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 ␣-spinasterol reduced the nociception and edema induced by capsaicin injection. Moreover, ␣-spinasterol demonstrated good oral absorption and high penetration into the brain and spinal cord of mice. ␣-Spinasterol was able to displace [ 3 H]resiniferatoxin binding and diminish calcium influx mediated by capsaicin. Oral administration of the dichloromethane fraction and ␣-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 ␣-spinasterol did not produce antinociceptive effect in mice systemically pretreated with resiniferatoxin. In addition, ␣-spinasterol and the dichloromethane fraction reduced the edema, mechanical, and heat hyperalgesia elicited by complete Freund's adjuvant paw injection. The dichloromethane fraction and ␣-spinasterol did not affect body temperature or locomotor activity. In conclusion, ␣-spinasterol is a novel efficacious and safe antagonist of the TRPV1 receptor with antinociceptive effect.

Tabernaemontana catharinensis ethyl acetate fraction presents antinociceptive activity without causing toxicological effects in mice

“…These results support the peripheral antinociceptive action of the Eta and are in accordance with previous studies of new compounds, which also presented peripheral antinociceptive activity in the same test (Oliveira et al, 2009;Trevisan et al, 2012).…”

Regioselectively controlled synthesis of 3(5)-(trifluoromethyl)pyrazolylbenzenesulfonamides and their effects on a pathological pain model in mice

“…In order to evaluate the possible nonspecific muscle-relaxant or sedative effects, we examined the spontaneous or forced locomotor activity of the animals using the open-field and rotarod test, respectively, as previously reported by Trevisan et al [30]. To evaluate the spontaneous locomotor activity of animals, a glass box measuring 40 Â 60 Â 50 cm was used.…”

Novel Therapeutic Strategy to Prevent Chemotherapy-Induced Persistent Sensory Neuropathy By TRPA1 Blockade

“…The test was done as previously described (35). Briefly, 24 hours before the experiments, the animals were trained on the rotarod apparatus, programmed at 8 rpm, until they remained without falling for 60 seconds.…”