CSIR – National Institute for Interdisciplinary Science and Technology (NIIST)

Council of Scientific & Industrial Research (CSIR), Govt.Of India Thiruvananthapuram.

Licarin B from Myristica fragrance improves insulin sensitivity by activating PPARγ and subsequently up-regulating GLUT4 via PI3/AKT Signaling Pathway

 

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors regulating lipid and glucose metabolism. Ongoing drug discovery programs aim to develop partial PPARγ agonists devoid of the side effects of the marketed antidiabetic agents thiazolidinediones. Here, we evaluated the therapeutic potential of Licarin B (LB), a major bioactive constituent of Myristica fragrans in improving peroxisome proliferator-activated receptor (PPAR)-γ activity and insulin sensitivity in 3T3 L1 adipocytes. LB moderately promoted lipid accumulation in 3T3-L1 cells, upregulated peroxisome proliferator-activated receptor (PPAR)-γ and acted as a ligand for PPARγ in competitive binding assay as well as docking studies. Moreover, LB increased adiponectin secretion and modulated the expression of PPAR target genes such as IRS-2 , LPL and C/EBPα. Additionally, it promoted insulin-dependent glucose uptake into 3T3-L1 adipocytes and increased glucose transporter (GLUT) 4 translocation in to the plasma membrane via IRS-1/PI3K/AKT signaling pathway. In summary, these findings suggest that LB, which promoted adipogenesis moderately and insulin sensitivity in3T3-L1 cells, might be a photochemical with potent insulin-sensitizing effects

(RSC Adv., 2016, 6, 79859–79870)