Stephalagine, an aporphine alkaloid from Annona crassiflora fruit peel, induces antinociceptive effects by TRPA1 and TRPV1 channels modulation in mice.

Autor: Justino AB; Graduate Program in Genetics and Biochemistry, Institute of Biotechnology, Federal University of Uberlândia, 38408-100 Uberlândia, MG, Brazil., Barbosa MF; Graduate Program in Chemistry, Institute of Chemistry, Federal University of Uberlândia, 38400-902 Uberlândia, MG, Brazil., Neves TV; Graduate Program in Genetics and Biochemistry, Institute of Biotechnology, Federal University of Uberlândia, 38408-100 Uberlândia, MG, Brazil., Silva HCG; Graduate Program in Genetics and Biochemistry, Institute of Biotechnology, Federal University of Uberlândia, 38408-100 Uberlândia, MG, Brazil., Brum EDS; Graduate Program in Biological Sciences: Toxicological Biochemistry, Biochemistry and Molecular Biology Department, Federal University of Santa Maria (UFSM), 97105-900 Santa Maria, RS, Brazil., Fialho MFP; Graduate Program in Biological Sciences: Toxicological Biochemistry, Biochemistry and Molecular Biology Department, Federal University of Santa Maria (UFSM), 97105-900 Santa Maria, RS, Brazil., Couto AC; Graduate Program in Genetics and Biochemistry, Institute of Biotechnology, Federal University of Uberlândia, 38408-100 Uberlândia, MG, Brazil., Saraiva AL; Graduate Program in Genetics and Biochemistry, Institute of Biotechnology, Federal University of Uberlândia, 38408-100 Uberlândia, MG, Brazil., Avila VMR; Graduate Program in Genetics and Biochemistry, Institute of Biotechnology, Federal University of Uberlândia, 38408-100 Uberlândia, MG, Brazil., Oliveira SM; Graduate Program in Biological Sciences: Toxicological Biochemistry, Biochemistry and Molecular Biology Department, Federal University of Santa Maria (UFSM), 97105-900 Santa Maria, RS, Brazil., Pivatto M; Graduate Program in Chemistry, Institute of Chemistry, Federal University of Uberlândia, 38400-902 Uberlândia, MG, Brazil., Espindola FS; Graduate Program in Genetics and Biochemistry, Institute of Biotechnology, Federal University of Uberlândia, 38408-100 Uberlândia, MG, Brazil., Silva CR; Graduate Program in Genetics and Biochemistry, Institute of Biotechnology, Federal University of Uberlândia, 38408-100 Uberlândia, MG, Brazil. Electronic address: cassia.regina@ufu.br.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2020 Mar; Vol. 96, pp. 103562. Date of Electronic Publication: 2020 Jan 16.
DOI: 10.1016/j.bioorg.2019.103562
Abstrakt: Pain relief represents a critical unresolved medical need. Consequently, the search for new analgesic agents is intensively studied. Annona crassiflora, a native species of the Brazilian Savanna, represents a potential source for painful treatment. This study aimed to investigate the antinociceptive potential of A. crassiflora fruit peel, focusing on its major alkaloid, stephalagine, in animal models of pain evoked by the activation of transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) channels. Male C57BL/6/J mice were submitted to formalin-, cinnamaldehyde-, and capsaicin-induced nociception tests to assess nociceptive behavior, and to the open-field and rotarod tests for motor performance analyses. Moreover, the stephalagine's effect was tested on capsaicin- and cinnamaldehyde-induced Ca 2+ influx in spinal cord synaptosomes. In silico assessments of the absorption, distribution, metabolism and central nervous system permeability of stephalagine were carried out. The ethanol extract and alkaloidal fraction reduced the nociception induced by formalin. 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 Ca 2+ influx, indicating a possible modulation of TRPV1 and TRPA1 channels, respectively. Together, our results support the antinociceptive and anti-edematogenic effects of the A. crassiflora fruit peel and suggest that these effects are triggered, at least in part, by TRPV1 and TRPA1 modulation by stephalagine.
Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: