Abstract
Among nine flavonols ( 1– 9) obtained from Sophorae Flos, we first isolated compounds 4, 5, 8, and 9. These isolates ( 1– 9) were evaluated for the phosphorylation of AMPK and ACC. Administered at 10 μM, 9 possessed high potent activity. Compound 9 displayed a dose-dependent stimulation of glucose uptake in 3T3-L1 cells, and this increase was obviously attenuated by compound C, an AMPK inhibitor. In addition, 9 also phosphorylated AMPK and its downstream substrate ACC in 3T3-L1 cells in a time- and dose-dependent manner. Moreover, we discovered that compound C inhibits 9-stimulated ACC phosphorylation and motivated the 9-inhibited C/EBP α and PPAR γ, and FAS gene expression, significantly. These results revealed the role of the AMPK downstream signaling pathway in 9-improved glucose metabolism in 3T3-L1 cells and 9-inhibited adipocyte differentiation. Differentiation was investigated by Oil Red O staining activity after 9 administration (0–20 μM) in 6 days. Compound 9 decreased mean droplet size in a dose-dependent manner. The results revealed that 9 blocked adipogenic conversion in 3T3-L1 cells together with several significant downregulating adipocyte-specific transcription factors, including PPAR γ, C/EBP α, and SREBP1. It also reduced FAS gene expression in a dose-dependent manner, which is crucial for adipogenesis in vitro.
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