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A Withanolide Coagulin-L Inhibits Adipogenesis Modulating Wnt/βCatenin and Cell Cycle Arrest in Mitotic Clonal Expansion

หน่วยงาน Central Drug Research Institute (CDRI), India

รายละเอียด

ชื่อเรื่อง : A Withanolide Coagulin-L Inhibits Adipogenesis Modulating Wnt/βCatenin and Cell Cycle Arrest in Mitotic Clonal Expansion
นักวิจัย : Beg, Muheeb , Chauhan, Parul , Varshney, Salil , Shankar, Kripa , Rajan, Sujith , Saini, Deepika , Srivastava, M N , Yadav, P P , Gaikwad, A N
คำค้น : Coagulin-L , Mitotic clonal expansion , Obesity , 3T3-L1 , Adipocytes , Adipogenesis
หน่วยงาน : Central Drug Research Institute (CDRI), India
ผู้ร่วมงาน : -
ปีพิมพ์ : 2557
อ้างอิง : Phytomedicine,2014, 21(4),406-14 , http://hdl.handle.net/123456789/1425
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : CSIR-CDRI communication No. 8557
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

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. Coagulanolides, particularly coagulin-L isolated from W. coagulan has earlier been reported for anti-hyperglycemic activity. In this study, we investigated 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 γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), 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 phosophorylation of C/EBPβ, modulation in expression of cell cycle regulatory proteins, and upregulation of Wnt/βcatenin 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.

บรรณานุกรม :
Beg, Muheeb , Chauhan, Parul , Varshney, Salil , Shankar, Kripa , Rajan, Sujith , Saini, Deepika , Srivastava, M N , Yadav, P P , Gaikwad, A N . (2557). A Withanolide Coagulin-L Inhibits Adipogenesis Modulating Wnt/βCatenin and Cell Cycle Arrest in Mitotic Clonal Expansion.
    : Central Drug Research Institute (CDRI), India.
Beg, Muheeb , Chauhan, Parul , Varshney, Salil , Shankar, Kripa , Rajan, Sujith , Saini, Deepika , Srivastava, M N , Yadav, P P , Gaikwad, A N . 2557. "A Withanolide Coagulin-L Inhibits Adipogenesis Modulating Wnt/βCatenin and Cell Cycle Arrest in Mitotic Clonal Expansion".
    : Central Drug Research Institute (CDRI), India.
Beg, Muheeb , Chauhan, Parul , Varshney, Salil , Shankar, Kripa , Rajan, Sujith , Saini, Deepika , Srivastava, M N , Yadav, P P , Gaikwad, A N . "A Withanolide Coagulin-L Inhibits Adipogenesis Modulating Wnt/βCatenin and Cell Cycle Arrest in Mitotic Clonal Expansion."
    : Central Drug Research Institute (CDRI), India, 2557. Print.
Beg, Muheeb , Chauhan, Parul , Varshney, Salil , Shankar, Kripa , Rajan, Sujith , Saini, Deepika , Srivastava, M N , Yadav, P P , Gaikwad, A N . A Withanolide Coagulin-L Inhibits Adipogenesis Modulating Wnt/βCatenin and Cell Cycle Arrest in Mitotic Clonal Expansion. : Central Drug Research Institute (CDRI), India; 2557.