Ursolic acid from Agastache mexicana aerial parts produces antinociceptive activity involving TRPV1 receptors, cGMP and a serotonergic synergism

Jazmín Verano, Ma Eva González-Trujano, Myrna Déciga-Campos, Rosa Ventura-Martínez, Francisco Pellicer

Research output: Contribution to journalArticle

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Abstract

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. © 2013 Elsevier Inc. All rights reserved.
Original languageAmerican English
Pages (from-to)255-264
Number of pages228
JournalPharmacology Biochemistry and Behavior
DOIs
StatePublished - 1 Jan 2013

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Agastache
Antennas
Capsaicin
NG-Nitroarginine Methyl Ester
Pain Measurement
Formaldehyde
Flumazenil
Quinoxalines
Triterpenes
Receptor, Serotonin, 5-HT1A
Nociception
Phosphodiesterase Inhibitors
Diclofenac
Guanylate Cyclase
Sleep Initiation and Maintenance Disorders
Traditional Medicine
Theophylline
Naloxone
Constriction
Nitric Oxide Synthase

Cite this

@article{2d137e6404884fd2bb9c260087ec3e0e,
title = "Ursolic acid from Agastache mexicana aerial parts produces antinociceptive activity involving TRPV1 receptors, cGMP and a serotonergic synergism",
abstract = "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. {\circledC} 2013 Elsevier Inc. All rights reserved.",
author = "Jazm{\'i}n Verano and Gonz{\'a}lez-Trujano, {Ma Eva} and Myrna D{\'e}ciga-Campos and Rosa Ventura-Mart{\'i}nez and Francisco Pellicer",
year = "2013",
month = "1",
day = "1",
doi = "10.1016/j.pbb.2013.07.020",
language = "American English",
pages = "255--264",
journal = "Pharmacology Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",

}

Ursolic acid from Agastache mexicana aerial parts produces antinociceptive activity involving TRPV1 receptors, cGMP and a serotonergic synergism. / Verano, Jazmín; González-Trujano, Ma Eva; Déciga-Campos, Myrna; Ventura-Martínez, Rosa; Pellicer, Francisco.

In: Pharmacology Biochemistry and Behavior, 01.01.2013, p. 255-264.

Research output: Contribution to journalArticle

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

PY - 2013/1/1

Y1 - 2013/1/1

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. © 2013 Elsevier Inc. All rights reserved.

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. © 2013 Elsevier Inc. All rights reserved.

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