Si-Accumulation In Artemisia annua Glandular Trichomes Increases Artemisinin Concentration, but Does Not Interfere In the Impairment of Toxoplasma gondii Growth

Abstract

Artemisia annua is used as a source of artemisinin, a potent therapeutic agent used for the treatment of infectious diseases, chiefly malaria. However, the low concentration (from 0.01 to 1.4% of dried leaf matter) of artemisinin in the plant obtained with the traditional cropping system makes it a relatively expensive drug, especially in developing countries. Considering that artemisinin and silicon (Si) are both stored in A. annua glandular trichomes, and that Si accumulation has never been investigated, this study aimed to look into Si effects on A. annua trichome artemisinin concentration, and whether leaf infusion from Si-treated A. annua plants is able to control Toxoplasma gondii growth. T. gondii is the etiologic agent of toxoplasmosis, a zoonotic parasitic disease whose traditional treatment shows significant side effects. The experimental design consisted of A. annua seedlings randomly planted in soil treated with different doses of calcium/magnesium silicate (0, 200, 400, 800, and 1600 kg ha-1). Analysis of foliar macronutrients showed significant increases of nitrogen content only at the highest dose of silicate. Foliar micronutrients, Si concentrations, and plant height were not affected by any of the silicate doses. However, the dose of 400 kg ha-1 of silicate increased the trichome size, which in turn raised artemisinin concentration in leaves and the infusion. In contrast, the 800 and 1600 kg ha-1 doses dramatically decreased artemisinin concentration. HeLa cell treatment with the infusion of A. annua grown in soil treated with 400 kg ha-1 of silicate decreased parasite proliferation in a dose-dependent manner when the treatment was carried out after or along with T. gondii infection. However, this effect was similar to A. annua grown in soil without silicate treatment. Thus, it can be concluded that, even though Si applied to the soil at 400 kg ha-1 has a positive effect on the A. annua glandular trichome size and the artemisinin concentration, this outcome cannot be directly associated with the efficiency of A. annua infusion on T. gondii growth, suggesting that other components from A. annua leaves could be acting in synergy with artemisinin.

Lectins from Synadenium carinatum (ScLL) and Artocarpus heterophyllus (ArtinM) Are Able to Induce Beneficial Immunomodulatory Effects in a Murine Model for Treatment of Toxoplasma gondii Infection

“…Currently, toxoplasmosis is still treated with the synergistic combination of sulfadiazine and pyrimethamine or triple sulfonamides, which cause bone marrow damage, in addition to the potential life-threatening allergic reactions. For these reasons, alternative drugs as treatment options, including azithromycin, clarithromycin, dapsone, and artemisinin, have been studied for toxoplasmosis treatment, but an extensive number of side effects still persists (Araujo et al, 1992a,b; Bosch-Driessen et al, 2002; D'Angelo et al, 2009; de Oliveira et al, 2009; Yan et al, 2013; Rostkowska et al, 2016). Thus, it is necessary to investigate alternative approaches to find efficient and well-tolerated therapeutic agents against T. gondii infection.…”

Accumulation of Secondary Metabolites and Improved Size of Glandular Trichomes in Artemisia annua

“…Silicon is one of the abundant elements found in soil and also accumulates in glandular trichome. Knowing this fact, Rostkowska et al [38] found that silicon application in the form of calcium/magnesium silicate can increase trichome size with higher artemisinin accumulation. Similar to these elements, cadmium also has stimulatory impact on artemisinin biosynthesis in A. annua.…”

Production of Plant Secondary Metabolites: Examples, Tips and Suggestions for Biotechnologists

“…A study on the medicinal plant A. annua L. showed that application of 400 kg ha −1 of silicate increased the trichome sizes and, consequently, the production of artemisinin [ 171 ]. Therefore, the addition of Si may be useful for the increased production of secondary metabolites produced in glandular trichomes.…”