Publikationsdatenbank

Dual activities of artemisinin and its derivatives:
on parasitic nematodes and host immune response 27.0 (2022)

Art

Vortrag

Autor

Musimbi, Zaneta D. (WE 6)

Kongress

Research Training Group 2046: retreat 27. + 28.10.2022

Berlin, 27. – 28.10.2022

Quelle

Sprache

Englisch

Kontakt

Institut für Immunologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51834
immunologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Artemisinin and its derivatives; artemether, artesunate and dihydroartemisinin, (ARTs) are drugs with well characterized pharmacological properties against Plasmodium falciparum as well as helminths e.g. schistosome spp., viruses such as SARs Cov-2, multiple cancers like lung carcinoma and autoimmune diseases such as inflammatory bowel syndrome.
The aim of the current study is to investigate the direct and indirect antinematode and anti-immune cell activities of ARTs in vitro and in vivo during a gastrointestinal nematode infection. In vitro assays are utilised to investigate the direct effect ARTs have on the larval stages of Ascaris suum (A. suum) as well as on Th2 priming of immune cells and cellular proliferation is studied.
To determine the effect on metabolic processes, A. suum L3 were exposed to artemisinin, artesunate and artemether for 24 hours. Effects of the drugs were evaluated by resazurin assay and bioluminescence ATP assay. To determine the effect on macrophages, RAW264.7 murine macrophage cells were exposed to artemisinin, artesunate and artemether for 24 hours followed by stimulation with LPS/IFN-γ for another 24 hours. ELISA and Griess test were used to evaluate the effect on cytokine and NO production respectively.
We report a dose dependent inhibiting effect artemisinin, artesunate and artemether had on general metabolic activity as well as intracellular ATP production of A. suum L3. Further we intend to use fluorescence lifetime imaging microscopy (FLIM) to determine whether the drug effect on general metabolic activity is as a result of reduced NADH production possibly due to inhibition of glycolysis or altered NADH/NAD+ oxidation possibly as a result of altered mitochondrial electron transport chain complex I activity. Preliminary results on the drug effect on macrophages indicate an inhibitory effect by artesunate on TNF-α, IL-6 and NO production. Artemether and artemisinin were observed to have no effect on the cytokine and NO production.
In conclusion, ARTs as multi-functional drugs may have an influence on nematode larval metabolic activity as well as macrophage activity in vitro.