Anti-adipogenic activity of a new cyclic diarylheptanoid isolated from Alnus japonica on 3T3-L1 cells via modulation of PPARγ, C/EBPα and SREBP1c signaling.
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 γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), 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/EBPβ and C/EBPδ 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 PPARγ, C/EBPα, and SREBP1c signaling.
College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul, Republic of Korea.
Sang Hyun
SH
Sung
College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul, Republic of Korea; College of Pharmacy, Sunchon National University, 255 Jungang-ro, Suncheon-si, Jeollanam-do, Republic of Korea. Electronic address: minalee@sunchon.ac.kr.
Mina
M
Lee
D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D029661:Alnus / Q000737:chemistry*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D036381:Diarylheptanoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005638:Fruit / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
D022763:CCAAT-Enhancer-Binding Protein-alpha; D036381:Diarylheptanoids; D047495:PPAR gamma; D012333:RNA, Messenger; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1
3T3-L1 cells; Adipocyte differentiation; Adipogenesis; Alnus japonica; Betulaceae; Diarylheptanoids; Obesity