Climatic Change

, Volume 132, Issue 2, pp 295–306 | Cite as

Historical and experimental evidence for enhanced concentration of artemesinin, a global anti-malarial treatment, with recent and projected increases in atmospheric carbon dioxide

  • C. Zhu
  • Q. Zeng
  • A. McMichael
  • K. L. Ebi
  • K. Ni
  • A. S. Khan
  • J. Zhu
  • G. Liu
  • X. Zhang
  • Lei Cheng
  • L.H. Ziska


Although the role of rising atmospheric carbon dioxide concentration [CO2] on plant growth and fecundity is widely acknowledged as important within the scientific community; less research is available regarding the impact of [CO2] on secondary plant compounds, even though such compounds can play a significant role in human health. At present, Artemisia annua, an annual plant species native to China, is widely recognized as the primary source of artemesinin used in artemesinin combination therapies or ACTs. ACTs, in turn, are used globally for the treatment of simple Plasmodium falciparum malaria, the predominant form of malaria in Africa. In this study, artemesinin concentration was quantified for multiple A. annua populations in China using a free-air CO2 enrichment (FACE) system as a function of [CO2]-induced changes both in situ and as a function of the foliar ratio of carbon to nitrogen (C:N). The high correlation between artemesinin concentration and C:N allowed an historical examination of A. annua leaves collected at 236 locations throughout China from 1905 through 2009. Both the historical and experimental data indicate that increases in artemesinin foliar concentration are likely to continue in parallel with the ongoing increase in atmospheric [CO2]. The basis for the [CO2]-induced increase in artemesinin is unclear, but could be related to the carbon: nutrient hypothesis of Bryant et al. (1983). Overall, these data provide the first evidence that historic and projected increases in atmospheric [CO2] may be associated with global changes in artemesinin chemistry, potentially allowing a greater quantity of drug available for the same area of cultivation.


Malaria Hypericin Isotope Ratio Mass Spectrometer Secondary Plant Compound Great Mekong Subregion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We gratefully acknowledge the contribution and life-long achievements of Professor Tony McMichael, National Academy of Science member, who passed away on September 25, 2014. The work was supported by the National Basic Research Program (973 Program, 2014CB954500), the National Natural Science Foundation of China (Grant No. 31370457, 41301209, 31261140364, 31201126) and Natural Science Foundation of Jiangsu province in China (grant No. BK20131051 and BK20140063) to C. Zhu. The FACE system instruments were supplied by the National Institute of Agro-Environmental Sciences and the Agricultural Research Center of Tohoku Region (Japan). We also thank Dr. Kim Knowlton of Columbia University for her review and suggestions to the manuscript.


C.Z. and Q.Z. share equal credit as first authors who along with L.Z. conceived the experiments; C.Z., Q.Z., K.N., J. Z., G.L. and X.Z. provided the A. annua herbarium samples and performed the experiments; C.Z. and L.Z. co-wrote the paper; T.M., K.E. and A.S.K. analyzed the data and edited the manuscript.

Conflict of interest


Supplementary material

10584_2015_1421_MOESM1_ESM.docx (33 kb)
Table S1 (DOCX 33 kb)


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Copyright information

© Springer Science+Business Media Dordrecht (outside the USA) 2015

Authors and Affiliations

  • C. Zhu
    • 1
  • Q. Zeng
    • 2
  • A. McMichael
    • 3
  • K. L. Ebi
    • 4
  • K. Ni
    • 1
  • A. S. Khan
    • 5
  • J. Zhu
    • 1
  • G. Liu
    • 1
  • X. Zhang
    • 6
  • Lei Cheng
    • 7
  • L.H. Ziska
    • 8
  1. 1.State Key Laboratory of Soil and Sustainable AgricultureChinese Academy of SciencesNanjingPeople’s Republic of China
  2. 2.Jiangsu Institute of BotanyChinese Academy of ScienceNanjingPeople’s Republic of China
  3. 3.College of Medicine, Biology and EnvironmentAustralian National UniversityCanberraAustralia
  4. 4.School of Public HealthUniversity of WashingtonSeattleUSA
  5. 5.College of Public HealthUniversity of Nebraska Medical CenterOmahaUSA
  6. 6.The Herbarium, State Key Laboratory of Systematic and Evolutionary Botany, Institute of BotanyChinese Academy of SciencesBeijingPeople’s Republic of China
  7. 7.College of Life SciencesZhejiang UniversityHangzhouChina
  8. 8.USDA-ARS, Crop Systems and Global Change LabBeltsvilleUSA

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