8-O-Acetylharpagide is not an ecdysteroid agonist

We have reinvestigated the activity of 8-O-acetylharpagide, an iridoid glucoside, as an ecdysteroid agonist. Elbrecht et al. (Insect Biochem. Mol. Biol. 26 (1996) 519) isolated a preparation of this compound from Ajuga reptans L: and ascribed ecdysteroid agonist activity on the basis of the induction of an ecdysteroid-like response in Drosophila melanogaster KcO cells, the displacement of [H-3]ponasterone A from the Drosophila receptor and the activation of an ecdysteroid-regulated gene in a transactivation assay. We provide evidence that the agonist activity derives from contaminating ecdysteroids; A. reptans is a species rich in ecdysteroids. Purified 8-O-acetylharpagide is not active in the D. melanogaster Bu cell bioassay, neither as an agonist nor as an antagonist, nor does it displace [H-3]panasterone A from dipteran or lepidopteran ecdysteroid receptor complexes. (C) 2001 Elsevier Science Ltd. All rights reserved.