1Abstract ART has been found, for the first time, to alkylate the heme-containing
enzymes (hemoenzymes) by covalently conjugating the prosthetic heme. A high
dose of ART can kill cancer cells and bacteria through compromising protective
NO production. A low dose of ART can mimic CR to extend lifespan and reduce
weight by triggering mitochondrial biogenesis. Therefore, ART can exert versatile
beneficial effects on human health in addition to antimalaria.
Keywords ART · Hemoenzymes · NO · Target-guided effects
ART (Qinghaosu in Chinese) is an endoperoxide lactone naturally occurring in the
medicinal herbal plant Artemisia annua L. (Qinghao in Chinese). A Chinese phar-
macologist, Ms. You-You Tu, won the Lasker-DeBakey Clinical Medical Research
Award in 2011 for her pioneering and excellent contributions to the discovery of
ART’s antimalarial effects. Although originally developed as an antimalarial drug,
ART actually possesses many other therapeutic potentials on human diseases.
As a star molecule, NO was proclaimed “a molecule of the year” in 1992.
With the discovery of NO’s pleiotropic functions, Mrs. Louis J. Ignarro, Robert
F. Furchgott, and Ferid Murad won the 1998 Nobel Prize in Physiology or
Medicine. The physiology and pathology of NO are now the fundamentals and
hot-spot topics in many biological and medical fields, including neurology, physi-
ology, and immunology.
What is the relevance of ART to NO in health and disease? How to associate
ART with NO functionally? These questions reminded me to retrospect our innova-
tive and interesting findings during the past 5 years. In 2010, we found for the first
time that ART inhibits the heme-containing protein (hemoprotein) NOS by cova-
lently conjugating the prosthetic heme in tumor cells (Zeng and Zhang 2011 ) and
in bacteria (Zeng et al. 2011 ). Afterwards, we revealed that ART is able to amelio-
rate and even abort articular synovitis, an early phase of rheumatoid arthritis (RA),
in mice by abrogating NO production (Bao et al. 2012 ; Wu et al. 2012 ).
Chapter 1
Background
© The Author(s) 2015
Q.-P. Zeng, Artemisinin and Nitric Oxide, SpringerBriefs in Molecular Science,
DOI 10.1007/978-3-662-47688-8_