Isolation and characterization of filaricidal compounds from the stem bark of Voacanga africana, a plant used in the traditional treatment of onchocerciasis in Cameroon

This study was carried out to isolate active ingredients from Voacanga africana Stapf (Apocynaceae) used as herbal medicine in Cameroon, and also to assess the efficacy of the compounds on Onchocerca ochengi and Loa loa worms. The compounds were isolated using solvent partitioning, column chromatography and fractional crystallization. The O. ochengi worms were isolated from cow skin while Loa loa was isolated from humans. Filaricidal activity was determined based on motility for adult male worms and microfilariae (Mfs), while adult female worm viability was assessed biochemically by the dimethylthiazol (MTT)/formazan assay. Cytotoxicity was assessed using monkey kidney epithelial cells. Auranofin was used as the positive control drug. Two compounds, voacangine (compound 1) and voacamine (compound 2) were isolated from the stem bark of Voacanga africana. Both compounds were found to inhibit the motility of both the microfilariae (Mfs) and adult male worms of O. ochengi in a concentration-dependent manner, but were only moderately active on the adult female worms upon biochemical assessment at 30 µM drug concentration. The IC50s for voacangine were 5.49 µM for Mfs and 9.07 µM for adult male worms; while for voacamine the values were 2.49 µM for Mfs and 3.45 µM for adult males. At 10 µM, voacamine showed 100% inhibition of Loa loa Mfs motility after 24 h. This is the first report of the anti-Onchocerca activity of voacangine (compound 1) and voacamine (compound 2) as well as activity of voacamine (compound 2) on L. loa. The results of this study support the traditional use of V. africana in the treatment of human onchocerciasis.   Key words: Voacanga africana, voacangine, voacamine, anti-Onchocerca activity.

[1]  Brian M. Suzuki,et al.  Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis , 2015, PLoS neglected tropical diseases.

[2]  H. Kwon,et al.  A natural small molecule voacangine inhibits angiogenesis both in vitro and in vivo. , 2012, Biochemical and biophysical research communications.

[3]  A. Hensel,et al.  In vitro activity of Cameroonian and Ghanaian medicinal plants on parasitic (Onchocerca ochengi) and free-living (Caenorhabditis elegans) nematodes , 2010, Journal of Helminthology.

[4]  M. Boussinesq,et al.  Analysis of the mdr-1 gene in patients co-infected with Onchocerca volvulus and Loa loa who experienced a post-ivermectin serious adverse event. , 2010, The American journal of tropical medicine and hygiene.

[5]  Y. Ameyaw,et al.  The alkaloid contents of the ethno-plant organs of three antimalarial medicinal plant species in the Eastern Region of Ghana. , 2009 .

[6]  A. D. Oliveira,et al.  Chemical constituents from Tabernaemontana catharinensis root bark: a brief NMR review of indole alkaloids and in vitro cytotoxicity , 2008 .

[7]  C. Okaka,et al.  Prevalence and socio-economic effects of onchocerciasis in Okpuje, Owan West Local Government Area, Edo State, Nigeria. , 2008 .

[8]  V. Titanji,et al.  Preparation and characterization of specific monoclonal antibodies for the detection of adult worm infections in onchocerciasis. , 2005, Hybridoma.

[9]  G. J. Vidotti,et al.  Qualitative determination of indole alkaloids of Tabernaemontana fuchsiaefolia (Apocynaceae) , 2005 .

[10]  M. Nicoletti,et al.  Antiplasmodial activity of the alkaloids of Peschiera fuchsiaefolia. , 2009, Planta medica.

[11]  W. Harnett,et al.  Onchocerca ochengi transmission dynamics and the correlation of O. ochengi microfilaria density in cattle with the transmission potential. , 2000, Veterinary research.

[12]  Steven A. Williams,et al.  Identification of Potential Vaccine and Drug Target Candidates by Expressed Sequence Tag Analysis and Immunoscreening of Onchocerca volvulus Larval cDNA Libraries , 2000, Infection and Immunity.

[13]  S. Graham,et al.  Onchocerca ochengi infections in cattle as a model for human onchocerciasis: recent developments , 2000, Parasitology.

[14]  E. Rodrigues-Filho,et al.  Two known bis‐indole alkaloids isolated from Tabernaemontana laeta: complete 1H and 13C chemical shift assignments , 1999 .

[15]  M. Boussinesq,et al.  Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection , 1997, The Lancet.

[16]  J. Comley New macrofilaricidal leads from plants? , 1990, Tropical medicine and parasitology : official organ of Deutsche Tropenmedizinische Gesellschaft and of Deutsche Gesellschaft fur Technische Zusammenarbeit.

[17]  J. Comley,et al.  Colorimetric quantitation of filarial viability. , 1989, International journal for parasitology.