Effects of Crude Alkaloids Isolated from Peganum harmala Seeds on the Growth and Metabolism of Leishmania tropica Promastigotes

Abstract

The present work aimed to examine the efficacy of Peganum harmala Linn. alkaloids as potential antilieshmanial agents in vitro, and to determine their toxicity in mice. The study included extraction and isolation of Peganum harmala crude alkaloids from seeds. The isolated fraction that contains alkaloids was detected, using Myer`s and modified Dragendorff`s reagents. Then, the crude alkaloids were tested for their antileishmanial activity against Leishmania tropica promastigotes in vitro including their effects on parasite growth and metabolism. It was found that the studied alkaloids inhibited growth of the parasite remarkably. The inhibitory concentration of 50% of the promastigotes (IC50) at the log phase (96) hrs was 50 µg of the alkaloids/ ml of culture. Furthermore, the extracted alkaloidal fraction from Peganum harmala seeds, resulted in decline of RNA, DNA, and protein content of the parasite and reduced specific activity of dihydrofolate reductase and thymidine phosphorelase enzymes. It also had obvious inhibitory effects on energy metabolism of the parasite. Oral median lethal dose (oral LD50) of the extracted alkaloids was 1070 mg / kg body weight in Balb/c mice, using the up-and-down method. It can be concluded that Peganum harmala alkaloids show promising antilieshmaneal activity and may have potential role in the search for novel antilieshmaneal drugs, as they affect metabolism of proteins, nucleic acids and energy of the parasite (in vitro) with a slight toxicity in mice (in vivo).