Aleurites moluccana and its main active ingredient, the flavonoid 2″-O-rhamnosylswertisin, have promising antinociceptive effects in experimental models of hypersensitivity in mice

This study investigated the antinociceptive effect of Aleurites moluccana dried extract (DE; 125 to 500mg/kg, p.o.) and the isolated flavonoid 2″-O-rhamnosylswertisin (5 to 50.6μmol/kg, p.o.) using different models of long-lasting inflammatory and neuropathic pain in mice. Attempts were made to analyse the mechanisms through which A. moluccana exerted its effects. A. moluccana DE inhibited complete Freund's adjuvant (CFA)-induced mechanical nociception. It was also evidenced by a reduction of sensitization in the contralateral hindpaw. The extract reversed the mechanical hypersensitivity of partial ligation of sciatic nerve (PLSN)-treated animals, similar to gabapentin. In PLSN model, the opioid, dopaminergic and oxidonitrergic pathways were involved in the A. moluccana DE antinociceptive effects. A single dose of 2″-O-rhamnosylswertisin inhibited the carrageenan- and CFA-induced mechanical nociception. Furthermore, the compound caused expressive antinociception in PLSN-mice, with inhibition value greater than obtained with gabapentin. Oral treatment with the extract or the isolated compound attenuated the neutrophil migration and IL-1β levels following carrageenan injection. Of note, A. moluccana DE did not interfere with thermal sensitivity in healthy mice. The absence of side effects, including interference in locomotor activity, motor performance in animals treated with the extract, showed excellent potential for the therapeutic use of this medicinal plant in treating persistent pain in humans. ► Neuropathic pain-like behaviour is attenuated by A. moluccana extract. ► Inflammatory nociception is attenuated by A. moluccana extract. ► The flavonoid 2″-O-rhamnosylswertisin is important for the A. moluccana effects. ► Opioid, dopamine and oxidonitric pathways, and inflammatory mediators are involved. ► A. moluccana represent an interesting alternative for treating long lasting pain.