Attenuation of visceral nociception by alpha- and beta-amyrin, a triterpenoid mixture isolated from the resin of Protium heptaphyllum, in mice.
In the search for novel natural compounds effective against visceral nociception, the triterpenoid mixture alpha- and beta-amyrin, isolated from Protium heptaphyllum resin, was assessed in two established mouse models of visceral nociception. Mice were pretreated orally with alpha- and beta-amyrin (3, 10, 30, and 100 mg/kg) or vehicle, and the pain-related behavioral responses to intraperitoneal cyclophosphamide or to intracolonic mustard oil were analyzed. The triterpenoid mixture showed a dose-related significant antinociception against the cyclophosphamide-induced bladder pain, and at 100 mg/kg, the nociceptive behavioral expression was almost completely suppressed. Intracolonic mustard oil-induced nociceptive behaviors were maximally inhibited by 10 mg/kg alpha- and beta-amyrin mixture in a naloxone-reversible manner. While pretreatment with ruthenium red (3 mg/kg, s. c.), a non-specific transient receptor potential cation channel V1 (TRPV1) antagonist, also caused significant inhibition, the alpha (2)-adrenoceptor antagonist, yohimbine (2 mg/kg, s. c.), showed no significant effect. The triterpene mixture (10 mg/kg, p. o.) neither altered significantly the pentobarbital sleeping time, nor impaired the ambulation or motor coordination in open-field and rotarod tests, respectively, indicating the absence of sedative or motor abnormalities that could account for its antinociception. These results indicate that the antinociceptive potential of alpha- and beta-amyrin possibly involves the opioid and vanilloid (TRPV1) receptor mechanisms and further suggests that it could be useful to treat visceral pain of intestinal and pelvic origins.
Lima-Júnior
Roberto C P
RC
Department of Physiology and Pharmacology, Federal University of Ceara, Fortaleza, CE, Brazil.
Oliveira
Francisco A
FA
Gurgel
Luilma A
LA
Cavalcante
Italo J
IJ
Santos
Kelcyana A
KA
Campos
Deive A
DA
Vale
Cinthia A
CA
Silva
Regilane M
RM
Chaves
Mariana H
MH
Rao
Vietla S N
VS
Santos
Flávia A
FA
D000317:Adrenergic alpha-Antagonists; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D029403:Burseraceae / Q000737:chemistry*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009619:Nociceptors / Q000187:drug effects*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D010147:Pain Measurement; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D012116:Resins, Plant / Q000737:chemistry / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology; D014781:Viscera; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D010936:Plant Extracts; D012116:Resins, Plant; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D014315:Triterpenes; D012430:Ruthenium Red; D015016:Yohimbine; D009828:Oleanolic Acid; C036380:beta-amyrin