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Ficus pumila获得的同型半乳糖醛酸 (HG) FPLP据报道，L. 具有抗糖尿病活性，但它如何受 HG 的甲基酯化 (DM) 程度的影响尚不清楚。为全面分析DM在抗胰岛素HepG2细胞降血糖中的作用，以FPLP(DM25)为原料，通过乙酰氯酸化碱或甲醇制备HG衍生物(0 < DM < 100)。有趣的是，二次曲线关系显示，降血糖作用随着 DM 的增加而增加，然后减少，并且以 DM54 最为明显。DM 可能通过细胞摄取改变细胞内药物浓度来调节活性。此外，HG-DMn (0 < n < 100) 依赖于大胞饮作用，而 HG-DMn (30 < n < 100) 也依赖于小窝介导的内吞作用。对于 HG，亲油性更高，粒径更小，并且涉及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。这项工作为未来研究结构-活性关系提供了思路。