HGSD attenuates neuronal apoptosis through enhancing neuronal autophagy in the brain of diabetic mice: The role of AMP-activated protein kinase.
Life Sci
; 153: 23-34, 2016 May 15.
Article
em En
| MEDLINE
| ID: mdl-27067476
ABSTRACT
AIMS:
Berberine (BBR) holds promising effect for neuronal injury in diabetes because its anti-apoptotic activity and our laboratory developed the Huang-Gui Solid Dispersion (HGSD) to improve oral bioavailability of BBR. However, anti-apoptotic effect and the mechanism of HGSD in the brain of diabetic mice are not clear. We hypothesized that the AMPK/mTOR signaling pathway could exert a protective role in high glucose induced cellular apoptotic death via inducing autophagy and HGSD could inhibit apoptosis by activating AMPK/mTOR pathway. MAINMETHODS:
In vivo, we established C57/BL6 mice diabetic model by STZ and detected apoptosis, autophagy and AMPK/mTOR to explore the effect of HGSD. In vitro, we established high glucose-induced apoptotic death model, treating cells with 3-MA, compound C and AICAR to explore the anti-apoptotic mechanism of BBR. KEYFINDINGS:
HGSD significantly inhibited cell apoptosis, enhanced cell autophagy and activated the AMPK/mTOR pathway in the hippocampi of diabetic C57/BL6 mice, and the function of BBR is not obvious at the same dosage. Moreover, BBR significantly attenuated apoptotic death, enhanced autophagy and activated the AMPK/mTOR pathway in high glucose-treated SH-SY5Y cells. Pretreated cells with 3-MA, an inhibitor of autophagy, abolished BBR-inhibited apoptosis. Pretreated cells with Compound C, an AMPK inhibitor, blocked BBR-inhibited apoptotic and BBR-induced cell autophagy. AICAR, an AMPK activator, strengthened the function of BBR.SIGNIFICANCE:
HGSD protected against neurotoxicity induced by high glucose through activating autophagy and eventually inhibiting neuronal apoptosis, which was activated by the AMPK/mTOR signaling pathway.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Medicinas Tradicionais:
Medicinas_tradicionales_de_asia
/
Medicina_china
Assunto principal:
Medicamentos de Ervas Chinesas
/
Apoptose
/
Proteínas Quinases Dependentes de AMP Cíclico
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Modelos Animais de Doenças
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Neurônios
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China