Inhibitory effects of coumarins from the stem barks of Fraxinus rhynchophylla on adipocyte differentiation in 3T3-L1 cells.
In the course of screening anti-adipogenic activity of natural products employing the preadipocyte cell line, 3T3-L1 as an in vitro assay system, the EtOAc fraction of the stem barks of Fraxinus rhynchophylla DENCE (Oleaceae) showed significant inhibitory activity on adipocyte differentiation as assessed by measuring fat accumulation using Oil Red O staining. Activity-guided fractionation led to the isolation of six coumarins such as esculetin (1), scopoletin (2), fraxetin (3), fraxidin (4) esculin (5) and fraxin (6). Among the six coumarins isolated, esculetin (1) showed the most potent inhibitory activity on adipocyte differentiation, followed by fraxetin (3). Further studies with interval treatment demonstrated that esculetin (1) exerted inhibitory activity on adipocyte differentiation when treated within 2 d (days 0-2) after differentiation induction. We further investigated the effect of esculetin (1) on peroxisome proliferator activated receptor gamma (PPARgamma), one of the early adipogenic transcription factors. Esculetin (1) significantly blocked the induction of PPARgamma protein expression and inhibited adipocyte differentiation induced by troglitazone, a PPARgamma agonist. Taken together, these results suggest that esculetin (1), an active compound from F. rhynchophylla, inhibited early stage of adipogenic differentiation, in part, via inhibition of PPARgamma-dependent pathway.
Shin
Eunjin
E
College of Pharmacy, Chungbuk National University, Cheongju, Korea.
Choi
Kyeong-Mi
KM
Yoo
Hwan-Soo
HS
Lee
Chong-Kil
CK
Hwang
Bang Yeon
BY
Lee
Mi Kyeong
MK
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology*; D031661:Fraxinus; D006131:Growth Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors; D024301:Plant Bark; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D018547:Plant Stems; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014468:Umbelliferones / Q000302:isolation & purification / Q000494:pharmacology
D003374:Coumarins; D006131:Growth Inhibitors; D047495:PPAR gamma; D010936:Plant Extracts; D014468:Umbelliferones; C007628:esculetin