Antinociceptive Action of Moringa peregrina is Mediated by Interaction with α2-Adrenergic Receptor

Moringa peregrina is an edible, drought resistant tree native to semiarid countries. It is used in folk medicine as painkiller.In this study, the antinociceptive effect of the leaf extract of M. peregrina was studied in mice.Animal experimentation.Thermal (hot plate and tail immersion tests) and chemical (writhing and formalin tests) pain models in male BALB/c mice (8 animals per group) were used to investigate the mechanism of the antinociceptive action of this plant. In addition, the chemical constituents of the extract were identified using LC-MS analysis and the possible active constituents that interact with the receptor were predicted based on molecular docking.In writhing test, 200 mg/kg M. peregrina extract inhibited abdominal cramps by 55.97 % (p< 0.001). Also, it reduced the time of paw licking in early and late phases of formalin test by 56.8 % and 65.5%, respectively compared to 50.5% and 48.4% inhibition produced by 30 mg/kg diclofenac sodium in early and late phases, respectively (p< 0.05). This effect was abrogated by yohimbine (1 mg/kg, i.p) but not by methysergide (5 mg/kg, i.p) in late phase only, an indication that the action of M. peregrina in formalin test is not mediated by 5-HT2 serotonin receptors but rather via α2-adrenergic receptors. In hot-plate but not tail-immersion test, the high dose (400 mg/kg) of the extract increased the latency time after 30 min of extract administration. Yohimbine antagonized the action of M. peregrina in hot plate test. Based on LC-MS analysis, the major constituents in M. peregrina methanolic extract were chrysoeriol 7-O-diglucoside, lupeol acetate, quercetin and rutin. Depending on molecular docking results, the activity of M. peregrina extract could be due to the binding of chrysoeriol 7-O-diglucoside, quercetin and rutin to α2-adrenergic receptor.Our results suggest an interaction with α2-adrenergic receptor as a possible mechanism of M. peregrina analgesic action.