| Sammanfattning: | This study aimed to systematically explore the chemical constituents of <i>D. nobile</i> and its hypoglycemic effect by UPLC-ESI-Q-Orbitrap, network pharmacology and in vivo experiment. The chemical constituents of <i>D. nobile</i> 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 <i>D. nobile</i>. 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 <i>D. nobile</i> extract and <i>D. nobile</i> polysaccharide for two months by gavage. The results showed that a total of 39 chemical constituents of <i>D. nobile</i>, including alkaloids, bibenzyls, phenanthrenes and other types of compounds, were identified. <i>D. nobile</i> extract and <i>D. nobile</i> 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, <i>trans-N</i>-feruloyltyramine, gigantol, moscatilin, 4-<i>O</i>-methylpinosylvic acid, venlafaxine, nordendrobin and tristin were regarded as the key hypoglycemic compounds of <i>D. nobile</i>, 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 <i>D. nobile</i> 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 <i>D. nobile</i> might be associated with liver glycogen synthesis and gluconeogenesis, contributing to improving insulin resistance and abnormal glucose metabolism in the T2DM rats.
|
|---|