Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, PR China.
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, PR China.
Int J Biol Macromol. 2019 Mar 15;125:605-611. doi: 10.1016/j.ijbiomac.2018.12.064. Epub 2018 Dec 7.
Epigallocatechin-3-O-gallate (EGCG), a tea polyphenol is renowned for its anti-diabetic properties, however limited studies elucidate its hypoglycemic mechanism from multi-perspectives. In the present study, the interaction between EGCG and α-glucosidase was investigated through kinetics analysis, fluorescence spectra, Fourier transform infrared (FT-IR) spectra and molecular docking studies. Additionally, the effect of EGCG on glucose uptake and its related signaling pathway in L6 muscle cells were also investigated. The results showed that the α-glucosidase inhibitory activity of EGCG (IC = 19.5 ± 0.3 μM) was higher than that acarbose (IC = 278.7 ± 1.1 μM). EGCG inhibited α-glucosidase in a reversible and non-competitive manner. EGCG quenched the fluorescence of α-glucosidase due to the complex formation between EGCG and α-glucosidase, where the hydrogen bonds played a critical role. Microenvironment and the secondary structure of α-glucosidase were highly influenced by EGCG. Molecular docking results indicated that the binding sites on α-glucosidase for EGCG were close to the active site pocket of the enzyme. EGCG was also found to enhance the glucose uptake and promote GLUT4 translocation to plasma membrane via PI3K/AKT signaling pathway in L6 skeletal muscle cells. Overall, these results revealed the possible hypoglycemic mechanism of EGCG.
没食子酸表没食子儿茶素酯（EGCG）是一种著名的具有抗糖尿病特性的茶多酚，但有限的研究从多角度阐明了其降血糖机制。在本研究中，通过动力学分析、荧光光谱、傅里叶变换红外（FT-IR）光谱和分子对接研究，研究了 EGCG 与α-葡萄糖苷酶之间的相互作用。此外，还研究了 EGCG 对 L6 肌细胞葡萄糖摄取及其相关信号通路的影响。结果表明，EGCG（IC=19.5±0.3μM）对α-葡萄糖苷酶的抑制活性高于阿卡波糖（IC=278.7±1.1μM）。EGCG 以可逆和非竞争性方式抑制α-葡萄糖苷酶。EGCG 由于 EGCG 与α-葡萄糖苷酶之间的复合物形成而猝灭了α-葡萄糖苷酶的荧光，其中氢键起着关键作用。EGCG 高度影响α-葡萄糖苷酶的微环境和二级结构。分子对接结果表明，EGCG 在α-葡萄糖苷酶上的结合位点靠近酶的活性位点口袋。还发现 EGCG 通过 PI3K/AKT 信号通路增强 L6 骨骼肌细胞中的葡萄糖摄取并促进 GLUT4 向质膜易位。总体而言，这些结果揭示了 EGCG 可能的降血糖机制。
