Lupin (Lupinus spp.) seeds exert anthelmintic activity associated with their alkaloid content

O Dubois ,Cédric Neveu ,Christophe Huau ,Claude Charvet ,Élise Courtot ,Thierry Fassier ,Annabelle Troegeler‐Meynadier ,Cécile Enguehard‐Gueiffier ,Isabelle Théry-Koné ,Fabrice Guégnard ,Frédéric Bouvier ,J.-B Magnin-Robert ,Jacques Cortet ,C Allanic ,Didier Marcon ,Christine Koch ,Leslie Boudesocque-Delaye ,Nicolas Peineau ,Hélène Février ,Guillaume Sallé

doi:10.1038/s41598-019-45654-6

Abstract

The growing range of drug resistant parasitic nematode populations threatens the sustainability of ruminant farming worldwide. In this context, nutraceuticals, animal feed that provides necessary dietary requirements while ensuring parasite control, could contribute to increase farming sustainability in developed and low resource settings. In this study, we evaluated the anthelmintic potential of lupin seed extracts against the major ruminant trichostrongylids, Haemonchus contortus and Teladorsagia circumcincta. In vitro observations showed that seed extracts from commercially available lupin varieties could significantly but moderately inhibit larval migration. This anthelmintic effect was mediated by the seed alkaloid content and was potent against both fully susceptible and multidrug resistant H. contortus isolates as well as a susceptible T. circumcincta isolate. Analytical chemistry revealed a set of four lupanine and sparteine-derivatives with anthelmintic activity, and electrophysiology assays on recombinant nematode acetylcholine receptors suggested an antagonistic mode of action for lupin alkaloids. An in vivo trial in H. contortus infected lupin-fed ewes and goats failed to demonstrate any direct anthelmintic effect of crude lupin seeds but infected lupin-fed goats suffered significantly less parasite-mediated blood losses. Altogether, our findings suggest that the anthelmintic potential of lupin remains limited. However, the potent alkaloids identified could lead to the development of novel drugs or may be used in combination with current anthelmintics to improve their efficacy.

Highlights

Anthelmintic resistance is a major issue for the sustainable management of both human-1 and livestock-infective helminth species[2,3,4]
In an initial attempt to establish the contribution of alkaloids to this inhibitory effect, H. contortus larvae were exposed to the sole alkaloid fraction from alkaloid-rich varieties
(Supplementary Table 3) was minimal for LL151 in the fully susceptible H. contortus isolate (52% ± 2.77% s.d.) and the strongest effect was observed for E063 on the multidrug resistant H. contortus isolate (82% ± 3.58% s.d.)

Summary

Introduction

Anthelmintic resistance is a major issue for the sustainable management of both human-1 and livestock-infective helminth species[2,3,4]. The selective breeding of more resistant strains[12,13], targeted-specific treatment approaches[14], and the use of tannin-rich plant extracts[15,16] have been studied This latter strategy relies on the combined properties of certain forage species with good nutritional properties and bioactive compounds, known as “nutraceuticals”[15]. Regulations in Australian and some European countries impose that lupin seeds should contain no more than 0.02% of alkaloids[26,27] and genetic selection program have established commercial varieties with low alkaloid content[27] This dual property of lupin seeds could be leveraged for the control of GIN in livestock based on the fact that GIN nAChRs are well characterized pharmacological targets for the control of parasitic nematodes[28]. An in vivo trial with commercial lupin seed in growing ewe and goats was implemented to determine whether lupin could serve as a nutraceutical

Methods

Results

Conclusion