Compounds from Artemisia argyi as potential leads for the development of new immunosuppressive drugs

The need for novel drugs for the treatment of autoimmune diseases is rising since available pharmaceuticals are often characterized by severe side effects and a limited efficacy [1]. Therefore, we investigated the immunosuppressive potential of a library of 435 extracts prepared from plants used in Traditional Chinese Medicine.Immunosuppressive activity of extracts was assessed in a proliferation-based assay utilizing physiologically relevant anti-CD3 and anti-CD28 stimulated primary human T lymphocytes [2]. Among others, an ethyl acetate extract of Artemisia argyi (Asteraceae) was found to be highly active. The observed inhibitory effect on T cell proliferation was not based on toxic effects of the extract, as shown by apoptose-/necrosis induction analysis of T lymphocytes. The A. argyi extract was submitted to HPLC-based activity profiling [3]. A T cell proliferation assay identified two active regions in the chromatogram, and a highly active peak with an IC₅₀ of 0.25 µg/ml was identified in the first region. Fractionation of this peak finally determined (1R,2S,3R,4S,5S,6S,7S,10R)-canin (1) and two seco-tanapartholides as constituents responsible for most of the activity. IC₅₀ values of 0.71 µg/ml for 1, and 0.24 µg/mland 0.28 µg/ml, respectively, for the (4R,5R,6S,7S)- and (4S,5S,6S,7S)-seco-tanapartholides (2 and 3), respectively, qualify these compounds as potential immunosuppressive leads. Further investigations focusing on the mode of action are underway.

Fig. 1

[1] Steinman L. Immune Science 2004; 305: 212

[2] Quah BJC, Parish CR. J Visualized Exp 2010: 2259

[3] Potterat O, Hamburger M. Planta Med 2014; 80: 1171 – 1181