.1055/s-2000-11115 · Cited by 281 · cited 2× · see citing works
“annua has two main chemotypes with one producing mainly artemisinin and the other producing mainly artemisinic acid, so such discrepancies are reasonable (Wallaart et al. 2000; Wu et al. 2011).”
Background
Dissection of the phytohormonal regulation of trichome formation and biosynthesis of the antimalarial compound artemisinin in Artemisia annua plants
Maes, L., Van Nieuwerburgh, F. C. W., Zhang, Y., Reed, D. W., Pollier, J., Vande Casteele, S. R. F., Inzé, D., Covello, P. S., Deforce, D. L. D., & Goossens, A. (2011) · New Phytologist · doi:10.1111/j.1469-8137.2010.03466.x · Cited by 240 · see citing works
Global characterization of Artemisia annua glandular trichome transcriptome using 454 pyrosequencing
Wang, W., Wang, Y., Zhang, Q., Qi, Y., & Guo, D. (2009) · BMC Genomics · doi:10.1186/1471-2164-10-465 · Cited by 224 · see citing works
Cytokinins Mediate Resistance againstPseudomonas syringaein Tobacco through Increased Antimicrobial Phytoalexin Synthesis Independent of Salicylic Acid Signaling
Großkinsky, D. K., Naseem, M., Abdelmohsen, U. R., Plickert, N., Engelke, T., Griebel, T., Zeier, J., Novák, O., Strnad, M., Pfeifhofer, H. W., et al. (2011) · PLANT PHYSIOLOGY · doi:10.1104/pp.111.182931 · Cited by 211 · see citing works
Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin
Svensson, & Ashton (1999) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.1999.00044.x · Cited by 207 · see citing works
Artemisinin production in Artemisia annua: studies in planta and results of a novel delivery method for treating malaria and other neglected diseases
Weathers, P. J., Arsenault, P. R., Covello, P. S., McMickle, A., Teoh, K. H., & Reed, D. W. (2010) · Phytochemistry Reviews · doi:10.1007/s11101-010-9166-0 · Cited by 202 · see citing works
Self-citation
The Biological Activities of 20 Nature Identical Essential Oil Constituents
van Zyl, R. L., Seatlholo, S. T., van Vuuren, S. F., & Viljoen, A. M. (2006) · Journal of Essential Oil Research · doi:10.1080/10412905.2006.12067134 · Cited by 190 · see citing works
Antimalarial activity of Artemisia annua flavonoids from whole plants and cell cultures
Liu, K. C.-S., Yang, S., ROBERTS, M. F., Elford, B. C., & Phillipson, J. D. (1992) · Plant Cell Reports · doi:10.1007/bf00236389 · Cited by 189 · see citing works
Common dietary flavonoids inhibit the growth of the intraerythrocytic malaria parasite
Lehane, A. M., & Saliba, K. J. (2008) · BMC Research Notes · doi:10.1186/1756-0500-1-26 · Cited by 175 · see citing works
Potentiation of the antimalarial activity of qinghaosu by methoxylated flavones
Elford, B. C., Roberts, M. F., Phillipson, J. D., & Wilson, R. J. M. (1987) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(87)90161-1 · Cited by 159 · see citing works
Differential accumulation of isoprenoids in glanded and glandless Artemisia annua L
Tellez, M. R., Canel, C., Rimando, A. M., & Duke, S. O. (1999) · Phytochemistry · doi:10.1016/s0031-9422(99)00308-8 · Cited by 148 · see citing works
Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria
Mueller, M. S., Runyambo, N., Wagner, I., Borrmann, S., Dietz, K., & Heide, L. E. (2004) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/j.trstmh.2003.09.001 · Cited by 146 · see citing works
PHARMACOKINETIC STUDY OF ARTEMISININ AFTER ORAL INTAKE OF A TRADITIONAL PREPARATION OF ARTEMISIA ANNUA L. (ANNUAL WORMWOOD)
RÄTH, K., Taxis, K., WALZ, G., Gleiter, C. H., Li, S.-M., & Heide, L. E. (2004) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2004.70.128 · Cited by 144 · see citing works
Dried Whole Plant Artemisia annua as an Antimalarial Therapy
Elfawal, M. A., Towler, M. J., Reich, N. G., Golenbock, D. T., Weathers, P. J., & Rich, S. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052746 · Cited by 128 · see citing works
Self-citation
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Elfawal, M. A., Towler, M. J., Reich, N. G., Weathers, P. J., & Rich, S. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1413127112 · Cited by 124 · see citing works
Self-citation
Trichome Dynamics and Artemisinin Accumulation during Development and Senescence ofArtemisia annuaLeaves
Lommen, W. J., Schenk, E., Bouwmeester, H. J., & Verstappen, F. W. (2006) · Planta Medica · doi:10.1055/s-2005-916202 · Cited by 119 · see citing works
Metabolic fingerprinting investigation of Artemisia annua L. in different stages of development by gas chromatography and gas chromatography–mass spectrometry
Ma, C., Wang, H., Lu, X., Xu, G., & Liu, B. (2007) · Journal of Chromatography A · doi:10.1016/j.chroma.2007.09.023 · Cited by 103 · see citing works
Anti-inflammatory effect and modulation of cytochrome P450 activities by Artemisia annua tea infusions in human intestinal Caco-2 cells
de Magalhães, P. M., Dupont, I. E., Hendrickx, A., Joly, A., Raas, T., Dessy, S., Sergent, T., & Schneider, Y. (2012) · Food Chemistry · doi:10.1016/j.foodchem.2012.02.195 · Cited by 98 · see citing works
Artemisinin, Related Sesquiterpenes, and Essential Oil inArtemisia annuaDuring a Vegetation Period in Vietnam
Woerdenbag, H., Pras, N., Chan, N., Bang, B., Bos, R., van Uden, W., Van Y, P., Van Boi, N., Batterman, S., & Lugt, C. (1994) · Planta Medica · doi:10.1055/s-2006-959474 · Cited by 97 · cited 1× · see citing works
“Developmentally, maximum artemisinin production is usually observed at floral bud formation, but before full flowering (Ferreira 2008; Ferreira and Janick 1996; Ferreira et al. 1995; Ma et al. 2008; Nair et al. 2013; Singh et al. 1988; Woerdenbag et al. 1994).”
Background
Anti-Plasmodial Polyvalent Interactions in Artemisia annua L. Aqueous Extract – Possible Synergistic and Resistance Mechanisms
Suberu, J., Gorka, A. P., Jacobs, L., Roepe, P. D., Sullivan, N., Barker, G. C., & Lapkin, A. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080790 · Cited by 92 · see citing works
Distribution of artemisinin and bioactive flavonoids from Artemisia annua L. during plant growth
Baraldi, R., Isacchi, B., Predieri, S., Marconi, G., Vincieri, F. F., & Bilia, A. R. (2008) · Biochemical Systematics and Ecology · doi:10.1016/j.bse.2007.11.002 · Cited by 77 · see citing works
DMSO triggers the generation of ROS leading to an increase in artemisinin and dihydroartemisinic acid in Artemisia annua shoot cultures
Mannan, A., Liu, C., Arsenault, P. R., Towler, M. J., Vail, D. R., Lorence, A., & Weathers, P. J. (2010) · Plant Cell Reports · doi:10.1007/s00299-009-0807-y · Cited by 75 · see citing works
Self-citation
Evalutation ofArtemisia annuaStrains for Higher Artemisinin Production*
Singh, A., Vishwakarma, R., & Husain, A. (1988) · Planta Medica · doi:10.1055/s-2006-962515 · Cited by 73 · cited 2× · see citing works
“Developmentally, maximum artemisinin production is usually observed at floral bud formation, but before full flowering (Ferreira 2008; Ferreira and Janick 1996; Ferreira et al. 1995; Ma et al. 2008; Nair et al. 2013; Singh et al. 1988; Woerdenbag et al. 1994).”
Background
Dried-leaf Artemisia annua : A practical malaria therapeutic for developing countries?
Weathers, P. J. (2014) · World Journal of Pharmacology · doi:10.5497/wjp.v3.i4.39 · Cited by 72 · see citing works
Self-citation
The complexity of medicinal plants: The traditional Artemisia annua formulation, current status and future perspectives
van der Kooy, F., & Sullivan, S. E. (2013) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2013.08.021 · Cited by 66 · see citing works
The Flavonoids Casticin and Artemetin Are Poorly Extracted and Are Unstable in an Artemisia annua Tea Infusion
Weathers, P. J., & Towler, M. J. (2012) · Planta Medica · doi:10.1055/s-0032-1314949 · Cited by 55 · see citing works
Self-citation
Morphogenetic variation for artemisinin and volatile oil in Artemisia annua
Gupta, S. K., Singh, P., Bajpai, P., Ram, G., Singh, D., Gupta, M. M., Jain, D. C., Khanuja, S. P., & Kumar, S. (2002) · Industrial Crops and Products · doi:10.1016/s0926-6690(02)00049-3 · Cited by 55 · see citing works
Pharmacokinetics of artemisinin delivered by oral consumption of Artemisia annua dried leaves in healthy vs. Plasmodium chabaudi-infected mice
Weathers, P. J., Elfawal, M. A., Towler, M. J., Acquaah-Mensah, G. K., & Rich, S. M. (2014) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2014.03.037 · Cited by 54 · see citing works
Self-citation
Relationship of Artemisinin Content of Tissue-Cultured, Greenhouse-Grown, and Field-Grown Plants ofArtemisia annua1
Ferreira, J., Simon, J. E., & Janick, J. (1995) · Planta Medica · doi:10.1055/s-2006-958098 · Cited by 53 · see citing works
Artemisinin and Sesquiterpene Precursors in Dead and Green Leaves of Artemisia annua L. Crops
Lommen, W. J. M., Elzinga, S., Verstappen, F. W. A., & Bouwmeester, H. J. (2007) · Planta Medica · doi:10.1055/s-2007-981567 · Cited by 42 · see citing works
Differentially Expressed Genes during Contrasting Growth Stages of Artemisia annua for Artemisinin Content
Nair, P., Misra, A., Singh, A., Shukla, A. K., Gupta, M. M., Gupta, A. K., Gupta, V., Khanuja, S. P. S., & Shasany, A. K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060375 · Cited by 38 · see citing works
Changes in key constituents of clonally propagated Artemisia annua L. during preparation of compressed leaf tablets for possible therapeutic use
Weathers, P. J., & Towler, M. J. (2014) · Industrial Crops and Products · doi:10.1016/j.indcrop.2014.08.033 · Cited by 36 · see citing works
Self-citation
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Singh, M., & Chaturvedi, R. (2010) · Plant Cell Tissue and Organ Culture (PCTOC) · doi:10.1007/s11240-010-9774-9 · Cited by 34 · see citing works
Volatile fingerprints of artemisinin‐rich Artemisia annua cultivars by headspace solid‐phase microextraction gas chromatography/mass spectrometry
Reale, S., Fasciani, P., Pace, L. G., Angelis, F. D., & Marcozzi, G. (2011) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.5155 · Cited by 32 · see citing works
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Aftab, T., Ferreira, J. F., Khan, M. M., & Naeem, M. (2014) · Springer Berlin Heidelberg · doi:10.1007/978-3-642-41027-7 · Cited by 31 · see citing works
Essential Oil Constituents ofArtemisia annuaDuring Different Growth Periods at Monsoon Conditions of Subtropical North Indian Plains
Bagchi, G. D., Haider, F., Dwivedi, P. D., Singh, A. D., & Naqvi, A. A. (2003) · Journal of Essential Oil Research · doi:10.1080/10412905.2003.9712131 · Cited by 30 · see citing works
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Xia, B., Feng, M., Xu, G., Xu, J., Li, S., Chen, X., Ding, L., & Zhou, Y. (2014) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf5009204 · Cited by 28 · see citing works
Composition and antimicrobial activity of essential oil from the aerial part of Artemisia annua
Li, Y., Hu, H., Zheng, X., Jihua, Z., & Liu, L. (2011) · Journal of Medicinal Plants Research · doi:10.5897/jmpr.9000391 · Cited by 26 · see citing works
The Surprising Efficiency of Artemisia annua Powder Capsules
Onimus, M. (2013) · Medicinal & Aromatic Plants · doi:10.4172/2167-0412.1000125 · Cited by 25 · see citing works
Chemotype-dependent Metabolic Response to Methyl Jasmonate Elicitation inArtemisia annua
Wu, W., Yuan, M., Zhang, Q., Zhu, Y., Li, Y., Wang, W., Yan, Q., & Guo, D. (2011) · Planta Medica · doi:10.1055/s-0030-1250744 · Cited by 24 · see citing works
Whole Plant Approaches to Therapeutic Use of Artemisia annua L. (Asteraceae)
Weathers, P. J., Reed, K., Hassanali, A., Lutgen, P., & Engeu, P. O. (2013) · Springer eBooks · doi:10.1007/978-3-642-41027-7_4 · Cited by 18 · see citing works
Self-citation
Conceptual Process Synthesis for Recovery of Natural Products from Plants: A Case Study of Artemisinin from Artemisia annua
Malwade, C. R., Qu, H., Rong, B., & Christensen, L. P. (2013) · Industrial & Engineering Chemistry Research · doi:10.1021/ie302495w · Cited by 16 · see citing works
Seasonal and Post-harvest Accumulation of Artemisinin, Artemisinic Acid, and Dihydroartemisinic Acid in Three Accessions of Artemisia annua Cultivated in West Virginia, USA
Ferreira, J. (2008) · Planta Medica · doi:10.1055/s-2008-1075155 · Cited by 12 · see citing works
Essential oil composition of Artemisia annua L. at different growth stages
Rana, V. S., Abirami, K., Blázquez, M. A., & Maiti, S. (2013) · Journal of Spices and Aromatic Crops · Cited by 10 · see citing works
Comparison of terpene components from flowers of Artemisia annua
Zhan-nan, Y., Zhu, S.-Q., & Yu, Z. (2012) · Bangladesh Journal of Pharmacology · doi:10.3329/bjp.v7i2.10815 · Cited by 9 · see citing works
Comparative profiling and dynamics of artemisinin related metabolites using efficient protocol and expression of biosynthetic pathway genes during developmental span of two elite varieties of Artemisia annua L
Yadav, R. K., Sangwan, R. S., Srivastava, A. K., Maurya, S., & Sangwan, N. S. (2013) · Journal of Plant Biochemistry and Biotechnology · doi:10.1007/s13562-013-0249-z · Cited by 8 · see citing works

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Ferreira FS Janick J Janick J 1996 Distribution of artemisinin in Artemisia annua Progress in new crops ASHA Press Arlington VA 579 584

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Comparative profiling and dynamics of artemisinin related metabolites using efficient protocol and expression of biosynthetic pathway genes during developmental span of two elite varieties of Artemisia annua L
Yadav, R. K., Sangwan, R. S., Srivastava, A. K., Maurya, S., & Sangwan, N. S. (2013) · Journal of Plant Biochemistry and Biotechnology · doi:10.1007/s13562-013-0249-z · Cited by 8 · see citing works
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Weathers, P. J., Arsenault, P. R., Covello, P. S., McMickle, A., Teoh, K. H., & Reed, D. W. (2010) · Phytochemistry Reviews · doi:10.1007/s11101-010-9166-0 · Cited by 202 · see citing works
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Arsenault, P. R., Vail, D. R., Wobbe, K. K., Erickson, K., & Weathers, P. J. (2010) · PLANT PHYSIOLOGY · doi:10.1104/pp.110.162552 · Cited by 85 · see citing works
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Baraldi, R., Isacchi, B., Predieri, S., Marconi, G., Vincieri, F. F., & Bilia, A. R. (2008) · Biochemical Systematics and Ecology · doi:10.1016/j.bse.2007.11.002 · Cited by 77 · see citing works
Differentially Expressed Genes during Contrasting Growth Stages of Artemisia annua for Artemisinin Content
Nair, P., Misra, A., Singh, A., Shukla, A. K., Gupta, M. M., Gupta, A. K., Gupta, V., Khanuja, S. P. S., & Shasany, A. K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060375 · Cited by 38 · see citing works

Authors: Towler, M. J., & Weathers, P. J.
Affiliations: Worcester Polytechnic Institute (US)
Corresponding author: Weathers, Pamela J.
ORCID: Weathers, Pamela J.
Venue: Industrial Crops and Products
Publisher: Elsevier BV
Published: 2015-05
Volume: 67
Pages: 185-191
ISSN: 0926-6690 (ISSN-L)
DOI: 10.1016/j.indcrop.2015.01.007
PMC: PMC4341905
OpenAlex: W2053421361
Cited by: 51
References: 50
Citations by year: 2026: 4 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 4
FWCI: 2.75
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Industrial Crops and Products (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Worcester Polytechnic Institute
University of Massachusetts Center for Clinical and Translational Science (20110001)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Sesquiterpenes and Asteraceae Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phytochemical compounds biological activities
Keywords: Artemisia annua, artemisinin, secondary metabolites, leaf development, plant ontogeny, shoot apical meristem, terpenes, flavonoids, coumarins, phenolic acids, antimalarial compounds, plant growth stages

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Variations in key artemisinic and other metabolites throughout plant development in Artemisia annua L. for potential therapeutic use

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