Hedera helix-derived α−hederin (IVL-11) demonstrates both ex vivo and in vivo flukicidal activities against Fasciola hepatica

TY - JOUR

T1 - Hedera helix-derived α−hederin (IVL-11) demonstrates both ex vivo and in vivo flukicidal activities against Fasciola hepatica

AU - Davey, Sarah D.

AU - Chakroborty, Anand

AU - Payne, Joseph

AU - Burgess, Adam M.G.

AU - Hulme, Benjamin J.

AU - Bouillon, Marc E.

AU - Thomas, Dafydd A.

AU - Cervi, Anna

AU - Padalino, Gilda

AU - Cookson, Alan

AU - Al-Najjar, Ayman

AU - Frame, Laura

AU - Fenn, Caroline

AU - Holdsworth, Peter

AU - Lahmann, Martina

AU - McNally, Vincent

AU - Fisher, Maggie

AU - Baird, Mark S.

AU - Hoffmann, Karl F.

N1 - Publisher Copyright: © 2026 The Authors.

PY - 2026/2/13

Y1 - 2026/2/13

N2 - Infection with Fasciola hepatica (liver flukes) causes fascioliasis in humans and fasciolosis in ruminants. The current strategy for controlling fascioliasis/fasciolosis is predominantly mediated by chemotherapy with triclabendazole (TCBZ). As this flukicide targets newly excysted juveniles (NEJs), immature flukes and mature liver flukes, it’s use as the frontline chemotherapy for over four decades has led to widespread drug resistance. New chemotherapeutics are, therefore, urgently required. Here, continuing our studies of flukicidal phytochemicals derived from Hedera helix (common ivy), we investigated the anthelmintic properties of three ivy fruit saponins, including α-hederin ( IVL-11 ), against F. hepatica . During ex vivo culture, IVL-11 was as effective as TCBZ in killing NEJs and immature flukes. However, this saponin acted more quickly than TCBZ when tested against mature flukes. Microscopic examination of IVL-11 treated liver flukes revealed surface integrity breaches, actin disorganisation and cell membrane permeabilisation. Upon in vivo studies, using a novel method to isolate IVL-11 in large quantities from H. helix leaf, oral delivery of IVL-11 (up to 250 mg/kg bodyweight) to Ovis aries (sheep) was found to be safe, well-tolerated and detectable in the liver, peripheral blood, hepatic portal blood and bile. IVL-11 (250 mg/kg bodyweight) treatment of O. aries infected with F. hepatica led to a significant reduction in fluke body sizes as well as a delay and decrease in fecundity during in vivo efficacy studies. Together, our results confirm that IVL-11 exhibits flukicidal characteristics suitable for progression as a renewably obtained, natural product for treating fasciolosis.

AB - Infection with Fasciola hepatica (liver flukes) causes fascioliasis in humans and fasciolosis in ruminants. The current strategy for controlling fascioliasis/fasciolosis is predominantly mediated by chemotherapy with triclabendazole (TCBZ). As this flukicide targets newly excysted juveniles (NEJs), immature flukes and mature liver flukes, it’s use as the frontline chemotherapy for over four decades has led to widespread drug resistance. New chemotherapeutics are, therefore, urgently required. Here, continuing our studies of flukicidal phytochemicals derived from Hedera helix (common ivy), we investigated the anthelmintic properties of three ivy fruit saponins, including α-hederin ( IVL-11 ), against F. hepatica . During ex vivo culture, IVL-11 was as effective as TCBZ in killing NEJs and immature flukes. However, this saponin acted more quickly than TCBZ when tested against mature flukes. Microscopic examination of IVL-11 treated liver flukes revealed surface integrity breaches, actin disorganisation and cell membrane permeabilisation. Upon in vivo studies, using a novel method to isolate IVL-11 in large quantities from H. helix leaf, oral delivery of IVL-11 (up to 250 mg/kg bodyweight) to Ovis aries (sheep) was found to be safe, well-tolerated and detectable in the liver, peripheral blood, hepatic portal blood and bile. IVL-11 (250 mg/kg bodyweight) treatment of O. aries infected with F. hepatica led to a significant reduction in fluke body sizes as well as a delay and decrease in fecundity during in vivo efficacy studies. Together, our results confirm that IVL-11 exhibits flukicidal characteristics suitable for progression as a renewably obtained, natural product for treating fasciolosis.

KW - Fasciola hepatica

KW - Hedera helix

KW - saponin

KW - α-hederin

UR - https://www.scopus.com/pages/publications/105029974280

U2 - 10.1016/j.biopha.2026.119123

DO - 10.1016/j.biopha.2026.119123

M3 - Article

C2 - 41689997

AN - SCOPUS:105029974280

SN - 0753-3322

VL - 196

JO - Biomedicine and Pharmacotherapy

JF - Biomedicine and Pharmacotherapy

M1 - 119123

ER -