The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, PR China.
Shanghai Frontiers Science Center for Traditional Chinese Medicine Chemical Biology, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, PR China.
Carbohydr Polym. 2022 Oct 1;293:119741. doi: 10.1016/j.carbpol.2022.119741. Epub 2022 Jun 18.
A homogalacturonan (HG) FPLP obtained from Ficus pumila L. was reported to have anti-diabetic activity but how this is influenced by degree of methyl-esterification (DM) of HG is unknown. To comprehensively analyze the role of DM in hypoglycemic activity in insulin-resistant HepG2 cells, HG derivatives (0 < DM < 100) were prepared from FPLP (DM25) by alkali or methanol acidified with acetyl chloride. Interestingly, a quadratic curve relationship revealed that hypoglycemic effect increased and then decreased with DM, and which was the most pronounced with DM54. DM might regulate activity by altering the intracellular drug concentration through cellular uptake. Furthermore, HG-DMn (0 < n < 100) were dependent on macropinocytosis, while HG-DMn (30 < n < 100) were also dependent on caveolae-mediated endocytosis. For HG, higher lipophilicity, smaller particle size, and more endocytosis mechanisms involved were favorable for cellular uptake, thereby increasing the intracellular drug concentration and enhancing the hypoglycemic activity. This work provides ideas for future investigations on structure-activity relationships.
从榕属植物中提取的均质半乳糖醛酸（HG） FPLP 具有抗糖尿病活性，但 HG 的甲酯化程度（DM）如何影响其活性尚不清楚。为了全面分析 DM 在胰岛素抵抗 HepG2 细胞中降血糖活性中的作用，用碱或甲醇（用乙酰氯酸化）从 FPLP（DM25）制备了 HG 衍生物（0<DM<100）。有趣的是，二次曲线关系表明，降血糖作用随着 DM 的增加而先增加后降低，在 DM54 时最为明显。DM 可能通过改变细胞内药物浓度来调节活性，这是通过细胞摄取实现的。此外，HG-DMn（0<n<100）依赖巨胞饮作用，而 HG-DMn（30<n<100）也依赖网格蛋白介导的内吞作用。对于 HG，更高的亲脂性、更小的粒径和更多的内吞作用机制有利于细胞摄取，从而增加细胞内药物浓度并增强降血糖活性。这项工作为进一步研究结构-活性关系提供了思路。
