Wedelolactone inhibits adipogenesis through the ERK pathway in human adipose tissue-derived mesenchymal stem cells.
Wedelolactone is an herbal medicine that is used to treat septic shock, hepatitis and venom poisoning. Although in differentiated and cancer cells, wedelolactone has been identified as anti-inflammatory, growth inhibitory, and pro-apoptotic, the effects of wedelolactone on stem cell differentiation remain largely unknown. Here, we report that wedelolactone inhibits the adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAMSCs). Wedelolactone reduced the formation of lipid droplets and the expression of adipogenesis-related proteins, such as CCAAT enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein aP2 (aP2). Wedelolactone mediated this process by sustaining ERK activity. In addition, inhibition of ERK activity with PD98059 resulted in reversion of the wedelolactone-mediated inhibition of adipogenic differentiation. Taken together, these results indicate that wedelolactone inhibits adipogenic differentiation through ERK pathway and suggest a novel inhibitory effect of wedelolactone on adipogenic differentiation in hAMSCs.
School of Nano-Bioscience & Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Seyoung
S
Lim
Hyun-Jun
HJ
Jang
Eun Hee
EH
Park
Jung Kuk
JK
Kim
Jung-Min
JM
Kim
Eung-Kyun
EK
Kim
Kyungmoo
K
Yea
Yun-Hee
YH
Kim
Whaseon
W
Lee-Kwon
Sung Ho
SH
Ryu
Pann-Ghill
PG
Suh
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000328:Adult; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000037:antagonists & inhibitors / Q000235:genetics; D002454:Cell Differentiation; D003374:Coumarins / Q000494:pharmacology*; D050556:Fatty Acid-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics; D061251:Primary Cell Culture; D050151:Subcutaneous Fat / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D019440:Anti-Obesity Agents; D022763:CCAAT-Enhancer-Binding Protein-alpha; D003374:Coumarins; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D005419:Flavonoids; D047495:PPAR gamma; C051122:wedelolactone; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D008071:Lipoprotein Lipase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one