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Epilepsy is a neurological disorder characterized by recurrent seizures,resulting from excessive neuronal discharges. Sideroxylonobtusifolium is used in Brazil for itsanti-inflammatory/antioxidant properties, known to be involved withepilepsy. The anticonvulsant effects of the methanol fraction from S.obtusifolium leaves, rich inN-methyl-(2S,4R)-trans-4-hydroxy-L-proline,were investigated on pilocarpine- and pentylenetetrazole-induced convulsionmodels. Mice were pretreated withN-methyl-(2S,4R)-trans-4-hydroxy-L-proline(50, 100, 200 mg/kg, p.o.) and, 1 h later, by pilocarpine(400 mg/kg, i.p.) or pentylenetetrazole(80 mg/kg, i.p.). The animals were observed for latency tothe first convulsion and latency to death. Immediately after death, brainareas from the pilocarpine groups were harvested for biochemicalmeasurements. The latency to the first convulsion and latency to deathincreased afterN-methyl-(2S,4R)-trans-4-hydroxy-L-prolinetreatment compared with the pilocarpine- or pentylenetetrazole-only groups.In both convulsion models, sodium valproate (reference drug) was used as apositive control. Additionally, the decreases in striatal dopamine and3,4-dihydroxyphenylacetic acid contents observed in the pilocarpine-onlygroup were partially prevented in theN-methyl-(2S,4R)-trans-4-hydroxy-L-proline-treatedgroups. While brain gamma-aminobutyric acid and glutamate contents decreasedand increased, respectively, after pilocarpine only, these changes were alsoprevented byN-methyl-(2S,4R)-trans-4-hydroxy-L-proline.Similarly,N-methyl-(2S,4R)-trans-4-hydroxy-L-prolinereduced the brain oxidative stress by decreasing the levels of nitrite andlipid peroxidation and increasing the glutathione content of thepilocarpine-only group. The increases in hippocampal expressions forinterleukin 6, interferon-gamma, and glial fibrillary acidic protein, afterpilocarpine only, were decreased to normal levels byN-methyl-(2S,4R)-trans-4-hydroxy-L-proline.In conclusion, the study showed significant anticonvulsant effects forN-methyl-(2S,4R)-trans-4-hydroxy-L-proline,probably related to its anti-inflammatory/antioxidant properties.N-Methyl-(2S,4R)-trans-4-hydroxy-L-prolineeffects were potentiated by VPA (sodium valproate), thus it may alsointeract with the GABAergic system, as we had recently shown.

planta medica international open

The N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline-Enriched Methanol Fraction from Sideroxylon obtusifolium Shows an Anticonvulsant Activity Associated with its Anti-inflammatory/Antioxidant Actions