The selected flavonol glycoside derived from Sophorae Flos improves glucose uptake and inhibits adipocyte differentiation via activation AMPK in 3T3-L1 cells.
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/EBPα and PPARγ, 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 PPARγ, C/EBPα, and SREBP1. It also reduced FAS gene expression in a dose-dependent manner, which is crucial for adipogenesis in vitro.
Ha
Do Thi
do T
College of Pharmacy, Chungnam National University, Daejeon, South Korea.
Trung
Trinh Nam
TN
Phuong
Tran Thi
TT
Yim
Namhui
N
Chen
Quan Cheng
QC
Bae
Kihwan
K
D041721:3T3-L1 Cells; D000091162:AMP-Activated Protein Kinase Kinases; D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002240:Carbohydrate Sequence; D044948:Flavonols / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D029909:Sophora / Q000737:chemistry*
D044948:Flavonols; D006027:Glycosides; D047495:PPAR gamma; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D005947:Glucose