PT - JOURNAL ARTICLE AU - Gabriela Trevisan AU - Mateus Fortes Rossato AU - Cristiani Isabel Banderó Walker AU - Jonatas Zeni Klafke AU - Fernanda Rosa AU - Sara Marchesan Oliveira AU - Raquel Tonello AU - Gustavo Petri Guerra AU - Aline Augusti Boligon AU - Ricardo Basso Zanon AU - Margareth Linde Athayde AU - Juliano Ferreira TI - Identification of the Plant Steroid α-Spinasterol as a Novel Transient Receptor Potential Vanilloid 1 Antagonist with Antinociceptive Properties AID - 10.1124/jpet.112.195909 DP - 2012 Nov 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 258--269 VI - 343 IP - 2 4099 - http://jpet.aspetjournals.org/content/343/2/258.short 4100 - http://jpet.aspetjournals.org/content/343/2/258.full SO - J Pharmacol Exp Ther2012 Nov 01; 343 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.