生化学と薬理学: オープンアクセス
オープンアクセス

概要

Stephalagine, a derived aporphine alkaloid, induces antinociceptive effects by TRPA1 and TRPV1 channels modulation in mice

Cassia R Silva

Pain relief represents a critical unresolved medical need. Consequently, the search for new analgesic agents is intensively studied. Plant-derived alkaloids have previously demonstrated antinociceptive effects with suggested modulation of transient receptor potential (TRP) channels. This study aimed to investigate the antinociceptive properties of stephalagine, a Brazilian Savanna aporphine alkaloid from Annona crassiflora Mart. fruit peel. Stephalagine was administered by oral and intraplantar routes in male C57BL/6/J mice, and the animals were submitted to cinnamaldehyde-, capsaicin- and formalin-induced nociception tests to assess nociceptive behavior, and to the open-field and rotarod tests for motor performance analyses. Moreover, the stephalagine’ effect was tested on capsaicin- and cinnamaldehyde-induced Ca2+ influx in spinal cord synaptosomes. In addition, in silico assessments of the absorption, distribution, metabolism and central nervous system permeability of stephalagine were carried out. When administered by oral route (1 mg/kg), stephalagine reduced the spontaneous nociception and paw edema induced by TRPV1 agonist, capsaicin, and by TRPA1 agonists, cinnamaldehyde- and formalin, without altering the animals’ locomotor activity. The prediction of in silico pharmacokinetic properties of stephalagine suggests its capacity to cross the blood-brain barrier. Furthermore, this alkaloid reduces the capsaicin- and cinnamaldehyde- mediated Ca2+ influx, indicating a possible modulation of TRPV1 and TRPA1 channels, respectively. Together, our results support the antinociceptive and anti-edematogenic effects of the aporphine alkaloid stephalagine, and suggest that these effects are triggered, at least in part, by TRPV1 and TRPA1 modulation.