Wubuli Abudukahaer, Chai Junwei, Liu Haoqiang, Nijat Dilaram, Li Jianmin, Xia Guoyu, Cao Qi, Zhang Saidan, Huang Weidong, Aipire Adila, Li Jinyao
Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, China.
Urumqi Xinze Ziqi Biotechnology Company, Limited, Urumqi, China.
Front Pharmacol. 2024 Jul 19;15:1431221. doi: 10.3389/fphar.2024.1431221. eCollection 2024.
polysaccharides (GUPS) are widely applied in biomedicine and functional food due to their multiple pharmacological activities and low toxicity. Despite their widespread use, the metabolic profile of GUPS remains poorly understood. To address this gap, we developed a quantitative analysis method that involves labeling GUPS with visible fluorescein (5-DTAF) and near-infrared (NIR) fluorescein (Cy7), resulting in stable conjugates with substitution degrees of 0.81% for 5-DTAF and 0.39% for Cy7. The pharmacokinetic studies showed a biphasic elimination pattern in the blood concentration-time curve following both intravenous and oral administration, consistent with a two-compartment model. Using fluorescence quantification and NIR imaging, we observed that GUPS was distributed to various tissues, exhibiting higher concentrations particularly in liver, kidney and lung. Excretion studies indicated that feces were the major excretion pathway of GUPS after oral administration (60.98%), whereas urine was the main pathway after intravenous administration (31.16%). Notably, GUPS could be absorbed rapidly by gut (T 1 ± 0.61 h) and showed a biological half-time t 26.4 ± 7.72 h after oral administration. Furthermore, the Caco-2 cells uptake studies illustrated that macropinocytosis and clathrin-mediated endocytosis were participated in the transport of GUPS in intestine epithelium. This comprehensive analysis of the pharmacokinetics of GUPS not only enhances our understanding of its metabolic pathways but also establishes a foundational basis for its clinical application, optimizing its therapeutic potential and safety profile.
由于具有多种药理活性且毒性低，葡聚糖（GUPS）在生物医学和功能性食品中得到广泛应用。尽管其应用广泛，但人们对GUPS的代谢概况仍知之甚少。为了填补这一空白，我们开发了一种定量分析方法，该方法涉及用可见荧光素（5 - DTAF）和近红外（NIR）荧光素（Cy7）标记GUPS，从而得到取代度分别为5 - DTAF的0.81%和Cy7的0.39%的稳定共轭物。药代动力学研究表明，静脉注射和口服给药后，血药浓度 - 时间曲线呈现双相消除模式，符合二室模型。通过荧光定量和近红外成像，我们观察到GUPS分布于各种组织，在肝脏、肾脏和肺中浓度尤其较高。排泄研究表明，口服给药后，粪便为GUPS的主要排泄途径（60.98%），而静脉注射后，尿液是主要途径（31.16%）。值得注意的是，GUPS可被肠道快速吸收（T 1 ± 0.61小时），口服给药后生物半衰期为t 26.4 ± 7.72小时。此外，Caco - 2细胞摄取研究表明，巨胞饮作用和网格蛋白介导的内吞作用参与了GUPS在肠上皮中的转运。对GUPS药代动力学的这种全面分析不仅加深了我们对其代谢途径的理解，还为其临床应用奠定了基础，优化了其治疗潜力和安全性。
