Rubiscolins: Biologically active peptides of plant origin

Abstract

Two food-derived opioid peptides with high δ-opioid receptor affinity and selectivity, rubiscolin-5 and rubiscolin-6, were isolated from spinach leaves in 2001. Ribulose 1,5-bisphosphate carboxylase/oxygenase [EC 4.1.1.39 (RuBisCO)], digested by pepsin, is known as a precursor for them. The most important advantage of rubiscolins is their oral bioavailability. Both peptides produced analgesia not only after intracerebroventricular administration, but also orally. Moreover, rubiscolin-6 enhanced memory consolidation, influenced the processes of learning and memory, and reduced anxiety. In an animal model of acute stress, rubiscolin-6 induced an antidepressive-like effect. Moreover, this peptide regulated food intake, stimulated appetite in mice fed a balanced diet and suppressed food intake in case of high-fat diet. This review summarizes various biological activities of rubiscolins and recent developments on the structure-activity relationship of rubiscolin analogs, aimed at improving their pharmacological properties. Naturally occurring opioids, such as rubiscolins, can serve as the basis of new therapeutics or functional foods.