Rubiscolin‑6 rapidly suppresses the postprandial motility of the gastric antrum and subsequently increases food intake via δ‑opioid receptors in mice

Abstract

rubiscolin-6 is a food-derived opioid peptide found in Spinacia oleracea that has anti-nociceptive, memory-enhancing, anxiolytic-like and anti-depressant effects. rubiscolin-6 has been reported to have two opposing effects on food intake. Food intake is closely connected to gut motility; however, to the best of our knowledge, the effect of rubiscolin-6 on gut motility has not been reported. The present study aimed to investigate the effect of rubiscolin-6 on postprandial motility of the gastric antrum in conscious mice. a catheter was implanted in the gastric antrum of male c57Bl/6J mice. Manometric measurements were performed in fasted male mice and chow was then provided to assess motility in the fed state. rubiscolin-6, the δ-opioid receptor antagonist naltrindole, a mixture of rubiscolin-6 and naltrindole, or vehicle was administered intraperitoneally 30 min after eating. The percentage motor index (%Mi) was then calculated. cumulative food intake was measured in both ad libitum-fed and overnight-fasted mice. The %Mi was significantly lower in mice treated with rubiscolin-6 compared with that in the other groups, but normalized by treatment with the rubiscolin-6/naltrindole mixture. The decrease in %Mi induced by rubiscolin-6 remained for 1 h after administration. Cumulative food intake was significantly higher 4 and 6 h after rubiscolin-6 administration in ad libitum-fed mice but was normalized by the rubiscolin-6/naltrindole mixture. Food intake 30 min after rubiscolin-6 administration was normal, but was higher in mice treated with the rubiscolin-6/naltrindole mixture. Thus, rubiscolin-6 may have a rapid effect to reduce postprandial antral motility and may subsequently increase food intake after this inhibitory effect disappears. These effects were revealed to be mediated through δ-opioid receptors. The orexigenic effect of rubiscolin-6 may be applicable to the treatment of anorexia and cachexia.

Coexpressed δ-, μ-, and κ-Opioid Receptors Modulate Voltage-Gated Ca2+ Channels in Gastric-Projecting Vagal Afferent Neurons

“…These findings may suggest that KOR agonists inhibit vagal afferents that detect gastric distention and regulate satiety and postprandial fullness in healthy individuals, but not in individuals with functional dyspepsia. To our knowledge, no study to date has assessed whether DOR agonists modulate gastric reflexes in clinical populations, but preclinical studies have shown that two delta opioid receptor agonists, Rubiscolin-6 and SNC-80, decrease gastric motility (Broccardo et al, 1998;Ataka et al, 2022).…”

RuBisCO: a sustainable protein ingredient for plant-based foods

“…Similarly, it may play a role in reducing anxiety (Karasawa et al, 2023). In mice, intraperitoneally administration of rubiscolin-6 showed the orexigenic effect that may apply to treat anorexia and cachexia, conditions linked with severe loss of food intake and appetite (Ataka et al, 2022). Spinach-origin rubiscolin-contains naturally occurring opioid peptides, which are selective δ-opioid receptor agonists with antinociceptive effects.…”