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: Although antidiabetic drugs show good insulin-sensitizing property for T2DM, 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 PI3K-dependent glucose uptake. A PI3K/AKT-dependent activation of GLUT4 translocation and an inactivation of GSK3β 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 PTP1B and partial agonism to peroxisome proliferator-activated receptor γ which could be a promising therapeutic agent in the management of obesity and diabetes.
authors.affiliation: Tissue culture and Drug Discovery Laboratory, Centre for Food Technology, Department of Biotechnology, Anna University, Sardar Patel Road, Guindy, Chennai-600 025, India.
authors.forename: Gopal
authors.initials: G
authors.lastname: Thiyagarajan
authors.affiliation: Tissue culture and Drug Discovery Laboratory, Centre for Food Technology, Department of Biotechnology, Anna University, Sardar Patel Road, Guindy, Chennai-600 025, India.
authors.forename: Padmanaban
authors.initials: P
authors.lastname: Muthukumaran
authors.affiliation: Tissue culture and Drug Discovery Laboratory, Centre for Food Technology, Department of Biotechnology, Anna University, Sardar Patel Road, Guindy, Chennai-600 025, India.
authors.forename: Baskaran
authors.initials: B
authors.lastname: Sarath Kumar
authors.affiliation: Tissue culture and Drug Discovery Laboratory, Centre for Food Technology, Department of Biotechnology, Anna University, Sardar Patel Road, Guindy, Chennai-600 025, India.
authors.forename: Velusamy Shanmuganathan
authors.initials: VS
authors.lastname: Muthusamy
authors.affiliation: Tissue culture and Drug Discovery Laboratory, Centre for Food Technology, Department of Biotechnology, Anna University, Sardar Patel Road, Guindy, Chennai-600 025, India.
authors.forename: Baddireddi Subhadra
authors.initials: BS
authors.lastname: Lakshmi
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007333:Insulin Resistance; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D047495:PPAR gamma / Q000819:agonists*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D051381:Rats; D027842:Syzygium / Q000737:chemistry*
chemical_list: C520270:4'-O-coumaroyl-isovitexine; D052242:Adiponectin; D003374:Coumarins; D007529:Isoflavones; D047495:PPAR gamma; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Vitalboside A; adipogenesis; diabetes; peroxisome proliferator-activated receptor γ; protein tyrosine phosphatase 1B