Review on medicinal plants and natural compounds as anti-Onchocerca agents.

Onchocerciasis is a filarial vector borne disease which affects several million people mostly in Africa. The therapeutic approach of its control was based on a succession of drugs which always showed limits. The last one: ivermectin is not the least. It was shown to be only microfilaricidal and induced resistance to the human parasite Onchocerca volvulus. The approach using medicinal plants used in traditional medicine is a possible alternative method to cure onchocerciasis. Onchocerca ochengi and Onchocerca gutturosa are the parasite models used to assess anthelmintic activity of potentially anthelmintic plants. Numerous studies assessed the in vitro and/or in vivo anthelmintic activity of medicinal plants. Online electronic databases were consulted to gather publications on in vitro and in vivo studies of anti-Onchocerca activity of plants from 1990 to 2017. Globally, 13 plant families were investigated for anti-Onchocerca activity in 13 studies. The most active species were Anacardium occidentale, Euphorbia hirta and Acacia nilotica each with an LC50 value of 2.76, 6.25 and 1.2 µg/mL, respectively. Polycarpol, voacamine, voacangine, ellagic acid, gallic acid, gentisic acid, 3-O-acetyl aleuritolic acid and (-)-epigallocatechin 3-O-gallate were the isolated plant compounds with anti-Onchocerca activity. Most of the assessed extract/compounds showed a good safety after in vivo acute toxicity assays and/or in vitro cytotoxicity test. The exception was the ethanol extract of Trichilia emetica, which killed completely and drastically mice at a dose of 3000 mg/kg. Several plant groups of compounds were shown active against Onchocerca sp. such as tannins, alkaloids, triterpenoids and essential oils. Nevertheless, none of the active compounds was subjected to clinical trial, to assessment of its diffusibility through nodular wall or its capability to induce genetic resistance of Onchocerca sp.

Anti-Onchocerca and Anti-Caenorhabditis Activity of a Hydro-Alcoholic Extract from the Fruits of Acacia nilotica and Some Proanthocyanidin Derivatives.

Acacia nilotica fruits with high tannin content are used in the northern parts of Cameroon as anti-filarial remedies by traditional healers. In this study, the hydro-alcoholic fruit extract (crude extract (CE)) and, one of the main constituents in its most active fractions, (+)-catechin-3-O-gallate (CG), as well as four related proanthocyanidins, (-)-epicatechin-3-O-gallate (ECG), (+)-gallocatechin (GC), (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-O-gallate (EGCG), were assessed for their potential in vitro anthelmintic properties against the free-living model organism Caenorhabditis elegans and against the cattle filarial parasite Onchocerca ochengi. Worms were incubated in the presence of different concentrations of fruit extract, fractions and pure compounds. The effects on mortality were monitored after 48 h. The plant extract and all of the pure tested compounds were active against O. ochengi (LC50 ranging from 1.2 to 11.5 µg/mL on males) and C. elegans (LC50 ranging from 33.8 to 350 µg/mL on wild type). While high LC50 were required for the effects of the compounds on C. elegans, very low LC50 were required against O. ochengi. Importantly, tests for acute oral toxicity (lowest dose: 10 mg/kg) in Wistar rats demonstrated that crude extract and pure compounds were non-toxic and safe to use. Additionally, the results of cytotoxicity tests with the Caco-2 cell line (CC50 ranging from 47.1 to 93.2 µg/mL) confirmed the absence of significant toxicity of the crude extract and pure compounds. These results are in good accordance with the use of A. nilotica against nematode infections by traditional healers, herdsmen and pastoralists in Cameroon.

Anogeissus leiocarpus extract on the parasite nematode Onchocerca ochengi and on drug resistant mutant strains of the free-living nematode Caenorhabditis elegans.

The ethanolic extract of Anogeissus leiocarpus was assessed for the in vitro anthelmintic activity by using the cattle parasite nematode Onchocerca ochengi as well as levamisole-, ivermectin- and albendazole-resistant mutant strains of the free-living nematode Caenorhabditis elegans, a model organism for research on nematode parasites. Worms were incubated in the presence of different concentrations of the plant extract and effects on survival were monitored after each 12 h to 96 h. The A. leiocarpus extract affected O. ochengi microfilaria, adults, and C. elegans wild-type worms with LC(50) values of 0.06 mg/ml, 0.09 mg/ml after 24h and 0.44 mg/ml after 48 h, respectively. Remarkably, the efficacy of the plant extract was not significantly altered in the ivermectin- and levamisole-resistant C. elegans mutant strains lev-1(e211), glc-2(ok1047), lev-9(x16) and avr-14(ad1302), avr-15(ad1051), glc-1(pk54). The albendazole resistant strain ben-1(e1880) exhibited a moderate increase of the LC(50) value to 1.5mg/ml after 48 h. These results are in good accordance with the use of A. leiocarpus extract against nematode infections by traditional healers, herdsmen and pastoralists. Moreover, the data indicate that the plant extract could be used to treat nematode infections even in cases of drug resistance towards established anthelmintic drugs.