Evidence for the involvement of opioid receptor in Ajuga chamaepitys action in chemical and thermal models of pain in BALB/c mice

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Ajuga chamaepitys is a small herbaceous annual or biannual plant that belongs to Lamiaceae family. It grows in Europe and Eastern parts of the Mediterranean. One of the ethno-pharmacological uses of this plant is its use as a painkiller. In the present experimental work, the antinociceptive effect of the methanolic extract of A. chamaepitys collected from Jordan was investigated using chemical and thermal models of pain in mice. A. chamaepitys extract decreased significantly the number of writhes that were induced in mice by the injection of 1% acetic acid compared to negative control group. The inhibitory effect produced by 300 mg/kg of the extract given i.p was comparable to that of 300 mg/kg aspirin. The i.p administration of 450 mg/kg A. chamaepitys caused a remarkable decrease in paw licking time during the early and late phases of formalin test. Furthermore, the latency time increased in hot plate test but not in tail flick test in animals that were treated i.p with 300 mg/kg A. chamaepitys extract compared to control animals. The involvement of opioid receptor was proven in formalin and hot-plate tests by abolishing the effect of A. chamaepitys extract by pretreatment with naloxone, an opioid antagonist. LC-MS analysis resulted in the identification of 19 compounds. Isovitexin, orientin, flavonol, and cyanidin were the major compounds. Our results suggest that the methanolic extract of A. chamaepitys has pronounced antinociceptive effects, which provide the scientific basis of the traditional therapeutic use of A. chamaepitys in folk medicine.