Eriodictyol: a flavonoid antagonist of the TRPV1 receptor with antioxidant activity.

Abstract

The transient potential vanilloid 1 receptor (TRPV1) is a calcium-permeable channel responsible for the transduction and modulation of acute and chronic pain signaling. As such, this receptor is a potential target for the treatment of a number of pain disorders. However, AMG517, a TRPV1 antagonist, presents several clinical limitations that include the induction of severe hyperthermia. The aim of this study was to investigate the possible interaction of the flavonoid eriodictyol with the TRPV1 receptor and to determine its putative antinociceptive and hyperthermic effects. Eriodictyol was able to displace [(3)H]-resiniferatoxin binding (IC(50)=47; 21-119nM) and to inhibit calcium influx mediated by capsaicin (IC(50)=44; 16-125nM), suggesting that eriodictyol acts as a TRPV1 antagonist. Moreover, eriodictyol induced antinociception in the intraplantar capsaicin test, with maximal inhibition of 49±10 and 64±4% for oral (ID(50)=2.3; 1.1-5.7mg/kg) and intrathecal (ID(50)=2.2; 1.7-2.9nmol/site) administration, respectively. Eriodictyol did not induce any change in body temperature or locomotor activity. Orally administered eriodictyol (4.5mg/kg) prevented the nociception induced by intrathecal injections of capsaicin, as well as the non-protein thiol loss and 3-nitrotyrosine (3-NT) formation induced by capsaicin in spinal cord. Eriodictyol also reduced the thermal hyperalgesia and mechanical allodynia elicited by complete Freund's adjuvant (CFA) paw injection. In conclusion, eriodictyol acts as an antagonist of the TRPV1 receptor and as an antioxidant; it induces antinociception without some of the side effects and limitations such as hyperthermia that are expected for TRPV1 antagonists.

• Authors: Mateus Fortes Rossato, Gabriela Trevisan, Cristiani Isabel Banderó Walker, Jonatas Zeni Klafke, Ana Paula de Oliveira, Jardel Gomes Villarinho, Ricardo Basso Zanon, Luiz Fernando Freire Royes, Margareth Linde Athayde, Marcus Vinicius Gomez, Juliano Ferreira
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 81 Issue 4 Pg. 544-51 (Feb 15 2011) ISSN: 1873-2968 [Electronic] England
• PMID: 21087598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010. Published by Elsevier Inc.

Chemical References

• Analgesics
• Antioxidants
• Flavanones
• Flavonoids
• TRPV Cation Channels
• eriodictyol
• Capsaicin

Topics

• Analgesics (administration & dosage, adverse effects, pharmacology)
• Animals
• Antioxidants
• Capsaicin (pharmacology)
• Flavanones (administration & dosage, adverse effects, pharmacology)
• Flavonoids
• Hyperalgesia (drug therapy)
• Mice
• Pain (drug therapy)
• Rats
• TRPV Cation Channels (antagonists & inhibitors)