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

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.