Filaricidal properties of Lantana camara and Tamarindus indica extracts, and Lantadene A from L. camara against Onchocerca ochengi and Loa loa

Abstract

Background: Ivermectin is the only drug currently recommended for the treatment of onchocerciasis, the second leading infectious cause of blindness in the world. This drug kills only the first stage larvae-microfilariae (mf) of Onchocerca volvulus and is to be used cautiously in areas where Loa loa is prevalent because of severe adverse events observed with coinfected patients.

Methodology/principal findings: This study investigated the anti-filarial activities of two Cameroonian medicinal plants, Lantana camara and Tamarindus indica locally used to treat onchocerciasis. Twelve (12) extracts were prepared and tested in vitro on the bovine model parasite, O. ochengi as well as L. loa mf. Both mf and adult male worm viabilities were assessed by motility scoring, while adult female worm viability was determined biochemically by standard MTT/formazan colorimetry. Cytotoxicity and acute toxicity were determined respectively, in monkey kidney epithelial cells and in BALB/c mice. Pure compounds were isolated by LC/MS using a bio-assay guided strategy. All the extracts showed 100% activity at 500 μg/mL against O. ochengi adult worms and mf. The highest activity against O. ochengi was observed with the hexane extract of L. camara leaves (LCLhex), with IC50 of 35.1 μg/mL for adult females and 3.8 μg/mL for the mf. Interestingly, this extract was more active against O. ochengi mf than L. loa mf. Further studies on the extracts led to the isolation of lantadene A from the methylene chloride extract of L. camara leaves, with IC50s of 7.85 μg/mL for adult males, 10.38 μg/mL for adult females, 10.84 μg/mL for O. ochengi mf and 20.13 μg/mL for L. loa mf.

Conclusions/significance: We report for the first time the anti-onchocercal activities of these locally consumed medicinal plants and lantadene A, a potential lead for further development as an onchocerciasis cure.

Fig 1. Scheme showing the bioassay guided fractionation of the methylene chloride extract of Lantana camara leaves (LCL _mc) and the structure of lantadene A contained in fraction C+D-D4.

Fig 2. Graphical representation of IC₅₀ and IC₁₀₀ of active extracts against microfilariae of L. loa compared to the values for O. ochengi.

(TIL_mc: methylene chloride extract from Tamarindus indica leaves; LCL_hex: hexane extract from Lantana camara leaves; LCL_mc: methylene chloride extract from Lantana camara leaves).

Fig 3

Dose dependent relationships of lantadene A to parasite viability: A) % inhibition of motility of O. ochengi male worms. B) % inhibition of formazan by O. ochengi females. C) % inhibition of motility of Loa loa microfilariae (mf). D) % inhibition of motility of O. ochengi mf.