Artemisinin, a Constituent of Annual Wormwood (Artemisia annua), is a Selective Phytotoxin

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Abstract
Artemisinin (qinghaosu), a sesquiterpenoid lactone peroxide constituent of annual wormwood (Artemisia annua L. # ARTAN) that is used as an antimalarial drug, was tested for phytotoxic properties. It inhibited germination of lettuce (Lactuca sativa L.) and annual wormwood, and growth of roots and shoots of lettuce, redroot pigweed (Amaranthus retroflexus L. # AMARE), pitted morningglory (Ipomoea lacunosa L. # IPOLA), annual wormwood, and common purslane (Portulaca oleracea L. # POROL) was inhibited at 33 μM. No effects of 33 μM artemisinin were detected on growth of velvetleaf (Abutilon theophrasti Medik. # ABUTH) and grain sorghum [Sorghum bicolor (L.) Moench.]. Chlorophyll content was not affected in lettuce, and chlorosis was not observed in any species tested. The probable biosynthetic precursors of artemisinin, arteannuin B and qinghao acid, had no effect on growth or chlorophyll content of lettuce; however, they inhibited lettuce seed germination. Artemisinin and cinmethylin {exo-1-methyl-4-(1-methylethyl)-2-[(2-methylphenyl)methoxy]-7-oxabicyclo [2.2.1] heptane} were equally effective in reducing growth of lettuce; however, cinmethylin had no effect on germination. Respiration of lettuce roots or cotyledons was not inhibited by artemisinin. Artemisinin only marginally increased the mitotic index of lettuce root tips at 33 μM. At the ultrastructural level, however, chromosomes were less condensed during mitosis in artemisinin-treated than control meristematic cells. The growth-inhibiting ability of artemisinin could not be reduced by feeding the plants with hydrolyzed protein or treatment with putrescine. Artemisinin is a selective phytotoxin that reduces growth by a mechanism other than mitotic disruption or inhibition of protein synthesis.