Hot cuisine as a source of anti-inflammatory drugs

The shift in nutritional sciences from survival and safety to the promotion of well-being has led to systematic investigations on the biological activity of natural products of dietary origin, questioning the assumption that food plants contain little if any secondary metabolites apart those revealed by our senses and responsible for their colour, taste, and flavour. With 25% of the human population consuming chilli pepper every day, capsaicin is the most important pharmacological agent we get from our diet, and the study of its pungency set in motion a multidisciplinary investigation that ultimately led to the discovery of vanilloid receptors (TRPVs), a class of ion channels involved in thermo-, chemo-, and mechanosensation, and whose malfunctioning is implicated in neurogenic inflammation and a host of other pathological conditions. A series of studies centred on the modification of capsaicin will be described, focusing on a) the preparation of a library of unnatural natural capsaicinoids and the identification of leads with the lipophilic C-moiety amenable to structure-activity study, and b) the reversal of the biological activity of capsaicin from a TRPV1 agonist into an antagonist by modification of its vanillyl moiety.