A withanolide coagulin-L inhibits adipogenesis modulating Wnt/beta-catenin pathway and cell cycle in mitotic clonal expansion

作者：Beg Muheeb; Chauhan Parul; Varshney Salil; Shankar Kripa; Rajan Sujith; Saini Deepika; Srivastava M N; Yadav Prem P^*; Gaikwad Anil Nilkanth

来源：Phytomedicine, 2014, 21(4): 406-414.

DOI：10.1016/j.phymed.2013.10.009

• Coagulin-L
• Withania coagulans
• Mitotic clonal expansion
• Obesity
• 3T3-L1
• Adipocytes
• Adipogenesis

Obesity is a result of adipocyte hypertrophy followed by hyperplasia. It is a risk factor for several metabolic disorders such as dyslipidemia, type-2 diabetes, hypertension, and cardiovascular diseases. Coagulano-lides, particularly coagulin-L isolated from W. coagulan has earlier been reported for anti-hyperglycemic activity. In this study, we investigated the effect of coagulin-L on in vitro models of adipocyte differentiation including 3T3-L1 pre-adipocyte, mouse stromal mesenchymal C3H10T1/2 cells and bone marrow derived human mesenchymal stem cells (hMSCs). Our results showed that, coagulin-L reduces the expressions of peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer-binding protein (C/EBP alpha), the major transcription factors orchestrating adipocyte differentiation. Detailed analysis further proved that early exposure of coagulin-L is sufficient to cause significant inhibition during adipogenesis. Coagulin-L inhibited mitotic clonal expansion (MCE) by delayed entry in G1 to S phase transition and S-phase arrest. This MCE blockade was caused apparently by-decreased phosphorylation of C/EBP beta, modulation in expression of cell cycle regulatory proteins, and upregulation of Wnt/beta-catenin pathway, the early stage regulatory proteins of adipogenic induction.
Taken together all evidences, a known anti-hyperglycemic agent coagulin-L has shown potential to inhibit adipogenesis significantly, which can be therapeutically exploited for treatment of obesity and metabolic syndrome.

• 出版日期2014-3-15