TY - JOUR
T1 - Ursolic acid from Agastache mexicana aerial parts produces antinociceptive activity involving TRPV1 receptors, cGMP and a serotonergic synergism
AU - Verano, Jazmín
AU - González-Trujano, Ma Eva
AU - Déciga-Campos, Myrna
AU - Ventura-Martínez, Rosa
AU - Pellicer, Francisco
N1 - Funding Information:
We are thankful to Dr. Eva Aguirre for her participation in the collection of the plant material and to the student Roberto Sosa, Mr. Rubén Luviano, Mr. Raúl Cardoso and Mr. José Luis Calderón for the technical assistance. We also thank M. Sánchez-Álvarez for proof reading the English version of this manuscript. This work was partially supported by CONACYT 80811 and INP3280 projects. Fellowship PIFI-IPN and CONACyT- 232656 and 253243 (Alejandra Cortés and Jazmín Verano, respectively).
PY - 2013
Y1 - 2013
N2 - Agastachemexicana is a plant that has long been used in large demands inMexican folk medicine to treat anxiety, insomnia and pain, among others affections. Chromatographic technique was used to identify ursolic acid (UA), 130.7 mg/g and 20.3 mg/g, as an antinociceptive active compound identified in ethyl acetate and methanol extracts of A. mexicana aerial parts, respectively. Temporal course curves of the antinociceptive response demonstrated a dose-dependent and significant activity of UA (1 to 100 mg/kg, i.p.) with an ED50 = 2 mg/kg in comparison to the efficacy of diclofenac (1 or 30 to 100 mg/kg, i.p.), a non-steroidal anti-inflammatory drug, with an ED 50 = 11.56 mg/kg. The antinociceptive response consisted in the reduction of abdominal constrictions induced with 1% acetic acid in mice. Similarly, UA at 2 mg/kg produced significant antinociception in the intracolonic administration of 0.3% capsaicin (a TRPV1 agonist) in mice. It has been reported the inhibition produced by UA on the calcium-flux induced by capsaicin on TRPV1 receptor suggesting the antagonistic activity of this receptor. Finally, an ED50 = 44 mg/kg was calculated in the neurogenic and inflammatory nociception induced in the formalin test in rats. The antinociceptive response of UA in the formalin test was not modified in presence of naloxone, flumazenil or L-arginine. Nevertheless, it was reverted in presence of 1-H-(1,2,4)- oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, an inhibitor of soluble guanylyl cyclase) and increased in presence of N(G)-L-nitro-arginine methyl ester (L-NAME, inhibitor of nitric oxide synthase), theophylline (inhibitor of phosphodiesterase) and WAY100635 (an antagonist of 5-HT 1A receptors). Current results provide evidence that the antinociceptive response of A. mexicana depends in part on the presence of UA.Moreover, this triterpene may exerts its antinociceptive effect mediated by the presence of cGMP and an additive synergism with 5HT1A receptors, but also an antagonistic activity towards TRPV1 receptors may be involved.
AB - Agastachemexicana is a plant that has long been used in large demands inMexican folk medicine to treat anxiety, insomnia and pain, among others affections. Chromatographic technique was used to identify ursolic acid (UA), 130.7 mg/g and 20.3 mg/g, as an antinociceptive active compound identified in ethyl acetate and methanol extracts of A. mexicana aerial parts, respectively. Temporal course curves of the antinociceptive response demonstrated a dose-dependent and significant activity of UA (1 to 100 mg/kg, i.p.) with an ED50 = 2 mg/kg in comparison to the efficacy of diclofenac (1 or 30 to 100 mg/kg, i.p.), a non-steroidal anti-inflammatory drug, with an ED 50 = 11.56 mg/kg. The antinociceptive response consisted in the reduction of abdominal constrictions induced with 1% acetic acid in mice. Similarly, UA at 2 mg/kg produced significant antinociception in the intracolonic administration of 0.3% capsaicin (a TRPV1 agonist) in mice. It has been reported the inhibition produced by UA on the calcium-flux induced by capsaicin on TRPV1 receptor suggesting the antagonistic activity of this receptor. Finally, an ED50 = 44 mg/kg was calculated in the neurogenic and inflammatory nociception induced in the formalin test in rats. The antinociceptive response of UA in the formalin test was not modified in presence of naloxone, flumazenil or L-arginine. Nevertheless, it was reverted in presence of 1-H-(1,2,4)- oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, an inhibitor of soluble guanylyl cyclase) and increased in presence of N(G)-L-nitro-arginine methyl ester (L-NAME, inhibitor of nitric oxide synthase), theophylline (inhibitor of phosphodiesterase) and WAY100635 (an antagonist of 5-HT 1A receptors). Current results provide evidence that the antinociceptive response of A. mexicana depends in part on the presence of UA.Moreover, this triterpene may exerts its antinociceptive effect mediated by the presence of cGMP and an additive synergism with 5HT1A receptors, but also an antagonistic activity towards TRPV1 receptors may be involved.
KW - Agastache mexicana
KW - Antinociception
KW - CGMP
KW - Serotonin
KW - TRPV1
KW - Ursolic acid
UR - http://www.scopus.com/inward/record.url?scp=84886896145&partnerID=8YFLogxK
U2 - 10.1016/j.pbb.2013.07.020
DO - 10.1016/j.pbb.2013.07.020
M3 - Artículo
C2 - 23932918
SN - 0091-3057
VL - 110
SP - 255
EP - 264
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
ER -