Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells

Chemical Research in Toxicology
Kodihalli C RavindraSteven R Tannenbaum

Abstract

The antimalarial drug artesunate is a semisynthetic derivative of artemisinin, the principal active component of a medicinal plant Artemisia annua. It is hypothesized to attenuate allergic asthma via inhibition of multiple signaling pathways. We used a comprehensive approach to elucidate the mechanism of action of artesunate by designing a novel biotinylated dihydroartemisinin (BDHA) to identify cellular protein targets of this anti-inflammatory drug. By adopting an untargeted proteomics approach, we demonstrated that artesunate may exert its protective anti-inflammatory effects via direct interaction with multiple proteins, most importantly with a number of mitochondrial enzymes related to glucose and energy metabolism, along with mRNA and gene expression, ribosomal regulation, stress responses, and structural proteins. In addition, the modulatory effects of artesunate on various cellular transcription factors were investigated using a transcription factor array, which revealed that artesunate can simultaneously modulate multiple nuclear transcription factors related to several major pro- and anti-inflammatory signaling cascades in human bronchial epithelial cells. Artesunate significantly enhanced nuclear levels of nuclear fa...Continue Reading

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Citations

Apr 30, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ujjal SarkarSteven R Tannenbaum
Jun 24, 2017·Medicinal Research Reviews·Yin Kwan WongJigang Wang
Oct 20, 2018·Journal of Drug Targeting·Guilherme Curty LechugaSaulo C Bourguignon
Apr 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Uthpala SeneviratneSteven R Tannenbaum
Nov 5, 2016·Expert Review of Proteomics·Shankar SumanYogeshwer Shukla
Jul 28, 2020·Molecular Biology Reports·Bushra Hafeez KianiBushra Mirza
Jul 22, 2021·Medicinal Research Reviews·Thomas Efferth, Franz Oesch

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