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).
Highlights
تأثير القلويدات الخام المعزولة من بذور الحرمل Peganum harmalaفي نمو وايض أمامي السوط لطفيليات اللشمانيا الجلدية Leishmania tropica
INTRODUCTION Leishmaniasis is a global parasitic infection, which is prevalent in 88 countries from Tropical to Mediterranean regions, where 12 million people are infected and approximately 350 million people are at risk, with 1-2 million new cases registered annually (WHO,2001 ). It is a vector-borne disease transmitted by sand flies and caused by an obligate intracellular protozoa of the genus Leishmania
The pharmacologically active compounds of Peganum harmala are several alkaloids, which are found especially in the seeds and the roots. These include β-carbonile alkaloids such as harmine, harmaline, harmalol and harman, and quinazoline alkaloides such as vasicine and vasicinone (Kamel et al, 1970)
Summary
Isolation of Peganum harmala crude alkaloids Seeds of Peganum harmala were collected from local markets in Mosul city and taxonomically identified by the botanists Mr Salim AL-Sufaji, in herbarium of Biology department /College of Science /University of Mosul. The seeds were milled into coarse powder, extracted with ethanolic alcohol 80% that contains diluted HCL (1N); pigments and unwanted materials were removed by shaking with chloroform. The extracted fraction which contains alkaloids was detected, using Myers reagent (Potassiomercuric iodide solution) (Sousek et al, 1999) and modified Dragendorffs reagent (Potassium bismuth solution) (AL-Shahaat, 1986). The culture was obtained from the College of Medicine AL-Nahreen University, which has been characterized using isoenzyme method according to AL-Jeboori and Evans (1980). The obtained culture was cultivated in Tobies medium (Tobie et al, 1950)
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