Evidence for the involvement of descending pain-inhibitory mechanisms in the antinociceptive effect of hecogenin acetate.

Abstract

Hecogenin is a sapogenin present in the leaves of species from the Agave genus, with a wide spectrum of reported pharmacological activities. The present study was undertaken to evaluate whether hecogenin acetate (1) has antinociceptive properties and to determine its mechanism of action. The nociceptive threshold was evaluated using the tail flick test in mice. Mice motor performance was evaluated in a Rotarod test. By using Fos expression as a marker of neural activation, the involvement of the periaqueductal gray in 1-induced antinociception was evaluated. Intraperitoneal administration of 1 (5-40 mg/kg) produced a dose-dependent increase in the tail flick latency time compared to vehicle-treated group (p < 0.01). Mice treated with 1 (40 mg/kg) did not show motor performance alterations. The antinociception of 1 (40 mg/kg) was prevented by naloxone (nonselective opioid receptor antagonist; 5 mg/kg), CTOP (μ-opioid receptor antagonist; 1 mg/kg), nor-BNI (κ-opioid receptor antagonist; 0.5 mg/kg), naltrindole (δ-opioid receptor antagonist; 3 mg/kg), or glibenclamide (ATP-sensitive K(+) channel blocker; 2 mg/kg). Systemic administration of 1 (5-40 mg/kg) increased the number of Fos positive cells in the periaqueductal gray. The present study has demonstrated for the first time that 1 produces consistent antinociception mediated by opioid receptors and endogenous analgesic mechanisms.

• Authors: Kelly Barbosa Gama, Jullyana S S Quintans, Angelo R Antoniolli, Lucindo J Quintans-Júnior, Wagno Alcântara Santana, Alexsandro Branco, Milena Botelho Pereira Soares, Cristiane Flora Villarreal
• Journal: Journal of natural products (J Nat Prod) Vol. 76 Issue 4 Pg. 559-63 (Apr 26 2013) ISSN: 1520-6025 [Electronic] United States
• PMID: 23437926 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• KATP Channels
• Receptors, Opioid, kappa
• Receptors, Opioid, mu
• Spiro Compounds
• Steroids
• hecogenin acetate
• Naltrexone
• Glyburide

Topics

• Agave (chemistry)
• Analgesics (pharmacology)
• Animals
• Glyburide (pharmacology)
• KATP Channels (antagonists & inhibitors)
• Male
• Mice
• Molecular Structure
• Naltrexone (pharmacology)
• Pain (drug therapy)
• Periaqueductal Gray (drug effects)
• Plant Leaves (chemistry)
• Receptors, Opioid, kappa (antagonists & inhibitors)
• Receptors, Opioid, mu (antagonists & inhibitors)
• Spiro Compounds (pharmacology)
• Steroids (pharmacology)