School of Pharmacy, Guizhou Medical University, Guiyang 550025, China.
School of Medicine, Western Sydney University, Penrith, NSW 2751, Australia.
Molecules. 2023 Mar 16;28(6):2683. doi: 10.3390/molecules28062683.
This study aimed to systematically explore the chemical constituents of and its hypoglycemic effect by UPLC-ESI-Q-Orbitrap, network pharmacology and in vivo experiment. The chemical constituents of were qualitatively analyzed, and the hypoglycemic compounds were quickly identified. Network pharmacological analysis and molecular docking technique were applied to assist in the elucidation of the hypoglycemic mechanisms of . A type 2 diabetic mellitus (T2DM) rat model was established using the HFD and STZ method for in vivo experimental verification, and these T2DM rats were treated with extract and polysaccharide for two months by gavage. The results showed that a total of 39 chemical constituents of , including alkaloids, bibenzyls, phenanthrenes and other types of compounds, were identified. extract and polysaccharide could significantly ameliorate the body weight, hyperglycemia, insulin resistance, dyslipidemia and morphological impairment of the liver and pancreas in the T2DM rats. α-Linolenic acid, dihydroconiferyl dihydro-p-coumarate, naringenin, -feruloyltyramine, gigantol, moscatilin, 4--methylpinosylvic acid, venlafaxine, nordendrobin and tristin were regarded as the key hypoglycemic compounds of , along with the hypoglycemic effect on the PI3K-AKT signaling pathway, the insulin signaling pathway, the FOXO signaling pathway, the improvement of insulin resistance and the AGE-RAGE signaling pathway. The Western blotting experiment results confirmed that activated the PI3K/AKT pathway and insulin signaling pathway, promoted glycogen synthesis via regulating the expression of glycogen synthase kinase 3 beta (GSK-3β) and glucose transporter 4 (GLUT4), and inhibited liver gluconeogenesis by regulating the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6pase) in the liver. The results suggested that the hypoglycemic mechanism of might be associated with liver glycogen synthesis and gluconeogenesis, contributing to improving insulin resistance and abnormal glucose metabolism in the T2DM rats.
本研究旨在通过 UPLC-ESI-Q-Orbitrap、网络药理学和体内实验系统地探索 和其降血糖作用的化学成分。定性分析 的化学成分，快速鉴定降血糖化合物。应用网络药理学分析和分子对接技术辅助阐明 的降血糖机制。采用 HFD 和 STZ 法建立 2 型糖尿病（T2DM）大鼠模型，进行体内实验验证，并用 提取物和 多糖灌胃治疗两个月。结果表明，共鉴定出 中的 39 种化学成分，包括生物碱、二苄基、菲等类型的化合物。 提取物和 多糖可显著改善 T2DM 大鼠的体重、高血糖、胰岛素抵抗、血脂异常以及肝、胰腺的形态损伤。α-亚麻酸、二氢松柏酰基对香豆酸、柚皮素、-阿魏酰酪胺、大蓟苷、迷迭香酸、4--甲基松柏酸、文拉法辛、北美黄连碱和 tristin 被认为是 的关键降血糖化合物，同时对 PI3K-AKT 信号通路、胰岛素信号通路、FOXO 信号通路、改善胰岛素抵抗和 AGE-RAGE 信号通路具有降血糖作用。Western blot 实验结果证实， 通过激活 PI3K/AKT 通路和胰岛素信号通路，通过调节糖原合酶激酶 3β（GSK-3β）和葡萄糖转运蛋白 4（GLUT4）的表达促进糖原合成，并通过调节磷酸烯醇丙酮酸羧激酶（PEPCK）和葡萄糖 6 磷酸酶（G6pase）的表达抑制肝脏糖异生。结果表明， 的降血糖机制可能与肝糖原合成和糖异生有关，有助于改善 T2DM 大鼠的胰岛素抵抗和异常葡萄糖代谢。
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