Absorption and plasma kinetics of collagen tripeptide after peroral or intraperitoneal administration in rats

Abstract

Collagen tripeptide (CTP) is a collagen-derived compound containing a high concentration of tripeptides with a Gly-X-Y sequence. In this study, the concentrations and metabolites of CTP were monitored in rat plasma after its administration. We performed a quantitative analysis using high-performance liquid chromatography tandem mass spectrometry according to the isotopic dilution method with stable isotopes. We confirmed that the tripeptides Gly-Pro-Hyp, Gly-Pro-Ala, and Gly-Ala-Hyp were transported into the plasma. Dipeptides, which are generated by degradation of the N- or C-terminus of the tripeptides Gly-Pro-Hyp, Gly-Pro-Ala, and Gly-Ala-Hyp, were also present in plasma. The plasma kinetics for peroral and intraperitoneal administration was similar. In addition, tripeptides and dipeptides were detected in no-administration rat blood. The pharmacokinetics were monitored in rats perorally administered with Gly-[(3)H]Pro-Hyp. Furthermore, CTP was incorporated into tissues including skin, bone, and joint tissue. Thus, administering collagen as tripeptides enables efficient absorption of tripeptides and dipeptides.

Absorption and Urinary Excretion of Peptides after Collagen Tripeptide Ingestion in Humans

“…PEPT1 mediates tripeptide and dipeptide transport from the intestinal tract both in humans and in rats; therefore, we propose that Gly-Pro-Hyp was digested into Pro-Hyp in the blood and liver via the same mechanism as in rats, after being absorbed into blood in an intact form. 19) Various physiological roles have been described for Pro-Hyp 13,14) and our results indicate that administration of the Gly-Pro-Hyp precursor is a potentially effective means of delivering a high concentration of Pro-Hyp to the body. Although Ichikawa et al reported a Pro-Hyp T max of 2 h in their study monitoring metabolites in the blood after ingestion of fish-scale gelatin (molecular weight (MW) ca.…”

“…In that experiment, we found that metabolites represented by Gly-Pro-Hyp, Pro-Hyp, and Gly-Pro appeared in the blood at comparable rates and concentrations for the two administration routes. 19) This result suggests that the body can absorb peptides efficiently if they are ingested in the tripeptide form. The beneficial effects of ingestion of collagen hydrolysate containing Gly-X-Y tripeptides include bone healing, 20) protection against photoaging, 21) anti-pruritus, 22) and decrease in atherosclerotic plaques.…”

Production Method for Cyclic Dipeptide Derived from Native Collagen

“…The tripeptide fraction (CTP) was isolated by reverse-phase HPLC. The mean molecular weight of CTP was approximately 300, and Gly-Pro-Hyp and Gly-Pro-Ala contents were 34% and 15%, respectively (Yamamoto et al 2015).…”

Gelatin versus its two major degradation products, prolyl‐hydroxyproline and glycine, as supportive therapy in experimental colitis in mice

“…In fact, colonic bacteria have been shown to possess high proteolytic activities (Macfarlane, Cummings, & Allison, ), and amino acids and di‐ or tripeptides can be absorbed in mammalian distal colon by diffusion and the peptide transporter PEPT1, respectively (Binder, ; Wuensch et al., ). Orally administered glycine and Pro‐Hyp, which can be very efficiently absorbed in the small intestine (Craft, Geddes, Hyde, Wise, & Matthews, ; Yamamoto et al., ), should therefore induce higher peak concentrations of glycine and Pro‐Hyp in circulating blood than gelatin, and this may explain their superior anticolitis activities.…”