Anti-inflammatory effect of natural and semi-synthetic phthalides

Eur J Pharmacol. 2015 Apr 5:752:40-8. doi: 10.1016/j.ejphar.2015.01.026. Epub 2015 Jan 23.

Abstract

This study evaluated the potential anti-inflammatory effects of natural phthalides, isolated from Ligusticum porteri, and of semi-synthetic phthalides. Anti-inflammatory activity was investigated in two mouse models; one with ear edema, induced with 12-O-tetradecanoylphorbol-13-acetate, and the other with paw edema, induced with carrageenan. The effect on the RAW 264.7 stimulated with lipopolysaccharide cells was evaluated and after application of 12-O-tetradecanoylphorbol-13-acetate, the activity of myeloperoxidase was assessed to serve as an index of leukocytes infiltration together with the histological evaluations. We also assessed the inhibition of cyclooxygenases 1 and 2 in vitro. Our results demonstrated that administration of semi-synthetic phthalides significantly inhibited the ear edema induced by 12-O-tetradecanoylphorbol-13-acetate, and reduced the paw edema caused by carrageenan. The anti-inflammatory activity of phthalides could, in part, be explained by the reduction in myeloperoxidase activity and the infiltration of leukocytes. The semi-synthetic phthalides also inhibited the production of oxide nitric in RAW cells.

Keywords: 12-O-tetradecanoylphorbol-13-acetate; Carrageenan; Inflammation; Myeloperoxidase; Oxide nitric synthase; Semi-synthetic phthalides; Z-ligustilide (PubChem CID: 529865); diligustilide (PubChem CID: 70698035); tokinolide B (PubChem CID: 70681959).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Benzofurans / chemical synthesis
  • Benzofurans / pharmacology*
  • Benzofurans / therapeutic use
  • Biological Products / pharmacology*
  • Biological Products / therapeutic use
  • Carrageenan / adverse effects
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / chemical synthesis
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / metabolism
  • Edema / pathology
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Mice
  • Nitric Oxide Synthase / metabolism
  • Nitrites / metabolism
  • Peroxidase / metabolism
  • RAW 264.7 Cells
  • Skin / drug effects
  • Skin / pathology
  • Tetradecanoylphorbol Acetate / adverse effects

Substances

  • Anti-Inflammatory Agents
  • Benzofurans
  • Biological Products
  • Cyclooxygenase 2 Inhibitors
  • Nitrites
  • phthalide
  • Carrageenan
  • Peroxidase
  • Nitric Oxide Synthase
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Tetradecanoylphorbol Acetate