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

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 antiinflammatory effects. The objective of this study was to investigate the antiinflammatory 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. K E Y W O R D Santipyretic, COX-2 inhibition, inflammation, vanillic acid

Technological prospection of anti-inflammatory vanilic acid activity, with emphasis on its semisynthetic derivative Isopropyl Vanilate

“…Results exposed in this work point out that, although the number of patents filed involving are a relatively small number, with a few hundred deposits, little has been applied in the development of new anti-inflammatory drugs, since the number of patent filing requests involving its association with the treatment of inflammation is scarce, and non-existent in the search for patents involving its semi-synthetic derivative, isopropyl vanylate, which has only one published article demonstrating the Efficacy of a phenol derivative, isopropyl vanillate, as an anti-inflammatory agent: A new small molecule inhibitor of COX and neutrophil migration (Nogueira et al, 2019), thus highlighting the potential of this substance and the importance of its patent.…”

“…In the context of these phenolic compounds, vanillic acid has been highlighted, where experimental studies have provided evidence of its efficacy in cardiovascular, gastrointestinal and liver diseases. In addition, it has anti-inflammatory activity by inhibiting the synthesis of numerous mediators that rise during inflammatory processes in addition to acting directly on lipid peroxidation (Sevgi, Tepe, Sarikurkcu, 2015;Calixto-campos et al, 2015;Dianat et al, 2016;Vinothiya and Ashokkumar, 2017;Nogueira et al, 2019).…”

Effect of 2% meloxicam injection in Holstein dairy cows on acute clinical mastitis without systemic symptoms

“…Additionally, a significant positive correlation ( P <0.05) was observed between the whey PGE 2 concentration and LS on day 2 in the C group but not in the T group. The anti-inflammatory and antipyretic properties of isopropyl vanillate (ISP-VT) in mice have been reported; the main mechanism of ISP-VT-induced anti-inflammatory activity is the inhibition of COX-2, which reduces foot edema induced by BK, histamine, and PGE 2 , and decreases neutrophil recruitment [ 10 ]. In our study, there was a significant positive correlation between whey PGE2 concentration and LS on day 2 in group C but not in group T. These findings suggest that COX-2 inhibition in mammary tissue by MX suppresses PGE 2 synthesis and decreases neutrophil mobilization.…”