Antidiabetic activity of some pentacyclic acid triterpenoids, role of PTP-1B: in vitro, in silico, and in vivo approaches

Juan José Ramírez-Espinosa; Maria Yolanda Rios; Sugey López-Martínez; Fabian López-Vallejo; José L Medina-Franco; Paolo Paoli; Guido Camici; Gabriel Navarrete-Vázquez; Rolffy Ortiz-Andrade; Samuel Estrada-Soto

doi:10.1016/j.ejmech.2011.03.005

Antidiabetic activity of some pentacyclic acid triterpenoids, role of PTP-1B: in vitro, in silico, and in vivo approaches

Eur J Med Chem. 2011 Jun;46(6):2243-51. doi: 10.1016/j.ejmech.2011.03.005. Epub 2011 Mar 30.

Authors

Juan José Ramírez-Espinosa¹, Maria Yolanda Rios, Sugey López-Martínez, Fabian López-Vallejo, José L Medina-Franco, Paolo Paoli, Guido Camici, Gabriel Navarrete-Vázquez, Rolffy Ortiz-Andrade, Samuel Estrada-Soto

Affiliation

¹ Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Avenida Universidad 1001, Col. Chamilpa, Cuernavaca, Morelos 62209, Mexico.

PMID: 21453996
DOI: 10.1016/j.ejmech.2011.03.005

Abstract

The aim of the current study was to investigate the oral antidiabetic activity of four structurally-related triterpenic acids: ursolic (RE-01), oleanolic (RE-02), moronic (RE-03) and morolic (RE-04) acids. STZ-nicotinamide diabetic rats were treated with these triterpenes (50 mg/kg) and the antidiabetic effects in acute experiment were determined. All compounds showed significant antidiabetic activity in comparison with control group (p<0.05). The in vitro inhibitory activity of compounds against protein tyrosine phosphatase 1B (PTP-1B) was also evaluated. At 50 μM, the enzymatic activity was almost completely inhibited. All compounds were docked with a crystal structure of PTP-1B. Docking results suggested the potential binding of the triterpenic acids in a binding pocket next to the catalytic site. An extensive hydrogen bond network with the carboxyl group and Van der Waals interactions stabilize the protein-ligand complexes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diabetes Mellitus, Experimental / drug therapy*
Diabetes Mellitus, Experimental / enzymology
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Enzyme Activation / drug effects
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Hypoglycemic Agents / chemistry
Hypoglycemic Agents / pharmacology*
Male
Models, Molecular
Molecular Conformation
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / isolation & purification
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Rats
Rats, Wistar
Recombinant Proteins / antagonists & inhibitors
Recombinant Proteins / isolation & purification
Recombinant Proteins / metabolism
Stereoisomerism
Structure-Activity Relationship
Triterpenes / chemistry
Triterpenes / pharmacology*

Substances

Enzyme Inhibitors
Hypoglycemic Agents
Recombinant Proteins
Triterpenes
Protein Tyrosine Phosphatase, Non-Receptor Type 1