Toxic cardenolides: chemical ecology and coevolution of specialized plant–herbivore interactions


Author for correspondence:
Anurag A. Agrawal
Tel: +1 607 254 4255



I.Historic background and introduction29
II.Diversity of cardenolide forms29
IV.Cardenolide variation among plant parts31
V.Phylogenetic distribution of cardenolides32
VI.Geographic distribution of cardenolides34
VII.Ecological genetics of cardenolide production34
VIII.Environmental regulation of cardenolide production34
IX.Biotic induction of cardenolides36
X.Mode of action and toxicity of cardenolides38
XI.Direct and indirect effects of cardenolides on specialist and generalist insect herbivores39
XII.Cardenolides and insect oviposition39
XIII.Target site insensitivity40
XIV.Alternative mechanisms of cardenolide resistance40
XV.Cardenolide sequestration41


Cardenolides are remarkable steroidal toxins that have become model systems, critical in the development of theories for chemical ecology and coevolution. Because cardenolides inhibit the ubiquitous and essential animal enzyme Na+/K+-ATPase, most insects that feed on cardenolide-containing plants are highly specialized. With a huge diversity of chemical forms, these secondary metabolites are sporadically distributed across 12 botanical families, but dominate the Apocynaceae where they are found in > 30 genera. Studies over the past decade have demonstrated patterns in the distribution of cardenolides among plant organs, including all tissue types, and across broad geographic gradients within and across species. Cardenolide production has a genetic basis and is subject to natural selection by herbivores. In addition, there is strong evidence for phenotypic plasticity, with the biotic and abiotic environment predictably impacting cardenolide production. Mounting evidence indicates a high degree of specificity in herbivore-induced cardenolides in Asclepias. While herbivores of cardenolide-containing plants often sequester the toxins, are aposematic, and possess several physiological adaptations (including target site insensitivity), there is strong evidence that these specialists are nonetheless negatively impacted by cardenolides. While reviewing both the mechanisms and evolutionary ecology of cardenolide-mediated interactions, we advance novel hypotheses and suggest directions for future work.