Magnolol and Honokiol Are Novel Antiparasitic Compounds from <i>Magnolia officinalis</i> That Target the Mitochondrial Electron Transport Chain

Parasitic worms are a global health concern in low- and middle-income countries, while also severely limiting livestock production. Treatment of worm infections relies on a limited number of synthetic anthelmintic drug classes, which may accelerate the development of resistance. Here, we identified two compounds, honokiol and magnolol, from <i>Magnolia officinalis</i>, which exhibit potent effects against <i>Ascaris suum</i> larvae, with EC₅₀ values of 8.128 μM and 11.08 μM, respectively. Using RNA-seq analysis on <i>Caenorhabditis elegans</i> and functional assays of mitochondrial membrane potential, we confirmed that the primary mechanism of action of these two compounds is the inhibition of the mitochondrial electron transport chain (ETC). The inhibition of mitochondrial ETC creates a critical bottleneck for the detoxification process in nematodes due to its disruption of ATP-binding cassette (ABC) transporter function, which is crucial for expelling foreign compounds. These data provide two strong candidates for novel anthelmintic development with a mechanism that targets a critical vulnerability in nematodes.