Chondroitin sulfate has been widely administered orally to improve knee osteoarthritis. Chondroitin sulfate also has various biological properties, such as anti-inflammatory, immunomodulatory, anti-oxidative, and antitumor activity. However, chondroitin sulfate absorption in the digestive system and bioavailability remains controversial owing to its large molecular weight. In this study, we aimed to evaluate the absorption of chondroitin sulfate oligosaccharides, depolymerized chondroitin sulfate with low molecular weight, in oral administration to humans. Four types of chondroitin sulfate with varying molecular weight [chondroitin sulfate tetrasaccharide (MW. 980), CSOS-1 (MW. 1,500), CSOS-2 (MW. 2,800), and HMWCS (MW. 70,000)] were orally administered and quantified in plasma and urine. Exogenous chondroitin sulfate in these samples was quantified using a high-performance liquid chromatography system equipped with a fluorescence detector. Quantitative changes of administered chondroitin sulfate tetrasaccharide showed similar patterns in plasma and urine, therefore it was presumed that the amount of exogenous chondroitin sulfate excreted in urine reflects its quantitative profile in blood. Considering urinary exogenous chondroitin sulfate as a parameter of intestinal chondroitin sulfate absorption, urinary contents of orally administered chondroitin sulfate with varying molecular weight were compared. Consequently, the amount of urinary exogenous chondroitin sulfate in 24 h after administration was higher in the chondroitin sulfate oligosaccharides group than that in the high molecular weight chondroitin sulfate group. Additionally, in the molecular weight distribution, urinary exogenous chondroitin sulfate after chondroitin sulfate oligosaccharides administration showed a lower content of chondroitin sulfate oligosaccharides with a higher molecular weight than that observed before administration. In summary, our results demonstrated for the first time that lower molecular weight of chondroitin sulfate is more efficiently absorbed through the digestive tract in human, and the improvement of its bioavailability is expected.

中文翻译：

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人血浆和尿液中口服硫酸软骨素低聚糖的定量。

硫酸软骨素已被广泛口服以改善膝骨关节炎。硫酸软骨素还具有多种生物学特性，如抗炎、免疫调节、抗氧化和抗肿瘤活性。然而，由于硫酸软骨素的分子量较大，其在消化系统中的吸收和生物利用度仍然存在争议。在本研究中，我们旨在评估硫酸软骨素低聚糖（低分子量解聚硫酸软骨素）在人体口服给药时的吸收情况。口服并定量四种不同分子量的硫酸软骨素[硫酸软骨素四糖（MW.980）、CSOS-1（MW.1,500）、CSOS-2（MW.2,800）和HMWCS（MW.70,000）]并进行定量血浆和尿液中。使用配备荧光检测器的高效液相色谱系统对这些样品中的外源硫酸软骨素进行定量。给予的硫酸软骨素四糖的定量变化在血浆和尿液中显示出相似的模式，因此推测尿液中排泄的外源性硫酸软骨素的量反映了其在血液中的定量特征。以尿外源性硫酸软骨素作为肠道硫酸软骨素吸收的参数，比较不同分子量口服硫酸软骨素的尿含量。因此，给药后24小时尿中外源性硫酸软骨素的量在硫酸软骨素寡糖组中高于高分子量硫酸软骨素组。另外，在分子量分布中，给予硫酸软骨素寡糖后的尿外源性硫酸软骨素显示，与给予之前观察到的相比，硫酸软骨素寡糖的含量较低，而分子量较高。总之，我们的研究结果首次证明，较低分子量的硫酸软骨素可以更有效地通过人体消化道吸收，并且有望提高其生物利用度。