International Journal of Molecular Sciences (Jun 2023)

Therapeutic Potential of Orally Administered Rubiscolin-6

  • Yusuke Karasawa,
  • Kanako Miyano,
  • Masahiro Yamaguchi,
  • Miki Nonaka,
  • Keisuke Yamaguchi,
  • Masako Iseki,
  • Izumi Kawagoe,
  • Yasuhito Uezono

DOI
https://doi.org/10.3390/ijms24129959
Journal volume & issue
Vol. 24, no. 12
p. 9959

Abstract

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Rubiscolins are naturally occurring opioid peptides derived from the enzymatic digestion of the ribulose bisphosphate carboxylase/oxygenase protein in spinach leaves. They are classified into two subtypes based on amino acid sequence, namely rubiscolin-5 and rubiscolin-6. In vitro studies have determined rubiscolins as G protein-biased delta-opioid receptor agonists, and in vivo studies have demonstrated that they exert several beneficial effects via the central nervous system. The most unique and attractive advantage of rubiscolin-6 over other oligopeptides is its oral availability. Therefore, it can be considered a promising candidate for the development of a novel and safe drug. In this review, we show the therapeutic potential of rubiscolin-6, mainly focusing on its effects when orally administered based on available evidence. Additionally, we present a hypothesis for the pharmacokinetics of rubiscolin-6, focusing on its absorption in the intestinal tract and ability to cross the blood–brain barrier.

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