Antinociceptive and Anti-Inflammatory Effects of Syringic Acid: In Vivo Evidence and In Silico Mechanistic Insights

Abstract

Based on the previously reported neuroprotective, neurochemical, and behavioral effects of syringic acid, the present study was designed to investigate its antinociceptive and anti-inflammatory potential and to elucidate its possible mechanisms of action using in vitro and in silico methods. The antinociceptive effects of syringic acid were evaluated using the tail-clip, tail-immersion, hot-plate, formalin, and acetic acid-induced writhing tests in Balb/c mice, whereas its anti-inflammatory activity was assessed using the carrageenan-induced paw edema model in Sprague-Dawley rats. Motor performance was examined using the activity meter and Rota-rod tests. The potential ulcerogenic effect was also evaluated. Syringic acid (50 and 100 mg/kg, p.o.) did not significantly alter motor performance. It also did not alter nociceptive response parameters in the tail-clip, tail-immersion, or hot-plate tests. However, it significantly decreased writhing behavior in the writhing test and reduced paw-licking time during the second phase of the formalin test. Moreover, syringic acid attenuated carrageenan-induced paw edema. These findings indicate that syringic acid exerts peripheral antinociceptive and anti-inflammatory activities. In addition, acute administration of syringic acid did not induce gastric ulceration in mice. Enzyme inhibition studies showed that syringic acid inhibited cyclooxygenase-2 and 5-lipoxygenase at μM concentrations. In silico studies further revealed stable interactions between syringic acid and both enzymes.