Anti-diabetic potential of apigenin, luteolin, and baicalein via partially activating PI3K/Akt/GLUT-4 signaling pathways in insulin-resistant HepG2 cells

Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities. In this study, apigenin, luteolin, and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant (IR) HepG2 cells. All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4 (GLUT4) and phosphor-glycogen synthase kinase (GSK-3 beta). These flavonoids significantly inhibited the production of reactive oxygen species (ROS) and advanced glycation end-products (AGEs), which were closely related to the suppression of the phosphorylation form of NF-kappa B and P65. The expression levels of insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in IR-HepG2 cells were all partially activated by the flavonoids, with variable effects. Furthermore, the intracellular metabolic conditions of the flavonoids were also evaluated.(c) 2023 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study evaluated the anti-diabetic effect of apigenin, luteolin, and baicalein in insulin-resistant HepG2 cells. These flavonoids improved glucose consumption and glycogen synthesis abilities by activating GLUT4 and GSK-3 beta. They also inhibited the production of ROS and AGEs, which were related to the inhibition of NF-kappa B and P65 phosphorylation. The expression levels of IRS-1, IRS-2, and PI3K/Akt pathway were partially activated by the flavonoids.