The traditional medicine Spilanthes acmella, and the alkylamides spilanthol and undeca-2E-ene-8,10-diynoic acid isobutylamide, demonstrate in vitro and in vivo antimalarial activity

Abstract

Spilanthes spp. are used as traditional herbal medicines in Africa and India to treat malaria. Yet, to date, there are no data on the active constituents or the most effective extraction methods for this indication. The isolated alkylamides, spilanthol and undeca-2E-ene-8,10-diynoic acid isobutylamide, found in S. acmella Murr., were shown to have IC₅₀s of 16.5 μg/mL and 41.4 μg/mL on Plasmodium falciparum strain PFB and IC₅₀s of 5.8 μg/mL and 16.3 μg/mL for the chloroquine resistant P. falciparum K1 strain, respectively. Further investigations revealed that at relatively low concentrations, spilanthol and the water extract of S. acmella reduced the parasitemia 59% and 53% in mice infected with P. yoelii yoelii 17XNL at 5 mg/kg and 50 mg/kg, respectively. Unexpectedly, the 95% ethanol extract of S. acmella was less effective (36% reduction in parasitemia) at 50 mg/kg. These results provide the first evidence supporting S. acmella against malaria and demonstrating active constituents in S. acmella against P. falciparum.

Figure 1. Spilanthol and undeca-2E-ene-8,10-diynoic acid isobutylamide(UDA) in vitro inhibition of P.falciparum strains

1A Spilanthol and UDA show IC50son the P. falciparum strain PFB at 16.5 and 41.4 μg/mL. 1B Spilanthol and UDA demonstrate IC50s of5.8 and 16.3 μg/mL on the chloroquine resistantstrain P. falciparum K1. 1C . Molecular structures of spilanthol and UDA. Growth inhibition was determined by comparison of the radioactivity incorporated into the treated culture with that in control culture from the same plate. Chloroquine served as a positive control (IC50s: PFB–28.4 nM; K1–100 nM). Values are mean± S.E.M.of experiments performed in triplicate.

Figure 2. Spilanthol and extracts of whole plant S. acmella reduce parasitemia in Plasmodium y. yoelli-infected mice

Spilanthol, water extract, or (70%) ethanol extract of Spilanthes acmella inhibit parasitemia as compared to the control group. Mice were inoculated with P. yoelli yoelli 17XNLand treatment started 2 hours later. Treatments (twice daily spilanthol 2.5mg/kg; water extract 25 mg/kg; ethanol extract 25mg/kg) were given two times aday for four days. Parasitaemia was determined 5 days after infection by microscopic examination of Giemsa stained-thin blood smears. Values are mean± S.E.M. (n = 5 for each group). †p = 0.01; *p< 0.001