posted on 2023-11-10, 18:35authored byRenan
Fernandes do Espírito-Santo, Dourivaldo Silva Santos, Pedro Santana Sales Lauria, Alyne Almeida de Lima, Lucas Silva Abreu, Josean Fechine Tavares, Marcelo Santos Castilho, Milena Botelho Pereira Soares, Cristiane Flora Villarreal
Tonantzitlolone B (TZL-B) is a diterpene isolated from
the roots
of Stillingia loranthacea. Its antinociceptive effects
were investigated in male Swiss mice using the following models of
pain: formalin test, inflammation induced by Complete Freund’s
Adjuvant (CFA), tail flick test, and cold plate test. The influence
of TZL-B on the opioid system was assessed in vivo, using opioid antagonists; in silico, investigating
the chemical similarity among TZL-B and opioid agonists; and ex vivo, measuring preproenkephalin (PENK) gene expression
in the spinal cord by RT-qPCR. TZL-B (10–1000 μg/kg)
promoted antinociception in the four experimental models without impairing
mice’s motor function. TZL-B did not alter paw edema during
CFA-induced inflammation. The antinociceptive effects of TZL-B in
the tail flick and cold plate tests were diminished by the opioid
antagonists naloxone (5 mg/kg), NOR-BNI (0.5 mg/kg), naltrindole (3
mg/kg), and CTOP (1 mg/kg), indicating the involvement of κ-,
δ-, and μ-opioid receptors. TZL-B showed no significant
chemical similarity to opioid agonists, but the treatment with TZL-B
(1000 μg/kg) increased PENK gene expression in the spinal cord
of mice. These data suggest that TZL-B promotes antinociception by
enhancing the transcription of PENK, hence modulating the endogenous
opioid system.