title: Oleanolic Acid, a pentacyclic triterpene attenuates the mustard oil-induced colonic nociception in mice.
abstract: Many natural terpenoid compounds from plants exhibit antinociceptive property but very few studies have addressed their efficacy in visceral models of nociception. The present study evaluated the antinociceptive potential of oleanolic acid, a pentacyclic triterpene in the mouse model of colonic nociception induced by mustard oil. We further examined the possible participation of opioid, alpha2-adrenergic, and transient receptor potential vanilloid 1 (TRPV1)-receptors in its mechanism. Mice were pretreated orally with oleanolic acid (3, 10, 30 mg/kg) or vehicle, and the pain-related behavioral responses to intracolonic injection of mustard oil was analysed. Oleanolic acid significantly suppressed the mustard oil-induced nociceptive behaviors at test doses of 10 and 30 mg/kg, in a dose-related manner. The antinociceptive effect of oleanolic acid (30 mg/kg) was significantly blocked by pretreatment with the opioid antagonist, naloxone (2 mg/kg, i.p.), while the alpha2-adrenoceptor antagonist, yohimbine (2 mg/kg, s.c.), had no effect. Pretreatment with ruthenium red (3 mg/kg, s.c.), a non-competitive TRPV1 antagonist alone caused significant inhibition of mustard oil-induced nociception but its co-administration with oleanolic acid produced neither antagonism nor potentiation of oleanolic acid antinociception. In the open-field test that detects sedative or motor abnormality, mice received 30 mg/kg oleanolic acid did not show any per se influence, but significantly inhibited the mustard oil-induced decrease in ambulation frequency. These data demonstrate the visceral antinociceptive potential of oleanolic acid that involves an opioid mechanism and possibly a modulatory influence on vanilloid-receptors, which needs further study.
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Brazil.
authors.forename: Juliana Lemos
authors.initials: JL
authors.lastname: Maia
authors.forename: Roberto César Pereira
authors.initials: RC
authors.lastname: Lima-Júnior
authors.forename: Juceni Pereira
authors.initials: JP
authors.lastname: David
authors.forename: Jorge Mauricio
authors.initials: JM
authors.lastname: David
authors.forename: Flávia Almeida
authors.initials: FA
authors.lastname: Santos
authors.forename: Vietla Satyanarayana
authors.initials: VS
authors.lastname: Rao
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003108:Colonic Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009149:Mustard Plant / Q000737:chemistry / Q000633:toxicity*; D009828:Oleanolic Acid / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced* / Q000517:prevention & control*; D010938:Plant Oils / Q000633:toxicity*; D012430:Ruthenium Red / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D010938:Plant Oils; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D012430:Ruthenium Red; D015016:Yohimbine; D009828:Oleanolic Acid; C027793:mustard oil