Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 20, Issue 20, Pages 6076-6081Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2010.08.054
Keywords
Sophorae Flos; Glucose uptake; AMPK; Adipocyte differentiation; Anti-obesity; 3T3-L1
Categories
Funding
- Ministry of Education, Science and Technology [KOSEF2009-007-4808]
- National Research Foundation of Korea [과09B2106] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 mu M, 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 alpha and PPAR gamma, 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 mu M) 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 gamma, C/EBP alpha, and SREBP1. It also reduced FAS gene expression in a dose-dependent manner, which is crucial for adipogenesis in vitro. (C) 2010 Elsevier Ltd. All rights reserved.
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