Antiprotozoal Activity of Extracts and a Major Compound from the Leaves of Ranunculus multifidus Forrsk.
| dc.contributor.advisor | Asres, Kaleab(Professor) | |
| dc.contributor.author | Sirak, Betelhem | |
| dc.date.accessioned | 2021-10-17T06:55:11Z | |
| dc.date.accessioned | 2023-11-29T04:35:13Z | |
| dc.date.available | 2021-10-17T06:55:11Z | |
| dc.date.available | 2023-11-29T04:35:13Z | |
| dc.date.issued | 2021-06 | |
| dc.description.abstract | Protozoal diseases caused by the genera Leishmania, Plasmodium and Trypanosoma have devastating impact mostly on the poorest countries of the world due to their prevalence, virulence and drug resistance ability. This calls for the development and discovery of new effective and safe chemotherapeutic agents from alternative sources such as medicinal plants. This study aimed at investigating the antiprotozoal activity of Ranunculus multifidus Forrsk. (Ranunculaceae), a medicinal plant used to treat leishmaniasis, malaria and trypanosomiasis in several African countries. Fresh leaves of R. multifidus were subjected to maceration using 80% methanol and hydrodistillation to obtain hydroalcoholic extract (RM-M) and hydrodistilled extract (RM-H), respectively. Antileishmanial activities of the extracts were studied on clinical isolates of the promastigote and amastigote forms of Leishmania aethiopica and Leishmania donovani, whilst 4-day-suppressive, Rane’s and prophylactic tests were employed to investigate in vivo antimalarial activity against chloroquine sensitive Plasmodium berghei infected mice. In vitro and in vivo antitrypanosomal effects of the extracts were also investigated against Trypanosoma congolense field isolate. Results of the study revealed that both extracts were active against the studied protozoans, although RM-H demonstrated superior activity (p < 0.001) compared the RM-M. The IC 50 values of RM-H were 0.490 and 0.984 μg/ml against promastigotes and 1.49 and 1.84 μg/ml against macrophage amastigotes of L. aethiopica and L. donovani, respectively. At a dose of 35.00 mg/kg/day, RM-H demonstrated a chemosuppression value of 70% in 4-day-suppressive test. Furthermore, at a concentration of 4 mg/ml, RM-H ceased motility of T. congolense within 20 min. Further phytochemical analysis of RM-H using preparative thin layer chromatography (PTLC) led to the isolation of an α,β-unsaturated dilactone characterized as anemonin on the basis of FT-IR, APCI-MS, 1D- and 2D-NMR spectral assignments and also by comparison with the reported spectroscopic data of the same compound. Anemonin displayed significant (p < 0.001) antileishmanial activity with IC 50 of 1.33 nM and 1.58 nM against promastigotes and 1.24 nM and 1.91 nM against amastigotes of L. aethiopica and L. donovani, respectively. Anemonin was found to be relatively less toxic to macrophage cells with selectivity indices (macrophage cytotoxic/antileishmanial ratios) of 22 and 14, respectively. In a 4-day suppressive, Rane’s and prophylactic antimalarial tests, anemonin showed median effective doses (ED 50 s) of 2.17, 2.78 and 2.70 μM, respectively. At a concentration of 4 mg/ml, anemonin completely immobilized trypanosomes within 5 min of incubation, while the standard dug diminazene diaceturate immobilized the parasites within 10 min. In the in vivo antitrypanosomal assay, anemonin eliminates parasites at all the tested doses (8.75, 17.00 and 35.00 mg/kg/day) and prevented relapse. Results of the present study provided evidence that the leaves of R. multifidus possess genuine antileishmanial, antiplasmodial and antitrypanosomal activities, which may be attributed to the presence of anemonin. Thus, use of the plant in traditional medicine for the treatment of protozoal diseases seems to be well founded. values | en_US |
| dc.identifier.uri | http://etd.aau.edu.et/handle/123456789/28210 | |
| dc.language.iso | en_US | en_US |
| dc.publisher | Addis Abeba University | en_US |
| dc.subject | Ranunculus multifidus, Traditional medicine, Antiplasmodial, Antileishmanial and cytotoxic/antiprotozoal ratios, Antitrypanosomal activities, Anemonin. | en_US |
| dc.title | Antiprotozoal Activity of Extracts and a Major Compound from the Leaves of Ranunculus multifidus Forrsk. | en_US |
| dc.type | Thesis | en_US |