Plasmodium falciparum: Effect of Solanum nudum steroids on thiol contents and β-hematin formation in parasitized erythrocytes

• Published in: Experimental parasitology 2009-08, Vol.122 (4), p.273-279
• Main Authors: Pabón, Adriana, Deharo, Eric, Zuluaga, Lina, Maya, Juan D., Saez, Jairo, Blair, Silvia
• Format: Article
• Language: English
• Subjects: Animal, plant and microbial ecology; Animals; Applied ecology; Biological and medical sciences; Buthionine Sulfoximine - pharmacology; Cysteine; Cysteine - analysis; Cysteine - drug effects; Ecotoxicology, biological effects of pollution; Erythrocytes - chemistry; Erythrocytes - drug effects; Erythrocytes - parasitology; Fundamental and applied biological sciences. Psychology; Glutathione; Glutathione - analysis; Glutathione - drug effects; Hemeproteins - biosynthesis; Hemeproteins - drug effects; Life cycle. Host-agent relationship. Pathogenesis; Linear Models; Malaria, Falciparum - drug therapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Plasmodium falciparum; Plasmodium falciparum - drug effects; Protozoa; Solanum - chemistry; Solanum nudum; Spiro Compounds - pharmacology; Steroids - pharmacology; Steroids - therapeutic use; Sulfhydryl Compounds - analysis; Sulfhydryl Compounds - metabolism; Techniques; Triterpenes - pharmacology; β-Hematin
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2009.04.014

We studied the effects on total thiols glutathione (GSH) and cysteine contents in Plasmodium falciparum in vitro when treated with four steroid derivatives and a sapogenin (Diosgenone) extracted from Solanum nudum. We also determined their capacity to inhibit β-hematin formation. We showed that SN-1 (16α-acetoxy-26-hydroxycholest-4-ene-3,22-dione) increased total glutathione and cysteine concentrations while SN-4 (26-O-β- d-glucopyranosyloxy-16α-acetoxycholest-4-ene-3,22-dione) decreased the concentration of both thiols. Acetylation in C16 was crucial for the effect of SN-1 while type furostanol and terminal glucosidation were necessary for the inhibitory properties of SN-4. The combination of steroids and buthionine sulfoximine, a specific inhibitor of a step-limiting enzyme in GSH synthesis, did not modify the glutathione contents. Finally, we found that SN-1 inhibited more than 80% of β-hematin formation at 5.0 mM, while the other steroids did not show any effect.