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Abstract Title:

Selective inhibition of PTP1B by Vitalboside A from Syzygium cumini enhances insulin sensitivity and attenuates lipid accumulation via partial agonism to PPARγ: In Vitro and In Silico investigation.

Abstract Source:

Chem Biol Drug Des. 2016 Mar 15. Epub 2016 Mar 15. PMID: 26989847

Abstract Author(s):

Thiyagarajan Gopal, Muthukumaran Padmanaban, Sarath Kumar Baskaran, Muthusamy Velusamy Shanmuganathan, Lakshmi Baddireddi Subhadra

Article Affiliation:

Thiyagarajan Gopal

Abstract:

Although, antidiabetic drugs show good insulin sensitizing property for T2DM, they also exhibit undesirable side effects. Partial PPARγ agonism with PTP1B inhibition is considered as an alternative therapeutic approach towards 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 (VBA), which showedantidiabetic and antiadipogenic activities, as measured by glucose uptake in L6 and 3T3-L1 adipocytes and Nile red assay. A noncompetitive allosteric inhibition of PTP1B by VBA was observed, which was confirmed by docking studies. Inhibitor studies with wortmanin and genistein showed an IRTK and PI3K dependent glucose uptake. A PI3K/AKT dependent activation of GLUT4 translocation and an inactivation of GSK3β was observed, confirming its insulin sensitizing potential. VBA exhibited partial transactivation of PPARγ with an increase in adiponectin secretion, which was confirmed using docking analysis. VBA is a bi-functional molecule derived from edible plant showing inhibition of PTP1B and partial agonism to PPARγ which could be a promising therapeutic agent in the management of obesity and diabetes. This article is protected by copyright. All rights reserved.

Study Type : In Vitro Study

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