title: 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.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Mateus Fortes
authors.initials: MF
authors.lastname: Rossato
authors.forename: Gabriela
authors.initials: G
authors.lastname: Trevisan
authors.forename: Cristiani Isabel Banderó
authors.initials: CI
authors.lastname: Walker
authors.forename: Jonatas Zeni
authors.initials: JZ
authors.lastname: Klafke
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: de Oliveira
authors.forename: Jardel Gomes
authors.initials: JG
authors.lastname: Villarinho
authors.forename: Ricardo Basso
authors.initials: RB
authors.lastname: Zanon
authors.forename: Luiz Fernando Freire
authors.initials: LF
authors.lastname: Royes
authors.forename: Margareth Linde
authors.initials: ML
authors.lastname: Athayde
authors.forename: Marcus Vinicius
authors.initials: MV
authors.lastname: Gomez
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants; D002211:Capsaicin / Q000494:pharmacology; D044950:Flavanones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005419:Flavonoids; D006930:Hyperalgesia / Q000188:drug therapy; D051379:Mice; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
chemical_list: D000700:Analgesics; D000975:Antioxidants; D044950:Flavanones; D005419:Flavonoids; D050916:TRPV Cation Channels; C007619:eriodictyol; D002211:Capsaicin