Abstract: In order to develop natural plant-derived hypoglycemic agents for the treatment of type 2 diabetes, an extract rich in flavonoids with a brownish-yellow color was obtained from the leaves of Cyclocarya paliurus, a medicinal and edible plant, by sequential refluxing ethanol extraction and polyamide column chromatography. In the extract, 17 flavonoids were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Meanwhile, the flavonoid-rich extract and the standards of its three representative flavonoid components were evaluated for their ameliorative effect on insulin resistance. A HepG2 cell model of insulin resistance was established under optimized conditions (4.5 g/L glucose, 0.001 μmol/L insulin, 3.5 μmol/L dexamethasone, and 24 induction), which was stable for 48 h and could be treated with metformin, an oral hypoglycemic agent. The flavonoid-rich extract as well as hyperoside and scutellarin at a concentration of 10-2 mg/mL and kaempferol at 10-4 mg/mL were the most effective in ameliorating insulin resistance. Furthermore, we found that the mechanism for the ameliorative effect of flavonoids from Cyclocarya paliurus leaves on insulin resistance may be by alleviating glycogen metabolism disorders and increasing oxidative stress in the insulin resistance model.

Key words: Cyclocarya paliurus leaves; flavonoids; insulin resistance; HepG2 cells