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

Pedro Everson Alexandre de Aquino; Ítalo Rosal Lustosa; Caren Nádia Soares de Sousa; Adriano José Maia Chaves-Filho; Francisco Arnaldo Viana Lima; Alan Diego da Conceição Santos; Nilce Viana Gramosa; Edilberto Rocha Silveira; Glauce Socorro de Barros Viana

doi:10.1055/a-1328-5093

Planta Medica International Open, Table of Contents

CC BY-NC-ND 4.0 · Planta Medica International Open 2020; 07(04): e158-e169
DOI: 10.1055/a-1328-5093

Original Papers

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

Pedro Everson Alexandre de Aquino

¹Laboratory of Neuropharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil

,

Ítalo Rosal Lustosa

¹Laboratory of Neuropharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil

,

Caren Nádia Soares de Sousa

¹Laboratory of Neuropharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil

,

Adriano José Maia Chaves-Filho

¹Laboratory of Neuropharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil

,

Francisco Arnaldo Viana Lima

¹Laboratory of Neuropharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil

,

Alan Diego da Conceição Santos

²Department of Organic and Inorganic Chemistry, Federal University of Ceará, Fortaleza, Brazil

,

Nilce Viana Gramosa

²Department of Organic and Inorganic Chemistry, Federal University of Ceará, Fortaleza, Brazil

,

Edilberto Rocha Silveira

²Department of Organic and Inorganic Chemistry, Federal University of Ceará, Fortaleza, Brazil

,

Glauce Socorro de Barros Viana

¹Laboratory of Neuropharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil

› Author Affiliations

Abstract

Epilepsy is a neurological disorder characterized by recurrent seizures, resulting from excessive neuronal discharges. Sideroxylon obtusifolium is used in Brazil for its anti-inflammatory/antioxidant properties, known to be involved with epilepsy. The anticonvulsant effects of the methanol fraction from S. obtusifolium leaves, rich in N-methyl-(2S,4R)-trans-4-hydroxy-L-proline, were investigated on pilocarpine- and pentylenetetrazole-induced convulsion models. Mice were pretreated with N-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 to the first convulsion and latency to death. Immediately after death, brain areas from the pilocarpine groups were harvested for biochemical measurements. The latency to the first convulsion and latency to death increased after N-methyl-(2S,4R)-trans-4-hydroxy-L-proline treatment compared with the pilocarpine- or pentylenetetrazole-only groups. In both convulsion models, sodium valproate (reference drug) was used as a positive control. Additionally, the decreases in striatal dopamine and 3,4-dihydroxyphenylacetic acid contents observed in the pilocarpine-only group were partially prevented in the N-methyl-(2S,4R)-trans-4-hydroxy-L-proline-treated groups. While brain gamma-aminobutyric acid and glutamate contents decreased and increased, respectively, after pilocarpine only, these changes were also prevented by N-methyl-(2S,4R)-trans-4-hydroxy-L-proline. Similarly, N-methyl-(2S,4R)-trans-4-hydroxy-L-proline reduced the brain oxidative stress by decreasing the levels of nitrite and lipid peroxidation and increasing the glutathione content of the pilocarpine-only group. The increases in hippocampal expressions for interleukin 6, interferon-gamma, and glial fibrillary acidic protein, after pilocarpine only, were decreased to normal levels by N-methyl-(2S,4R)-trans-4-hydroxy-L-proline. In conclusion, the study showed significant anticonvulsant effects for N-methyl-(2S,4R)-trans-4-hydroxy-L-proline, probably related to its anti-inflammatory/antioxidant properties. N-Methyl-(2S,4R)-trans-4-hydroxy-L-proline effects were potentiated by VPA (sodium valproate), thus it may also interact with the GABAergic system, as we had recently shown.

Key words

Sideroxylon obtusifolium - Sapotaceae family - pilocarpine-induced convulsions - PTZ-induced convulsions - GABAergic system

Full Text

References

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Supplementary Material

Supplementary Material