RT Journal Article
SR Electronic
T1 Identification of the Plant Steroid α-Spinasterol as a Novel Transient Receptor Potential Vanilloid 1 Antagonist with Antinociceptive Properties
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 258
OP 269
DO 10.1124/jpet.112.195909
VO 343
IS 2
A1 Gabriela Trevisan
A1 Mateus Fortes Rossato
A1 Cristiani Isabel Banderó Walker
A1 Jonatas Zeni Klafke
A1 Fernanda Rosa
A1 Sara Marchesan Oliveira
A1 Raquel Tonello
A1 Gustavo Petri Guerra
A1 Aline Augusti Boligon
A1 Ricardo Basso Zanon
A1 Margareth Linde Athayde
A1 Juliano Ferreira
YR 2012
UL http://jpet.aspetjournals.org/content/343/2/258.abstract
AB The transient receptor potential vanilloid 1 (TRPV1) receptor is relevant to the perception of noxious information and has been studied as a therapeutic target for the development of new analgesics. The goal of this study was to perform in vivo and in vitro screens to identify novel, efficacious, and safe TRPV1 antagonists isolated from leaves of the medicinal plant Vernonia tweedieana Baker. All of the fractions and the hydroalcoholic extract produced antinociception in mice during the capsaicin test, but the dichloromethane fraction also had antioedematogenic effect. Among the compounds isolated from the dichloromethane fraction, only α-spinasterol reduced the nociception and edema induced by capsaicin injection. Moreover, α-spinasterol demonstrated good oral absorption and high penetration into the brain and spinal cord of mice. α-Spinasterol was able to displace [3H]resiniferatoxin binding and diminish calcium influx mediated by capsaicin. Oral administration of the dichloromethane fraction and α-spinasterol also produced antinociceptive effect in the noxious heat-induced nociception test; however, they did not change the mechanical threshold of naive mice. The treatment with α-spinasterol did not produce antinociceptive effect in mice systemically pretreated with resiniferatoxin. In addition, α-spinasterol and the dichloromethane fraction reduced the edema, mechanical, and heat hyperalgesia elicited by complete Freund's adjuvant paw injection. The dichloromethane fraction and α-spinasterol did not affect body temperature or locomotor activity. In conclusion, α-spinasterol is a novel efficacious and safe antagonist of the TRPV1 receptor with antinociceptive effect.