Selective Inhibition of PTP 1B by Vitalboside A from Syzygium cumini Enhances Insulin Sensitivity and Attenuates Lipid Accumulation Via Partial Agonism to PPAR γ : In Vitro and In Silico Investigation

• Published in: Chemical biology & drug design 2016-08, Vol.88 (2), p.302-312
• Main Authors: Thiyagarajan, Gopal, Muthukumaran, Padmanaban, Sarath Kumar, Baskaran, Muthusamy, Velusamy Shanmuganathan, Lakshmi, Baddireddi Subhadra
• Format: Article
• Language: English
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.12757

Although antidiabetic drugs show good insulin‐sensitizing property for T2 DM , they also exhibit undesirable side‐effects. Partial peroxisome proliferator‐activated receptor γ agonism with protein tyrosine phosphatase 1B inhibition is considered as an alternative therapeutic approach toward the development of a safe insulin sensitizer. Bioactivity‐based fractionation and purification of Syzygium cumini seeds led to the isolation and identification of bifunctional Vitalboside A, which showed antidiabetic and anti‐adipogenic activities, as measured by glucose uptake in L6 and 3T3‐L1 adipocytes and Nile red assay. A non‐competitive allosteric inhibition of protein tyrosine phosphatase 1B by Vitalboside A was observed, which was confirmed by docking studies. Inhibitor studies with wortmannin and genistein showed an IRTK ‐ and PI 3K‐dependent glucose uptake. A PI 3K/ AKT ‐dependent activation of GLUT 4 translocation and an inactivation of GSK 3 β were observed, confirming its insulin‐sensitizing potential. Vitalboside A exhibited partial transactivation of peroxisome proliferator‐activated receptor γ with an increase in adiponectin secretion, which was confirmed using docking analysis. Vitalboside A is a bifunctional molecule derived from edible plant showing inhibition of PTP 1B and partial agonism to peroxisome proliferator‐activated receptor γ which could be a promising therapeutic agent in the management of obesity and diabetes.