Antinociceptive Activity of Various Extracts of Peganum harmala L. and Possible Mechanism of Action

The seeds of Peganum harmala L. (Pgh) (Zygophyllaceae) have been used in Moroccan traditional medicine to treat various diseases. The objective of this study was to investigate the analgesic effect of ethyl acetate (EAE), butanolic (BE) and aqueous (AqE) extracts of seeds of Peganum harmala and to elucidate the possible action mechanism of each extract. The antinociceptive action was assayed in experimental models of writhing, formalin, tail flick and hot plate tests in mice. The EAE, BE and AqE (i.p or p.o. routes) showed significant reduction in acetic acid-induced writhings in mice with a maximum effect of 35.12% reduction for BE (25 mg/kg, i.p.). In the formalin test, the pre-treatment with AEA and BE (12.5 and 25mg/kg, i.p.) caused marked dose-related inhibition of formalin-induced licking in both phases, whereas the AqE (25mg/kg, i.p.) reduced the nociception response only in the second phase of formalin test. Hot plate and tail flick tests showed a significant central acting analgesic properties of AEA and BE. The EAE and BE contain active analgesic components acting both centrally and peripherally. Preliminary phytochemical screening of the extracts showed the presence of alkaloids, flavonoids, sterols and saponin. The extracts' antinociceptive effect has been avoided by naloxone (1 mg/kg) in the first phase of formalin and hot plate tests indicating that these extracts act partly through an opioid-mediated mechanism. In conclusion, our results demonstrated that the different extracts of Peganum harmala had both central and peripheral antinociceptive activities that may be mediated by opioid receptors.