HGSD attenuates neuronal apoptosis through enhancing neuronal autophagy in the brain of diabetic mice: The role of AMP-activated protein kinase

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• 作者：Huan Xue¹ ; Yingshi Ji¹ ; Shengnan Wei ; Yang Yu ; Xin Yan ; Shuping Liu ; Ming Zhang ; Fan Yao ; Xiaoxin Lan ; Li Chen ; ^{zhouweichen@yahoo.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Diabetes ; Neuronal apoptosis ; Autophagy ; AMPK/m TOR pathway ; Huang-gui solid dispersion
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 May 2016
• 年：2016
• 卷：153
• 期：Complete
• 页码：23-34
• 全文大小：2411 K

文摘

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.

Main methods

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.

Key findings

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.