Royal Jelly-derived Two Compounds, 10-hydroxy-2-decenoic acid and a Biotinylated Royalisin-related Peptide, Alleviate Anaphylactic Hypothermia In vivo

Abstract

Abstract Platelet-activating factor (PAF) is an important mediator of allergic reactions such as anaphylaxis, and is therefore an anaphylactic drug target. Previously, we found marked inhibition of anaphylactic reactions by a synthetic N-terminally biotinylated peptide (BP21) capable of specifically binding PAF. In this study, we investigated the effects of 10-hydroxy-2-decenoic acid (10-HDA) and various peptides derived from royalisin, both of which are widely known to be major components of royal jelly from honeybees, on PAF/histamine-induced rat hind-paw edema and mouse anaphylactic hypothermia. In a rat model of hind paw edema, both 10-HDA (50 nmol/paw) and a royalisin-related N-terminally biotinylated peptide, Biotin-RL-Y11, (10 nmol/paw) markedly inhibited PAF-induced paw edema by 95.5±5.0% and 71.9±9.9%, respectively. 10-HDA also inhibited histamine-induced paw edema by 42.7±19.2%. In contrast, three peptides with N-terminal HDA modifications, namely 10-HDA-RL-Y11, 10-HDA-RL-R11, and 10-HDA-P21 only weakly inhibited PAF-induced paw edema. In a mouse model of anaphylaxis, the administration of 10-HDA (100-1000 nmol/mouse) and/or Biotin-RL-Y11 (100 nmol/mouse) showed the inhibitory effects on anaphylactic hypothermia. These results suggest that both 10-HDA and Biotin-RL-Y11 may exert an anti-anaphylactic effect targeting PAF. Graphical abstract