Quantification of orally administered chondroitin sulfate oligosaccharides in human plasma and urine.

Abstract

Chondroitin sulfate (CS) has been widely administered orally to improve knee osteoarthritis (OA). CS also has various biological properties, such as anti-inflammatory, immunomodulatory, anti-oxidative, and anti-tumour activity. However, CS absorption in the digestive system and bioavailability remain controversial owing to its large molecular weight (MW). In this study, we aimed to evaluate the absorption of CS oligosaccharides (CSOS), depolymerized CS with low MW, in oral administration to humans. Four types of CS with varying MW [CS tetrasaccharide (MW. 980), CSOS-1 (MW. 1500), CSOS-2 (MW. 2800), and HMWCS (MW. 70,000)] were orally administered and quantified in plasma and urine. Exogenous CS (Exo-CS) in these samples was quantified using a high-performance liquid chromatography system equipped with a fluorescence detector. Quantitative changes of administered CS tetrasaccharide showed similar patterns in plasma and urine, therefore it was presumed that the amount of Exo-CS excreted in urine reflects its quantitative profile in blood. Considering urinary Exo-CS as a parameter of intestinal CS absorption, urinary contents of orally administered CS with varying MW were compared. Consequently, the amount of urinary Exo-CS in 24hours after administration was higher in the CSOS group than that in the HMWCS group. Additionally, in the MW distribution, urinary Exo-CS after CSOS administration showed a lower content of CSOS with a higher MW than that observed before administration. In summary, our results demonstrated for the first time that lower MW of CS is more efficiently absorbed through the digestive tract in human, and the improvement of its bioavailability is expected.