Distribution of Prolylhydroxyproline and Its Metabolites after Oral Administration in Rats

Abstract

Prolylhydroxyproline (Pro-Hyp), which is derived from collagen hydrolysate, has been shown to be beneficial for skin and joint health. However, little is known about the distribution of Pro-Hyp in these tissues. In the present study, we investigated the biodistribution of orally administered [ 14 C]Pro-Hyp in rats. Whole-body autoradiography at 30 min after administration of [ 14 C]Pro-Hyp showed that radioactivity is widely distributed in tissues including skin and articular cartilage, with the highest level of radioactivity observed in the gastric and intestinal walls. Incorporation of radioactivity into cells known to respond to ProHyp such as dermal fibroblasts, synovial cells, chondrocytes, osteoblasts, and osteoclasts was observed. The chemical form of [ 14 C]Pro-Hyp-derived radioactivity detected in the tissues was investigated by thin layer chromatography. The radioactive constituents in cartilage extract were two proline-modified peptides (56%), intact Pro-Hyp (5%), and two nonpeptide metabolites (28%). Similar results were obtained for skin and bone marrow. Plasma analysis at 3 to 30 min post-dose suggested that the majority of Pro-Hyp is modified in its proline residue by a first-pass effect without peptide bond hydrolysis. In conclusion, we demonstrated that Pro-Hyp is partly distributed in observed tissues including skin and cartilage in its intact form, which might be responsible for its biological functions.

Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and anti-inflammatory in murine posttraumatic osteoarthritis

“…Once in the serum, these peptide fragments presumably have access to all organ systems, with one report confirming distribution of a radiolabeled preparation to skeletal elements, muscle, skin and cartilage in rats [63]. Another study performed in rats provides autoradiographic evidence for the presence of radiolabeled proline-hydroxyproline dipeptide in articular cartilage and synovium within 30 minutes of ingestion [64]. As mentioned earlier in this report, there are also in vitro data indicating that various types of collagen peptides can directly affect chondrocyte function [19, 45, 55, 57], supporting the hypothesis that absorbed collagen peptide fragments could directly influence cell behavior in the joint.…”

Oral Intake of Specific Bioactive Collagen Peptides Reduces Skin Wrinkles and Increases Dermal Matrix Synthesis

“…Especially the efficacy of orally administered collagen peptides on skin health has been demonstrated in several investigations [14,15,16,17]. …”

Effects of Food-Derived Collagen Peptides on the Expression of Keratin and Keratin-Associated Protein Genes in the Mouse Skin

“…Oral intake of collagen was proven safe in an animal model [13], and intestinal absorption and tissue distribution of gelatin hydrolysates, hydrolyzed products of collagen, were assessed in a study using 14 C-labeled hydrolysates [14,15]. Recent clinical studies have also established that oral intake of collagen peptides (CP) reduces skin wrinkles and improves biophysical parameters in aged skin [16,17].…”