Food protein-derived anxiolytic peptides: their potential role in anxiety management.

About one in three people are affected by anxiety disorders during their lifetime. Anxiety episodes can be brief due to a stressful event, but anxiety disorders can last at least 6 months. A wide variety of therapeutic drugs are available for the treatment of anxiety disorders, but due to the associated side effects of these anxiolytics, it is interesting to find alternatives. Some food protein hydrolysates or active peptide fragments present in such hydrolysates provide a natural and promising mean for preventing certain forms of anxiety. To date, only a small number of hydrolysates or peptides from food proteins with anxiolytic-like activity have been characterized. Most of these hydrolysates or peptides have displayed potent anxiolytic profiles in animal or clinical studies. The results suggest that these molecules may exert their effects at different levels. This paper reviews the data of the structure/activity relationship, physiological effects displayed in in vitro and in vivo assays, bioavailability, and safety profiles of anxiolytic peptides.

Orally administered δ opioid agonist peptide rubiscolin-6 stimulates food intake in aged mice with ghrelin resistance.

SCOPE: It is known that a decline in food intake occurs with aging. In this study, we investigated changes in parameters associated with food intake in response to aging, and whether orexigenic peptides stimulated food intake after peripheral administration even in aged mice. METHODS AND RESULTS: Food intake and body weight of 27-month-old male C57BL/6N mice were lower than those of 15-month-old mice. Epididymal and mesenteric fat mass, blood glucose, triglyceride, and leptin levels were also decreased. Meanwhile, the hypothalamic mRNA expression of endogenous orexigenic peptides such as neuropeptide Y (NPY) and agouti-related protein, also called agouti-related peptide, was increased. Next, we tested responsiveness to exogenously administered orexigenic peptides coupled to NPY in aged as well as young mice. Orally administered rubiscolin-6, a δ opioid agonist hexapeptide derived from a major green leaf protein Rubisco, stimulated food intake in 27-month-old mice. In contrast, ghrelin was ineffective after intraperitoneal administration to aged mice, suggesting that the NPY system downstream of ghrelin but not δ opioid receptors might be impaired in aged mice. CONCLUSION: Orally administered rubiscolin-6 stimulates food intake in aged mice with ghrelin resistance.