Anti-adipogenic activity of a new cyclic diarylheptanoid isolated from Alnus japonica on 3T3-L1 cells via modulation of PPAR gamma, C/EBP alpha and SREBP1c signaling

作者：Sung Sang Hyun; Lee Mina^*

来源：Bioorganic & Medicinal Chemistry Letters, 2015, 25(20): 4648-4651.

DOI：10.1016/j.bmcl.2015.08.032

• Alnus japonica
• Betulaceae
• Diarylheptanoids
• Adipogenesis
• Adipocyte differentiation
• Obesity
• 3T3-L1 cells

Total methanolic extract of Alnus japonica fruits exhibited significant anti-adipogenic activities in 3T3-L1 cells. A new cyclic diarylheptanoid (1) along with ten known compounds (2-11) were isolated by activity-guided fractionation. Compound 1, determined to be 4-hydroxy-alnus-3,5-dione, showed the most potent anti-adipogenic effect. Compound 1 significantly down-regulated expression of peroxisome proliferator-activated receptor gamma (PPAR gamma), CCAAT/enhancer binding protein alpha (C/EBP alpha), and sterol regulatory element binding protein 1 (SREBP1c) in 3T3-L1 cells, as determined by quantitative real-time PCR and Western blot analysis. Furthermore, compound 1 suppressed mRNA expression of C/EBP beta and C/EBP delta during the early stage of adipogenesis as well as stearoyl coenzyme A desaturase 1 (SCD-1) and fatty acid synthase (FAS), target genes of SREBP1c. Upon investigating the mechanism of natural products, we propose that cyclic diarylheptanoid (1), the most potent constituent of A. japonica, can be a potent therapeutic agent against obesity through anti-adipogenesis via down-regulation of PPAR gamma, C/EBP alpha, and SREBP1c signaling.

• 出版日期2015-10-15