Alterations in brain amino acid metabolism and inhibitory effects on PKC are possibly correlated with anticonvulsant effects of the isomeric mixture of α- and β-amyrin from Protium heptaphyllum

Abstract

Context: α- and β-Amyrin (AMY) from Protium heptaphyllum (Aubl) March (Burseraceae) is found in Brazil and used in diverse inflammation-related diseases. This species presents a central action, as previously described.Objective: The objectives were to evaluate the anticonvulsant effect of AMY in mice and to verify the mechanism of action.Material and methods: Seizures were induced by pentylenetetrazole followed by acute or subchronic treatments (5–25 mg/kg, p.o. and i.p.) and determination of brain amino acids (10 and 25 mg/kg, i.p., 7 d).Results: In the acute treatment, AMY (10, 25, and 50 mg/kg, p.o.) increased the latency to the first convulsion (FC) by 30, 44, and 40% and time to death (TD) by 36, 52, and 42%, respectively. When administered intraperitoneally, the same doses increased FC by 62, 75, and 73% and TD by 76, 82, and 119%, respectively. Combined with polymixin or staurosporine, AMY (25 mg/kg, i.p.) increased TD by 61 and 63%, respectively, as related to each drug alone. When subchronically administered (25 and 50 mg/kg, i.p.) increased FC by 75 and 101% and TD by 86 and 124%, respectively. AMY increased taurine (116 and 76%) and tyrosine concentrations (135 and 110%) in basal ganglia and hippocampus, respectively, and decreased by 68, 65, and 62% glutamate, aspartate, and GABA in basal ganglia.Conclusion: Thus, the AMY anticonvulsant activity is related to the GABAergic system and may be linked to the inhibition of the signaling cascade of PKC as well as to alterations in amino acids metabolism.