Isolation and structural characterization of flavonoids from E Se tea and their synergistic inhibitory effects on lipid accumulation via regulating AMPK/ACC pathway.

E Se tea, processed by the tender leaves of Malus toringoides (Rehd.) Hughes, has been traditionally used as healthy tea to prevent hyperglycemic, hyperlipidemia and hypertensive disease. This paper firstly performed to explore its bioactive compounds and the possible protective mechanism on lipid accumulation. As a result, 13 flavonoids were isolated and identified, and phlorizin (2) was the most abundant compound in E Se tea. All the flavonoids could reduce TG level in 3T3-L1 preadipocytes. Oil red O staining results also verified that these flavonoids could inhibit the production of lipid droplet. Among them, compounds 2 and 6 have the strongest inhibitory effects on lipid accumulation. In addition, the synergistic effects between compound 2 and other compounds were further evaluated. Compared with individual flavonoid, most of combinations significantly reduced lipid accumulation, especially compounds 2 and 6. Western blotting analysis suggested compounds 2 and 6 could promote the phosphorylation of AMPK and ACC proteins. Furthermore, molecular docking results suggested that compounds 2 and 6 tightly bonded to AMPK by hydrogen bonding and electrostatic interaction. All the results suggested there was a significant synergistic effect between compounds 2 and 6 for inhibiting the lipid accumulation in 3T3-L1 preadipocytes. Therefore, E Se tea could be served as healthy tea to regulate lipid metabolism. [Display omitted] • The 13 Flavonoids were isolated and identified from the extract of E Se tea. • The inhibitory effects of 13 flavonoids on lipid accumulation were evaluated in adipocytes. • Synergistic inhibitory effects of flavonoid combinations were evaluated on lipid accumulation. • Molecular docking technology and western blotting were determined the mechanism. [ABSTRACT FROM AUTHOR]