title: Antinociceptive effect of the essential oil of Zingiber zerumbet in mice: possible mechanisms.
abstract: BACKGROUND
  Zingiber zerumbet (L.) Smith, a wild edible ginger species or locally known as "lempoyang", commonly used in the Malays traditional medicine as an appetizer or to treat stomachache, toothache, muscle sprain and as a cure for swelling sores and cuts.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Human Anatomy, Universiti Putra Malaysia, Serdang, Malaysia.
authors.forename: Mohamed Hanief
authors.initials: MH
authors.lastname: Khalid
authors.forename: Muhammad Nadeem
authors.initials: MN
authors.lastname: Akhtar
authors.forename: Azam Shah
authors.initials: AS
authors.lastname: Mohamad
authors.forename: Enoch Kumar
authors.initials: EK
authors.lastname: Perimal
authors.forename: Ahmad
authors.initials: A
authors.lastname: Akira
authors.forename: Daud Ahmad
authors.initials: DA
authors.lastname: Israf
authors.forename: Nordin
authors.initials: N
authors.lastname: Lajis
authors.forename: Mohd Roslan
authors.initials: MR
authors.lastname: Sulaiman
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020939:Zingiber officinale; D018698:Glutamic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D009822:Oils, Volatile / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010938:Plant Oils / Q000008:administration & dosage / Q000494:pharmacology*; D018517:Plant Roots; D010946:Plants, Medicinal; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism
chemical_list: D000700:Analgesics; D054086:KATP Channels; D009822:Oils, Volatile; D010938:Plant Oils; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D009569:Nitric Oxide; D018698:Glutamic Acid; D001120:Arginine; D011493:Protein Kinase C; D006152:Cyclic GMP