Entada phaseoloides extract suppresses hepatic gluconeogenesis via activation of the AMPK signaling pathway

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• 作者：Tao Zheng^a ; ^b ; Xincai Hao^c ; Qibin Wang^a ; Li Chen^a ; Si Jin^b ; ^d ; ^{jinsi@hust.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Fang Bian^b ; ^e ; ^{bianfang45@sina.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ACC ; acetyl coenzyme A carboxylase ; AICAR ; 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside ; AMPK ; AMP-activated protein kinase ; CCK-8 ; cell counting kit-8 ; Dex/cAMP ; dexamethasone/cAMP ; Entada phaseoloides ; Entada phaseoloides (L.) Merr. ; G6pase ; glucose-6-phosphatase ; GSK3β ; glycogen synthase kinase 3β ; HG ; high glucose ; IR ; insulin resistance ; IRS-1 ; insulin receptor substrate-1 ; Δψm ; mitochondrial membrane potential ; PI3K ; phosphatidylinositol 3-kinase ; PEPCK ; phosphoenoylpyruvate carboxy
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：4 December 2016
• 年：2016
• 卷：193
• 期：Complete
• 页码：691-699
• 全文大小：1818 K

文摘

The seed of Entada phaseoloides (L.) Merr. (Entada phaseoloides) has been long used as a folk medicine for the treatment of Diabetes mellitus by Chinese ethnic minorities. Recent reports have demonstrated that total saponins from Entada phaseoloides (TSEP) could reduce fasting blood glucose in type 2 diabetic rats. However, the mechanism has not been fully elucidated. The aim of this study was to explore the underlying mechanisms of TSEP on type 2 Diabetes mellitus (T2DM).

Materials and methods

Primary mouse hepatocytes and HepG2 cells were used to investigate the effects of TSEP on gluconeogenesis. After treatment with TSEP, glucose production, genes expression levels of Glucose-6-phosphatase (G6pase) and Phosphoenoylpyruvate carboxykinase (Pepck) were detected. The efficacy and underlying mechanism of TSEP on AMP-activated protein kinase (AMPK) signaling pathway were determinated.

Results

TSEP significantly inhibited glucose production and the gluconeogenic gene expression. Treatment with TSEP elevated the phosphorylation of AMPK, which in turn promoted the phosphorylation of acetyl coenzyme A (ACC) and Akt/glycogen synthase kinase 3β (GSK3β), respectively. Furthermore, TSEP reduced lipid accumulation and improved insulin sensitivity in hepatocytes.

Conclusion

These findings provide evidence that TSEP exerts an antidiabetic effect by suppressing hepatic gluconeogenesis via the AMPK signaling pathway.