Efficacy of a phenol derivative, isopropyl vanillate, as an anti-inflammatory agent: A new small molecule inhibitor of COX and neutrophil migration

Drug Dev Res. 2019 Aug;80(5):666-679. doi: 10.1002/ddr.21546. Epub 2019 May 21.

Abstract

Inflammation is the response of the body to noxious stimuli such as infections, trauma, or injury. Experimental studies have shown that vanillic acid has anti-inflammatory effects. The objective of this study was to investigate the anti-inflammatory and antipyretic properties of the derivative of vanillic acid, isopropyl vanillate (ISP-VT), in mice. The results of this study indicated that ISP-VT reduced paw edema induced by carrageenan, dextran sulfate (DEX), compound 48/80, serotonin, bradykinin (BK), histamine (HIST), and prostaglandin E2 (PGE2). Furthermore, ISP-VT reduced recruitment of leukocytes and neutrophils and reduced its adhesion and rolling, and decreased myeloperoxidase enzyme activity (MPO), cytokine levels (tumor necrosis factor-α and interleukin-6), and vascular permeability. ISP-VT also significantly reduced the expression of cyclooxygenase-2 (COX-2) in subplantar tissue of mice. ISP-VT inhibited COX-2 selectively compared to the standard drug. Our results showed that although ISP-VT binds to COX-1, it is less toxic than indomethacin, as evidenced by MPO analysis of gastric tissue. Treatment with the ISP-VT significantly reduced rectal temperature in yeast-induced hyperthermia in mice. Our results showed that the main mechanism ISP-VT-induced anti-inflammatory activity is by inhibition of COX-2. In conclusion, our results indicate that ISP-VT has potential as an anti-inflammatory and antipyretic therapeutic compound.

Keywords: COX-2 inhibition; antipyretic; inflammation; vanillic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Antibodies, Monoclonal / drug effects
  • Carrageenan / adverse effects*
  • Cyclooxygenase Inhibitors / administration & dosage*
  • Cyclooxygenase Inhibitors / chemical synthesis
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology
  • Disease Models, Animal
  • Female
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Models, Molecular
  • Phenols / adverse effects*
  • Phenols / chemical synthesis
  • Phenols / chemistry
  • Phenols / pharmacology
  • Small Molecule Libraries / administration & dosage
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Vanillic Acid / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Cyclooxygenase Inhibitors
  • Phenols
  • Small Molecule Libraries
  • Carrageenan
  • techneticum TC-99M fanolesomab
  • Vanillic Acid