phytosterols and artemisinin

The effect of 16 alpha-acetoxy-26-hydroxycholest-4-ene-3,22-dione (SN-1) isolated from Solanum nudum Dunal (a Solanaceae traditionally used for treating fever in Colombia) on Plasmodium falciparum erythrocyte stages and its in vitro antiplasmodial activity when combined with the following conventional drugs was studied: chloroquine (CQ), amodiaquine (AQ), desethylamodiaquine (desethyl-AQ), quinine (QN), artemisinin (AR), atovaquone (ATV) and quinine (QN). It was found that SN-1 targeted trophozoites and had a synergistic effect when combined with CQ and QN; however, it had an antagonist effect when used with the other combinations.

Topics: Amodiaquine; Antimalarials; Artemisinins; Atovaquone; Chloroquine; Drug Synergism; Erythrocytes; Flow Cytometry; Humans; Phytosterols; Plasmodium falciparum; Quinine; Solanum; Trophozoites

To investigate the dynamic fluctuation of terpenoid relevant transcriptomics in transgenic ARTEMISIA ANNUA plants that express the genomic integrated antisense squalene synthase gene ( ASSS), we have quantified the transcript levels of the sterol anabolic SS gene as well as artemisinin biogenetic amorphadiene synthase (ADS), cytochrome P450 monooxygenase (CYP71AV1) and cytochrome P450 reductase (CPR) genes by real-time fluorescent quantitative polymerase chain reaction (RFQ-PCR). The SS mRNA level in transgenic plants sharply droped to 7.4 % - 55.3 % (i. e., 44.7 - 92.6 % reduction as the wild-type control), strongly implying that the expression of endogenous SS gene is significantly suppressed by the exogenous ASSS gene. In a synchronous fashion, ADS, CYP71AV1 and CPR mRNA levels elevated with the decline of SS mRNA level in transgenic plants, and the maximal ADS, CYP71AV1 and CPR mRNA levels in transgenic plants were 3.0-, 4.4- and 2.5-fold, respectively, higher than those in the control. Without a lethal effect but with a distinguishable impact on the organogenesis and morphology of transgenic plants, the down-regulation of SS gene has also led to the coordinated overexpression of ADS, CYP71AV1 and CPR genes together with the overproduction of artemisinin although no fully perfect correlation among the available experimental data has been shown.

Topics: Artemisia annua; Artemisinins; Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme System; Farnesyl-Diphosphate Farnesyltransferase; Gene Expression Profiling; Gene Expression Regulation, Plant; Genes, Plant; Genome, Plant; NADPH-Ferrihemoprotein Reductase; Phytosterols; Plant Proteins; Plants, Genetically Modified; Polymerase Chain Reaction; RNA, Messenger