Raffinose from Costus speciosus attenuates lipid synthesis through modulation of PPARs/SREBP1c and improves insulin sensitivity through PI3K/AKT.

Among several metabolic disorders, the pathogenesis of insulin resistance is considered to be multifactorial. Raffinose, an oligosaccharide isolated from the rhizome of Costus speciosus showed ≤50% inhibition of lipid accumulation in differentiated HepG2 and 3T3-L1 cells through exhibiting partial agonism to PPARγ, and, an enhanced secretion of adiponectin in 3T3-L1 adipocytes. Raffinose was also observed to attenuate the expression of SREBP1c, ACC and FAS which are involved in the fatty acid synthesis. A corresponding upregulation of PPARα and ACO involved in fatty acid oxidation was observed in steatotic HepG2 hepatocytes and 3T3-L1 adipocytes. In vitro evaluation of its anti-diabetic potential showed a dose dependent enhancement of glucose uptake. Investigation of the insulin sensitizing efficacy of Raffinose revealed an increase in Glut4 translocation via phosphorylation of IRβ/PI3K/Akt in differentiated L6 myocytes and 3T3-L1 preadipocytes. In addition, Raffinose was potentially involved in glycogen synthesis by inhibiting the activation of GSK3β. Hence, Raffinose could be a useful therapeutic agent for metabolic maladies.