title: Identification of the plant steroid α-spinasterol as a novel transient receptor potential vanilloid 1 antagonist with antinociceptive properties.
abstract: 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.
authors: Departamento de Química, Universidade Federal de Santa Maria, Avenida Roraima, 1000, Camobi, 97105-900, Santa Maria, RS, Brazil. gabitrev@hotmail.com
authors: Gabriela
authors: G
authors: Trevisan
authors: Mateus Fortes
authors: MF
authors: Rossato
authors: Cristiani Isabel Banderó
authors: CI
authors: Walker
authors: Jonatas Zeni
authors: JZ
authors: Klafke
authors: Fernanda
authors: F
authors: Rosa
authors: Sara Marchesan
authors: SM
authors: Oliveira
authors: Raquel
authors: R
authors: Tonello
authors: Gustavo Petri
authors: GP
authors: Guerra
authors: Aline Augusti
authors: AA
authors: Boligon
authors: Ricardo Basso
authors: RB
authors: Zanon
authors: Margareth Linde
authors: ML
authors: Athayde
authors: Juliano
authors: J
authors: Ferreira
mesh_terms: D000700:Analgesics; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D005620:Freund's Adjuvant; D006358:Hot Temperature; D008297:Male; D051379:Mice; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D013265:Stigmasterol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D014018:Tissue Distribution; D035741:Vernonia / Q000737:chemistry*
chemical_list: D000700:Analgesics; D004224:Diterpenes; D010936:Plant Extracts; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C031312:spinasterol; D005620:Freund's Adjuvant; D013265:Stigmasterol; C024353:resiniferatoxin; D002211:Capsaicin; D002118:Calcium