The N-methyl-(2S,4R)-trans-4-hydroxy-L-proline-enriched fraction (NMP) from Sideroxylon obtusifolium was evaluated as a neuroprotective agent in the intracerebroventricular (icv) pilocarpine (Pilo) model. To this aim, male mice were subdivided into sham (SO, vehicle), Pilo (300 μg/1 μL icv, followed by the vehicle per os, po) and NMP-treated groups (Pilo 300 μg/1 μL icv, followed by 100 or 200 mg/kg po). The treatments started one day after the Pilo injection and continued for 15 days. The effects of NMP were assessed by characterizing the preservation of cognitive function in both the Y-maze and object recognition tests. The hippocampal cell viability was evaluated by Nissl staining. Additional markers of damage were studied—the glial fibrillary acidic protein (GFAP) and the ionized calcium-binding adaptor molecule 1 (Iba-1) expression using, respectively, immunofluorescence and western blot analyses. We also performed molecular docking experiments revealing that NMP binds to the γ-aminobutyric acid (GABA) transporter 1 (GAT1). GAT1 expression in the hippocampus was also characterized. Pilo induced cognitive deficits, cell damage, increased GFAP, Iba-1, and GAT1 expression in the hippocampus. These alterations were prevented, especially by the higher NMP dose. These data highlight NMP as a promising candidate for the protection of the hippocampus, as shown by the icv Pilo model.

A proline derivative-enriched fraction from Sideroxylon obtusifolium protects against intracerebroventricular pilocarpine-induced injury associated with status epilepticus in mice / Everson Alexandre de Aquino, Pedro; Rabelo Bezerra, Jéssica; de Souza Nascimento, Tyciane; Tavares, Juliete; ROSAL LUSTOSA, Italo; José Maia Chaves Filho, Adriano; Mottin, Melina; Macêdo Gaspar, Danielle; Matos de Andrade, Geanne; Rose Tavares Neves, Kelly; Biagini, Giuseppe; Rocha Silveira, Edilberto; Socorro de Barros Viana, Glauce. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 21:11(2020), pp. 1-22. [10.3390/ijms21114188]

A proline derivative-enriched fraction from Sideroxylon obtusifolium protects against intracerebroventricular pilocarpine-induced injury associated with status epilepticus in mice

Ítalo Rosal Lustosa;Giuseppe Biagini
;
2020

Abstract

The N-methyl-(2S,4R)-trans-4-hydroxy-L-proline-enriched fraction (NMP) from Sideroxylon obtusifolium was evaluated as a neuroprotective agent in the intracerebroventricular (icv) pilocarpine (Pilo) model. To this aim, male mice were subdivided into sham (SO, vehicle), Pilo (300 μg/1 μL icv, followed by the vehicle per os, po) and NMP-treated groups (Pilo 300 μg/1 μL icv, followed by 100 or 200 mg/kg po). The treatments started one day after the Pilo injection and continued for 15 days. The effects of NMP were assessed by characterizing the preservation of cognitive function in both the Y-maze and object recognition tests. The hippocampal cell viability was evaluated by Nissl staining. Additional markers of damage were studied—the glial fibrillary acidic protein (GFAP) and the ionized calcium-binding adaptor molecule 1 (Iba-1) expression using, respectively, immunofluorescence and western blot analyses. We also performed molecular docking experiments revealing that NMP binds to the γ-aminobutyric acid (GABA) transporter 1 (GAT1). GAT1 expression in the hippocampus was also characterized. Pilo induced cognitive deficits, cell damage, increased GFAP, Iba-1, and GAT1 expression in the hippocampus. These alterations were prevented, especially by the higher NMP dose. These data highlight NMP as a promising candidate for the protection of the hippocampus, as shown by the icv Pilo model.
2020
11-giu-2020
21
11
1
22
A proline derivative-enriched fraction from Sideroxylon obtusifolium protects against intracerebroventricular pilocarpine-induced injury associated with status epilepticus in mice / Everson Alexandre de Aquino, Pedro; Rabelo Bezerra, Jéssica; de Souza Nascimento, Tyciane; Tavares, Juliete; ROSAL LUSTOSA, Italo; José Maia Chaves Filho, Adriano; Mottin, Melina; Macêdo Gaspar, Danielle; Matos de Andrade, Geanne; Rose Tavares Neves, Kelly; Biagini, Giuseppe; Rocha Silveira, Edilberto; Socorro de Barros Viana, Glauce. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 21:11(2020), pp. 1-22. [10.3390/ijms21114188]
Everson Alexandre de Aquino, Pedro; Rabelo Bezerra, Jéssica; de Souza Nascimento, Tyciane; Tavares, Juliete; ROSAL LUSTOSA, Italo; José Maia Chaves Filho, Adriano; Mottin, Melina; Macêdo Gaspar, Danielle; Matos de Andrade, Geanne; Rose Tavares Neves, Kelly; Biagini, Giuseppe; Rocha Silveira, Edilberto; Socorro de Barros Viana, Glauce
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