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

作者：Jose Ramirez Espinosa Juan; Yolanda Rios Maria; Lopez Martinez Sugey; Lopez Vallejo Fabian; Medina Franco Jose L; Paoli Paolo; Camici Guido; Navarrete Vazquez Gabriel; Ortiz Andrade Rolffy; Estrada Soto Samuel^*

来源：European Journal of Medicinal Chemistry, 2011, 46(6): 2243-2251.

DOI：10.1016/j.ejmech.2011.03.005

• Diabetes
• Pentacyclic triterpenoids
• PTP-1B
• Docking
• Enzyme inhibition

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 (PIP-1B) was also evaluated. At 50 mu M, 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.

• 出版日期2011-6