AIM: The present study was conducted to investigate the possible mechanism of actions underlying the systemic antinociception activity of the essential oil of Zingiber zerumbet (EOZZ) in chemical-induced nociception tests in mice.
MATERIALS AND METHODS: Acetic acid-induced abdominal constriction, capsaicin-, glutamate- and phorbol 12-myristate 13-acetate-induced paw licking tests in mice were employed in the study. In all experiments, EOZZ was administered systemically at the doses of 50, 100, 200 and 300 mg/kg.
RESULTS: It was shown that EOZZ given to mice via intraperitoneal and oral routes at 50, 100, 200 and 300 mg/kg produced significant dose dependent antinociception when assessed using acetic acid-induced abdominal writing test with calculated mean ID(50) values of 88.84 mg/kg (80.88-97.57 mg/kg) and 118.8 mg/kg (102.5-137.8 mg/kg), respectively. Likewise, intraperitoneal administration of EOZZ at similar doses produced significant dose dependent inhibition of neurogenic pain induced by intraplantar injection of capsaicin (1.6 μg/paw), glutamate (10 μmol/paw) and phorbol 12-myristate 13-acetate (1.6μg/paw) with calculated mean ID(50) of 128.8 mg/kg (118.6-139.9 mg/kg), 124.8 mg/kg (111.4-139.7 mg/kg) and 40.29 (35.39-45.86) mg/kg, respectively. It was also demonstrated that pretreatment with l-arginine (100mg/kg, i.p.), a nitric oxide precursor significantly reversed antinociception produced by EOZZ suggesting the involvement of l-arginine/nitric oxide pathway. In addition, methylene blue (20mg/kg, i.p.) significantly enhanced antinociception produced by EOZZ. Administration of glibenclamide (10mg/kg, i.p.), an ATP-sensitive K(+) channel antagonist significantly reversed antinociceptive activity induced by EOZZ.
CONCLUSION: Together, the present results suggested that EOZZ-induced antinociceptive activity was possibly related to its ability to inhibit glutamatergic system, TRPV1 receptors as well as through activation of l-arginine/nitric oxide/cGMP/protein kinase C/ATP-sensitive K(+) channel pathway.
MATERIALS AND METHODS: The MEZZ was prepared by macerating oven-dried (50 degrees C) powdered rhizomes (1.2 kg) of Z. zerumbet in 80% methanol in a ratio of 1:20 (w/v) for 48 h. The supernatant was collected, filtered and evaporated to dryness under reduced pressure (50 degrees C) yielding approximately 21.0 g of the crude dried extract. The crude dried extract was stored at -20 degrees C prior to use and was dissolved in normal saline (0.9% NaCl) immediately before administration at concentrations required to produce doses of 25, 50 and 100 mg/kg.
RESULTS: All dosages of MEZZ showed significant (p < 0.05) antiedema activity when assessed using the carrageenan-induced paw edema test and the cotton-pellet-induced granuloma test. The MEZZ exhibited significant (p < 0.05) antinociceptive activity when assessed by the writhing, hot plate and formalin tests. Pretreatment with naloxone (5 mg/kg) significantly decreased the latency of discomfort produced by the 100 mg/kg dose of MEZZ in the hot plate test.
CONCLUSION: MEZZ produced antiinflammatory and antinociceptive activities which may involve the inhibition of bradykinin-, prostaglandin-, histamine- and opioid-mediated processes.