Water-soluble artemisinin derivatives as promising therapeutic immunosuppressants of autoimmune diseases.

Abstract

Artemisinin, which contains a sesquiterpene trioxane skeleton, was originally isolated from Artemisia annua L., a traditional Chinese medicine with antimalarial activity. The 2015 Nobel Prize in Physiology or Medicine was awarded to Youyou Tu for her discoveries concerning a novel therapy against malaria. Over the past several decades, a series of novel artemisinin derivatives have been synthesized and evaluated for antimalarial and immunosuppressive activities.1 Artesunate, artemether and dihydroartemisinin have expanded the clinical applications of artemisinin, which has indeed become a gift from traditional Chinese medicine to the world. Our groups have identified several water-soluble artemisinin derivatives that exhibit strong immunosuppressive activity, among which SM905 and SM934 exert notable anti-inflammatory effects in vitro and in vivo.2, 3, 4 SM905 and SM934 significantly inhibit the proliferation of splenocytes induced by various mitogens and IFN-γ production triggered by anti-CD3/CD28 in vitro, as well as the immune response against ovalbumin in vivo.4, 5 These artemisinin derivatives have been investigated for potential therapeutic effects and underlying mechanisms in models of autoimmune diseases such as systemic lupus erythematosus (SLE), experimental autoimmune encephalomyelitis, membranous nephropathy, collagen-induced arthritis and inflammatory bowel disease (Yan, 2017, unpublished data), as listed in Figure 1.