Uterotonic plants and their bioactive constituents

Abnormalities in the process of uterine muscle contractility during pregnancy and birth can have major clinical implications, including preterm labour, which is the single largest cause of maternal and prenatal mortality in the Western world and a major contributor to childhood developmental problems. In contrast, induction of labour may be necessary in certain conditions. Currently used interventional therapies to suppress (tocolytic agents) or to induce (uterotonic agents) uterine contractions lack potency and/or selectivity and can have harmful side effects for mother and baby. Nature's diversity has always been, and still is, one of the biggest resources of therapeutic lead compounds. Many natural products exhibit biological activity against unrelated targets, thus providing researchers with starting points for drug development. In this review we will provide an overview of uterine muscle physiology, describe currently available biological screening procedures for testing of uterotonic plant compounds and will summarise traditionally-used uterotonic plants, their active components and their mechanisms, primarily focusing on uterotonic active circular plant peptides called cyclotides. Finally we will comment on the discovery of novel cyclotide-producing plant species and the possibility for the development of novel plant-derived uterotonic and tocolytic drugs