From ethnopharmacology to drug design

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Abstract
Nature’s diversity is one of the biggest resources of therapeutic lead compounds. Traditionally-used herbal remedies harbor a variety of bioactive compounds providing researchers with starting points for drug development. Ethnopharmacological investigations of uterotonic plant preparations identified a class of circular and disulfide-rich peptides, called cyclotides, to exhibit strong uterine contractions. In humans one of the physiological regulators of the myometrial contractility is the nonapeptide oxytocin acting on its cognate G protein-coupled receptors. They are considered to represent one of the most promising drug targets with ~30% of all currently marketed drugs acting on these transmembrane receptors. Based on observed similarities regarding the activity and structure of plant cyclotides with human oxytocin we analyzed the pharmacological principle of their action and identified the oxytocin and vasopressin 1a receptors as molecular targets of cyclotides from the Rubiaceae plant Oldenlandia aff...

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