Antiprotozoal Activity Of Extracts And A Major Compound From The Leaves Of Ranunculus Multifidus Forrsk.

Protozoal diseases caused by the genera Leishmania, Plasmodium and Trypanosoma have rndevastating impact mostly on the poorest countries of the world due to their prevalence, rnvirulence and drug resistance ability. This calls for the development and discovery of new rneffective and safe chemotherapeutic agents from alternative sources such as medicinal plants. rnThis study aimed at investigating the antiprotozoal activity of Ranunculus multifidus Forrsk. rn(Ranunculaceae), a medicinal plant used to treat leishmaniasis, malaria and trypanosomiasis in rnseveral African countries. Fresh leaves of R. multifidus were subjected to maceration using 80% rnmethanol and hydrodistillation to obtain hydroalcoholic extract (RM-M) and hydrodistilled rnextract (RM-H), respectively. Antileishmanial activities of the extracts were studied on clinical rnisolates of the promastigote and amastigote forms of Leishmania aethiopica and Leishmania rndonovani, whilst 4-day-suppressive, Rane’s and prophylactic tests were employed to investigate rnin vivo antimalarial activity against chloroquine sensitive Plasmodium berghei infected mice. In rnvitro and in vivo antitrypanosomal effects of the extracts were also investigated against rnTrypanosoma congolense field isolate. Results of the study revealed that both extracts were rnactive against the studied protozoans, although RM-H demonstrated superior activity (p < 0.001) rncompared the RM-M. The ICrn50 rnvalues of RM-H were 0.490 and 0.984 μg/ml against rnpromastigotes and 1.49 and 1.84 μg/ml against macrophage amastigotes of L. aethiopica and L. rndonovani, respectively. At a dose of 35.00 mg/kg/day, RM-H demonstrated a chemosuppression rnvalue of 70% in 4-day-suppressive test. Furthermore, at a concentration of 4 mg/ml, RM-H rnceased motility of T. congolense within 20 min. Further phytochemical analysis of RM-H using rnpreparative thin layer chromatography (PTLC) led to the isolation of an α,β-unsaturated rndilactone characterized as anemonin on the basis of FT-IR, APCI-MS, 1D- and 2D-NMR rnspectral assignments and also by comparison with the reported spectroscopic data of the same rncompound. Anemonin displayed significant (p < 0.001) antileishmanial activity with ICrn50 rnof 1.33 nM and 1.58 nM against promastigotes and 1.24 nM and 1.91 nM against amastigotes of rnL. aethiopica and L. donovani, respectively. Anemonin was found to be relatively less toxic to rnmacrophage cells with selectivity indices (macrophage cytotoxic/antileishmanial ratios) of 22 rnand 14, respectively. In a 4-day suppressive, Rane’s and prophylactic antimalarial tests, rnanemonin showed median effective doses (EDrn50rns)rn rnof 2.17, 2.78 and 2.70 μM, respectively. At a rnconcentration of 4 mg/ml, anemonin completely immobilized trypanosomes within 5 min of rnincubation, while the standard dug diminazene diaceturate immobilized the parasites within 10 rnmin. In the in vivo antitrypanosomal assay, anemonin eliminates parasites at all the tested doses rn(8.75, 17.00 and 35.00 mg/kg/day) and prevented relapse. Results of the present study provided rnevidence that the leaves of R. multifidus possess genuine antileishmanial, antiplasmodial and rnantitrypanosomal activities, which may be attributed to the presence of anemonin. Thus, use of rnthe plant in traditional medicine for the treatment of protozoal diseases seems to be well founded. rnvalues

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