Yinebeb Tariku

In vitro Evaluation of Antileishmanial Activity and Toxicity of Essential Oils of Artemisia absinthium and Echinops kebericho

Potential toxicity, costs, and drug‐resistant pathogens necessitate the development of new antileishmanial agents. Medicinal and aromatic plants constitute a major source of natural organic compounds. In this study, essential oils of Artemisia absinthium L. and Echinops kebericho Mesfin were investigated by GC and GC/MS analyses. Isolated oils were screened for antileishmanial activity against two Leishmania strains (L. aethiopica and L. donovani), and toxicity on the human monocytic leukemia (THP‐1) cell line and red blood cells in vitro. GC/MS Analysis revealed 65 compounds (93.74%) for Artemisia absinthium and 43 compounds (92.85%) for Echinops kebericho oil. The oils contained the oxygenated monoterpene camphor (27.40%) and the sesquiterpene lactone dehydrocostus lactone (41.83%) as major constituents, respectively. Both oils showed activity against promastigote (MIC 0.0097–0.1565 μl/ml) and axenic amastigote forms (EC50 0.24–42.00 nl/ml) of both leishmania species. Weak hemolytic effect was observed for both oils, showing a slightly decreased selectivity index (SI 0.8–19.2) against the THP‐1 cell line. Among the two oils tested, E. kebericho exerted strong antileishmanial activity that was even higher than that of amphotericin B with significant cytotoxicity. This study, therefore, demonstrated the potential use of both oils as source of novel agents for the treatment of leishmaniasis.

Essential-oil composition, antileishmanial, and toxicity study of Artemisia abyssinica and Satureja punctata ssp. punctata from Ethiopia.

Essential oils of Artemisia abyssinica and Satureja punctata ssp. punctata from Ethiopia were analyzed by GC and GC/MS, and screened for leishmanicidal activity against promastigote and axenic amastigotes of Leishmania donovani and L. aethiopica, including toxicity studies on human monocytic leukemia cells (THP‐1) and erythrocytes in vitro. GC/MS of A. abyssinica oil revealed 67 compounds (99.94%) with the major constituents yomogi alcohol (38.47%), artemisyl acetate (24.88%), and artemisia alcohol (6.70%), and oxygenated monoterpenes (84.00%) as the dominant group. The oil of S. punctata contained 67 compounds (99.49%) with the main constituents geranial (27.62%), neral (21.72%), α‐bisabolol (13.62%), and (E)‐nerolidol (4.82%), of which oxygenated mono‐ and sesquiterpenes (58.39 and 26.91%, resp.) showed highest abundance. Both oils showed effect on promastigotes (MIC 76.5 to 312.5 nl/ml) and amastigotes (EC50 4.06 to 131.00 nl/ml) of L. donovani and L. aethiopica, and varying toxicities on THP‐1 cells (CC50 0.013 to 350 nl/ml with selectivity index between 0.001 and 28) and erythrocytes (with LC50 0.35 to 1.52 μl/ml). S. punctata oil exerted highest activity against both Leishmania sp. and toxicity. The revealed antileishmanial activities support further isolation and investigation of oil constituents for in vitro/in vivo evaluation.

Evaluation of Antibacterial Activities of Compounds Isolated From Sida rhombifolia Linn. (Malvaceae)

The main objective of this study was to isolate compounds from roots of Sida rhombifolia and subsequently evaluate their antibacterial activities. Crude gradient extracts were obtained from three solvents (petroleum ether, chloroform and methanol) with increasing solvent polarity using cold maceration technique. The in vitro antibacterial activity evaluation of gradient extracts and isolated compounds was done on four different pathogenic bacterial strains (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhimurium) using agar disc diffusion technique. The results showed that antibacterial activities were comparable to each other. But their activities were relatively weaker as compared to that of the reference compound (ciprofloxacin). Among the three crude extracts, the chloroform extract was subjected to column chromatographic separation that led to isolation of SRL-1, SRL-2 and SRL-3. The chemical structures of the compounds were found to be n-hexacos-11-enoic acid, stigmasterol and β-sitosterol, respectively, based on physical properties and spectroscopic (IR and NMR) data as well as literature reports. The observed antibacterial activities of the crude extracts and the isolated compounds could justify the traditional use of the plant for the treatment of different bacterial infections. Thus, further test is recommended on large number of bacterial strains to decide the potentials of the compounds as candidates in development of antibacterial drugs.

Chapter 11 - Plant-Derived Natural Products for the Treatment of Leishmaniasis

Leishmaniasis is a vector-borne parasitic disease caused by protozoan parasites belonging to the family Trypanosomatidae and genus Leishmania. The disease prevails in 88 subtropical and tropical countries in five continents where about 350 million people live. Approximately two million incidences of new cases are recorded every year, causing high morbidity and mortality with a wide spectrum of clinical manifestations in humans. Treatment for leishmaniasis depends on pentavalent antimonials developed 50 years ago as first-line drugs, whereas a limited range of other drugs such as paromomycin, miltefosine, and amphotericin B exist to supplement them. However, potential toxicity, costs, and emergence of drug-resistant pathogens are the most serious obstacles for successful treatment of the disease in most endemic areas. This demands the development of new antileishmanial agents. In this regard, the search for new drugs from various synthetic products continues, and involves also compounds isolated from natural sources and drugs used for the treatment of other ailments (cancer, viral infections, TB, immunosuppression, etc.) in order to discover compounds with unknown chemical structures and with potential novel modes of action. Medicinal and aromatic plants are a major source of natural organic compounds which are widely used as medicine. The extensive ethnomedicinal knowledge, diversity of plant species, and the disease burden worldwide necessitates the status of natural products in treatments of leishmaniasis to be assessed. This chapter will review plant crude extracts and fractions/active principles obtained from medicinal plants which are used in or have potential for the treatment of leishmaniasis. Plant species are systematically presented by family, bioactive phytochemicals in various classes, and results obtained on specific organisms tested. Recent empirical and rationale approaches for antileishmanial drug targeting and development of novel drugs derived from natural products will be discussed.