Toxicity of the spiny thick‐foot Pachypodium

Premise of the Study Pachypodium (Apocynaceae) is a genus of iconic stem‐succulent and poisonous plants endemic to Madagascar and southern Africa. We tested hypotheses about the mode of action and macroevolution of toxicity in this group. We further hypothesized that while monarch butterflies are highly resistant to cardenolide toxins (a type of cardiac glycoside) from American Asclepias , they may be negatively affected by Pachypodium defenses, which evolved independently. Methods We grew 16 of 21 known Pachypodium spp. and quantified putative cardenolides by HPLC and also by inhibition of animal Na + /K + ‐ ATP ase (the physiological target of cardiac glycosides) using an in vitro assay. Pachypodium extracts were tested against monarch caterpillars in a feeding bioassay. We also tested four Asclepias spp. and five Pachypodium spp. extracts, contrasting inhibition of the cardenolide‐sensitive porcine Na + /K + ‐ ATP ase to the monarch's resistant form. Key Results We found evidence for low cardenolides by HPLC , but substantial toxicity when extracts were assayed on Na + /K + ‐ ATP ases. Toxicity showed phylogenetic signal, and taller species showed greater toxicity (this was marginal after phylogenetic correction). Application of Pachypodium extracts to milkweed leaves reduced monarch growth, and this was predicted by inhibition of the sensitive Na + /K + ‐ ATP ase in phylogenetic analyses. Asclepias extracts were 100‐fold less potent against the monarch compared to the porcine Na + /K + ‐ ATP ase, but this difference was absent for Pachypodium extracts. Conclusions Pachypodium contains potent toxicity capable of inhibiting sensitive and cardenolide‐adapted Na + /K + ‐ ATP ases. Given the monarch's sensitivity to Pachypodium , we suggest that these plants contain novel cardiac glycosides or other compounds that facilitate toxicity by binding to Na + /K + ‐ ATP ases.