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Biosci Rep ; 38(5)2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-30287501

RESUMO

Background: Fangjing decoction is a Traditional Chinese Medicine that exhibits anticonvulsive effects in treating febrile seizures (FS). Its action mechanism and the regulation on Akt/mammalian target of rapamycin (mTOR) pathway were revealed in the present study.Methods: FS model was established in Sprague-Dawley rats with or without Fangjing decoction treatment. On day 5, following initiation of drug treatment, seizures were monitored. Hippocampal neuron apoptosis was assessed using terminal dUTP nick end-labeling method. The levels of Bax, protein kinase B (Akt), phospho-Akt (p-Akt), mTOR, and p-mTOR proteins were analyzed using Western blotting. The content of hippocampal γ-aminobutyric acid (GABA) was measured by using ELISA assay.Results: Compared with the control group (n=8), Fangjing decoction effectively prolonged the latency but shortened the duration of FS in rats (n=8). Concomitantly, the apoptosis of hippocampal neurons, as well as Bax protein levels were also decreased in FS rats which were treated with Fangjing decoction. In addition, the Akt/mTOR signaling was found to be activated in rat hippocampus following FS, as evidenced by increased p-Akt and p-mTOR, while Fangjing decoction could inhibit the activation of Akt/mTOR signaling. Furthermore, the low GABA content in rat hippocampus following FS was significantly elevated by Fangjing decoction treatment. More importantly, SC79, a specific activator for Akt, apparently attenuated the protective effects of Fangjing decoction on FS rats.Conclusion: These results suggest that Fangjing decoction protects the hippocampal neurons from apoptosis by inactivating Akt/mTOR pathway, which may contribute to mitigating FS-induced brain injury.


Assuntos
Anticonvulsivantes/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas c-akt/genética , Convulsões Febris/tratamento farmacológico , Serina-Treonina Quinases TOR/genética , Acetatos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Benzopiranos/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Neurônios/metabolismo , Neurônios/patologia , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Convulsões Febris/genética , Convulsões Febris/metabolismo , Convulsões Febris/patologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Ácido gama-Aminobutírico/metabolismo
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