Natural phosphodiesterase-4 (PDE4) inhibitors from Crotalaria ferruginea

Fitoterapia. 2014 Apr:94:177-82. doi: 10.1016/j.fitote.2014.02.010. Epub 2014 Mar 2.

Abstract

Bioassay-guided fractionation of the ethanol extract of the Chinese folk medicine Crotalaria ferruginea led to the isolation of a new isoflavonoid, 4'-hydroxy-2'-methylalpinum-isoflavone (1), and eight known analogs (2-9). Their structures were elucidated by spectroscopic analysis. Compounds 1, 2, 5, and 8 showed inhibitory activities against phosphodiesterase-4 (PDE4), a therapeutic target of asthma, with IC50 values ranging from 2.57 to 8.94 μM. The possible action mechanism and the structure-activity relationship (SAR) of the active isoflavonoids were explored by using molecular docking and molecular dynamics (MD) simulation methods. Our study herein may explain the anti-inflammatory function of this plant in Chinese folk medicine.

Keywords: Crotalaria ferruginea; Isoflavonoids; Molecular dynamics simulation; PDE4; SAR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Crotalaria / chemistry*
  • Inhibitory Concentration 50
  • Isoflavones / chemistry
  • Isoflavones / isolation & purification
  • Isoflavones / pharmacology*
  • Medicine, Chinese Traditional
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Phosphodiesterase 4 Inhibitors / chemistry
  • Phosphodiesterase 4 Inhibitors / isolation & purification
  • Phosphodiesterase 4 Inhibitors / pharmacology*
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Structure-Activity Relationship

Substances

  • 4'-hydroxy-2'-methylalpinum-isoflavone
  • Anti-Inflammatory Agents
  • Isoflavones
  • Phosphodiesterase 4 Inhibitors
  • Plant Extracts