TY - JOUR
T1 - Antinociceptive effect of 7-hydroxy-3,4-dihydrocadalin isolated from Heterotheca inuloides
T2 - Role of peripheral 5-HT1 serotonergic receptors
AU - Rocha-González, Héctor Isaac
AU - Blaisdell-López, Everardo
AU - Granados-Soto, Vinicio
AU - Navarrete, Andrés
PY - 2010/12/15
Y1 - 2010/12/15
N2 - The purpose of this study was to investigate the possible antinociceptive effect of Heterotheca inuloides in inflammatory pain and to identify the main compounds involved in this effect. Dose-response curves were obtained for hexane, dichlorometane, ethyl acetate and methanol extracts from Heterotheca inuloides inflorescences in the formalin test. Hexane extract was more potent and effective than other extracts. Bio-guided fractionation was performed to determine the main antinociceptive compounds of the plant. Gas chromatography-mass spectrometry technique demonstrated the composition of the most active fraction from hexane extract revealing the presence of caryophyllene oxide, cedrene, 7-hydroxy-3,4-dihydrocadalin, 7-hydroxycadalene and a compound not identified. The isolated compounds were individually evaluated in the formalin test in a preliminary dose of 100μg/paw and only 7-hydroxy-3,4-dihydrocadalin showed a significant antinociceptive effect. Dose-response curves were then obtained for 7-hydroxy-3,4-dihydrocadalin and diclofenac, a prototypical analgesic drug. Both drugs were equieffective and equipotent in the second phase of the formalin test, but 7-hydroxy-3,4-dihydrocadalin was more effective and potent in the first phase than diclofenac. In addition, 7-hydroxy-3,4-dihydrocadalin reduced carrageenan-induced mechanical hyperalgesia and inflammation in a dose-dependent manner. Finally, in mechanistic studies, the antinociceptive effect of 7-hydroxy-3,4-dihydrocadalin in the formalin test was prevented by methiothepin, WAY100635, SB224289 and BRL15572 but not by naltrexone. Results support the use of H. inuloides inflorescences as analgesic in the Mexican traditional medicine. Moreover, data indicate that 7-hydroxy-3,4-dihydrocadalin is partly responsible of this pharmacological activity, and suggest that 5-HT1A, 5-HT1B, and 5-HT1D serotonergic, but not opioid, receptors participate in the antinociceptive effect of this drug.
AB - The purpose of this study was to investigate the possible antinociceptive effect of Heterotheca inuloides in inflammatory pain and to identify the main compounds involved in this effect. Dose-response curves were obtained for hexane, dichlorometane, ethyl acetate and methanol extracts from Heterotheca inuloides inflorescences in the formalin test. Hexane extract was more potent and effective than other extracts. Bio-guided fractionation was performed to determine the main antinociceptive compounds of the plant. Gas chromatography-mass spectrometry technique demonstrated the composition of the most active fraction from hexane extract revealing the presence of caryophyllene oxide, cedrene, 7-hydroxy-3,4-dihydrocadalin, 7-hydroxycadalene and a compound not identified. The isolated compounds were individually evaluated in the formalin test in a preliminary dose of 100μg/paw and only 7-hydroxy-3,4-dihydrocadalin showed a significant antinociceptive effect. Dose-response curves were then obtained for 7-hydroxy-3,4-dihydrocadalin and diclofenac, a prototypical analgesic drug. Both drugs were equieffective and equipotent in the second phase of the formalin test, but 7-hydroxy-3,4-dihydrocadalin was more effective and potent in the first phase than diclofenac. In addition, 7-hydroxy-3,4-dihydrocadalin reduced carrageenan-induced mechanical hyperalgesia and inflammation in a dose-dependent manner. Finally, in mechanistic studies, the antinociceptive effect of 7-hydroxy-3,4-dihydrocadalin in the formalin test was prevented by methiothepin, WAY100635, SB224289 and BRL15572 but not by naltrexone. Results support the use of H. inuloides inflorescences as analgesic in the Mexican traditional medicine. Moreover, data indicate that 7-hydroxy-3,4-dihydrocadalin is partly responsible of this pharmacological activity, and suggest that 5-HT1A, 5-HT1B, and 5-HT1D serotonergic, but not opioid, receptors participate in the antinociceptive effect of this drug.
KW - 7-hydroxy-3,4-dihydrocadalin
KW - Formalin test
KW - Heterotheca inuloides
KW - Inflammation
KW - Inflammatory hyperalgesia
KW - Pain
UR - http://www.scopus.com/inward/record.url?scp=78049288583&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2010.09.022
DO - 10.1016/j.ejphar.2010.09.022
M3 - Artículo
C2 - 20863828
SN - 0014-2999
VL - 649
SP - 154
EP - 160
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -