Effects on sheep of the milkweeds Asclepias eriocarpa and A. labriformis and of cardiac glycoside-containing derivative material

Benson, Janet M.; Seiber, James N.; Bagley, Clell V.; Keeler, R. F.; Johnson, Alexis; Young, Stuart

doi:10.1016/0041-0101(79)90294-0

Cited by 20 publications

(8 citation statements)

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“…Voruscharin, uscharin, and labriformin are structurally similar nitrogen-containing cardenolides, yet we only found voruscharin to be a highly potent inhibitor of porcine Na + /K + -ATPase. Nonetheless, labriformin was reported to be toxic to livestock (Benson et al 1979) and highly emetic to bird predators, but is metabolically converted and not stored by monarchs (Brower et al 1982); thus, perhaps the defensive function of these compounds goes beyond inhibition of (porcine) Na + /K + -ATPase. Farrell and Mitter (1998) proposed a very attractive hypothesis of cardenolide escalation that was based on Ehrlich and Raven's (1964) coevolutionary model.…”

Section: Discussionmentioning

confidence: 99%

Toxicity of Milkweed Leaves and Latex: Chromatographic Quantification Versus Biological Activity of Cardenolides in 16 Asclepias Species

et al. 2018

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Cardenolides are classically studied steroidal defenses in chemical ecology and plantherbivore coevolution. Although milkweed plants (Asclepias spp.) produce up to 200 structurally different cardenolides, all compounds seemingly share the same well-characterized mode of action, inhibition of the ubiquitous Na + /K + ATPase in animal cells. Over their evolutionary radiation, milkweeds show a quantitative decline of cardenolide production and diversity. This reduction is contrary to coevolutionary predictions and could represent a costsaving strategy, i.e. production of fewer but more toxic cardenolides. Here we test this hypothesis by tandem cardenolide quantification using HPLC (UV absorption of the unsaturated lactone) and a pharmacological assay (in vitro inhibition of a sensitive Na + /K + ATPase) in a comparative study of 16 species of Asclepias. We contrast cardenolide concentrations in leaf tissue to the subset of cardenolides present in exuding latex. Results from the two quantification methods were strongly correlated, but the enzymatic assay revealed that milkweed cardenolide mixtures often cause stronger inhibition than equal amounts of a nonmilkweed reference cardenolide, ouabain. Cardenolide concentrations in latex and leaves were positively correlated across species, yet latex caused 27% stronger enzyme inhibition than equimolar amounts of leaf cardenolides. Using a novel multiple regression approach, we found three highly potent cardenolides (identified as calactin, calotropin, and voruscharin) to be 2 primarily responsible for the increased pharmacological activity of milkweed cardenolide mixtures. However, contrary to an expected trade-off between concentration and toxicity, laterdiverging milkweeds had the lowest amounts of these potent cardenolides, perhaps indicating an evolutionary response to milkweed's diverse community of specialist cardenolidesequestering insect herbivores.

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Section: Discussionmentioning

confidence: 99%

Toxicity of Milkweed Leaves and Latex: Chromatographic Quantification Versus Biological Activity of Cardenolides in 16 Asclepias Species

et al. 2018

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“…Much of the veterinary literature from Africa and North America strongly implicates cardenolides as potent plant defenses against do mestic livestock, including sheep, horses, cattle, and goats (Watt and Breyer-Brandwijk, 1962;Benson et al, , 1979Cronin et al, 1978;Laycock, 1978;Seiber et al, 1983;Joubert, 1989). Brower and colleagues (1988) also illustrated very clearly with photographs how grazing cattle leave intact the highly toxic milkweeds A. curassavica in Florida and A. eriocarpa in California (see also Figure 1).…”

Section: A Mammalian Herbivores and Milkweedsmentioning

confidence: 99%

Cardenolide-Mediated Interactions between Plants and Herbivores

Malcolm¹

1991

Herbivores: Their Interactions With Secondary Plant Metabolites

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“…3 Plants of the genus Asclepias (milkweed family) are widely distributed, mainly in the tropics and subtropics, and are well known causes of death in sheep and cattle in open-range grazing. 4,5 It is common in grassland and is often planted in gardens because it attracts butterflies.…”

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confidence: 99%