Antinociceptive Effect of Lupeol: Evidence for a Role of Cytokines Inhibition

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...

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Published in:Phytotherapy research 2013-10, Vol.27 (10), p.1557-1563
Main Authors: de Lima, Flávia Oliveira, Alves, Vivian, Filho, José Maria Barbosa, da Silva Almeida, Jackson Roberto Guedes, Rodrigues, Luis Cezar, Soares, Milena Botelho Pereira, Villarreal, Cristiane Flora
Format: Article
Language:English
Subjects:
Adrenergic receptors
Analgesics - adverse effects
Analgesics - pharmacology
Animals
antinociception
Carrageenan - adverse effects
cytokines
Cytokines - metabolism
Disease Models, Animal
Fabaceae - chemistry
Hyperalgesia - drug therapy
Inflammation - drug therapy
inflammatory pain
Interleukin-1beta - metabolism
Lonchocarpus araripensis
lupeol
Male
Mice
Motor Activity - drug effects
Pain - chemically induced
Pain - drug therapy
Pain Measurement
Pain, Postoperative - drug therapy
Pentacyclic Triterpenes - pharmacology
Plant Bark - chemistry
Plant Extracts - adverse effects
Plant Extracts - pharmacology
post-operative pain
Tumor Necrosis Factor-alpha - metabolism
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Summary: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. Copyright © 2012 John Wiley & Sons, Ltd.
ISSN:0951-418X
1099-1573
DOI:10.1002/ptr.4902