Selaginellin and biflavonoids as protein tyrosine phosphatase 1B inhibitors from Selaginella tamariscina and their glucose uptake stimulatory effects

Bioorg Med Chem. 2015 Jul 1;23(13):3730-7. doi: 10.1016/j.bmc.2015.04.007. Epub 2015 Apr 10.

Abstract

As part of an ongoing search for new antidiabetic agents from medicinal plants, the methanol extract of the aerial parts of Selaginella tamariscina was found to possess stimulatory effect on glucose uptake in 3T3-L1 adipocyte cells. Thus, bioassay-guided isolation of this active extract yielded two new compounds (1 and 2) along with five known biflavonoids (3-7). Their structures were elucidated by extensive analysis of spectroscopic and physicochemical data. The absolute configuration of compound 2 was determined by specific rotation and CD data analysis. All isolates exhibited potent inhibitory effects on PTP1B enzyme with IC50 values ranging from 4.5±0.1 to 13.2±0.8μM. Furthermore, the isolates (1-7) showed significant stimulatory effects on 2-NBDG uptake in 3T3-L1 adipocyte cells. Of these, compounds (1, 6, and 7) which exhibited mixed-competitive inhibition modes against PTP1B, showed potent stimulatory effects on 2-NBDG uptake. This result indicated the potential of these biflavonoids as lead molecules for development of antidiabetic agents and the beneficial use of S. tamariscina against hyperglycemia.

Keywords: 2-NBDG; Biflavonoids; PTP1B inhibitors; Selaginella tamariscina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • 4-Chloro-7-nitrobenzofurazan / analogs & derivatives
  • 4-Chloro-7-nitrobenzofurazan / metabolism
  • Animals
  • Biflavonoids / chemistry
  • Biflavonoids / isolation & purification
  • Biflavonoids / pharmacology*
  • Biological Transport / drug effects
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / isolation & purification
  • Biphenyl Compounds / pharmacology*
  • Cell Survival / drug effects
  • Cyclohexanones / chemistry
  • Cyclohexanones / isolation & purification
  • Cyclohexanones / pharmacology*
  • Deoxyglucose / analogs & derivatives
  • Deoxyglucose / metabolism
  • Glucose / metabolism
  • Humans
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / isolation & purification
  • Hypoglycemic Agents / pharmacology*
  • Methanol
  • Mice
  • Plant Extracts / chemistry
  • Plants, Medicinal
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / chemistry
  • Republic of Korea
  • Selaginellaceae / chemistry*
  • Solvents

Substances

  • Biflavonoids
  • Biphenyl Compounds
  • Cyclohexanones
  • Hypoglycemic Agents
  • Plant Extracts
  • Solvents
  • Deoxyglucose
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • 4-Chloro-7-nitrobenzofurazan
  • Glucose
  • 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose
  • Methanol