Oral Ingestion of Jellyfish Collagen Hydrolysate Effectively Delivers a Bioactive Tripeptide, Gly-3Hyp-4Hyp, into the Blood and Skin.

A growing body of literature reports the health benefits of the jellyfish collagen hydrolysate. However, although hydroxyproline (Hyp)-containing oligopeptides absorbed into the bloodstream are considered responsible for the biological functions of collagen hydrolysate, the active ingredient specific to jellyfish collagen remains unclear. Here, we revealed that a collagenase-digested cannonball jellyfish collagen hydrolysate is highly enriched with a bioactive tripeptide, Gly-3Hyp-4Hyp (15.6 mg/g). In humans, oral ingestion of the jellyfish collagen hydrolysate resulted in a 7.8-fold higher blood absorption of Gly-3Hyp-4Hyp than that of ingesting bovine collagen hydrolysate. Remarkably, its concentration surpassed that of Pro-Hyp, which is conventionally the predominant blood-absorbable peptide. Furthermore, in mice, Gly-3Hyp-4Hyp was efficiently delivered to the skin after jellyfish collagen hydrolysate administration, showing a 19-fold greater accumulation compared with the bovine group, whereas other Hyp-containing oligopeptides exhibited minimal transport. This remarkable bioavailability and effective tissue delivery suggest that Gly-3Hyp-4Hyp is a major candidate driving the biological functions of the jellyfish collagen hydrolysate.