Antinociceptive properties of esculetin in non‐inflammatory and inflammatory models of pain in rats

Abstract

Some studies suggest that 5-lipoxygenase (5-LOX) inhibition or leukotriene receptor antagonism may effectively attenuate different kinds of pain. In the present study, we investigated whether esculetin (which, among other actions, potently inhibits 5-LOX) possesses analgesic activity in acute non-inflammatory pain and acute inflammatory pain models in rats. We also examined the effects of zileuton, a selective 5-LOX inhibitor, on esculetin activity. Plasma concentrations of leukotriene B4 (LTB4 ) after administration of esculetin were also determined. Esculetin (1.25-20 mg/kg, i.p.) dose-dependently alleviated hyperalgesia and exhibited antinociceptive effects in both experimental models. The greatest effect of esculetin was observed with a dose of 20 mg/kg. In carrageenan-induced inflammatory pain in rats, 20 mg/kg esculetin reversed or mitigated hyperalgesia, increasing the threshold to mechanical stimuli from a control value of -23.8 ± 1.8% to 15.2 ± 2.2% (P < 0.01) and that to thermal stimuli from -52.5 ± 6.1% to -9.5 ± 3.9% (P < 0.01). In non-inflammatory pain, after esculetin (20 mg/kg) administration the threshold values to mechanical and thermal stimuli increased to 75.9 ± 4.2% and 59.2 ± 4.3%, respectively (P < 0.01 for both). Zileuton (30 mg/kg, p.o.) alone slightly but significantly increased the pain threshold in the non-inflammatory and inflammatory acute pain models. Pretreatment with 30 mg/kg, p.o., zileuton significantly enhanced the analgesic activity of 5 mg/kg, i.p., esculetin in both pain models. Moreover, esculetin (10 mg/kg, i.p.) decreased LTB4 concentrations in the blood from 244 ± 29 pg/mL in the control group to 185 ± 11 pg/mL (P < 0.005). The results of the present study suggest the involvement of the 5-LOX pathway in esculetin analgesia.

Carrageenan‐induced inflammation promotes ROS generation and neutrophil extracellular trap formation in a mouse model of peritonitis

“…It has been previously shown that carrageenan is able to induce neutrophil migration in different animal models [14][15][16][17]21]. We first sought to characterize the effect of carrageenan on neutrophil migration to mice peritoneum.…”

Pharmacological Activities and Synthesis of Esculetin and Its Derivatives: A Mini-Review

“…and F. stylosa Lingelsh. It has been indicated that Cortex Fraxini possesses various pharmacological effects, including anti-pathogenic [ 1 ], anti-inflammatory [ 2 ], analgesic [ 3 ], anti-cancer [ 4 ], antioxidative stress [ 5 ], neuroprotective [ 6 ] and vascular protective effects [ 7 ]. There are many active ingredients in Cortex Fraxini .…”

Amleorative Role of Esculetin􀇧mediated Renoprotection Against Gentamicin􀇧induced Nephrotoxicity and Possible Involvement of N􀇧methyl􀇧d􀇧aspartate Receptors

“…Esc also reported to possesses analgesic, anti-inflammatory activity [33] by blocking NF-kB activation, by inhibiting the generation of ROS, by inhibiting LPS-induced nitric oxide and prostaglandin E2 production. It also significantly suppresses the production of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β [34] and in cocultured macrophages and adipocytes through up-regulation of heme oxygenase-1 (HO-1) [35].…”