title: Antinociceptive effect of lupeol: evidence for a role of cytokines inhibition.
abstract: The present study investigates the antinociceptive properties of lupeol in models of inflammatory and post-operative pain, as well as its mechanisms of action. The effects of lupeol were tested against acetic acid-induced writhing, formalin test, carrageenan-induced hyperalgesia, and post-operative pain model. Cytokine levels were determined by ELISA. Mice motor performance was evaluated in the rota rod and open-field tests. Pre-treatment of mice with lupeol (5-100 mg/kg IP) produced a dose-related inhibition of writhing in mice. The maximal antinociception produced by lupeol (60 mg/kg) was unaffected in mice pre-treated with yohimbine (α2 adrenoceptor antagonist; 2 mg/kg IP), L-arginine (substrate for nitric oxide synthase; 600 mg/kg IP), glibenclamide (the KATP-channel blocker; 2 mg/kg IP), and methysergide maleate (serotoninergic receptors antagonist; 5 mg/kg IP). Furthermore, lupeol (25-100 mg/kg) inhibited the late phase of formalin test. Pre-treatment with lupeol (50 and 100 mg/kg) inhibited the hyperalgesia and the local increase in tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels induced by carrageenan. In contrast, lupeol did not inhibit the post-operative pain. Lupeol-treated mice did not show any motor performance alterations or apparent systemic toxicity. Our results demonstrate that lupeol has consistent antinociceptive properties during inflammatory pain, but not post-operative pain, acting through the inhibition of IL-1β and TNF-α production.
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil; Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil.
authors.forename: Flávia Oliveira
authors.initials: FO
authors.lastname: de Lima
authors.forename: Vivian
authors.initials: V
authors.lastname: Alves
authors.forename: José Maria
authors.initials: JM
authors.lastname: Barbosa Filho
authors.forename: Jackson Roberto Guedes da Silva
authors.initials: JR
authors.lastname: Almeida
authors.forename: Luis Cezar
authors.initials: LC
authors.lastname: Rodrigues
authors.forename: Milena Botelho Pereira
authors.initials: MB
authors.lastname: Soares
authors.forename: Cristiane Flora
authors.initials: CF
authors.lastname: Villarreal
mesh_terms: D000700:Analgesics / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D002351:Carrageenan / Q000009:adverse effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007887:Fabaceae / Q000737:chemistry; D006930:Hyperalgesia / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000094042:Lupanes
chemical_list: D000700:Analgesics; D002351:Carrageenan; D016207:Cytokines; D053583:Interleukin-1beta; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C010480:lupeol; D000094042:Lupanes